Antibody-based therapeutics have become a major class of therapeutics with over 120 recombinant antibodies approved or under review in the EU or US. This therapeutic class has experienced a remarkable expansion with an expected acceleration in 2021–2022 due to the extraordinary global response to SARS-CoV2 pandemic and the public disclosure of over a hundred anti-SARS-CoV2 antibodies. Mainly delivered

Extracellular vesicles (EVs), including exosomes and microvesicles, are lipid bilayer particles naturally released from the cell. While exosomes are formed as intraluminal vesicles (ILVs) of the multivesicular endosomes (MVEs) and released to extracellular space upon MVE-plasma membrane fusion, microvesicles are generated through direct outward budding of the plasma membrane. Exosomes and microvesicles

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine encoded within a functionally polymorphic genetic locus. MIF was initially recognized as a cytokine generated by activated T cells, but in recent days it has been identified as a multipotent key cytokine secreted by many other cell types involved in immune response and physiological processes. MIF is a highly conserved 12.5 kDa

Riboflavin (vitamin B2) is essential for cellular growth and function. It is enzymatically converted to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which participate in the metabolic oxidation-reduction reactions of carbohydrates, amino acids, and lipids. Human riboflavin transporters RFVT1, RFVT2, and RFVT3 have been identified and characterized since 2008. They are highly specific

The mammalian/mechanistic target of rapamycin (mTOR) is a regulatory protein kinase involved in cell growth and proliferation. mTOR is usually assembled in two different complexes with different regulatory mechanisms, mTOR complex 1 (mTORC1) and mTORC2, which are involved in different functions such as cell proliferation and cytoskeleton assembly, respectively. In cancer cells, mTOR is hyperactivated

Oxidative metabolism is one of the major biotransformation reactions that regulates the exposure of xenobiotics and their metabolites in the circulatory system and local tissues and organs, and influences their efficacy and toxicity. Although cytochrome (CY)P450s play critical roles in the oxidative reaction, extensive CYP450-independent oxidative metabolism also occurs in some xenobiotics, such as

Among the various biological properties presented by Mesenchymal Stem Cells (MSCs), their ability to control the immune response and fight pathogen infection through the production of antimicrobial peptides (AMPs) have been the subject of intense research in recent years. AMPs secreted by MSCs exhibit activity against a wide range of microorganisms, including bacteria, fungi, yeasts, and viruses. The

Overdose deaths are often viewed as the leading edge of the opioid epidemic which has gripped the United States over the past two decades (Skolnick, 2018a). This emphasis is perhaps unsurprising because opioid overdose is both the number-one cause of death for individuals between 25 and 64 years old (Dezfulian et al., 2021) and a significant contributor to the decline in average lifespan (Dowell et

Chronic obstructive pulmonary disease (COPD) is a major incurable global health burden and currently, the 3rd largest cause of death in the world with approximately 3.23 million deaths per year. Globally, the financial burden of COPD is approximately €82 billion per year and causes substantial morbidity and mortality. Importantly, much of the disease burden and health care utilisation in COPD is associated

Classically, the fate of internalized membrane receptors includes receptor degradation and receptor recycling. However, recent findings have begun to challenge these views. Much research demonstrated that many internalized membrane receptors can trigger distinct signal activation rather than being desensitized inside the cell. Here, we introduce the concept of “internalized activation” which not only

Dietary polyphenols have been the focus of major interest for their potential benefits on human health. Several preclinical studies have been conducted to provide a rationale for their potential use as therapeutic agents in preventing or ameliorating cognitive decline. However, results from human studies are scarce and poorly documented. The aim of this review was to discuss the potential mechanisms

Endogenous opioid peptides and prescription opioid drugs modulate pain, anxiety and stress by activating four opioid receptors, namely μ (mu, MOP), δ (delta, DOP), κ (kappa, KOP) and the nociceptin/orphanin FQ receptor (NOP). Interestingly, several other receptors are also activated by endogenous opioid peptides and influence opioid-driven signaling and biology. However, they do not meet the criteria

Programmed cell death (PCD) is an essential part of organismal development and plays fundamental roles in host defense against pathogens and the maintenance of homeostasis. However, excess activation of PCD pathways has proven to be detrimental and can drive disease. Additionally, resistance to PCD can also contribute to disease development. Modulation of PCD, therefore, has great therapeutic potential

The breast cancer type 1 susceptibility protein (BRCA1) and its partner – the BRCA1-associated RING domain protein 1 (BARD1) – are key players in a plethora of fundamental biological functions including, among others, DNA repair, replication fork protection, cell cycle progression, telomere maintenance, chromatin remodeling, apoptosis and tumor suppression. However, mutations in their encoding genes

Lymphatic vessels have crucial roles in the regulation of interstitial fluids, immune surveillance, and the absorption of dietary fat in the intestine. Lymphatic function is also closely related to the pathogenesis of various disease states such as inflammation, lymphedema, endometriosis, liver dysfunction, and tumor metastasis. Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing

Breast cancer has become a serious threat to women's health. Cancer progression is mainly derived from resistance to apoptosis induced by procedures or therapies. Therefore, new drugs or models that can overcome apoptosis resistance should be identified. Ferroptosis is a recently identified mode of cell death characterized by excess reactive oxygen species-induced lipid peroxidation. Since ferroptosis

The liver has the ability to repair itself after injury; however, a variety of pathological changes in the liver can affect its ability to regenerate, and this could lead to liver failure. Mesenchymal stem cells (MSCs) are considered a good source of cells for regenerative medicine, as they regulate liver regeneration through different mechanisms, and their efficacy has been demonstrated by many animal

The past thirty years have seen a surge in interest in pathophysiological roles of mitochondrial, and the accurate quantification of mitochondrial DNA copy number (mCN) in cells and tissue samples is a fundamental aspect of assessing changes in mitochondrial health and biogenesis. Quantification of mCN between studies is surprisingly variable due to a combination of physiological variability and diverse

In eukaryotes, precursor mRNAs (pre-mRNA) produce a unique class of biologically active molecules namely circular RNAs (circRNAs) with a covalently closed-loop structure via back-splicing. Because of this unconventional circular form, circRNAs exhibit much higher stability than linear RNAs due to the resistance to exonuclease degradation and thereby play exclusive cellular regulatory roles. Recent

The extracellular matrix is an active participant, modulator and mediator of the cell, tissue, organ and organismal response to injury. Recent research has highlighted the role of hyaluronan, an abundant glycosaminoglycan constituent of the extracellular matrix, in many fundamental biological processes underpinning homeostasis and disease development. From this basis, emerging studies have demonstrated

Although treatment outcomes of multiple myeloma patients have improved significantly during the last two decades, myeloma is still an incurable disease. There are newly emerging immunotherapies to treat multiple myeloma including monoclonal antibodies, antibody-drug conjugate, bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy. Impressive response rate and clinical efficacy in

“Modern” vaping involving battery-operated electronic devices began approximately one dozen years and has quickly evolved into a multibillion dollar industry providing products to an estimated 50 million users worldwide. Originally developed as an alternative to traditional cigarette smoking, vaping now appeals to a diverse demographic including substantial involvement of young people who often have

Air pollution is associated with staggering levels of cardiovascular morbidity and mortality. Airborne particulate matter (PM), in particular, has been associated with a wide range of detrimental cardiovascular effects, including impaired vascular function, raised blood pressure, alterations in cardiac rhythm, blood clotting disorders, coronary artery disease, and stroke. Considerable headway has been

Sphingolipids (SLs) are a family of bioactive lipids implicated in a variety of cellular processes, and whose levels are controlled by an interlinked network of enzymes. While the spatial distribution of SL metabolism throughout the cell has been understood for some time, the implications of this for SL signaling and biological outcomes have only recently begun to be fully explored. In this review

Helicobacter pylori (H. pylori) is a major causative agent of chronic gastritis, gastric ulcer and gastric carcinoma. H. pylori cytotoxin associated antigen A (CagA) plays a crucial role in the development of gastric cancer. Gastric cancer is associated with glycosylation alterations in glycoproteins and glycolipids on the cell surface. H. pylori cytotoxin associated antigen A (CagA) plays a significant

Kisspeptin (encoded by the Kiss1 gene) and its receptor, KISS1R (encoded by the Kiss1r gene), have well-established roles in stimulating reproduction via central actions on reproductive neural circuits, but recent evidence suggests that kisspeptin signaling also influences metabolism and energy balance. Indeed, both Kiss1 and Kiss1r are expressed in many metabolically-relevant peripheral tissues, including

Obesity-mediated metabolic syndrome remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves the heme oxygenase (HO) system, specifically its inducible form, HO-1. This review collects and updates much of the current knowledge relevant to pharmacology and clinical medicine concerning HO-1 in metabolic diseases and its

Probiotics are live microorganisms, which when administered in adequate amounts present a health benefit for the host. While the beneficial effects of probiotics on gastrointestinal function are generally well recognized, new animal research and clinical studies have found that alterations in gut microbial communities can have a broad range of effects throughout the body. Non-intestinal sites impacted

Neuroinflammation was initially thought of as a consequence of neurodegenerative disease pathology, but more recently it is becoming clear that it plays a significant role in the development and progression of disease. Thus, neuroinflammation is seen as a realistic and valuable therapeutic target for neurodegeneration. Neuroinflammation can be modulated by neuron-glial signaling through various soluble

Overcoming refractory epilepsy's resistance to the combination of antiepileptic drugs (AED), mitigating side effects, and preventing sudden unexpected death in epilepsy are critical goals for therapy of this disorder. Current therapeutic strategies are based primarily on neurocentric mechanisms, overlooking the participation of astrocytes and microglia in the pathophysiology of epilepsy. This review

Alzheimer’s disease (AD) is an intractable neurodegenerative disease showing a clinical manifestation with memory loss, cognitive impairment and behavioral dysfunction. The predominant pathological characteristics of AD include neuronal loss, β-amyloid (Aβ) deposition and hyperphosphorylated Tau induced neurofibrillary tangles (NFTs), while considerable studies proved these could be triggered by neuronal

The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is a member of the opioid receptor superfamily with N/OFQ as its endogenous agonist. Wide expression of the NOP receptor and N/OFQ, both centrally and peripherally, and their ability to modulate several biological functions has led to development of NOP receptor modulators by pharmaceutical companies as therapeutics, based upon their efficacy

Fibrosis, which is characterized by excessive extracellular matrix (ECM) deposition, is a wound-healing response to organ injury and may promote cancer and failure in various organs, such as the heart, liver, lung, and kidney. Aging associated with oxidative stress and inflammation exacerbates cellular dysfunction, tissue failure, and body function disorders, all of which are closely related to fibrosis

Tumor-associated macrophages (TAM) plasticity and diversity are both essential hallmarks of the monocyte-macrophage lineage and the tumor-derived inflammation. TAM exemplify the perfect adaptable cell with dynamic phenotypic modifications that reflect changes in their functional polarization status. Under several tumor microenvironment (TME)-related cues, TAM shift their polarization, hence promoting

Cancer stem cells (CSCs) are a distinct population of cells within tumors with capabilities of self-renewal and tumorigenicity. CSCs play a privotal role in cancer progression, metastasis, and relapse and tumor resistance to cytotoxic therapy. Emerging scientific evidence indicates that CSCs adopt several mechanisms, driven by cellular plasticity, senescence and quiescence, to maintain their self-renewal

Pulmonary hypertension (PH) is a devastating condition characterized by pulmonary vascular remodelling, leading to progressive increase in pulmonary artery pressure and subsequent right ventricular failure. Aldosterone and the mineralocorticoid receptor (MR), a nuclear transcription factor, are key drivers of cardiovascular disease and MR antagonists are well-established in heart failure. Now, a growing

G protein-coupled receptors (GPCRs) are the largest group of receptors involved in cellular signaling across the plasma membrane and a major class of drug targets. The canonical model for GPCR signaling involves three components — the GPCR, a heterotrimeric G protein and a proximal plasma membrane effector — that have been generally thought to be freely mobile molecules able to interact by ‘collision

Tissue vascularization remains one of the outstanding challenges in regenerative medicine. Beyond its role in circulating oxygen and nutrients, the vasculature is critical for organ development, function and homeostasis. Importantly, effective vascular regeneration is key in generating large 3D tissues for regenerative medicine applications to enable the survival of cells post-transplantation, organ

The intestine has important gate-keeping functions that can profoundly affect the systemic blood exposure of orally administered drugs. Thus, characterizing a new molecular entity's (NME) disposition within the intestine is of utmost importance in drug development. While currently used in vitro systems, such as Ussing chamber, precision-cut intestinal slices, immortalized cell lines, and primary enterocytes

Cancer treatment has been deeply changed by immunotherapy, achieving unprecedented improvement in overall and progression-free survival in several advanced and metastatic cancers. Currently, immune checkpoint inhibitor (ICI) antibodies against cytotoxic T-lymphocyte antigen (CTLA-4) and programmed death/ligand 1 (PD-1/PD-L1) are being tested and approved for different tumors, ranging from melanoma

Lipopolysaccharides (LPS) are the main components of the external leaflet of the Gram-negative outer membrane and consist of three different moieties: lipid A, core oligosaccharide, and O-polysaccharide. The lipid A is a glucosamine disaccharide with different levels of acylation and phosphorylation, beside carrying, in certain cases, additional substituents on the sugar backbone. It is also the main

Sphingosine 1-phosphate (S1P) is a potent bioactive sphingolipid binding to specific G protein-coupled receptors expressed in several organs. The relevance of S1P-S1P receptor axis in the pathophysiology of immune and nervous systems has encouraged the development of S1P receptor modulators for the treatment of neurological, autoimmune and/or inflammatory disorders. Currently, four S1P receptor modulators

The underlying mechanism of tumor immune evasion is a highly concerning subject for researchers. Increasing evidences reveal that the over-activated signal transducer and activator of transcription 3 (STAT3) is a crucial molecular hub in malignant tumors. STAT3 controls autophagy molecules that impair CTL-mediated tumor cell lysis, inhibiting natural killer cells and inducing apoptosis in T lymphocytes

Phosphorylation is a reversible post-translational modification regulated by phosphorylase and dephosphorylase to mediate important cellular events. Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) encoded by PTPN11 is the first identified oncogenic protein in protein tyrosine phosphatases family. Serving as a convergent node, SHP2 is involved in multiple cascade signaling pathways including

The concepts of developing RNAs as new molecular entities for therapies have arisen again and again since the discoveries of antisense RNAs, direct RNA-protein interactions, functional noncoding RNAs, and RNA-directed gene editing. The feasibility was demonstrated with the development and utilization of synthetic RNA agents to selectively control target gene expression, modulate protein functions or

p130 Crk-associated substrate (Cas) functions as an adapter protein and plays important roles in certain cell functions, such as cell proliferation, spreading, migration, and invasion. Furthermore, it has recently been reported to have a new function as a mechanosensor. Since bone is a tissue that is constantly under gravity, it is exposed to mechanical stress. Mechanical unloading, such as in a microgravity

Our understanding of the progression and mechanism underlying the onset of Parkinson's disease (PD) has grown enormously in the past few decades. There is growing evidence suggesting that poly (ADP-ribose) polymerase 1 (PARP-1) hyperactivation is involved in various neurodegenerative disorders, including PD, and that poly (ADP-ribose) (PAR)-dependent cell death is responsible for neuronal loss. In

Cancer cells require a massive supply of nutrients, including sugars and amino acids—the upregulation of transporters for each nutrient contributes to meet the demand. Distinct from glucose transporters, amino acid transporters include ones whose expression is specific to cancer cells. For example, LAT1 (SLC7A5) displays protein expression mostly limited to the plasma membrane of cancer cells. The

In recent decades, technological advantages have allowed scientists to isolate medicinal compounds from marine organisms that exhibit unique structure and bioactivity. The mangrove fungus Xylaria sp. from the South China Sea is rich in metabolites and a potent therapeutic compound, xyloketal B, has been isolated in 2001. Since then, xyloketal B has been extensively studied in a wide variety of cell

The discovery of the essential requirement for kisspeptin and subsequently neurokinin B signalling for human reproductive function has sparked renewed interest in the neuroendocrinology of reproduction. A key discovery has been a population of cells co-expressing both these neuropeptides and dynorphin in the hypothalamus, directly regulating gonadotropin hormone releasing hormone (GnRH) secretion and

Fibromyalgia (FM) is a complex syndrome, with an indefinite aetiology and intricate pathophysiology that affects 2 – 3% of the world population. From the beginning of the 2000s, experimental animal models have been developed to mimic clinical FM and help obtain a better understanding of the relevant neurobiology. These animal models have enabled a broad study of FM symptoms and mechanisms, as well

Morphine and other mu-opioid receptor (MOR) agonists remain the mainstay treatment of acute and prolonged pain states worldwide. The major limiting factor for continued use of these current opioids is the high incidence of side effects that result in loss of life and loss of quality of life. The development of novel opioids bereft, or much less potent, at inducing these side effects remains an intensive

G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that are the targets for many different classes of pharmacotherapy. The islets of Langerhans are central to appropriate glucose homeostasis through their secretion of insulin, and islet function can be modified by ligands acting at the large number of GPCRs that islets express. The human islet GPCRome is not a static entity

Biased pharmacological modulators provide potential therapeutic benefits, including greater pharmacodynamic specificity, increased efficiency and reduced adverse effects. Therefore, the identification of such modulators as drug candidates is highly desirable. Currently, attention was mainly paid to biased signaling modulators targeting G protein-coupled receptors (GPCRs). The biased signaling modulation