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As a class of mycotoxins with regulatory and public health significance, aflatoxins (e.g., aflatoxin B1, B2, G1 and G2) have attracted unparalleled attention from government, academia and industry due to their chronic and acute toxicity. Aflatoxins are secondary metabolites of various Aspergillus species, which are ubiquitous in the environment and can grow on a variety of crops whereby accumulation is impacted by climate influences. Consumption of foods and feeds contaminated by aflatoxins are hazardous to human and animal health, hence the detection and quantification of aflatoxins in foods and feeds is a priority from the viewpoint of food safety. Since the first purification and identification of aflatoxins from feeds in the 1960s, there have been continuous efforts to develop sensitive and rapid methods for the determination of aflatoxins. This review aims to provide a comprehensive overview on advances in aflatoxins analysis and highlights the importance of sample pretreatments, homogenization and various cleanup strategies used in the determination of aflatoxins. The use of liquid-liquid extraction (LLE), supercritical fluid extraction (SFE), solid phase extraction (SPE) and immunoaffinity column clean-up (IAC) and dilute and shoot for enhancing extraction efficiency and clean-up are discussed. Furthermore, the analytical techniques such as gas chromatography (GC), liquid chromatography (LC), mass spectrometry (MS), capillary electrophoresis (CE) and thin-layer chromatography (TLC) are compared in terms of identification, quantitation and throughput. Lastly, with the emergence of new techniques, the review culminates with prospects of promising technologies for aflatoxin analysis in the foreseeable future.

Grape byproducts are a rich source of phenolics having immense medicinal properties, but usually wasted from juice/wine processing industries. The present study investigates the phenolic antioxidants and the insulinotropic effect of extracts prepared from seed, skin and stems of two red wine grape cultivars: Pusa Navarang and Merlot. Pusa Navarang cultivar has shown high amounts of total phenolics (95.8 mg/ml), flavonoids (30.5 mg/ml) and flavan-3-ols (21.8 mg/ml) in seed extract and total anthocyanin (4.9 mg/ml) in its skin extract as compared to Merlot cultivar. As determined using HPLC, higher amounts of catechin hydrate (14909 mg/l) and epicatechin (9299 mg/l) were observed in its seed extract, while quercetin hydrate (5849 mg/l) was abundant in its skin extract. Similarly, ferric reducing antioxidant power (FRAP) and ABTS + . [2,2′-azinobis (3-ethylbenzothiazoline)-6-sulfonic acid] and DPPH. (1,1-diphenyl-2-picrylhy- drazyl) radicals scavenging, were higher in its seed extract, respectively being 134.8 mg/ml of Quercetin equivalent (QE), 18.7 mM of trolox equivalent (TE) and 33.5 mM of TE. Strong correlation was obtained between FRAP and total phenolics, flavonoids and flavan-3-ols contents with correlation coefficients (r 2 ) of 0.915, 0.738 and 0.838 respectively. Interestingly, there was a 2–8 fold increase in insulin secretion by isolated mice pancreatic islets at 5.5 mM and 16.5 mM glucose concentration in presence of various extracts. Overall, the seed, skin and stem byproducts of both cultivars are rich sources of phenolics and antioxidants and represent a source of new insulin secretagogues.

Despite increases in routine vaccination coverage during the past three decades, the percent of children completing the recommended vaccination schedule remains below expected targets in many low and middle income countries. In 2008, the World Health Organization Strategic Advisory Group of Experts on Immunization requested more information on the reasons that children were under-vaccinated (receiving at least one but not all recommended vaccinations) or not vaccinated in order to develop effective strategies and interventions to reach these children. A systematic review of the peer-reviewed literature published from 1999 to 2009 was conducted to aggregate information on reasons and factors related to the under-vaccination and non-vaccination of children. A standardized form was used to abstract information from relevant articles identified from eight different medical, behavioural and social science literature databases. Among 202 relevant articles, we abstracted 838 reasons associated with under-vaccination; 379 (45%) were related to immunization systems, 220 (26%) to family characteristics, 181 (22%) to parental attitudes and knowledge, and 58 (7%) to limitations in immunization-related communication and information. Of the 19 reasons abstracted from 11 identified articles describing the non-vaccinated child, 6 (32%) were related to immunization systems, 8 (42%) to parental attitudes and knowledge, 4 (21%) to family characteristics, and 1 (5%) to communication and information. Multiple reasons for under-vaccination and non-vaccination were identified, indicating that a multi-faceted approach is needed to reach under-vaccinated and unvaccinated children. Immunization system issues can be addressed through improving outreach services, vaccine supply, and health worker training; however, under-vaccination and non-vaccination linked to parental attitudes and knowledge are more difficult to address and likely require local interventions.

Pediatric high-grade gliomas (pHGGs) are the leading cause of cancer-related deaths in children in the USA. Sixteen percent of hemispheric pediatric and young adult HGGs encode Gly34Arg/Val substitutions in the histone H3.3 (H3.3-G34R/V). The mechanisms by which H3.3-G34R/V drive malignancy and therapeutic resistance in pHGGs remain unknown. Using a syngeneic, genetically engineered mouse model (GEMM) and human pHGG cells encoding H3.3-G34R, we demonstrate that this mutation led to the downregulation of DNA repair pathways. This resulted in enhanced susceptibility to DNA damage and inhibition of the DNA damage response (DDR). We demonstrate that genetic instability resulting from improper DNA repair in G34R-mutant pHGG led to the accumulation of extrachromosomal DNA, which activated the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway, inducing the release of immune-stimulatory cytokines. We treated H3.3-G34R pHGG-bearing mice with a combination of radiotherapy (RT) and DNA damage response inhibitors (DDRi) (i.e., the blood-brain barrier-permeable PARP inhibitor pamiparib and the cell-cycle checkpoint CHK1/2 inhibitor AZD7762), and these combinations resulted in long-term survival for approximately 50% of the mice. Moreover, the addition of a STING agonist (diABZl) enhanced the therapeutic efficacy of these treatments. Long-term survivors developed immunological memory, preventing pHGG growth upon rechallenge. These results demonstrate that DDRi and STING agonists in combination with RT induced immune-mediated therapeutic efficacy in G34-mutant pHGG.

Peanut and its processed products are recurrently contaminated with aflatoxins (AFs) which are of potential public health concern. Among the different types of AFs, Aflatoxin B1 (B1) is the most frequently detected in peanuts over the maximum level (ML), and thus has warranted considerable research interest in the domain of food safety. In this study, we investigated the decontamination of B1 in three naturally-incurred lots (4, 12, and 40 µg/kg) of peanuts by a range of cooking treatments, including frying, pressure cooking, and roasting. B1 concentrations were determined by ultra-high performance liquid chromatography- fluorescence detection. The method provided a limit of quantification of 0.25 µg/kg for B1, which was much lower than any of its national and international MLs. The recoveries of B1 in fresh and cooked peanuts (positive-control) were in the range of 90–100%. Overall, all the cooking methods demonstrated a significant reduction in B1 loads. The degree to which the processing methods reduced the B1 content followed the pattern: roasting with a combination of NaCl and citric acid > pressure-cooking with a combination of NaCl and citric acid > frying. As the cooking procedures did not involve any complicated steps or sophisticated equipment, these could be readily adopted for decontamination or reduction in the level of B1 for a safer consumption of peanuts at the household level without affecting the organoleptic properties.

Tyrosinase is an important component of the enzyme polyphenol oxidase, which upon contact with the phenolic substrates forms the pigment melanin and induces undesirable food browning. The phenolic and triterpenoid compounds that naturally occur in plants are well known as tyrosinase inhibitors. Combretum micranthum (CM) leaves, Euphorbia hirta (EH) plant, and Anacardium occidentale (AO) fruits are traditionally known to have potential anti-tyrosinase activities. The aim of this study was to optimize the ultrasound-assisted extraction of secondary metabolites from these matrices, and to evaluate in tubo the antityrosinase activity of these extracts. Efforts were also taken to profile the secondary metabolites, mainly the phenolic and triterpenoid compounds, in order to understand their probable association with tyrosinase inhibition. The optimal ultrasound-assisted extraction conditions for simultaneous extraction of phenolic, and triterpenoid compounds were determined. The aqueous fraction of these extracts showed significant antityrosinase activity, with the CM leaves exhibiting the strongest inhibitory effect (IC50 of 0.58 g·L−1). The predominant metabolic compounds from these natural extracts were putatively identified by using a high-resolution quadrupole-time of flight (QToF) LC-MS instrument. The high-resolution accurate mass-based screening resulted in identification of 88 predominant metabolites, which included dihydrodaidzein-7-O-glucuronide, micromeric acid, syringic acid, morin, quercetin-3-O-(6″-malonyl-glucoside), 4-hydroxycoumarin, dihydrocaffeic acid-3-O-glucuronide, to name some, with less than 5 ppm of mass error.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in the adult population and it carries a dismal prognosis. Inefficient drug delivery across the blood brain barrier (BBB), an immunosuppressive tumor microenvironment (TME) and development of drug resistance are key barriers to successful glioma treatment. Since gliomas occur through sequential acquisition of genetic alterations, gene therapy, which enables to modification of the genetic make-up of target cells, appears to be a promising approach to overcome the obstacles encountered by current therapeutic strategies. Gene therapy is a rapidly evolving field with the ultimate goal of achieving specific delivery of therapeutic molecules using either viral or non-viral delivery vehicles. Gene therapy can also be used to enhance immune responses to tumor antigens, reprogram the TME aiming at blocking glioma-mediated immunosuppression and normalize angiogenesis. Nano-particles-mediated gene therapy is currently being developed to overcome the BBB for glioma treatment. Another approach to enhance the anti-glioma efficacy is the implementation of viro-immunotherapy using oncolytic viruses, which are immunogenic. Oncolytic viruses kill tumor cells due to cancer cell-specific viral replication, and can also initiate an anti-tumor immunity. However, concerns still remain related to off target effects, and therapeutic and transduction efficiency. In this review, we describe the rationale and strategies as well as advantages and disadvantages of current gene therapy approaches against gliomas in clinical and preclinical studies. This includes different delivery systems comprising of viral, and non-viral delivery platforms along with suicide/prodrug, oncolytic, cytokine, and tumor suppressor-mediated gene therapy approaches. In addition, advances in glioma treatment through BBB-disruptive gene therapy and anti-EGFRvIII/VEGFR gene therapy are also discussed. Finally, we discuss the results of gene therapy-mediated human clinical trials for gliomas. In summary, we highlight the progress, prospects and remaining challenges of gene therapies aiming at broadening our understanding and highlighting the therapeutic arsenal for GBM.

Mycotoxins are deleterious fungal secondary metabolites that contaminate food and feed, thereby creating concerns regarding food safety. Common fungal genera can easily proliferate in Indian tropical and sub-tropical conditions, and scientific attention is warranted to curb their growth. To address this, two nodal governmental agencies, namely the Agricultural and Processed Food Products Export Development Authority (APEDA) and the Food Safety and Standards Authority of India (FSSAI), have developed and implemented analytical methods and quality control procedures to monitor mycotoxin levels in a range of food matrices and assess risks to human health over the last two decades. However, comprehensive information on such advancements in mycotoxin testing and issues in implementing these regulations has been inadequately covered in the recent literature. The aim of this review is thus to uphold a systematic picture of the role played by the FSSAI and APEDA for mycotoxin control at the domestic level and for the promotion of international trade, along with certain challenges in dealing with mycotoxin monitoring. Additionally, it unfolds various regulatory concerns regarding mycotoxin mitigation in India. Overall, it provides valuable insights for the Indian farming community, food supply chain stakeholders and researchers about India’s success story in arresting mycotoxins throughout the food supply chain.

Gliomas are one of the most lethal types of cancers accounting for ∼80% of all central nervous system (CNS) primary malignancies. Among gliomas, glioblastomas (GBM) are the most aggressive, characterized by a median patient survival of fewer than 15  months. Recent molecular characterization studies uncovered the genetic signatures and methylation status of gliomas and correlate these with clinical prognosis. The most relevant molecular characteristics for the new glioma classification are IDH mutation, chromosome 1p/19q deletion, histone mutations, and other genetic parameters such as ATRX loss, TP53, and TERT mutations, as well as DNA methylation levels. Similar to other solid tumors, glioma progression is impacted by the complex interactions between the tumor cells and immune cells within the tumor microenvironment. The immune system’s response to cancer can impact the glioma’s survival, proliferation, and invasiveness. Salient characteristics of gliomas include enhanced vascularization, stimulation of a hypoxic tumor microenvironment, increased oxidative stress, and an immune suppressive milieu. These processes promote the neuro-inflammatory tumor microenvironment which can lead to the loss of blood-brain barrier (BBB) integrity. The consequences of a compromised BBB are deleteriously exposing the brain to potentially harmful concentrations of substances from the peripheral circulation, adversely affecting neuronal signaling, and abnormal immune cell infiltration; all of which can lead to disruption of brain homeostasis. In this review, we first describe the unique features of inflammation in CNS tumors. We then discuss the mechanisms of tumor-initiating neuro-inflammatory microenvironment and its impact on tumor invasion and progression. Finally, we also discuss potential pharmacological interventions that can be used to target neuro-inflammation in gliomas.

The heavy metal speciation analysis in sediments helps us understand and evaluate essential and unavoidable issues in terms of both health and environmental hazards imposed by these metals in our lives. Analyzing the total content of heavy metals enables us to understand only the quantity of the contaminants. To understand the different species or the chemical forms of heavy metals available in the sediments, we must study their speciation. Speciation studies help us determine their possible sources as well as their environmental stability in terms of availability to plants and other organisms. The heavy metals in this study were specified using four-stage sequential extraction, also known as the BCR technique. This study mainly highlights the quantification of metal contamination of Cu, Zn, Pb, Ni, Cd & Cr, and chemical forms as species in sediment samples collected from different Pune District, Maharashtra sites. Heavy metal contamination from the collected samples was analyzed with the use of flame atomic absorption spectrometry. This study indicated that Zn and Ni are among the most abundant metals in the sediment samples; however, Cu and Cd belong to the least abundant category. The oxidizable and residual forms (immobile and cannot be used by the organisms readily) appeared dominant for most heavy metals. Very significant differences were observed in the speciation of heavy metals from sample to sample, which was probably due to differences in water/soil composition and the agrochemicals like pesticides, weedicides, and fertilizers used in agricultural practices; the wastewater generated from different pharmaceuticals, chemical processing and manufacturing industries as well as the improper wastewater treatment methods.