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The progression of asbestosis is supposed to begin with the first order of respiratory bronchiole and extend outward. Recently, grade 4 asbestosis was reported to begin with the subpleural peripheral lobular area or the subpleural lobule. Grade 4 asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive numbers of asbestos fibers. Pathologically, the presence of more than two asbestos bodies/cm2 on a glass slide is required. There are many cases of diffuse interstitial pneumonia, mainly usual interstitial pneumonia, that does not fulfill the above criteria among asbestos workers or high-grade environmentally exposed persons. I call these cases “usual interstitial pneumonia seen in asbestos workers” and not idiopathic pulmonary fibrosis. In this chapter, I discuss the above subjects, including the dose-response relationship for asbestos exposure, the heterogeneous response to asbestos exposure, and the relationship between asbestosis and idiopathic pulmonary fibrosis.

Vanadium (V), a widely distributed transition metal, has been considered toxic, which depends on the valence of the compound. V pentoxide (V2O5) is considered the most harmful. Its long-term exposure produces neurotoxicity. Mice exposed to inhaled V2O5 displayed less tubulin+ in testicular cells and dendritic spines loss, cell death, and CA1 neuropil modifications, considered as the result of V interaction with the cytoskeleton, which made us suppose that V2O5 inhalation could initiate CA1 cell alterations comparable to what happen in the brains of Alzheimer disease (AD) patients. This study intends to demonstrate pyramidal CA1 cytoskeletal changes in rats which inhaled V2O5. Twenty rats were exposed to V2O5 0.02 M one hour, three times a week for several months. Our findings showed that V2O5-exposed rats had cell death that reached 56,57% after six months; we also observed collapsed strong argyrophilic nuclei and characteristic flame-shaped somas in all V2O5-exposed animals hippocampus CA1 compared to controls. We also found somatodendritic deformations. Neurite’s cytoskeleton exhibited visible thickening and nodosities and prominent dendritic spine loss. Our results demonstrate that V2O5 induces AD-like cell death with evident cytoskeletal and synaptic alterations.

Drug metabolism is a pharmacokinetic process whose main objective is to modify the chemical structure of drugs to easily excretable compounds. This process is carried out through phase I and phase II reactions. The enzymes of cytochrome P450 (CYP450) participate in phase I reactions, and their activity can be inhibited or induced by xenobiotics. The aim of this chapter is to study the clinical relevance of the induction and inhibition of CYP450, by describing the effect that some bioactive compounds present in medicinal plants or foods can modify, either increasing or decreasing the activity of CYP450 enzymes and with it modify the bioavailability and depuration of drugs. Examples will be described on the interaction of medicinal plants and foods of vegetal origin that when combined with some drugs can generate toxicity or therapeutic failure; this will allow gathering relevant information on the adequate pharmacological management in different clinical situations.

Antidotes are essential medicines for the management of some of the emergencies attended in the hospital environment, and the speed of administration can be a key element for the survival of the patient. The Hospital Pharmacy Services are responsible for guaranteeing its availability. However, this availability can be affected by some aspects like the frequency of presentation of an intoxication in a geographical area, urgency in administration, difficulties of acquisition, cost, and period of validity, among others. In Spain, a web-based application was developed (www.redantidotos.org). It includes a public site with general information, an updated antidote guide and a section where non-urgent toxicological consultations could be submitted. Design a virtual antidote network between hospitals could be really useful to help the location online of the hospitals that stocked those antidotes with the highest difficulty in terms of availability, and ensured that the medication will be loaned in case of necessity. Therefore, it is necessary to create a tool that facilitates the exchange of antidotes between hospitals and ensures their availability. The aim is to continue improving communication between professionals involved in intoxication management at national, European and international level, sharing knowledge and improving the care we offer to our patients.

The World Health Organization highlighted the increase in the resistance to conventional antibiotics for most pathogens and observed also a decrease of the threshold for all mechanisms of cell-cell microbial communication, leading to the formation of biofilms and to the increase of microbial pathogenicity. Scientific community is therefore oriented to the identification and study of alternative substances to antibiotics. In such context, substances of vegetal source, such as essential oils (EOs), always used in traditional medicine, stimulated—particularly in recent decades—the scientific world to discover and identify substances, intended as a mixture or single components capable to fight pathogenic microorganisms. From this point of view, the study of plants is very interesting and offers many interesting ideas and results. This brief chapter describes the basis of the microbial communication, until the formation of biofilm, and some mechanisms through which essential oils, or some of their main components, may decrease or inactivate the complex mechanisms that lead to pathogenicity, both of prokaryotes and eukaryotes.

Boron is an important element found in limited resources on earth, especially in Turkey, and is essential for living organisms. Boron plays key roles in human and animal systems. While boron shows its important effects as an essential element at low concentrations in the organism, it causes different toxic effects to occur at high concentrations. There are different studies on boron and boron-containing compounds effects on organisms, toxic effects mechanisms need to be detailed. Boron and its compounds can cause toxic effects in oral, dermal, and inhalation exposure and even deadly effects at very high concentrations. The use of disinfectant and cleaning products containing boron as sprays, fertilizers, etc., during the Covid-19 pandemic also increases the interest in this issue. Boron exposure could cause lung irritation, dermal irritation, genotoxicity in male reproductive system, teratogenicity in concentration-dependent manner. In vitro studies have tried to explain the toxic effects mechanisms. The aim of the current work is to explain the toxic effect mechanisms of boron and boron compounds on body systems.

Antineoplastic drugs may be neurotoxic and the clinical features frequently include distal sensory loss and neuropathic pain. This is related to a direct damage in sensory neurons and non-selective degeneration of sensory nerve fibers. Due to different mechanisms, there are agents that affects also motor or autonomic nerves. In the case of immune checkpoint inhibitors, an inflammatory response attacks the muscle, motor neurons or neuromuscular transmission. We present an easy-to-read article to understand first symptoms of chemotherapy-induced neuropathy (CIN) with describing each agent and the course of neuropathy as well as the clinical assessment with neurophysiological techniques. In addition, skin biopsy allows us to examine histological changes such as reinnervation. Neuroprotection with antioxidant therapy is possible but more effort in this field is needed.

The massive use of bisphenols, actually bisphenol A, in consumer products and food packaging has been associated with certain hazardous conditions for human health, which include their interactions with a family of specific membrane receptors and their effects as endocrine disruptors related to breast cancer. For this reason, bisphenol A was removed from many products, but it has been replaced by structural analogs whose pathways of action and metabolic effects are so far partially unknown. This chapter emphasizes the discovery of bisphenols, their uses in human life, and their impact on health population by focusing on breast cancer. Regarding their mechanisms of action, we have focused on the signaling routes activated by bisphenols following their binding to G protein–coupled receptors.

Approximately 70% of the world’s population has been using medicinal herbs as a complementary or alternative medicine that has grown tremendously in both developed and developing countries over the past 20 years (World Health Organization Drugs Strategy 2002–2005). This increase in consumer demand for medicinal plants continues, although scientific data are rare to create safety and efficacy profiles. Its popularity is also related to easy availability, cost-effectiveness leading to better purchasing power, and various factors that perceive that they are generally safe. Herbs are often administered simultaneously with therapeutic drugs for the treatment of major ailments, and herb-drug interactions (HDIs) increase their potential. The main routes proposed for HDIs include cytochrome P450 (CYP450)-mediated inhibition or induction and transport and flow proteins. In our review, we highlighted herbal medicines used for the treatment of various diseases with pharmacokinetic, pharmacodynamic analysis and case reports together with their adverse effects and herb-drug interactions. Therefore, this review can be used as a quick reference database for physicians and healthcare professionals involved in therapy, aiming to maximize clinical outcomes by reducing the negative and toxic effects of plants along with avoiding herb-drug interactions.

With the advancements in agriculture, farming community less or more started to rely on synthetic chemicals to increase the crop production and protection. But the negative impact of these chemicals on environment and cropping system urges the scientists to discover some new ways to combat with crop disease. By keeping in view, garlic is a well-known economically important vegetable throughout the world and recognized as reservoir for a number of bioactive compounds to treat various diseases; scientists have developed a strategy to identify and isolate antimicrobial genes from garlic. By using B. subtilis expression systems, a total of 48 antimicrobial genes, including AsR 416, were identified with the potential to significantly retard the growth of economically important fungal and bacterial pathogens. Furthermore, these antimicrobial genes exhibited the thermal stability along with nontoxic effects on mammalian blood cells, which indicate its potential use in the development of human medicines. These genes can revolutionize the way to treat with pathogens and also give a new wave of knowledge to explore the other organisms for the search of antimicrobial genes. This will also help to search the other cost-effective ways for the treatment of plant and human diseases.

Worldwide many different strong opioids and their formulations are available to control pain. Of which, morphine is considered as global opioid of choice and is widely used to control moderate to severe pain. The World Health Organization (WHO) has recommended morphine as one of the essential drug. Apart from analgesic use, research has proven its effectiveness for relief and treatment of various debilitating and distressing conditions like breathlessness, mucositis (oral and vaginal) and cough. However, its role in diarrhea and opioid substitution therapy (OST) is still nonconfirmatory. This chapter illustrates all available literature supporting effectiveness of morphine in above conditions and its impact on quality of life.

Foot-and-mouth disease (FMD) is a contagious viral infection which is caused by foot-and-mouth disease virus (FMDV). The disease appears in cloven-footed animals. Symptoms of the disease are abrupt manifestation of sores on the mouth, nose, feet, etc. Nowadays the control and treatment of FMDVare becoming a worldwide economic problem and challenge for the society. Currently, there is no particular treatment available for FMDV, as well as the limitations and disadvantages in the use of vaccines divert the focus of researchers toward natural sources like plant extracts which possess potential antiviral activity. Various researches documented in the literature demonstrated various plant extracts with antiviral potency against FMDV. In the current chapter, we discussed about FMDV and its possible treatment with plant extracts.

The quinazoline scaffold is found in the chemical structure of many marketed drugs used in CNS disorders as antidepressants, anxiolytics, or hypnotics. Also, the carbamate ester derivatives have different certain therapeutic actions, such as hypnotic or parasympathomimetic ones. We have obtained new 4(3H)-quinazolinones by bringing together in the same structure the quinazoline nucleus and carbamate ester group. The compounds named Q1–Q5 were characterized by measuring the melting points, by determining the infrared and NMR spectra, and by elemental analysis. The pharmacological tests evidenced that the compounds have a very low acute toxicity, lethal doses being >2000 mg/kg bw. The compounds had different actions observed in forced swimming test (FST), tail suspension test (TST), or elevated plus maze (EPM), probably influenced by the presence of different radicals on the nucleus. Thus, Q1 with a nitro group in structure manifested the highest antidepressant effect, showing a reduction of immobilization time in FST and TST. On the other hand, Q3 and Q5, with two groups methoxy, respective ethoxy, had a slight anxiolytic effect, highlighted by an increase of the time spent in open arms and a decrease of the time spent in closed arms of EPM.

The term resistant points out a clinical phenomenon in which there is a lack of response to one or more therapeutic interventions. Resistance to major depressive disorder treatment causes distress to patients and their relatives, and increases the number of hospital admissions, outpatient consultations, use of psychoactive drugs, and treatment costs. Despite its serious medical and psychosocial medical implications, the definition of treatment resistant depression continues to be ambiguous and controversial. The lack of an agreement on definition, as well as the research on the subject being difficult, limits the practical knowledge on the best treatment options for groups of treatment resistant depression (TRD) patients. We review the concept and definitions of treatment resistant depression as well as the medical literature on different treatment methods studied and comparative studies. Finally, some relevant neurobiological data are reviewed.

Electroconvulsive therapy (ECT) is highly effective both Major Depressive Disorder (MDD) and Bipolar Disorder (BD). Ketamine, an antagonist of the N-Methyl-D-aspartate receptor, has been described to have antidepressant properties. There is a hypothesis that ECT performed with anesthesia using ketamine is more effective than conventional ECT. Also, although ECT is the gold standard for BD and MDD, there are questions about which is more effective, ketamine treatment or ECT, and whether ketamine is more effective when used in combination with ECT. In this chapter, we review the current literature on the effectiveness of ECT and ketamine. Furthermore, we discuss whether ketamine can be an alternative treatment to ECT for patients with TRD.

The Republic of Suriname (South America) is among the culturally, ethnically, and religiously most diverse countries in the world. Suriname’s population of about 600,000 consists of peoples from all continents including the Javanese who arrived in the country between 1890 and 1939 as indentured laborers to work on sugar cane plantations. After expiration of their five-year contract, some Javanese returned to Indonesia while others migrated to The Netherlands (the former colonial master of both Suriname and Indonesia), but many settled in Suriname. Today, the Javanese community of about 80,000 has been integrated well in Suriname but has preserved many of their traditions and rituals. This holds true for their language, religion, cultural expressions, and forms of entertainment. The Javanese have also maintained their traditional medical practices that are based on Jamu. Jamu has its origin in the Mataram Kingdom era in ancient Java, some 1300 years ago, and is mostly based on a variety of plant species. The many Jamu products are called jamus. The first part of this chapter presented a brief background of Suriname, addressed the history of the Surinamese Javanese as well as some of the religious and cultural expressions of this group, focused on Jamu, and comprehensively dealt with four medicinal plants that are commonly used by the Javanese. This second part of the chapter continues with an equally extensive narrative of six more such plants and concludes with a few remarks on the contribution of Javanese jamus to Suriname’s traditional medicinal pharmacopeia.

The new coronavirus first appeared in December 2019 in Wuhan, China, being officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses (ICTV), as well as the name of the disease has been described as COVID-19 (coronavirus disease 2019). In March 2020, the disease was considered a global pandemic, with currently more than 514 million cases worldwide, with 6.4 million deaths. Severe cases of COVID-19 progress to acute respiratory distress syndrome (ARDS), on average about 8–9 days after the onset of symptoms. It is also worth mentioning that the severity of the disease in patients is not only due to the viral infection but also due to the host response. This phase, called a cytokine storm, reflects a state of systemic immune activation, with high levels of cytokines, such as IL-6, IL-1b, IL-2, IL-12, IL-18, TNF, and interferon gamma (IFN-γ). In this sense, the management of the disease largely depends on symptomatic and supportive treatments. For severely or critically ill patients with acute respiratory distress syndrome (ARDS) and sepsis, in addition to supplemental oxygen, mechanical ventilation, and ARDS-specific therapies, antiviral and antibiotic treatments should also be considered. Thus, the purpose of this chapter is to describe the pathophysiology and treatment of SARS-CoV-2 infection.

Drug discovery is an exciting yet highly costly endeavor. In the United States, developing a new prescription medicine that gains marketing approval takes near a decade and costs drugmakers for near 3 billion. More challengingly, the success rate of a compound entering phase I trials is just slightly under 10%. Because of these mounting hurdles, repurposing market approved drugs to new clinical indications has been a new trend on the rise. Another merit to this approach is the already confirmed toxicity profiles of the drugs and their possession of drug-like features. Thus, repurposed drugs can reach the market approved stage in a much faster, cheaper, and more efficient way. Notably, epigenetic enzymes play a critical role in the etiology and progression of different diseases. Researchers are now assessing the possibilities of using market approved drugs to target epigenetic enzymes as a novel strategy to curtail disease progression. Thus, in this book chapter, we will provide an outlook on repurposing market drugs to target epigenetic enzymes in various diseases. Consequently, this book chapter will not only provide the readers with current knowledge in this specific field, but also will shed light on the pathway forward for repurposing market drugs to target epigenetic enzymes in human diseases.

Both the animals and humans with generalized lipodystrophy develop signs of infertility syndrome in the absence of semen health. Infertility is defined as not being able to get pregnant (conceive) after one year (or longer) of unprotected sex. The treatment of disease is usually expensive. Their expertise and experience provide the most current knowledge to promote future research. Dietary habits need to be altered, for most of world people. Therefore, the conclusions and recommendations from the part of this chapters will provide a basis for change. We welcome your offers and criticisms for book improvement in next editions. Bisphenol has been used since the 1950s, in food packaging, industrial materials, dental sealants, and personal hygiene products. Everyone is exposed to Bisphenol through the skin, inhalation, and digestive system. Bisphenol disrupts endocrine pathways because it has weak estrogenic, antiandrogenic, and antithyroid activities. Known endocrine disruptor bisphenol A (BPA) has been shown to be a reproductive toxicant in animal models. This book chapter the current epidemiological literature on fertility outcomes associated with Bisphenol exposure. It also provides relevant resources for health care providers who are in a unique position to provide guidance in reducing exposure to this endocrine-disrupting chemical.

Copper complexes have previously been developed to target His37 in influenza M2 and are effective blockers of both the wild type (WT) and the amantadine-resistant M2S31N. Here, we report that the complexes were much less toxic to zebrafish than CuCl2. In addition, we characterized albumin binding, mutagenicity, and virus resistance formation of these metal complexes, and employed steered molecular dynamics simulations to explore whether the complexes would fit in M2. We also examined their anti-viral efficacy in a multi-generation cell culture assay to extend the previous work with an initial-infection assay, discovering that this is complicated by cell culture medium components. The number of copper ions binding to bovine serum albumin (BSA) correlates well with the number of surface histidines and BSA binding affinity is low compared to M2. No mutagenicity of the complexes was observed when compared to sodium azide. After 10 passages of virus in MDCK culture, the EC50 was unchanged for each of the complexes, i.e. resistance did not develop. The simulations revealed that the compounds fit well in the M2 channel, much like amantadine.

Early and effective pain control in trauma patients improves outcomes and limits disability, but analgesia is often missed in the unstable patient, or hemodynamically depressing medications are avoided for fear of losing stability. This chapter outlines the role of ketamine in managing traumatic emergencies in both out-of-hospital and hospital environment, and beyond. Low-dose ketamine also called a sub-dissociative dose is safe, efficient and effective analgesic that can be considered for trauma patients, pediatric or adults, as an alternative to opioids or in combination with opioids for on additive or synergistic effect, with minimal impact on hemodynamic stability. Ketamine at higher doses is also an excellent drug for induction of anesthesia in rapid sequence induction (RSI), post-intubation sedation maintenance or procedural sedation in the trauma patient. Also, can be used for acute agitation and excited delirium. In this chapter, we are describing this drug focusing on a deeper understanding of the safety and efficacy of this agent and, if supported, to encourage physicians to consider ketamine for pain control in trauma and beyond. Also, we are presenting the current literature surrounding ketamine’s evidences in the trauma condition to establish its utility and profile of safety for these patients.

Conventional drug administration has several issues and challenges such as full doses absorption and efficient targeting, some generate undesirable secondary effects and promote damage to organs and tissues such as the liver and kidneys, and others trigger inflammation and immune responses. Hence, drug carriers help to promote drug absorption, enhance targeting, avoid or decrease secondary effects, possess the ability to camouflage drugs from immune cells and proteins, and permit controlled release to provide prolonged drug delivery to maintain its blood concentration within therapeutic limits. Drug carriers have gained importance thanks to their various properties such as biocompatibility, biodegradability, mechanical properties, and high surface area, among others. Drug carriers are getting crucial to avoid or diminish secondary effects and improve the targeting of the administered drugs incrementing their effectiveness. Hence, this book chapter aims to introduce some drug carriers (electrospun nanofibers, aptamers, micelles, and liposomes), describing the properties and polymers used. It is observed that fast dissolving administration is the most recommended strategy for the use of drug carriers, where more evident therapeutics benefits can be appreciated.

The management of hepatocellular carcinoma (HCC) has been transformed by the incorporation of immune checkpoint inhibitor therapy. Compared to traditional chemotherapy, these regimens have markedly improved outcomes in patients with HCC. Additionally, they are generally well-tolerated in patients with impaired hepatic function. This chapter will review the landmark trials which have paved the way for the use of ICIs in the treatment of HCC and summarize current consensus on best practices regarding their use in this setting. It will also discuss other prospective uses of immunotherapy for the treatment of HCC currently being investigated, including further incorporation of both checkpoint inhibitor and non-checkpoint inhibitor agents into treatment strategies. Furthermore, it will summarize the existing safety and efficacy data regarding the use of checkpoint inhibitors in patients who have previously undergone liver transplant.

The present ethnobotanical study was carried out in Amarkantak region eastern part of Madhya Pradesh during January 2018 to January 2019 to document the medicinal plants used by the Baiga tribes. Traditional medicinal plants used by the Baiga tribes of 37 plant species belonging to 35 genera and 28 families used to menstrual disorder, piles, sore throat, respiratory disorder, haematuria, miscarriage, jaundice, fever, insanity, leucorrhoea, bleeding during pregnancy, spermatorrhea, infertility in women, motiabind, scorpion bite, wounds of animals, stomach disorder, intestinal worms, diabetes, leukoderma, rheumatism, scabies, wart and easy delivery etc. and other various unreported medicinal plants are reported here.

Cyanoprokaryotes are distributed worldwide and they produce various bioactive compounds, including cyanotoxins. The major route of human exposure to cyanotoxins is the oral intake by using contaminated drinking water, by incidental intake of contaminated water during recreational and professional activities, and by consuming contaminated food or dietary supplements prepared from cyanobacteria. The prolonged chronic exposure to low concentrations of cyanotoxins provokes cell damage and may increase the risk for cancer development. Due to the variety of cyanotoxin chemical structures, different mechanisms of their toxic effects are known. At the same time, some of the natural compounds produced by cyanoprokaryotes have anticancer potential and are promising sources for the development of novel drugs. This chapter is dedicated to the target mechanisms behind the effects of the widely distributed cyanotoxins with an impact on human health, microcystins, nodularins, and cylindrospermopsin.

This chapter is based in the compilation and analysis of different in vitro, preclinical, and clinical studies, which explored the potential beneficial bioactivity of supplementation with berries on some alterations in the central nervous system (CNS). The last section of the chapter describes the possible mechanisms of action of polyphenols, anthocyanins, and other compounds present in berries as well as their relationship with anxiety, depression, and Alzheimer’s (AD) and Parkinson’s diseases (PD) and their implication in the prevention of cognitive decline and senescence motor functions. Electronic databases as Springer, PubMed, Scopus, and Elsevier were used. Papers were selected by topic specially those related with berries, year of publication, and authors. The present chapter evidenced the potential health effect as neuroprotector of different berries and their bioactive compounds mainly flavonoids, polyphenols, and anthocyanins, on diseases such as anxiety, depression, and Alzheimer’s and Parkinson’s diseases. In conclusion, for human nutrition berry fruit supplementation might be an excellent source of antioxidant and alternative for prevention and reduction of symptoms in diseases such as anxiety, depression, Alzheimer’s, and Parkinson’s.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major global health concern given the increase in multiple forms of drug-resistant TB. This underscores the importance of a continuous pipeline of new anti-TB agents. From recent studies, it is evident that the increase in drug efficacy is being achieved through re-engineering old TB-drug families and repurposing known drugs. This approach has led to producing a newer class of compounds which not only saves time and investment in developing newer drugs but is also effective in identifying drug candidates with novel mechanisms to treat multi-drug resistant strains. The repurposed drugs moxifloxacin, linezolid, and clofazimine are used to treat extensively drug-resistant TB when first- and/or second-line drugs fail. The chapter covers a detailed background on the current status of the repurposed drugs in the TB drug-discovery pipeline and discusses a potential way forward.

Vaccines have evolved as widely applicable and available prophylaxes against infectious diseases. Advances in ribonucleic acid technologies revolutionized the biopharmaceutical field of vaccine manufacturing. Numerous novel mRNA-based vaccines that have been approved by the United States and European regulatory agencies are proven to be safe and effective in preventing disease. This chapter presents the history of RNA vaccine development in the context of preventing diseases caused by RNA viruses such as SARS-CoV-2, HIV, influenza, Chikungunya, Zika, RSV, PIV, HMPV viruses, Rabies, and Ebola. Advantages, disadvantages, and challenges in mRNA vaccine engineering, delivery, and safety are discussed. The formulation, safety, long-term effectiveness, and requirements for booster immunizations are presented using data from clinical trials. The results of these clinical trials highlight important milestones, setbacks, and ultimate advancements in vaccine development. mRNA vaccines have significantly impacted public health in a relatively short time, and they demonstrate great potential in serving as clinical public health prophylaxis against current and future pandemics. Future development is likely to include polyvalent, mosaic, and strain/lineage-specific individualized vaccines.

Traditional medicines can serve as the source of potential new drug candidates and initial research focuses on the isolation of bioactive lead compounds. Medicinal plants have a combination of secondary metabolites that are naturally occurred by giving different therapeutic benefits. Phytoconstituents have been recognized as an important role in the drug discovery process moreover the other sources. Presently, over hundred natural product-derived pharmaceuticals are being used in modern medicine. Plants and their secondary metabolites, with activity against targets associated with the viral infections could provide valuable leads for the development into drugs for the novel antiviral drugs. Some of them play as important tools in the immune system exhibiting antiviral potentials. The objective of this review is to conduct information regarding the potential of traditional medicines to which have shown antiviral activity against SARS-CoV-2 infection.

Depression and anxiety currently rank as the second and fifth most common causes worldwide of years lived with disability-a reality that has intensified the search for new treatments. There are many studies of herbal extracts and secondary metabolites from plants used in traditional medicine due to their antidepressant and anxiolytic properties. Clinical and preclinical studies about some of the mechanisms of action of metabolites like alkaloids, terpenes, flavonoids, and sterols, among others, have documented effects similar to those produced by clinically effective drugs. These metabolites have shown anxiolytic and antidepressant effects in various experimental models of anxiety by interacting with γ-aminobutyric acid subtype A receptors (GABAA-receptors) and by stimulating the serotonergic, noradrenergic, and dopaminergic neurotransmitter systems. These pharmacological effects can be attributed to plant metabolites that share structural similarities with monoamines, which allow them to bind to receptors. The objective of this chapter is to summarize the various mechanisms of action that have been identified in secondary metabolites with anxiolytic and antidepressant properties. Terpenes, alkaloids, flavonoids, and sterols can interact at different levels of the neurotransmission systems involved in the neurobiology of anxiety and depression, suggesting their potential for treating these mental illnesses.

Venomics projects have been conducted to disclose the divergent profiles and evolution of various venomous animals. Here, we describe the venomics project including genome and transcriptome of habu snake, leading to drug discovery. Venomics project including the decoding of their whole genomes revealed partly a producing mechanism of various venom proteins including accelerated evolution and alternative splicing and how the toxic organisms have evolved from the nontoxic ones. In addition, the venomics analysis of transcriptomes and proteomes beyond species reveals the relationship between the geographical distribution and evolution of toxic organisms. The abundance of different gene products within a gene family caused by accelerated evolution and alternative splicing may contribute to expand the repertoire of effective weapons to prey capture accompanied with neofunctionalization.

Currently, the development of conventional medicine is getting more advanced, it cannot be denied that medicinal plants still occupy their main role as medicine for various human diseases, especially in developing countries. This is rooted in the knowledge of the local community about plants that can be used as medicine for various diseases. Ethnomedicine is a field of study that raises local knowledge of the community to maintain their health. From numerous studies on the field, 33 species of plants have been found which are believed by the natives to West Sumatra as medicine. Ethnomedicinal data were analyzed using Index of Cultural Significance (ICS) value. The results of the analysis showed that the species of plants that is voted most important for the community were soursop (Annona muricata) and red betel (Piper sp.). In general, the part of plant that is most often used as medicine is the leaf, and the way to consume it is by boiling it so that you can get the herbs from the plant extract.

Unfortunately, to date, there is no approved specific antiviral drug treatment against COVID-19. Due to the costly and time-consuming nature of the de novo drug discovery and development process, in recent days, the computational drug repositioning method has been highly regarded for accelerating the drug-discovery process. The selection of drug target molecule(s), preparation of an approved therapeutics agent library, and in silico evaluation of their affinity to the subjected target(s) are the main steps of a molecular docking-based drug repositioning process, which is the most common computational drug re-tasking process. In this chapter, after a review on origin, pathophysiology, molecular biology, and drug development strategies against COVID-19, recent advances, challenges as well as the future perspective of molecular docking-based drug repositioning for COVID-19 are discussed. Furthermore, as a case study, the molecular docking-based drug repurposing process was planned to screen the 3CLpro inhibitor(s) among the nine Food and Drug Administration (FDA)-approved antiviral protease inhibitors. The results demonstrated that Fosamprenavir had the highest binding affinity to 3CLpro and can be considered for more in silico, in vitro, and in vivo evaluations as an effective repurposed anti-COVID-19 drug.

Toxicity and biocompatibility of silver nanoparticles are of a major concern due to their extensive production regardless of their application in current industries. Information about toxicology or biocompatibility is crucial regarding their proper utilization and application in clinical as well as environmental aspect. This chapter describes in detail about the different techniques and technology of synthesis of silver nanoparticles and explains their different physiochemical properties in context of the current research scenario. Further, it also explains the biocompatibility and toxicity of silver nanoparticles at cellular and molecular aspects. The mechanism of their toxicity has been described keeping in view of the recent research done. In brief, it reveals detail knowledge of the cellular and molecular impact of silver nanoparticles.

Duodenal disorders are difficult to identify clinically because of the non-specific symptoms. They may or may not be identifiable through routine radiographic, ultrasonographic, or laboratory evaluation methods, because many diseases of duodenum primarily involve the mucosal surface. Duodenal ulcers, inflammatory bowel disease (IBD), and small intestinal bacterial overgrowth (SIBO) are the duodenal disorders. Duodenoscopy is an efficient way of identifying the abnormalities of mucosal irregularities, distortion, ulceration, neoplasia, and inflammation, and it is also useful for obtaining mucosal biopsy and duodenal juice for routine histopathological and bacteriological studies. This paper will provide more detail about the advanced diagnostic methods and therapeutic measures for various duodenal disorders.

Venous thromboembolism (VTE) is a complex multifactorial disease with an average annual incidence of approximately 1 per 1000 in the adult population. Recommendations about pharmacological prophylaxis of VTE in adult hospitalized surgical and medical patients are available in clinical practice guidelines (CPGs) to optimize healthcare delivery and improve patient outcomes. The aim of this study was to examine the methodological quality of CPGs for pharmacological prophylaxis of VTE in adult hospitalized medical and surgical patients and to summarize the main categories to contextualize the recommendations included in high-quality CPGs. Methodology: The study used the ADAPTE to contextualize in categories the main recommendations of the high-quality CPGs assessed by the Appraisal of Guidelines for Research and Evaluation (AGREE II). Results: Fourteen CPGs were screened for assessment of quality methodology by AGREE II instrument. Seven of fourteen CPGs were selected as high-quality (>60%) across domains 3 and 6 to contextualize the recommendations in categories. Conclusion: Seven CPGs evaluated by AGREE had scores above 60% in domains 3 and 6. The scope addressed by the high-quality CPGs included important aspects of pharmacological prophylaxis of VTE in hospitalized patients.

Essential oils, as natural sprout inhibitor and safe fungicides, are a promising tool and good alternative compounds otherwise synthetic due to their high efficacy, biodegradability, eco-safety and volatile nature. They are consisting of a number of various components, i.e., terpenes, phenols, alcohols, esters, aldehydes and ketones in different composition or combinations. These effective compounds supply excess to prevent sprouting in potatoes and Jerusalem artichoke (JA) and less chance to development of resistance in fungi in JA, strawberry and broccoli with low concentrations. On contrary, high concentration of these oils induce the germination of seeds like broccoli and carob. This chapter explains the practical application of using essential oils as natural antisprouting, inducing quality, preserving fungal diseases, eco-friendly compounds, alternating synthetic chemicals, giving high benefits and easy to apply. The foliar application with essential oils increases the productivity, quality and marketable yield and storability and reduces weight losses and decay. Moreover, the essential oils increase broccoli seed germination, antioxidant content and other phytochemical parameters. The chapter provides a novel anti-sprouting agent for inhibiting growth of processing potato tubers and identification of terpenoids that use to inhibit tuber sprouting as well as application of Chloropropham (CIPC) isopropyl-N-(3-chlorophenyl) carbamate as a conventional chemical inhibitor.

The process of drug discovery is challenging and a costly affair. It takes about 12 to 15 years and costs over $1 billion dollars to develop a new drug and introduce the finished product in the market. With the increase in diseases, virus spread, and patients, it has become essential to invent new medicines. Consequently, today researchers are becoming interested in inventing new medicines faster by adopting higher throughput screening methods. One avenue of approach to discovering drugs faster is the High-Throughput Screening (HTS) method, which has gained a lot of attention in the previous few years. Today, High-Throughput Screening (HTS) has become a standard method for discovering drugs in various pharmaceutical industries. This review focuses on the advancement of technologies in High-Throughput Screening (HTS) methods, namely fluorescence resonance energy transfer (FRET), biochemical assay, fluorescence polarization (FP), homogeneous time resolved fluorescence (HTRF), Fluorescence correlation spectroscopy (FCS), Fluorescence intensity distribution analysis (FIDA), Nuclear magnetic resonance (NMR), and research advances in three major technology areas including miniaturization, automation and robotics, and artificial intelligence, which promises to help speed up the discovery of medicines and its development process.

Astrocytes are critical for the metabolic, structural and functional modulatory support of the brain. Lipotoxicity or high levels of saturated fatty acid as Palmitate (PA) has been associated with neurotoxicity, the loss or change of astrocytic functionality, and the etiology and progression of neurodegenerative diseases such as Parkinson or Alzheimer. Several molecular mechanisms of PA’s effect in astrocytes have been described, yet the role of epigenetic regulation and chromatin architecture have not been fully explored. In this study, we developed a multi-omic epigenetic-based model to identify the molecular mechanisms of lipotoxic PA activity in astrocytes. We used data from nine histone modifications, location of Topological Associated Domains (TADs) and transcriptional CTCF regions, where we identified the basal astrocyte epigenetic landscape. Moreover, we integrated transcriptomic data of astrocytic cellular response to PA with the epigenetic multi-omic model to identify lipotoxic-induced molecular mechanisms. The multi-omic model showed that chromatin conformation in astrocytes treated with PA have response genes located within shared topological domains, in which most of them also showed either repressive or enhancing marks in the Chip-Seq enrichment, reinforcing the idea that epigenetic regulation has a huge impact on the lipotoxic mechanisms of PA in the brain.

Innovative developments of science and engineering have progressed very fast toward the synthesis of nanomaterials to achieve unique properties that are not the same as the properties of the bulk materials. The particle reveals interesting properties at the dimension below 100 nm, mostly from two physical effects. The two physical effects are the quantization of electronic states apparent leading to very sensitive size-dependent effects such as optical and magnetic properties and the high surface-to-volume ratio modifies the thermal, mechanical, and chemical properties of materials. The nanoparticles’ unique physical and chemical properties render them most appropriate for a number of specialist applications.

Luffa cylindrica, popularly known as sponge gourd is a tropic and sub-tropical fibrous plant with fruits containing black seeds. The fruit is consumed by humans as a vegetable in many parts of Asia, while different parts of the plant are used for cosmetics and as medicine in many parts of the globe. The plant has been used in the treatment of many ailments including nose cancer, snake venom, wound healing, edema, enterobiasis, filaria, whooping cough, stomach upset, stomach pain and malaria. Many health-promoting compounds such as flavonoids (apigenin-7- glucuronide luteolin-7-O-β-D-glucuronide methyl ester, -O-feruloyl-β-D-glucose, luteolin-7-O-β-D-glucuronide methyl ester), phenolics acids (p-Coumaric, gallic, caffeic, chlorogenic), triterpenoids (oleanolic acid and echinocystic acid), saponins (Lucyoside A-M), tannins (catechin), ribosome-inactivating proteins (α- luffin), carotenoids (9 -cis neoxanthin, all-trans-lutein, all-trans-β-carotene), chlorophylls (chlorophyll a and b, pheophytin), cucurbitacin B and gypsogenin have been detected or isolated from different parts of the plants. Extracts of the plant and isolated compounds have wide spectrum pharmacological activities and have been shown to possess antiemetic, antidiabetic, antiviral, wound healing, anticancer, antipyretic, anti-inflammatory, antifungal, anti-bacteria, anthelmintic, hypoglycemic and antihyperglycemic, anti-inflammatory, antioxidant activity, and hepato-protective effects in animal models. However, further information is needed on its safety and mechanisms of action. The present article is an updated review of the ethnobotanical uses, pharmacological actions, phytochemistry, safety, and future application of Luffa cylindrica in translational medicine.

No preventive vaccines are available for the treatment of AIDS. To improve therapy, combinational antiretroviral drugs are given; however some patients develop resistance to particular combinational drug. Microbubble-mediated drug delivery technology solves the problem by reducing systemic dose and toxicity. Microbubbles are bubbles smaller than one millimeter in diameter but larger than one micrometer. The general composition of microbubble is gas core. The mechanism of microbubbles through which its delivery increases is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. Rapid isolation strategy of CD4+ cells is mixing blood and glass microbubbles which then bind with the specific target cells to the microbubble carrying specific antibodies on their surface. The target cells will spontaneously float to the top of the blood vial and can be quickly separated. The microbubbles are particularly used in the diagnosis of AIDS because of their cell isolation techniques which is rapid and inexpensive and their small size to pass through capillary for perfusion in tissue This review demonstrates the problems with the current treatment of the disease and shed light on the remarkable potential of microbubbles to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology, and microbicides.

Technological improvements in unbiased screening have accelerated drug target discovery. In particular, membrane-embedded and secreted proteins have gained attention because of their ability to orchestrate intercellular communication. Dysregulation of their extracellular protein–protein interactions (ePPIs) underlies the initiation and progression of many human diseases. Practically, ePPIs are also accessible for modulation by therapeutics since they operate outside of the plasma membrane. Therefore, it is unsurprising that while these proteins make up about 30% of human genes, they encompass the majority of drug targets approved by the FDA. Even so, most secreted and membrane proteins remain uncharacterized in terms of binding partners and cellular functions. To address this, a number of approaches have been developed to overcome challenges associated with membrane protein biology and ePPI discovery. This chapter will cover recent advances that use high-throughput methods to move towards the generation of a comprehensive network of ePPIs in humans for future targeted drug discovery.

Hospitals and other healthcare facilities are very essential for the cure and care of persons suffering from health issues and also to promote health in society. As the health care services are improving and increasing their reach even in underdeveloped countries, so is the problem of health care waste (HCW) as hospitals generate a relatively huge amount of HCW, which consists of general as well as hazardous waste. The persons handling HCW are at immediate risk, followed by persons residing near HCW dumping/processing areas and the general public. Infectious HCW is a major threat to the health of humans and animals as it has the potential to spread various infectious diseases to the human and animal population. Due to the uncontrolled use of disposable nonbiodegradable materials by healthcare systems and their processing or lack of it, the HCW has emerged as one of the major sources of environmental pollution including the emission of the significant amount of greenhouse gases, which stands from 3 to 10% of total emissions of nations. HCW also leads to leaching chemicals, heavy metals like Pb, Cd, Cr, radioactive substances, and even generating carcinogens like dioxin in the environment contaminating air, soil, and water in general and especially in areas surrounding HCW dumping or processing affecting health and quality of life of not only of humans but cohabiting flora and fauna in those areas. Thus, the HCW is becoming one of the major sources of environmental pollution and collectively contributing to the problem of global warming. The HCW needs to be given the desired attention and priority in actions and policy. The chapter focuses on sources, types, and various environmental and health hazards related to HCW, its global environmental impact and management strategies for minimum effects with an eco-friendly and sustainable approach.

Pulmonary administration is an effective method for treating lung and other diseases. Drugs can be transported directly to the lung by the pulmonary drug delivery system (PDDS). PDDS has the advantages of maintained local drug concentration, reduced side effects, controllable drug release, promoted drug absorption, prolonged drug action time, and improved patient compliance. Polymers have been extensively utilized to prepare novel PDDS. Among these polymers, chitosan (CS) is a natural cationic polysaccharide which is rich in its source. It has many unique physicochemical properties, good biocompatibility, and satisfactory biodegradability. CS has been a popular biomaterial in pharmaceutics for decades and is widely used in drug delivery. CS contains many amino groups. The contained positive charges can interact strongly with the negatively charged mucosa membranes, thereby facilitating CS adsorption on the mucosal surface, avoiding clearance by the cilia, and improving the adhesion and penetration rate on the cell membrane. Moreover, studies have shown that CS could open cell tight junctions, which would promote drug transportation across the epithelial tissue. Thus, CS is an especially suitable material for PDDS. In this chapter, we will focus on the research progress and the applications of CS in PDDS. Many representative and advanced studies on CS-based PDDS are reviewed in detail.

Lipoproteins are specialized particles involved in the transport and distribution of hydrophobic lipids, as cholesterol and triglycerides, throughout the body. The lipoproteins exhibit a basic spherical shape as complexes of lipids and proteins, and these latter are known as apolipoproteins. Initially, the proteins associated with lipoproteins were recognized as integral or peripheral proteins that only maintain the dynamics and metabolism of lipoproteins. However, there exist many studies on different lipoproteins evidencing that the quantity and type of apolipoproteins and lipoprotein-associated proteins are diverse and could be associated with different lipoprotein function outcomes. Here, we summarized recent processes in the determination of apolipoproteins and lipoprotein-associated proteins profiles through a proteomic approach, analyzing the major methods available and are used to achieve this. We also discuss the relevance of these lipoproteomic analyses on the human disease outcomes.

Natural and biodegradable polymers have been the key area for utilizing their advantages which make them a possible option for development of various drug delivery systems. The complexity of diseases and the intrinsic drug toxicity and side effects has led to an interest for development and optimization of drug delivery systems. The advancements in nanotechnology have favored the development of novel formulations which can modulate the biopharmaceutical properties of bioactives and thus improves the pharmacological and therapeutic action. The shape, size, and charge nanoscale delivery system, such as nanoparticles (NPs) are required to be investigated and changed in order to promote and optimize the formulations. The various natural polymeric NPs (PNPs) have been found to be key tool to enhance bioavailability or specific delivery to certain site of action. In this chapter, the uses of various polymeric materials for the development of NPs as drug delivery systems for various ailments have been described. The entrapment of bioactive compounds in PNPs systems is a hopeful move toward improvement of efficacy of drug toward the treatments of various diseases.

Since the advent of the twentieth century, several severe virus outbreaks have occurred—H1N1 (1918), H2N2 (1957), H3N2 (1968), H1N1 (2009) and recently COVID-19 (2019)—all of which have posed serious challenges to public health. Therefore, rapid identification of efficacious antiviral medications is of ongoing paramount importance in combating such outbreaks. Due to the long cycle of drug development, not only in the development of a “safe” medication but also in mandated and extensive (pre)clinical trials before a drug can be safely licensed for use, it is difficult to access effective and safe novel antivirals. This is of particular importance in addressing infectious disease in appropriately short period of time to limit stress to ever more interlinked societal infrastructures; including interruptions to economic activity, supply routes as well as the immediate impact on health care. Screening approved drugs or drug candidates for antiviral activity to address emergent diseases (i.e. repurposing) provides an elegant and effective strategy to circumvent this problem. As such treatments (in the main) have already received approval for their use in humans, many of their limitations and contraindications are well known, although efficacy against new diseases must be shown in appropriate laboratory trials and clinical studies. A clear in this approach in the case of antivirals is the “relative” simplicity and a high degree of conservation of the molecular mechanisms that support viral replication—which improves the chances for a functional antiviral to inhibit replication in a related viral species. However, recent experiences have shown that while repurposing has the potential to identify such cases, great care must be taken to ensure a rigourous scientific underpinning for repurposing proposals. Here, we present a brief explanation of drug repurposing and its approaches, followed by an overview of recent viral outbreaks and associated drug development. We show how drug repurposing and combination approaches have been used in viral infectious diseases, highlighting successful cases. Special emphasis has been placed on the recent COVID-19 outbreak, and its molecular mechanisms and the role repurposing can/has play(ed) in the discovery of a treatment.

Pharmacology in pediatric population has specific needs in pharmacovigilance. The lack of studies in children leads mostly to “off-label” prescribing and to an increased frequency of adverse drug reactions. Additionally, younger ages, male sex, prolonged and previous hospitalization, indication of antibiotics, and the number of prescribed drugs are factors associated with a higher risk of ADRs. Consequently, ADRs represent an additional burden of morbidity. This chapter will be focused on the most common adverse drug reactions in children (including infants and newborns), challenges, and new legislative tools in pediatric pharmacovigilance by using the Word Health Organization global individual case safety report database (VigiAccess) and results from a Latin American study.

Human beings have relied on herbs and medicinal plants as sources of food and remedy from time immemorial. Bioactive compounds from plants are currently the subject of much research interest, but their extraction as part of phytochemical and/or biological investigations present specific challenges. Herbalists or scientists have developed many protocols of extraction of bioactive ingredients to ensure the effectiveness and the efficacy of crude drugs that were used to get relief from sickness. With the advent of new leads from plants such as morphine, quinine, taxol, artemisinin, and alkaloids from Voacanga species, a lot of attention is paid to the mode of extraction of active phytochemicals to limit the cost linked to the synthesis and isolation. Thus, the extraction of active compounds from plants needs appropriate extraction methods and techniques that provide bioactive ingredients-rich extracts and fractions. The extraction procedures, therefore, play a critical role in the yield, the nature of phytochemical content, etc. This chapter aims to present, describe, and compare extraction procedures of bioactive compounds from herbs and medicinal plants.