Search

Memory, one of the most vital aspects of the human brain, is necessary for the effective survival of an individual. ‘Memory’ can be defined in various ways but in an overall view, memory is the retention of the information that the brain grasps. Different factors are responsible for the disbalance in the brain’s hippocampus region and the acetylcholine level, which masters the memory and cognitive functions. Plants are a source of pharmacologically potent drug molecules of high efficacy. Recently herbal medicine has evolved rapidly, gaining great acceptance worldwide due to their natural origin and fewer side effects. In this review, the authors have discussed the mechanisms and pharmacological action of herbal bioactive compounds to boost memory. Moreover, this review presents an update of different herbs and natural products that could act as memory enhancers and how they can be potentially utilized in the near future for the treatment of severe brain disorders. In addition, the authors also discuss the differences in biological activity of the same herb and emphasize the requirement for a higher standardization in cultivation methods and plant processing. The demand for further studies evaluating the interactions of herbal drugs is mentioned.

T-2 toxin and deoxynivalenol (DON) are type A and B trichothecenes, respectively. They widely occur as pollutants in food and crops and cause a series of toxicities, including immunotoxicity, hepatotoxicity, and neurotoxicity. Oxidative stress is the primary mechanistic basis of these toxic effects. Increasing amounts of evidence have shown that mitochondria are significant targets of apoptosis caused by T-2 toxin- and DON-induced oxidative stress via regulation of Bax/B-cell lymphoma-2 and caspase-3/caspase-9 signaling. DNA methylation and autophagy are involved in oxidative stress related to apoptosis, and hypoxia and immune evasion are related to oxidative stress in this context. Hypoxia induces oxidative stress by stimulating mitochondrial reactive oxygen species production and regulates the expression of cytokines, such as interleukin-1β and tumor necrosis factor-α. Programmed cell death-ligand 1 is upregulated by these cytokines and by hypoxia-inducible factor-1, which allows it to bind to programmed cell death-1 to enable escape of immune cell surveillance and achievement of immune evasion. This review concentrates on novel findings regarding the oxidative stress mechanisms of the trichothecenes T-2 toxin and DON. Importantly, we discuss the new evidence regarding the connection of hypoxia and immune evasion with oxidative stress in this context. Finally, the trinity of hypoxia, oxidative stress and immune evasion is highlighted. This work will be conducive to an improved understanding of the oxidative stress caused by trichothecene mycotoxins.

T-2 toxin is the most toxic trichothecene mycotoxin, and it exerts potent toxic effects, including immunotoxicity, neurotoxicity, and reproductive toxicity. Recently, several novel metabolites, including 3',4'-dihydroxy-T-2 toxin and 4',4'-dihydroxy-T-2 toxin, have been uncovered. The enzymes CYP3A4 and carboxylesterase contribute to T-2 toxin metabolism, with 3'-hydroxy-T-2 toxin and HT-2 toxin as the corresponding primary products. Modified forms of T-2 toxin, including T-2-3-glucoside, exert their immunotoxic effects by signaling through JAK/STAT but not MAPK. T-2-3-glucoside results from hydrolyzation of the corresponding parent mycotoxin and other metabolites by the intestinal microbiota, which leads to enhanced toxicity. Increasing evidence has shown that autophagy, hypoxia-inducible factors, and exosomes are involved in T-2 toxin-induced immunotoxicity. Autophagy promotes the immunosuppression induced by T-2 toxin, and a complex crosstalk between apoptosis and autophagy exists. Very recently, "immune evasion" activity was reported to be associated with this toxin; this activity is initiated inside cells and allows pathogens to escape the host immune response. Moreover, T-2 toxin has the potential to trigger hypoxia in cells, which is related to activation of hypoxia-inducible factor and the release of exosomes, leading to immunotoxicity. Based on the data from a series of human exposure studies, free T-2 toxin, HT-2 toxin, and HT-2-4-glucuronide should be considered human T-2 toxin biomarkers in the urine. The present review focuses on novel findings related to the metabolism, immunotoxicity, and human exposure assessment of T-2 toxin and its modified forms. In particular, the immunotoxicity mechanisms of T-2 toxin and the toxicity mechanism of its modified form, as well as human T-2 toxin biomarkers, are discussed. This work will contribute to an improved understanding of the immunotoxicity mechanism of T-2 toxin and its modified forms.

Mechanistic target of rapamycin (mTOR) is a highly conserved protein kinase acting as a central regulator of cell functions. The kinase forms two distinct mTOR complexes termed as mTORC1 and mTORC2. Dysregulation of mTOR activity is associated with various pathological conditions. Inhibition of overactivated mTOR represent a rational approach in the treatment of numerous human diseases. Rapamycin is a potent natural inhibitor of mTOR exhibiting significant antitumor and immunosuppressive activity. Derivatization of rapamycin provided rapalogs, the first generation of mTOR inhibitors that selectively inhibit mTORC1 activity. Further interest of research community resulted in creation of the second generation of mTOR inhibitors involving both, mTOR kinase inhibitors and dual phosphoinositide 3-kinase (PI3K)/mTOR inhibitors. Recently, combining advances of first and second generation of mTOR inhibitors yielded in the third generation of inhibitors termed as rapalinks. Nowadays, novel inhibitors belonging to all of the three generations are still under development. These inhibitors help us better to understand role of mTOR in mTOR signaling pathway as well as in diverse human diseases. In this review, we summarize recent reported mTOR inhibitors or methods of use thereof in the treatment of various diseases.

This article reviews available data regarding the possible association of organophosphorus (OP) pesticides with neurological disorders such as dementia, attention deficit hyperactivity disorder, neurodevelopment, autism, cognitive development, Parkinson's disease and chronic organophosphate-induced neuropsychiatric disorder. These effects mainly develop after repeated (chronic) human exposure to low doses of OP. In addition, three well defined neurotoxic effects in humans caused by single doses of OP compounds are discussed. Those effects are the cholinergic syndrome, the intermediate syndrome and organophosphate-induced delayed polyneuropathy. Usually, the poisoning can be avoided by an improved administrative control, limited access to OP pesticides, efficient measures of personal protection and education of OP pesticide applicators and medical staff.

To clarify the global status and research hotspots of heavy metal pollution phytoremediation, we used Web of Science, Cite Space software, and VOS viewer to analyse 1123 publications from the period of 2000-2020. Literature categories, research hotpots, and the most prolific publications by country, institution, and author were analysed separately. Around 34% of the articles are contributed from five countries: China (29.37%), India (11.00%), Spain (6.29%), Italy (6.20%), and Pakistan (5.67%). The hot research topic keywords were "diversity", "translocation", and "enhanced phytoremediation". Cadmium was the most highly concerned heavy metal in the phytoremediation. Twenty-three articles were highly cited, and they mainly focused on 1) enhancing the remediation ability of plants in heavy metal contaminated soil by microbial and chemical additives; 2) the molecular effect and mechanism of heavy metals on plant growth and development; 3) discovering novel heavy metal hyper-enriched plants which can remediate mixed heavy metal pollution. From the above analysis, we concluded that the future research directions should be 1) strengthening the plant remediation ability by biochemical means; 2) studying the molecular mechanism underlying heavy metal damage to plants; 3) studying the enrichment principle of plants for heavy metals. The present study provides a further understanding of the trends in phytoremediation of heavy metal pollution, and the data analysed can be used as a guide for future research directions.

The global recognition for the potential of nanoproducts and processes in human biomedicine has given impetus for the development of novel strategies for rapid, reliable, and proficient diagnosis, prevention, and control of animal diseases. Nanomaterials exhibit significant antifungal and antimycotoxin activities against mycosis and mycotoxicosis disorders in animals, as evidenced through reports published over the recent decade and more. These nanoantifungals can be potentially utilized for the development of a variety of products of pharmaceutical and biomedical significance including the nano-scale vaccines, adjuvants, anticancer and gene therapy systems, farm disinfectants, animal husbandry, and nutritional products. This review will provide details on the therapeutic and preventative aspects of nanoantifungals against diverse fungal and mycotoxin-related diseases in animals. The predominant mechanisms of action of these nanoantifungals and their potential as antifungal and cytotoxicity-causing agents will also be illustrated. Also, the other theragnostic applications of nanoantifungals in veterinary medicine will be identified.

Drug resistance among microbial pathogens and oxidative stress caused by reactive oxygen species are two of the most challenging global issues. Firstly, drug-resistant pathogens cause several fatalities every year. Secondly aging and a variety of diseases, such as cardiovascular disease and cancer, are associated with free radical generated oxidative stress. The treatments currently available are limited, ineffective, or less efficient, so there is an immediate need to tackle these issues by looking for new therapies to resolve resistance and neutralize the harmful effects of free radicals. In the 21st century, the best way to save humans from them could be by using plants as well as their bioactive constituents. In this specific context, Jasminum is a major plant genus that is used in the Ayurvedic system of medicine to treat a variety of ailments. The information in this review was gathered from a variety of sources, including books, websites, and databases such as Science Direct, PubMed, and Google Scholar. In this review, a total of 14 species of Jasminum have been found to be efficient and effective against a wide variety of microbial pathogens. In addition, 14 species were found to be active free radical scavengers. The review is also focused on the disorders related to oxidative stress, and it was concluded that Jasminum grandiflorum and J. sambac normalized various parameters that were elevated by free radical generation. Alkaloids, flavonoids (rutoside), terpenes, phenols, and iridoid glucosides are among the main phytoconstituents found in various Jasminum species. Furthermore, this review also provides insight into the mechanistic basis of drug resistance, the generation of free radicals, and the role of Jasminum plants in combating resistance and neutralizing free radicals.

According to Darwin’s theory, endless evolution leads to a revolution. One such example is the Clustered Regularly Interspaced Palindromic Repeats (CRISPR)–Cas system, an adaptive immunity system in most archaea and many bacteria. Gene editing technology possesses a crucial potential to dramatically impact miscellaneous areas of life, and CRISPR–Cas represents the most suitable strategy. The system has ignited a revolution in the field of genetic engineering. The ease, precision, affordability of this system is akin to a Midas touch for researchers editing genomes. Undoubtedly, the applications of this system are endless. The CRISPR–Cas system is extensively employed in the treatment of infectious and genetic diseases, in metabolic disorders, in curing cancer, in developing sustainable methods for fuel production and chemicals, in improving the quality and quantity of food crops, and thus in catering to global food demands. Future applications of CRISPR–Cas will provide benefits for everyone and will save countless lives. The technology is evolving rapidly; therefore, an overview of continuous improvement is important. In this review, we aim to elucidate the current state of the CRISPR–Cas revolution in a tailor-made format from its discovery to exciting breakthroughs at the application level and further upcoming trends related to opportunities and challenges including ethical concerns.

T-2 toxin and deoxynivalenol (DON) are type A and B trichothecenes, respectively. They widely occur as pollutants in food and crops and cause a series of toxicities, including immunotoxicity, hepatotoxicity, and neurotoxicity. Oxidative stress is the primary mechanistic basis of these toxic effects. Increasing amounts of evidence have shown that mitochondria are significant targets of apoptosis caused by T-2 toxin- and DON-induced oxidative stress via regulation of Bax/B-cell lymphoma-2 and caspase-3/caspase-9 signaling. DNA methylation and autophagy are involved in oxidative stress related to apoptosis, and hypoxia and immune evasion are related to oxidative stress in this context. Hypoxia induces oxidative stress by stimulating mitochondrial reactive oxygen species production and regulates the expression of cytokines, such as interleukin-1β and tumor necrosis factor-α. Programmed cell death-ligand 1 is upregulated by these cytokines and by hypoxia-inducible factor-1, which allows it to bind to programmed cell death-1 to enable escape of immune cell surveillance and achievement of immune evasion. This review concentrates on novel findings regarding the oxidative stress mechanisms of the trichothecenes T-2 toxin and DON. Importantly, we discuss the new evidence regarding the connection of hypoxia and immune evasion with oxidative stress in this context. Finally, the trinity of hypoxia, oxidative stress and immune evasion is highlighted. This work will be conducive to an improved understanding of the oxidative stress caused by trichothecene mycotoxins.

Twelve novel analogs of STAT3 inhibitor BP-1-102 were designed and synthesised with the aim to modify hydrophobic fragments of the molecules that are important for interaction with the STAT3 SH2 domain. The cytotoxic activity of the reference and novel compounds was evaluated using several human and two mouse cancer cell lines. BP-1-102 and its two analogs emerged as effective cytotoxic agents and were further tested in additional six human and two murine cancer cell lines, in all of which they manifested the cytotoxic effect in a micromolar range. Reference compound S3I-201.1066 was found ineffective in all tested cell lines, in contrast to formerly published data. The ability of selected BP-1-102 analogs to induce apoptosis and inhibition of STAT3 receptor-mediated phosphorylation was confirmed. The structure–activity relationship confirmed a demand for two hydrophobic substituents, i.e. the pentafluorophenyl moiety and another spatially bulky moiety, for effective cytotoxic activity and STAT3 inhibition.

Twelve novel analogs of STAT3 inhibitor BP-1-102 were designed and synthesised with the aim to modify hydrophobic fragments of the molecules that are important for interaction with the STAT3 SH2 domain. The cytotoxic activity of the reference and novel compounds was evaluated using several human and two mouse cancer cell lines. BP-1-102 and its two analogs emerged as effective cytotoxic agents and were further tested in additional six human and two murine cancer cell lines, in all of which they manifested the cytotoxic effect in a micromolar range. Reference compound S3I-201.1066 was found ineffective in all tested cell lines, in contrast to formerly published data. The ability of selected BP-1-102 analogs to induce apoptosis and inhibition of STAT3 receptor-mediated phosphorylation was confirmed. The structure–activity relationship confirmed a demand for two hydrophobic substituents, i.e. the pentafluorophenyl moiety and another spatially bulky moiety, for effective cytotoxic activity and STAT3 inhibition.

Oxazolomycin A and neooxazolomycin were firstly isolated in 1985 by the group of Uemura et al. from the Streptomyces sp. bacteria. To date, there have been reported 15 different natural compounds commonly classified as part of the oxazolomycin family. All oxazolomycin compounds possess extraordinary structures and they represent a synthetic challenge. Such molecules are additionally known for their wide range of biological activity including antibacterial, antiviral and cytotoxic effects. The present review summarizes the structural elucidation and classification of oxazolomycin compounds, their biosynthesis and biological activity. It is further focused on the total syntheses of oxazolomycins and one formal synthesis reported to date.

T-2 toxin is the most toxic trichothecene mycotoxin, and it exerts potent toxic effects, including immunotoxicity, neurotoxicity, and reproductive toxicity. Recently, several novel metabolites, including 3',4'-dihydroxy-T-2 toxin and 4',4'-dihydroxy-T-2 toxin, have been uncovered. The enzymes CYP3A4 and carboxylesterase contribute to T-2 toxin metabolism, with 3'-hydroxy-T-2 toxin and HT-2 toxin as the corresponding primary products. Modified forms of T-2 toxin, including T-2-3-glucoside, exert their immunotoxic effects by signaling through JAK/STAT but not MAPK. T-2-3-glucoside results from hydrolyzation of the corresponding parent mycotoxin and other metabolites by the intestinal microbiota, which leads to enhanced toxicity. Increasing evidence has shown that autophagy, hypoxia-inducible factors, and exosomes are involved in T-2 toxin-induced immunotoxicity. Autophagy promotes the immunosuppression induced by T-2 toxin, and a complex crosstalk between apoptosis and autophagy exists. Very recently, "immune evasion" activity was reported to be associated with this toxin; this activity is initiated inside cells and allows pathogens to escape the host immune response. Moreover, T-2 toxin has the potential to trigger hypoxia in cells, which is related to activation of hypoxia-inducible factor and the release of exosomes, leading to immunotoxicity. Based on the data from a series of human exposure studies, free T-2 toxin, HT-2 toxin, and HT-2-4-glucuronide should be considered human T-2 toxin biomarkers in the urine. The present review focuses on novel findings related to the metabolism, immunotoxicity, and human exposure assessment of T-2 toxin and its modified forms. In particular, the immunotoxicity mechanisms of T-2 toxin and the toxicity mechanism of its modified form, as well as human T-2 toxin biomarkers, are discussed. This work will contribute to an improved understanding of the immunotoxicity mechanism of T-2 toxin and its modified forms.

At present, Alzheimer’s disease (AD) and related dementias cannot be cured. Therefore, scientists all over the world are trying to find a new approach to prolong an active life of patients with initial dementia. Both pharmacological and non-pharmacological pathways are investigated to improve the key symptom of the disease, memory loss. In this respect, influencing the neuromodulator acetylcholine via muscarinic receptors, such as cevimeline, might be one of the therapeutic alternatives. The purpose of this study is to explore the potential of cevimeline on the cognitive functions of AD patients. The methodology is based on a systematic literature review of available studies found in Web of Science, PubMed, Springer, and Scopus on the research topic. The findings indicate that cevimeline has shown an improvement in experimentally induced cognitive deficits in animal models. Furthermore, it has demonstrated to positively influence tau pathology and reduce the levels of amyloid-β (Aβ) peptide in the cerebral spinal fluid of Alzheimer’s patients. Although this drug has not been approved by the FDA for its use among AD patients and there is a lack of clinical studies confirming and extending this finding, cevimeline might represent a breakthrough in the treatment of AD.

The ingestion of contaminated water and food is known to cause food illness. Moreover, on assessing the patients suffering from foodborne disease has revealed the role of microbes in such diseases. Concerning which different methods have been developed for protecting food from microbes, the treatment of food with chemicals has been reported to exhibit an unwanted organoleptic effect while also affecting the nutritional value of food. Owing to these challenges, the demand for natural food preservatives has substantially increased. Therefore, the interest of researchers and food industries has shifted towards fruit polyphenols as potent inhibitors of foodborne bacteria. Recently, numerous fruit polyphenols have been acclaimed for their ability to avert toxin production and biofilm formation. Furthermore, various studies have recommended using fruit polyphenols solely or in combination with chemical disinfectants and food preservatives. Currently, different nanoparticles have been synthesized using fruit polyphenols to curb the growth of pathogenic microbes. Hence, this review intends to summarize the current knowledge about fruit polyphenols as antibacterial agents against foodborne pathogens. Additionally, the application of different fruit extracts in synthesizing functionalized nanoparticles has also been discussed.

A stereoselective approach to C-3′ methyl attached γ-lactam derivatives as the precursors of pyroglutamate core of oxazolomycins is described. The synthesis started from d -xylose and utilized [3,3]-heterosigmatropic rearrangement. The key lactamization was achieved with intramolecular aldol reaction and ring-closing metathesis. The accomplished stereoselective aldol cyclization was elucidated with Zimmerman-Traxler transition state models. Stereoselectivity of the aldol reaction was explained as a consequence of chelation and bridgehead atoms linkage. The present work also encompasses proposed structures of (E)- and (Z)- generated enolates during intramolecular aldol reaction. Although stereocenters were not formed during ring-closing metathesis, a stereospecific reduction of prepared double bond functionality was successfully accomplished.