Showing papers in "Advances in Experimental Medicine and Biology in 2021"

Overview of Histone Modification.

Abstract: Epigenetics is the epi-information beyond the DNA sequence that can be inherited from parents to offspring. From years of studies, people have found that histone modifications, DNA methylation, and RNA-based mechanism are the main means of epigenetic control. In this chapter, we will focus on the general introductions of epigenetics, which is important in the regulation of chromatin structure and gene expression. With the development and expansion of high-throughput sequencing, various mutations of epigenetic regulators have been identified and proven to be the drivers of tumorigenesis. Epigenetic alterations are used to diagnose individual patients more accurately and specifically. Several drugs, which are targeting epigenetic changes, have been developed to treat patients regarding the awareness of precision medicine. Emerging researches are connecting the epigenetics and cancers together in the molecular mechanism exploration and the development of druggable targets.

Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans.

Abstract: As a functional amino acid (AA), L-arginine (Arg) serves not only as a building block of protein but also as an essential substrate for the synthesis of nitric oxide (NO), creatine, polyamines, homoarginine, and agmatine in mammals (including humans). NO (a major vasodilator) increases blood flow to tissues. Arg and its metabolites play important roles in metabolism and physiology. Arg is required to maintain the urea cycle in the active state to detoxify ammonia. This AA also activates cellular mechanistic target of rapamycin (MTOR) and focal adhesion kinase cell signaling pathways in mammals, thereby stimulating protein synthesis, inhibiting autophagy and proteolysis, enhancing cell migration and wound healing, promoting spermatogenesis and sperm quality, improving conceptus survival and growth, and augmenting the production of milk proteins. Although Arg is formed de novo from glutamine/glutamate and proline in humans, these synthetic pathways do not provide sufficient Arg in infants or adults. Thus, humans and other animals do have dietary needs of Arg for optimal growth, development, lactation, and fertility. Much evidence shows that oral administration of Arg within the physiological range can confer health benefits to both men and women by increasing NO synthesis and thus blood flow in tissues (e.g., skeletal muscle and the corpora cavernosa of the penis). NO is a vasodilator, a neurotransmitter, a regulator of nutrient metabolism, and a killer of bacteria, fungi, parasites, and viruses [including coronaviruses, such as SARS-CoV and SARS-CoV-2 (the virus causing COVID-19). Thus, Arg supplementation can enhance immunity, anti-infectious, and anti-oxidative responses, fertility, wound healing, ammonia detoxification, nutrient digestion and absorption, lean tissue mass, and brown adipose tissue development; ameliorate metabolic syndromes (including dyslipidemia, obesity, diabetes, and hypertension); and treat individuals with erectile dysfunction, sickle cell disease, muscular dystrophy, and pre-eclampsia.

Glucose Metabolism in Cancer: The Warburg Effect and Beyond.

Abstract: Otto Warburg observed a peculiar phenomenon in 1924, unknowingly laying the foundation for the field of cancer metabolism. While his contemporaries hypothesized that tumor cells derived the energy required for uncontrolled replication from proteolysis and lipolysis, Warburg instead found them to rapidly consume glucose, converting it to lactate even in the presence of oxygen. The significance of this finding, later termed the Warburg effect, went unnoticed by the broader scientific community at that time. The field of cancer metabolism lay dormant for almost a century awaiting advances in molecular biology and genetics, which would later open the doors to new cancer therapies [2, 3].

The Role of NCOA4-Mediated Ferritinophagy in Ferroptosis

Abstract: Nuclear receptor coactivator 4 (NCOA4) is a selective cargo receptor that mediates the autophagic degradation of ferritin, the cytosolic iron storage complex, in a process known as ferritinophagy. NCOA4-mediated ferritinophagy is required to maintain intracellular and systemic iron homeostasis and thereby iron-dependent physiologic processes such as erythropoiesis. Given this role of ferritinophagy in regulating iron homeostasis, modulating NCOA4-mediated ferritinophagic flux alters sensitivity to ferroptosis, a non-apoptotic iron-dependent form of cell death triggered by peroxidation of polyunsaturated fatty acids (PUFAs). A role for ferroptosis has been established in the pathophysiology of cancer and neurodegeneration; however, the importance of ferritinophagy in these pathologies remains largely unknown. Here, we review the available evidence on biochemical regulation of NCOA4-mediated ferritinophagy and its role in modulating sensitivity to innate and induced ferroptosis in neurodegenerative diseases and cancer. Finally, we evaluate the potential of modulating ferritinophagy in combination with ferroptosis inducers as a therapeutic strategy.

Neuropharmacological Effects of the Main Phytocannabinoids: A Narrative Review.

Abstract: Cannabis can synthetize more than 400 compounds, including terpenes, flavonoids, and more than 100 phytocannabinoids. The main phytocannabinoids are Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis-based products are used as medicines in several countries. In this text, we present an overview of the main neurochemical mechanisms of action of the phytocannabinoids, especially THC and CBD. We also reviewed the indications and adverse effects of the main cannabis-based medicinal products. THC acts as a partial agonist at cannabinoid 1/2 receptors (CB1/2). It is responsible for the characteristic effects of cannabis, such as euphoria, relaxation, and changes in perceptions. THC can also produce dysphoria, anxiety, and psychotic symptoms. THC is used therapeutically in nausea and vomiting due to chemotherapy, as an appetite stimulant, and in chronic pain. CBD acts as a noncompetitive negative allosteric modulator of the CB1 receptor, as an inverse agonist of the CB2 receptor, and as an inhibitor of the reuptake of the endocannabinoid anandamide. Moreover, CBD also activates 5-HT1A serotonergic receptors and vanilloid receptors. Its use in treatment-resistant epilepsy syndromes is approved in some countries. CBD does not produce the typical effects associated with THC and has anxiolytic and antipsychotic effects. Some of the most common adverse effects of CBD are diarrhea, somnolence, nausea, and transaminase elevations (with concomitant use of antiepileptics). The mechanisms of action involved in both the therapeutic and adverse effects of the phytocannabinoids are not fully understood, involving not only the endocannabinoid system. This "promiscuous" pharmacology could be responsible for their wide therapeutic spectrum.

Nutrition and Functions of Amino Acids in Fish.

Abstract: Aquaculture is increasingly important for providing humans with high-quality animal protein to improve growth, development and health. Farm-raised fish and shellfish now exceed captured fisheries for foods. More than 70% of the production cost is dependent on the supply of compound feeds. A public debate or concern over aquaculture is its environmental sustainability as many fish species have high requirements for dietary protein and fishmeal. Protein or amino acids (AAs), which are the major component of tissue growth, are generally the most expensive nutrients in animal production and, therefore, are crucial for aquatic feed development. There is compelling evidence that an adequate supply of both traditionally classified nutritionally essential amino acids (EAAs) and non-essential amino acids (NEAAs) in diets improve the growth, development and production performance of aquatic animals (e.g., larval metamorphosis). The processes for the utilization of dietary AAs or protein utilization by animals include digestion, absorption and metabolism. The digestibility and bioavailability of AAs should be carefully evaluated because feed production processes and AA degradation in the gut affect the amounts of dietary AAs that enter the blood circulation. Absorbed AAs are utilized for the syntheses of protein, peptides, AAs, and other metabolites (including nucleotides); biological oxidation and ATP production; gluconeogenesis and lipogenesis; and the regulation of acid-base balance, anti-oxidative reactions, and immune responses. Fish producers usually focus on the content or digestibility of dietary crude protein without considering the supply of AAs in the diet. In experiments involving dietary supplementation with AAs, inappropriate AAs (e.g., glycine and glutamate) are often used as the isonitrogenous control. At present, limited knowledge is available about either the cell- and tissue-specific metabolism of AAs or the effects of feed processing methods on the digestion and utilization of AAs in different fish species. These issues should be addressed to develop environment-friendly aquafeeds and reduce feed costs to sustain the global aquaculture.

Amino Acid Nutrition and Metabolism in Chickens.

Abstract: Both poultry meat and eggs provide high-quality animal protein [containing sufficient amounts and proper ratios of amino acids (AAs)] for human consumption and, therefore, play an important role in the growth, development, and health of all individuals. Because there are growing concerns about the suboptimal efficiencies of poultry production and its impact on environmental sustainability, much attention has been paid to the formulation of low-protein diets and precision nutrition through the addition of low-cost crystalline AAs or alternative sources of animal-protein feedstuffs. This necessitates a better understanding of AA nutrition and metabolism in chickens. Although historic nutrition research has focused on nutritionally essential amino acids (EAAs) that are not synthesized or are inadequately synthesized in the body, increasing evidence shows that the traditionally classified nutritionally nonessential amino acids (NEAAs), such as glutamine and glutamate, have physiological and regulatory roles other than protein synthesis in chicken growth and egg production. In addition, like other avian species, chickens do not synthesize adequately glycine or proline (the most abundant AAs in the body but present in plant-source feedstuffs at low content) relative to their nutritional and physiological needs. Therefore, these two AAs must be sufficient in poultry diets. Animal proteins (including ruminant meat & bone meal and hydrolyzed feather meal) are abundant sources of both glycine and proline in chicken nutrition. Clearly, chickens (including broilers and laying hens) have dietary requirements for all proteinogenic AAs to achieve their maximum productivity and maintain optimum health particularly under adverse conditions such as heat stress and disease. This is a paradigm shift in poultry nutrition from the 70-year-old "ideal protein" concept that concerned only about EAAs to the focus of functional AAs that include both EAAs and NEAAs.

Retrieval and Investigation of Data on SARS-CoV-2 and COVID-19 Using Bioinformatics Approach.

Abstract: Sudden emergence and a rapid outbreak of SARS-CoV-2 accompanied by a devastating impact on the economy and public health has driven extensive scientific mobilization to study and elucidate the various associated concerns about SARS-CoV-2. Bioinformatics plays a crucial role in addressing and providing solutions to questions about SARS-CoV-2. It helps shorten the duration for the vaccine development process and the discovery of potential clinical interventions through the simulation and information retrieval, and the development of well-ordered information hubs and resources, which are essential to derive data and meaningful findings from the current massive information about SARS-CoV-2. Advanced algorithms in this field also provide approaches that are essential to elucidate the relationship, origin, and evolutionary process of SARS-CoV-2. Here, we report essential bioinformatics entities, such as database and platform development, molecular evolution and phylogenetic analyses, and vaccine designs, that are useful to solve the SARS-CoV-2 conundrum.

IL-22 Signaling in the Tumor Microenvironment.

Abstract: Interleukin (IL)-22 belongs to the IL-10 cytokine family which performs biological functions by binding to heterodimer receptors comprising a type 1 receptor chain (R1) and a type 2 receptor chain (R2) IL-22 is mainly derived from CD4+ helper T cells, CD8+ cytotoxic T cells, innate lymphocytes, and natural killer T cells It can activate downstream signaling pathways such as signal transducer and activator of transcription (STAT)1/3/5, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) through these heterodimer receptors Although IL-22 is produced by immune cells, its specific receptor IL-22R1 is selectively expressed in nonimmune cells, such as hepatocytes, colonic epithelial cells, and pancreatic epithelial cells (Jiang et al Hepatology 54(3):900-9, 2011; Jiang et al BMC Cancer 13:59, 2013; Curd et al Clin Exp Immunol 168(2):192-9, 2012) Immune cells do not respond to IL-22 stimulation directly within tumors, reports from different groups have revealed that IL-22 can indirectly regulate the tumor microenvironment (TME) In the present chapter, we discuss the roles of IL-22 in malignant cells and immunocytes within the TME, meanwhile, the potential roles of IL-22 as a target for drug discovery will be discussed

COVID-19 and Its Global Economic Impact.

Abstract: Pandemics are enormous threats to the world that impact all aspects of our lives, especially the global economy. The COVID-19 pandemic has emerged since December 2019 and has affected the global economy in many ways. As the world becomes more interconnected, the economic impacts of the pandemic become more serious. In addition to increased health expenditures and reduced labor force, the pandemic has hit the supply and demand chain massively and caused trouble for manufacturers who have to fire some of their employees or delay their economic activities to prevent more loss. With the closure of manufacturers and companies and reduced travel rates, usage of oil after the beginning of the pandemic has decreased significantly that was unprecedented in the last 30 years. The mining industry is a critical sector in several developing countries, and the COVID-19 pandemic has hit this industry too. Also, world stock markets declined as investors started to become concerned about the economic impacts of the COVID-19 pandemic. The tourism industry and airlines have also experienced an enormous loss too. The GDP has reduced, and this pandemic will cost the world more than 2 trillion at the end of 2020.

Sex and Gender Differences in Lung Disease.

Abstract: Sex differences in the anatomy and physiology of the respiratory system have been widely reported. These intrinsic sex differences have also been shown to modulate the pathophysiology, incidence, morbidity, and mortality of several lung diseases across the life span. In this chapter, we describe the epidemiology of sex differences in respiratory diseases including neonatal lung disease (respiratory distress syndrome, bronchopulmonary dysplasia) and pediatric and adult disease (including asthma, cystic fibrosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, lymphangioleiomyomatosis, obstructive sleep apnea, pulmonary arterial hypertension, and respiratory viral infections such as respiratory syncytial virus, influenza, and SARS-CoV-2). We also discuss the current state of research on the mechanisms underlying the observed sex differences in lung disease susceptibility and severity and the importance of considering both sex and gender variables in research studies' design and analysis.

Cannabis and Depression.

Abstract: There is a growing body of evidence pointing to the co-occurrence of cannabis use and depression. There is also some evidence that the use of cannabis may lead to the onset of depression; however, strong evidence points to the inverse association; i.e. that depression may lead to the onset or increase in cannabis use frequency. Observational and epidemiological studies have not indicated a positive long-term effect of cannabis use on the course and outcome of depression. The association between cannabis use and depression may be stronger among men during adolescence and emerging adulthood and stronger in women during midlife. There is an indication for potential genetic correlation contributing to the comorbidity of cannabis dependence and major depression, namely that serotonin (5-HT) may mediate such association and there is also evidence for specific risk alleles for cannabis addiction. There is preclinical evidence that alteration in the endocannabinoid system could potentially benefit patients suffering from depression. However, the issue of using cannabis as an anti-depressant is at an early stage of examination and there is little evidence to support it. Finally, there has been little support to the notion that selective serotonin reuptake inhibitors (SSRIs) may be effective in decreasing depressive symptoms or rates of substance use in adolescents treated for depression and a co-occurring substance use disorder. In conclusion, despite methodological limitations, research in the past decades has broadened our knowledge on the association between cannabis use and depression from epidemiological, neurological, genetic, and pharmacological perspectives.

Cannabidiol Therapy for Refractory Epilepsy and Seizure Disorders.

Abstract: Cannabis-derived cannabinoids have neuroactive properties. Recently, there has been emerging interest in the use of cannabidiol (CBD)-enriched products for treatment of drug-resistant epilepsy. In 2018, the FDA approved the use of CBD-rich Epidiolex for two severe forms of epilepsy in children (Lennox-Gastaut and Dravet syndromes). Experimental research supports the use of CBD in many CNS disorders, though the mechanisms underlying its anticonvulsant and neuroprotective effects remain unclear. CBD has been shown to reduce inflammation, protect against neuronal loss, normalize neurogenesis, and act as an antioxidant. These actions appear to be due to the multimodal mechanism of action of CBD in the brain. This chapter briefly describes the current information on cannabis pharmacology with an emphasis on the clinical utility of CBD in the treatment of refractory epilepsies and other related seizure conditions. Clinical trials are ongoing for other forms of epilepsy and refractory seizures associated with infantile spasms, tuberous sclerosis, and Rett syndrome. Overall, adjunct CBD has been found to be generally safe and effective for treatment-resistant seizures in children with severe early-onset epilepsy. Whether an add-on CBD is efficacious for the long-term treatment of various epilepsy and seizure types in adults being tested in various clinical trials.

The Idiosyncratic Physiological Traits of the Naked Mole-Rat; a Resilient Animal Model of Aging, Longevity, and Healthspan.

Abstract: The subterranean-dwelling naked mole-rat (Heterocephalus glaber) is an extremophilic rodent, able to thrive in the harsh underground conditions of sub-Saharan Northeast Africa. This pelage-free mammal exhibits numerous unusual ecophysiological features including pronounced tolerance of thermolability, hypoxia, hypercapnia and noxious substances. As a mammal, the naked mole-rat provides a proof-of-concept that age-related changes in physiology are avoidable. At ages far beyond their expected lifespans given both their body size and/or the timing of early developmental milestones, naked mole-rats fail to exhibit meaningful changes in physiological health or demographic mortality. Lack of physiological deterioration with age is also evident in lean and fat mass, bone quality, and reproductive capacity. Rather, regardless of age, under basal conditions naked mole-rats appear to “idle on low” with their “shields up” as is manifested by low body temperature, metabolic rate, cardiac output and kidney concentrating ability, enabling better protection of organs and cellular function. When needed, they can nevertheless ramp up these functions, increasing cardiac output and metabolism 2–5 fold. Here we review many unusual aspects of their physiology and examine how these attributes facilitate both tolerance of the diverse suite of hostile conditions encountered in their natural milieu as well as contribute to their extraordinary longevity and resistance to common, age-related chronic diseases.

Amino Acids in Swine Nutrition and Production

Abstract: Amino acids are the building blocks of proteins in animals, including swine. With the development of new analytical methods and biochemical research, there is a growing interest in fundamental and applied studies to reexamine the roles and usage of amino acids (AAs) in swine production. In animal nutrition, AAs have been traditionally classified as nutritionally essential (EAAs) or nutritionally nonessential (NEAAs). AAs that are not synthesized de novo must be provided in diets. However, NEAAs synthesized by cells of animals are more abundant than EAAs in the body, but are not synthesized de novo in sufficient amounts for the maximal productivity or optimal health (including resistance to infectious diseases) of swine. This underscores the conceptual limitations of NEAAs in swine protein nutrition. Notably, the National Research Council (NRC 2012) has recognized both arginine and glutamine as conditionally essential AAs for pigs to improve their growth, development, reproduction, and lactation. Results of recent work have also provided compelling evidence for the nutritional essentiality of glutamate, glycine, and proline for young pigs. The inclusion of so-called NEAAs in diets can help balance AAs in diets, reduce the dietary levels of EAAs, and protect the small intestine from oxidative stress, while enhancing the growth performance, feed efficiency, and health of pigs. Thus, both EAAs and NEAAs are needed in diets to meet the requirements of pigs. This notion represents a new paradigm shift in our understanding of swine protein nutrition and is transforming pork production worldwide.

Transcription Factor RBPJ as a Molecular Switch in Regulating the Notch Response.

Abstract: The Notch signal transduction cascade requires cell-to-cell contact and results in the proteolytic processing of the Notch receptor and subsequent assembly of a transcriptional coactivator complex containing the Notch intracellular domain (NICD) and transcription factor RBPJ. In the absence of a Notch signal, RBPJ remains at Notch target genes and dampens transcriptional output. Like in other signaling pathways, RBPJ is able to switch from activation to repression by associating with corepressor complexes containing several chromatin-modifying enzymes. Here, we focus on the recent advances concerning RBPJ-corepressor functions, especially in regard to chromatin regulation. We put this into the context of one of the best-studied model systems for Notch, blood cell development. Alterations in the RBPJ-corepressor functions can contribute to the development of leukemia, especially in the case of acute myeloid leukemia (AML). The versatile role of transcription factor RBPJ in regulating pivotal target genes like c-MYC and HES1 may contribute to the better understanding of the development of leukemia.

Constituents of Cannabis Sativa.

Abstract: The Cannabis sativa plant has been used medicinally and recreationally for thousands of years, but recently only relatively some of its constituents have been identified. There are more than 550 chemical compounds in cannabis, with more than 100 phytocannabinoids being identified, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These phytocannabinoids work by binding to the cannabinoid receptors, as well as other receptor systems. Also within cannabis are the aromatic terpenes, more than 100 of which have been identified. Cannabis and its constituents have been indicated as therapeutic compounds in numerous medical conditions, such as pain, anxiety, epilepsy, nausea and vomiting, and post-traumatic stress disorder. This chapter provides an overview of some of the biological effects of a number of the cannabinoids and terpenes, as well as discussing their known mechanisms of action and evidence of potential therapeutic effects.

Nutrition and Functions of Amino Acids in Aquatic Crustaceans.

Abstract: Crustaceans (e.g., shrimp and crabs) are a good source of protein-rich foods for human consumption. They are the second largest aquaculture species worldwide. Understanding the digestion of dietary protein, as well as the absorption, metabolism and functions of amino acids (AAs) and small peptides is essential to produce cost-effective and sustainable aquafeeds. Hepatopancreas (the midgut gland) is the main site for the digestion of dietary protein as well as the absorption of small peptides and AAs into the hemolymph. Besides serving as the building blocks of protein, AAs (particularly aspartate, glutamate, glutamine and alanine) are the primary metabolic fuels for the gut and extra-hepatopancreas tissues (e.g., kidneys and skeletal muscle) of crustaceans. In addition, AAs are precursors for the syntheses of glucose, lipids, H2S, and low-molecular-weight molecules (e.g., nitric oxide, glutathione, polyamines, histamine, and hormones) with enormous biological importance, such as physical barrier, immunological and antioxidant defenses. Therefore, both nutritionally essential and nonessential AAs are needed in diets to improve the growth, development, molt rate, survival, and reproduction of crustaceans. There are technical difficulties and challenges in the use of crystalline AAs for research and practical production due to the loss of free AAs during feed processing, the leaching of in-feed free AAs to the surrounding water environment, and asynchronous absorption with peptide-bounded AAs. At present, much knowledge about AA metabolism and functions in crustaceans is based on studies of mammals and fish species. Basic research in this area is necessary to lay a solid foundation for improving the balances and bioavailability of AAs in the diets for optimum growth, health and wellbeing of crustaceans, while preventing and treating their metabolic diseases. This review highlights recent advances in AA nutrition and metabolism in aquatic crustacean species at their different life stages. The new knowledge is expected to guide the development of the next generation of their improved diets.

Redox Role of ROS and Inflammation in Pulmonary Diseases.

Abstract: Reactive oxygen species (ROS), either derived from exogenous sources or overproduced endogenously, can disrupt the body's antioxidant defenses leading to compromised redox homeostasis. The lungs are highly susceptible to ROS-mediated damage. Oxidative stress (OS) caused by this redox imbalance leads to the pathogenesis of multiple pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS). OS causes damage to important cellular components in terms of lipid peroxidation, protein oxidation, and DNA histone modification. Inflammation further enhances ROS production inducing changes in transcriptional factors which mediate cellular stress response pathways. This deviation from normal cell function contributes to the detrimental pathological characteristics often seen in pulmonary diseases. Although antioxidant therapies are feasible approaches in alleviating OS-related lung impairment, a comprehensive understanding of the updated role of ROS in pulmonary inflammation is vital for the development of optimal treatments. In this chapter, we review the major pulmonary diseases-including COPD, asthma, ARDS, COVID-19, and lung cancer-as well as their association with ROS.

Androgen Actions in the Testis and the Regulation of Spermatogenesis.

Abstract: Testosterone is essential for spermatogenesis and male fertility. In this review, topics related to testosterone control of spermatogenesis are covered including testosterone production and levels in the testis, classical and nonclassical testosterone signaling pathways, cell- and temporal-specific expression of the androgen receptor in the testis and autocrine and paracrine signaling of testis cells in the testis. Also discussed are the contributions of testosterone to testis descent, the blood-testis barrier, control of gonocyte numbers and spermatogonia expansion, completion of meiosis and attachment and release of elongaed spermatids. Testosterone-regulated genes identified in various mouse models of idsrupted Androgen receptor expression are discussed. Finally, examples of synergism and antagonism between androgen and follicle-stimulating hormone signaling pathways are summarized.

Composition of Amino Acids in Foodstuffs for Humans and Animals.

Abstract: Amino acids (AAs) are the building blocks of proteins that have both structural and metabolic functions in humans and other animals. In mammals, birds, fish, and crustaceans, proteinogenic AAs are alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. All animals can synthesize de novo alanine, asparagine, aspartate, glutamate, glutamine, glycine, proline, and serine, whereas most mammals (including humans and pigs) can synthesize de novo arginine. Results of extensive research over the past three decades have shown that humans and other animals have dietary requirements for AAs that are synthesizable de novo in animal cells. Recent advances in analytical methods have allowed us to determine all proteinogenic AAs in foods consumed by humans, livestock, poultry, fish, and crustaceans. Both plant- and animal-sourced foods contain high amounts of glutamate, glutamine, aspartate, asparagine, and branched-chain AAs. Cysteine, glycine, lysine, methionine, proline, threonine, and tryptophan generally occur in low amounts in plant products but are enriched in animal products. In addition, taurine and creatine (essential for the integrity and function of tissues) are absent from plants but are abundant in meat and present in all animal-sourced foods. A combination of plant- and animal products is desirable for the healthy diets of humans and omnivorous animals. Furthermore, animal-sourced feedstuffs can be included in the diets of farm and companion animals to cost-effectively improve their growth performance, feed efficiency, and productivity, while helping to sustain the global animal agriculture (including aquaculture).

Age-Related Macular Degeneration: Epidemiology and Clinical Aspects.

Abstract: Age-related macular degeneration (AMD) is a degenerative disease of the human retina affecting individuals over the age of 55 years. This heterogeneous condition arises from a complex interplay between age, genetics, and environmental factors including smoking and diet. It is the leading cause of blindness in industrialized countries. Worldwide, the number of people with AMD is predicted to increase from 196 million in 2020 to 288 million by 2040. By this time, Asia is predicted to have the largest number of people with the disease. Distinct patterns of AMD prevalence and phenotype are seen between geographical areas that are not explained fully by disparities in population structures. AMD is classified into early, intermediate, and late stages. The early and intermediate stages, when visual symptoms are typically absent or mild, are characterized by macular deposits (drusen) and pigmentary abnormalities. Through risk prediction calculators, grading these features helps predict the risk of progression to late AMD. Late AMD is divided into neovascular and atrophic forms, though these can coexist. The defining lesions are macular neovascularization and geographic atrophy, respectively. At this stage, visual symptoms are often severe and irreversible, and can comprise profoundly decreased central vision in both eyes. For these reasons, the condition has major implications for individuals and society, as affected individuals may experience substantially decreased quality of life and independence. Recent advances in retinal imaging have led to the recognition of an expanded set of AMD phenotypes, including reticular pseudodrusen, nonexudative macular neovascularization, and subtypes of atrophy. These developments may lead to refinements in current classification systems.

Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.

Abstract: Solute carriers form one of three major superfamilies of membrane transporters in humans, and include uniporters, exchangers and symporters. Following several decades of molecular characterisation, multiple solute carriers that form obligatory heteromers with unrelated subunits are emerging as a distinctive principle of membrane transporter assembly. Here we comprehensively review experimentally established heteromeric solute carriers: SLC3-SLC7 amino acid exchangers, SLC16 monocarboxylate/H+ symporters and basigin/embigin, SLC4A1 (AE1) and glycophorin A exchanger, SLC51 heteromer Ost α-Ost β uniporter, and SLC6 heteromeric symporters. The review covers the history of the heteromer discovery, transporter physiology, structure, disease associations and pharmacology - all with a focus on the heteromeric assembly. The cellular locations, requirements for complex formation, and the functional role of dimerization are extensively detailed, including analysis of the first complete heteromer structures, the SLC7-SLC3 family transporters LAT1-4F2hc, b0,+AT-rBAT and the SLC6 family heteromer B0AT1-ACE2. We present a systematic analysis of the structural and functional aspects of heteromeric solute carriers and conclude with common principles of their functional roles and structural architecture.

Sex Hormones and Lung Inflammation.

Abstract: Inflammation is a characteristic marker in numerous lung disorders. Several immune cells, such as macrophages, dendritic cells, eosinophils, as well as T and B lymphocytes, synthetize and release cytokines involved in the inflammatory process. Gender differences in the incidence and severity of inflammatory lung ailments including asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), lung cancer (LC), and infectious related illnesses have been reported. Moreover, the effects of sex hormones on both androgens and estrogens, such as testosterone (TES) and 17β-estradiol (E2), driving characteristic inflammatory patterns in those lung inflammatory diseases have been investigated. In general, androgens seem to display anti-inflammatory actions, whereas estrogens produce pro-inflammatory effects. For instance, androgens regulate negatively inflammation in asthma by targeting type 2 innate lymphoid cells (ILC2s) and T-helper (Th)-2 cells to attenuate interleukin (IL)-17A-mediated responses and leukotriene (LT) biosynthesis pathway. Estrogens may promote neutrophilic inflammation in subjects with asthma and COPD. Moreover, the activation of estrogen receptors might induce tumorigenesis. In this chapter, we summarize the most recent advances in the functional roles and associated signaling pathways of inflammatory cellular responses in asthma, COPD, PF, LC, and newly occurring COVID-19 disease. We also meticulously deliberate the influence of sex steroids on the development and progress of these common and severe lung diseases.

Recent Advances in the Potential of Cannabinoids for Neuroprotection in Alzheimer's, Parkinson's, and Huntington's Diseases.

Abstract: Three prevalent neurodegenerative diseases, Parkinson's, Alzheimer's, and Huntington's are in need of symptomatic relief of slowing disease progression or both. This chapter focuses on the potential of cannabinoids to afford neuroprotection, i.e. avoid or retard neuronal death. The neuroprotective potential of cannabinoids is known from the work in animal models and is mediated by the two cannabinoid receptors (CB1/CB2) and eventually, by their heteromers, GPR55, orphan receptors (GPR3/GPR6/GPR12/GPR18), or PPARγ. Now, there is the time to translate the findings into patients. The chapter takes primarily into account advances since 2016 and addresses the issue of proving neuroprotection in humans. One recent discovery is the existence of activated microglia with neuroprotective phenotype; cannabinoids are good candidates to skew phenotype, especially via glial CB2 receptors (CB2R), whose targeting has, a priori, less side effects those targeting the CBs1 receptor (CB1R), which are expressed in both neurons and glia. The fact that a cannabis extract (SativexTM) is approved for human therapy, such that cannabis use will likely be legalized in many countries and different possibilities that cannabinoid pharmacology suggests a successful route of cannabinoids (natural or synthetic) all the way to be approved and used in the treatment of neurodegeneration.

CXCL8 Signaling in the Tumor Microenvironment.

Abstract: The tumor microenvironment represents a dynamic and complex cellular network involving intricate communications between the tumor and highly heterogeneous groups of cells, including tumor-supporting immune and inflammatory cells, cancer-associated fibroblasts, endothelial cells, tumor-associated macrophages, adipose cells, and pericytes. Associated with a variety of growth factors, chemokines, cytokines, and other signaling molecules, the interaction between the tumor microenvironment and the tumor cells empowers aggressiveness of tumor by enhancing its survivability. CXCL8 (also known as Interleukin 8), a multifunctional proinflammatory chemokine that was initially classified as a neutrophil chemoattractant, recently has been found to be a key contributor in tumorigenesis. The upregulation of CXCL8 at the tumor invasion front in several human cancers suggests its interplay between the tumor and its microenvironment rendering tumor progression by enhancing angiogenesis, tumor genetic diversity, survival, proliferation, immune escape, metastasis, and multidrug resistance. The autocrine and paracrine modulation of CXCL8 via the chemokine receptors CXCR1/2 promotes several intracellular signaling cascades that fosters tumor-associated inflammation, reprogramming, epithelial-mesenchymal transition, and neovascularization. Hence, decrypting the regulatory/signaling cascades of CXCL8 and its downstream effects may harbor prognostic clinical prospects of a tumor microenvironment-oriented cancer therapeutics.

CCL2 in the Tumor Microenvironment

Abstract: The C-C motif chemokine ligand 2 (CCL2) is a crucial mediator of immune cell recruitment during microbial infections and tissue damage. CCL2 is also frequently overexpressed in cancer cells and other cells in the tumor microenvironment, and a large body of evidence indicates that high CCL2 levels are associated with more aggressive malignancies, a higher probability of metastasis, and poorer outcomes in a wide range of cancers. CCL2 plays a role in recruiting tumor-associated macrophages (TAMs), which adopt a pro-tumorigenic phenotype and support cancer cell survival, facilitate tumor cell invasion, and promote angiogenesis. CCL2 also has direct, TAM-independent effects on tumor cells and the tumor microenvironment, including recruitment of other myeloid subsets and non-myeloid cells, maintaining an immunosuppressive environment, stimulating tumor cell growth and motility, and promoting angiogenesis. CCL2 also plays important roles in the metastatic cascade, such as creating a pre-metastatic niche in distant organs and promoting tumor cell extravasation across endothelia. Due to its many roles in tumorigenesis and metastatic processes, the CCL2-CCR2 signaling axis is currently being pursued as a potential therapeutic target for cancer.

Notch Signaling and the Breast Cancer Microenvironment.

Abstract: Notch promotes breast cancer progression through tumor initiating cell maintenance, tumor cell fate specification, proliferation, survival, and motility. In addition, Notch is recognized as a decisive mechanism in regulating various juxtacrine and paracrine communications in the tumor microenvironment (TME). In this chapter, we review recent studies on stress-mediated Notch activation within the TME and sequelae such as angiogenesis, extracellular matrix remodeling, changes in the innate and adaptive immunophenotype, and therapeutic perspectives.

Turmeric and Curcumin: From Traditional to Modern Medicine.

Abstract: The rhizome of turmeric (Curcuma longa L.) has been used as an herbal medicine, coloring agent, spice, and food additive for thousands of years in different parts of the world particularly in Asian countries. It has been used for a range of diseases in many traditional medical schools, including Islamic traditional medicine, Chinese traditional medicine, and Ayurveda. It has been used mainly for digestive problems, as a cardio-, hepato-, and neuroprotective agent as well as in many inflammatory conditions such as arthritis and for enhancing immune system. Curcumin, a diarylheptanoid derivative found in turmeric, has anti-inflammatory, antioxidant, and anticancer properties; controls obesity and metabolic problems; and improves memory and mood disorders. Therapeutically, curcumin exhibits promising potential in preclinical and clinical studies and is currently in human trials for a variety of conditions, including metabolic syndrome, nonalcoholic fatty liver disease, rheumatoid arthritis, migraine, premenstrual syndrome, ulcerative colitis, knee osteoarthritis, polycystic ovarian syndrome, atherosclerosis, liver cirrhosis, amyotrophic lateral sclerosis, depression, psoriasis, and Alzheimer’s disease. Among all beneficial activities reported for curcumin, the research toward the obesity and metabolic-preventing/suppressing aspects of curcumin is growing. These findings emphasize that most of the traditional applications of turmeric is due to the presence of its key constituent, curcumin. According to the traditional background of turmeric use and clinical values of curcumin, further preclinical studies for unstudied properties and clinical studies with larger sample sizes for confirmed activities are expected.

The Histone H3 Family and Its Deposition Pathways.

Abstract: Within the cell nucleus, the organization of the eukaryotic DNA into chromatin uses histones as components of its building block, the nucleosome. This chromatin organization contributes to the regulation of all DNA template-based reactions impacting genome function, stability, and plasticity. Histones and their variants endow chromatin with unique properties and show a distinct distribution into the genome that is regulated by dedicated deposition machineries. The histone variants have important roles during early development, cell differentiation, and chromosome segregation. Recent progress has also shed light on how mutations and transcriptional deregulation of these variants participate in tumorigenesis. In this chapter we introduce the organization of the genome in chromatin with a focus on the basic unit, the nucleosome, which contains histones as the major protein component. Then we review our current knowledge on the histone H3 family and its variants-in particular H3.3 and CenH3CENP-A-focusing on their deposition pathways and their dedicated histone chaperones that are key players in histone dynamics.