Fentanyl and its derivatives: Pain-killers or man-killers?

Fentanyl is a synthetic µ-opioid receptor agonist approved to treat severe to moderate pain with faster onset of action and about 100 times more potent than morphine. Over last two decades, abuse of fentanyl and its derivatives has an increased trend, globally. Currently, the United States (US) faces the most serious situation related to fentanyl overdose, commonly referred to as the opioid epidemic. Nowadays, fentanyl is considered as the number one cause of death for adults aged 18-45 in the US. Synthesis and derivatization of fentanyl is inexpensive to manufacture and easily achievable. Indeed, more than 1400 fentanyl derivatives have been described in the scientific literature and patents. In addition, accessibility and efficacy of fentanyl and its derivatives can play a potential role in misuse of these compounds as a chemical weapon. In this review, the properties, general pharmacology, and overdose death cases associated with fentanyl and selected derivatives are presented. Moreover, current opioid epidemic in the US, Moscow theatre hostage crisis, and potential misuse of fentanyl and its derivatives as a chemical weapon are disclosed.

Comprehensive analysis of prohibited substances and methods in sports: Unveiling trends, pharmacokinetics, and WADA evolution.

This review systematically compiles sports-related drugs, substances, and methodologies based on the most frequently detected findings from prohibited lists published annually by the World Anti-Doping Agency (WADA) between 2003 and 2021. Aligned with structure of the 2023 prohibited list, it covers all proscribed items and details the pharmacokinetics and pharmacodynamics of five representatives from each section. Notably, it explores significant metabolites and metabolic pathways associated with these substances. Adverse analytical findings are summarized in tables for clarity, and the prevalence is visually represented through charts. The review includes a concise historical overview of doping and WADA's role, examining modifications in the prohibited list for an understanding of evolving anti-doping measures.

Dendrobine: A neuroprotective Sesquiterpenic Alkaloid for the Prevention and Treatment of Diseases: A Review.

A sesquiterpenic alkaloid dendrobine is the major bioactive compound extracted from Dendrobium nobile Lindl. This compound was structurally very similar to picrotoxinin (neurotoxin) containing bicyclic or tricyclic ring while dendrobine containing tetracyclic rings with up to 7 stereogenic centers showing numerous neuroprotective effects. Several sesquiterpenic alkaloids such as (+)-(1R,5R,6S,8R,9R)- 8,12-dihydroxy-copacamphan-3-en-2-one, dendrobine, denrine B, (+)- (1R,2S,3R,4S,5R,6S,9R)-3,11,12-trihydroxypicrotoxane-2(15)-lactone, dendroxine B, nobilonine, 13-Hydroxy-14-oxodendrobine, 6-Hydroxy-nobilonine and (-)-(1S,2R,3S,4R,5S,6R,9S,12R)- 3,11,13-trihydroxypicrotoxane-2(15)-lactone were isolated from D. nobile This comprehensive review summarizes the necessary information on the morphology, biochemistry and pharmacology of dendrobine. The phytochemical profile had potent in-vivo and in-vitro efficacy in neuroprotection, nerve function, memory enhancement, cognitive disorders, anxiety and depression, anti-oxidant, psychological conditions, increasing serotonin concentration in synapse anxiolytic, tranquilizing, anti-stress, neurodegenerative (Alzheimer's disease and Parkinson), anti-inflammatory and analgesic. The compound dendrobine activates neuro synapses, serotonergic synapse and signaling pathways during neurotransmission playing important role in Alzheimer's disease, Parkinson's disease, anxiety and long-term depression.

Targeted Inhibition of the PI3K/Akt/mTOR Signaling Axis: Potential for Sarcoma Therapy.

Sarcoma is a heterogeneous group of malignancies often resistant to conventional chemotherapy and radiation therapy. The phosphatidylinositol-3-kinase/ protein kinase B /mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway has emerged as a critical cancer target due to its central role in regulating key cellular processes such as cell growth, proliferation, survival, and metabolism. Dysregulation of this pathway has been implicated in the development and progression of bone sarcomas (BS) and soft tissue sarcomas (STS). PI3K/Akt/mTOR inhibitors have shown promising preclinical and clinical activity in various cancers. These agents can inhibit the activation of PI3K, Akt, and mTOR, thereby reducing the downstream signaling events that promote tumor growth and survival. In addition, PI3K/Akt/mTOR inhibitors have been shown to enhance the efficacy of other anticancer therapies, such as chemotherapy and radiation therapy. The different types of PI3K/Akt/mTOR inhibitors vary in their specificity, potency, and side effect profiles and may be effective depending on the specific sarcoma type and stage. The molecular targeting of PI3K/Akt/mToR pathway using drugs, phytochemicals, nanomaterials (NMs), and microbe-derived molecules as Pan-PI3K inhibitors, selective PI3K inhibitors, and dual PI3K/mTOR inhibitors have been delineated. While there are still challenges to be addressed, the preclinical and clinical evidence suggests that these inhibitors may significantly improve patient outcomes. Further research is needed to understand the potential of these inhibitors as sarcoma therapeutics and to continue developing more selective and effective agents to meet the clinical needs of sarcoma patients.

Frentizole derivatives with mTOR inhibiting and senomorphic properties.

Frentizole is immunosuppressive drug with low acute toxicity and lifespan-prolonging effect. Recently, frentizole´s potential to disrupt toxic amyloid ß (Aß) - Aß-binding alcohol dehydrogenase (ABAD) interaction in mitochondria in Alzheimer´s brains has been revealed. Another broadly studied drug with anti-aging and immunosuppressive properties is an mTOR inhibitor - rapamycin. Since we do not yet precisely know what is behind the lifespan-prolonging effect of rapamycin and frentizole, whether it is the ability to inhibit the mTOR signaling pathway, reduction in mitochondrial toxicity, immunosuppressive effect, or a combination of all of them, we have decided within our previous work to dock the entire in-house library of almost 240 Aß-ABAD modulators into the FKBP-rapamycin-binding (FRB) domain of mTOR in order to interlink mTOR-centric and mitochondrial free radical-centric theories of aging and thus to increase the chances of success. Based on the results of the docking study, molecular dynamic simulation and MM-PBSA calculations, we have selected nine frentizole-like compounds (1 - 9). Subsequently, we have determined their real physical-chemical properties (logP, logD, pKa and solubility in water and buffer), cytotoxic/cytostatic, mTOR inhibitory, and in vitro anti-senescence (senolytic and senomorphic) effects. Finally, the three best candidates (4, 8, and 9) have been forwarded for in vivo safety studies to assess their acute toxicity and pharmacokinetic properties. Based on obtained results, only compound 4 demonstrated the best results within in vitro testing, the ability to cross the blood-brain barrier and the lowest acute toxicity (LD50 in male mice 559 mg/kg; LD50 in female mice 575 mg/kg).

The role of redox active copper(II) on antioxidant properties of the flavonoid baicalein: DNA protection under Cu(II)-Fenton reaction and Cu(II)-ascorbate system conditions.

The antioxidant properties of flavonoids are mediated by their functional hydroxyl groups, which are capable of both chelating redox active metals such as iron, copper and scavenging free radicals. In this paper, the antioxidant vs. prooxidant and DNA protecting properties of baicalein and Cu(II)-baicalein complexes were studied under the conditions of the Copper-Fenton reaction and of the Copper-Ascorbate system. From the relevant EPR spectra, the interaction of baicalein with Cu(II) ions was confirmed, while UV-vis spectroscopy demonstrated a greater stability over time of Cu(II)-baicalein complexes in DMSO than in methanol and PBS and Phosphate buffers. An ABTS study confirmed a moderate ROS scavenging efficiency, at around 37%, for both free baicalein and Cu(II)-baicalein complexes (in the ratios 1:1 and 1:2). The results from absorption titrations are in agreement with those from viscometric studies and confirmed that the binding mode between DNA and both free baicalein and Cu-baicalein complexes, involves hydrogen bonds and van der Waals interactions. The DNA protective effect of baicalein has been investigated by means of gel electrophoresis under the conditions of the Cu-catalyzed Fenton reaction and of the Cu-Ascorbate system. In both cases, it was found that, at sufficiently high concentrations, baicalein offers some protection to cells from DNA damage caused by ROS (singlet oxygen, hydroxyl radicals and superoxide radical anions). Accordingly, baicalein may be useful as a therapeutic agent in diseases with a disturbed metabolism of redox metals such as copper, for example Alzheimer's disease, Wilson's disease and various cancers. While therapeutically sufficient concentrations of baicalein may protect neuronal cells from Cu-Fenton-induced DNA damage in regard to neurological conditions, conversely, in the case of cancers, low concentrations of baicalein do not inhibit the pro-oxidant effect of copper ions and ascorbate, which can, in turn, deliver an effective damage to DNA in tumour cells.

Multiple neurological effects associated with exposure to organophosphorus pesticides in man.

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.

Discovery of small molecule mechanistic target of rapamycin inhibitors as anti-aging and anti-cancer therapeutics.

To date, the most studied drug in anti-aging research is the mTOR inhibitor - rapamycin. Despite its almost perfect anti-aging profile, rapamycin exerts one significant limitation - inappropriate physicochemical properties. Therefore, we have decided to utilize virtual high-throughput screening and fragment-based design in search of novel mTOR inhibiting scaffolds with suitable physicochemical parameters. Seven lead compounds were selected from the list of obtained hits that were commercially available (4, 5, and 7) or their synthesis was feasible (1, 2, 3, and 6) and evaluated in vitro and subsequently in vivo. Of all these substances, only compound 3 demonstrated a significant cytotoxic, senolytic, and senomorphic effect on normal and cancerous cells. Further, it has been confirmed that compound 3 is a direct mTORC1 inhibitor. Last but not least, compound 3 was found to exhibit anti-SASP activity concurrently being relatively safe within the test of in vivo tolerability. All these outstanding results highlight compound 3 as a scaffold worthy of further investigation.

Traditional uses, phytochemistry, pharmacology and toxicology of garlic (Allium sativum), a storehouse of diverse phytochemicals: A review of research from the last decade focusing on health and nutritional implications.

Allium sativum L. (Garlic) is a fragrant herb and tuber-derived spice that is one of the most sought-after botanicals, used as a culinary and ethnomedicine for a variety of diseases around the world. An array of pharmacological attributes such as antioxidant, hypoglycemic, anti-inflammatory, antihyperlipidemic, anticancer, antimicrobial, and hepatoprotective activities of this species have been established by previous studies. A. sativum houses many sulfur-containing phytochemical compounds such as allicin, diallyl disulfide (DADS), vinyldithiins, ajoenes (E-ajoene, Z-ajoene), diallyl trisulfide (DATS), micronutrient selenium (Se) etc. Organosulfur compounds are correlated with modulations in its antioxidant properties. The garlic compounds have also been recorded as promising immune-boosters or act as potent immunostimulants. A. sativum helps to treat cardiovascular ailments, neoplastic growth, rheumatism, diabetes, intestinal worms, flatulence, colic, dysentery, liver diseases, facial paralysis, tuberculosis, bronchitis, high blood pressure, and several other diseases. The present review aims to comprehensively enumerate the ethnobotanical and pharmacological aspects of A. sativum with notes on its phytochemistry, ethnopharmacology, toxicological aspects, and clinical studies from the retrieved literature from the last decade with notes on recent breakthroughs and bottlenecks. Future directions related to garlic research is also discussed.

Privileged multi-target directed propargyl-tacrines combining cholinesterase and monoamine oxidase inhibition activities.

Twenty-four novel compounds bearing tetrahydroacridine and N-propargyl moieties have been designed, synthesised, and evaluated in vitro for their anti-cholinesterase and anti-monoamine oxidase activities. Propargyltacrine 23 (IC50 = 21 nM) was the most potent acetylcholinesterase (AChE) inhibitor, compound 20 (IC50 = 78 nM) showed the best inhibitory human butyrylcholinesterase (hBChE) profile, and ligand 21 afforded equipotent and significant values on both ChEs (human AChE [hAChE]: IC50 = 0.095 ± 0.001 µM; hBChE: IC50 = 0.093 ± 0.003 µM). Regarding MAO inhibition, compounds 7, 15, and 25 demonstrated the highest inhibitory potential towards hMAO-B (IC50 = 163, 40, and 170 nM, respectively). In all, compounds 7, 15, 20, 21, 23, and 25 exhibiting the most balanced pharmacological profile, were submitted to permeability and cell viability tests. As a result, 7-phenoxy-N-(prop-2-yn-1-yl)-1,2,3,4-tetrahydroacridin-9-amine hydrochloride (15) has been identified as a permeable agent that shows a balanced pharmacological profile [IC50 (hAChE) = 1.472 ± 0.024 µM; IC50 (hBChE) = 0.659 ± 0.077 µM; IC50 (hMAO-B) = 40.39 ± 5.98 nM], and consequently, as a new hit-ligand that deserves further investigation, in particular in vivo analyses, as the preliminary cell viability test results reported here suggest that this is a relatively safe therapeutic agent.

Contemporary mTOR inhibitor scaffolds to diseases breakdown: A patent review (2015-2021).

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.

Recent advances in the potential applications of luminescence-based, SPR-based, and carbon-based biosensors.

The need for biosensors has evolved in the detection of molecules, diseases, and pollution from various sources. This requirement has headed to the development of accurate and powerful equipment for analysis using biological sensing component as a biosensor. Biosensors have the advantage of rapid detection that can beat the conventional methods for the detection of the same molecules. Bio-chemiluminescence-based sensors are very sensitive during use in biological immune assay systems. Optical biosensors are emerging with time as they have the advantage that they act with a change in the refractive index. Carbon nanotube-based sensors are another area that has an important role in the biosensor field. Bioluminescence gives much higher quantum yields than classical chemiluminescence. Electro-generated bioluminescence has the advantage of miniature size and can produce a high signal-to-noise ratio and the controlled emission. Recent advances in biological techniques and instrumentation involving fluorescence tag to nanomaterials have increased the sensitivity limit of biosensors. Integrated approaches provided a better perspective for developing specific and sensitive biosensors with high regenerative potentials. This paper mainly focuses on sensors that are important for the detection of multiple molecules related to clinical and environmental applications. KEY POINTS: • The review focusses on the applications of luminescence-based, surface plasmon resonance-based, carbon nanotube-based, and graphene-based biosensors • Potential clinical, environmental, agricultural, and food industry applications/uses of biosensors have been critically reviewed • The current limitations in this field are discussed, as well as the prospects for future advancement.

Phytoremediation of heavy metal pollution: Hotspots and future prospects.

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.

Herbal drugs and natural bioactive products as potential therapeutics: A review on pro-cognitives and brain boosters perspectives.

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.

Neuropharmacology of Cevimeline and Muscarinic Drugs-Focus on Cognition and Neurodegeneration.

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-ß (Aß) 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.

Applications of Fruit Polyphenols and Their Functionalized Nanoparticles Against Foodborne Bacteria: A Mini Review.

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.

Antifungal Nano-Therapy in Veterinary Medicine: Current Status and Future Prospects.

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.

Mechanistic Insight into Antimicrobial and Antioxidant Potential of Jasminum Species: A Herbal Approach for Disease Management.

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.

Rapamycin: Drug Repurposing in SARS-CoV-2 Infection.

Since December 2019, SARS-CoV-2 (COVID-19) has been a worldwide pandemic with enormous consequences for human health and the world economy. Remdesivir is the only drug in the world that has been approved for the treating of COVID-19. This drug, as well as vaccination, still has uncertain effectiveness. Drug repurposing could be a promising strategy how to find an appropriate molecule: rapamycin could be one of them. The authors performed a systematic literature review of available studies on the research describing rapamycin in association with COVID-19 infection. Only peer-reviewed English-written articles from the world's acknowledged databases Web of Science, PubMed, Springer and Scopus were involved. Five articles were eventually included in the final analysis. The findings indicate that rapamycin seems to be a suitable candidate for drug repurposing. In addition, it may represent a better candidate for COVID-19 therapy than commonly tested antivirals. It is also likely that its efficiency will not be reduced by the high rate of viral RNA mutation.

Novel CRISPR-Cas Systems: An Updated Review of the Current Achievements, Applications, and Future Research Perspectives.

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.