Pentafuranosylnucleos(t)ides represent a class of natural compounds regulating diverse cell functions being preferably components of biopolymers and also participating as cyclic regulatory low-molecular ligands. Disaccharide nucleosides and related analogs are considered as therapeutically potent compounds for the treatment of cancer, viral diseases, and a variety of metabolic disorders by mimicking a structure of biochemically occurring molecules participating in nicotinamide adenine dinucleotide (NAD⁺) transformation. Several approaches have been developed on the way to the chemical synthesis of poly(adenosine diphosphate ribose) (PAR), a unique biopolymer taking part in DNA repair and associated functions, that would allow extensive studies of molecular mechanisms of a variety of diseases. The present review consists of the following main parts, the first one including structural characterization, biochemical roles, and chemical synthesis of disaccharide nucleosides from different sources and biopolymers on their basis, the second one describing therapeutic applications of disaccharide nucleosides and their analogs. General conclusion and perspectives are summarized in the last part.

Microbial pathogens with antibiotic resistance have become challenging to manage in the last few decades. The situation is alarming and a threat to humankind. Despite emerging new drug candidates, there are numerous strategies for efficient antibiotic delivery for treating such infections; antibiotic-resistant bacteria are still not eradicated adequately from the infected hosts. Recently, antimicrobial peptides (AMPs) have emerged as saviors in overcoming antibiotic resistance against bacteria. AMPs are being produced naturally as well as synthetically. Irrespective of the source of production, AMPs have shown higher specificity and lower toxicity to the host. Such functions have been attributed to distinct structures, functions, and varied mechanisms of action. This review highlights sources, structural and physiological characteristics, action mechanisms, and biological potency towards clinical applications. Most recently, AMPs have also been explored in treating cancers and tumors. Despite the entry of a few AMPs into clinical trials, there are limitations associated with their usage, like shorter half-life, protease cleavage, and toxicity. There is an urgent need to produce AMPs with intensified activity, biocompatibility, and lesser toxicity. This review sheds light on these aspects and the future of AMPs for the betterment of the human race.

Cancer remains the second leading cause of death globally, posing an ongoing threat to public health. A hallmark of cancer cells is their capacity to invade adjacent tissues and evolve into malignant forms, often resulting in aggressive tumors resistant to conventional treatments. At the heart of this therapeutic challenge are cancer stem cells (CSCs), which possess distinctive capabilities for self-renewal, differentiation, and generation of diverse tumor cell populations. These CSCs have been identified across multiple tissue types, including lung, colon, breast, pancreas, and ovary. Research has demonstrated that CSC subpopulations contribute significantly to therapeutic resistance, tumor recurrence, and metastasis by regulating multiple signaling pathways, making them compelling targets for cancer therapy. Notably, emerging evidence suggests that natural products may offer protective benefits against cancer development while potentially targeting CSCs. This review synthesizes current knowledge of CSCs, examining their identifying markers, isolation techniques, study methods, and associated signaling pathways. Additionally, we explore various natural products that specifically target CSCs across different cancer types, presenting potential strategies to address the persistent challenges of drug resistance and cancer relapse.

Metabolic syndrome is a complex, multifactorial disorder, with emerging research emphasizing the significant role of gut health in its prevention and management. Recent studies suggest that dietary strategies promoting a healthy gut microbiome, including the incorporation of fiber, fermented foods, and healthy fats, are crucial for regulating metabolism. Additionally, the use of postbiotics and supplements, such as probiotics, omega-3 fatty acids, and polyphenols, provides promising avenues for enhancing metabolic health. This holistic approach to managing metabolic syndrome not only supports gut health but also offers the potential for improving long-term health outcomes. This review examines the influence of the gut microbiome on metabolism, highlighting the increasing significance of dietary strategies and supplements in managing metabolic syndrome.

Epstein-Barr virus (EBV), human papillomavirus (HPV), and hepatitis C virus (HCV) are significant human pathogens associated with various diseases, employing complex molecular mechanisms for cellular entry and immune evasion. Peptide-based research, using more than 700 synthetic peptides, has deciphered some of the molecular interactions between viral proteins and host cell receptors, offering promising diagnostics and therapeutic strategies. In EBV, binding peptides have been identified: 11382, 11389, and 11416 derived from gp350/220; 11435, 11436, and 11438 from gp85 [glycoprotein H (gH)]; and 11521 from BNRF1/p140. Most of these peptide sequences are surface-exposed and are part of the contact regions with human cell receptors, making them promising candidates for strategies aimed at inhibiting EBV invasion of human cells. Peptide 11382 is the target of the neutralizing antibody 72A1; peptides 11382 and 11416 induce interleukin-6 production; peptide 11435 binds to integrin αvβ6, and peptide 11438 triggers a cytokine storm. In the HPV L1 protein, a major component of the viral capsid, peptides 18283 and 18294 have been identified as epithelial cell-binding peptides located on the virus surface. Parts of the sequences are recognized by anti-HPV neutralizing antibodies. These two peptides, along with peptide 18301, have been identified as potential biomarkers for HPV infection because they are recognized by antibodies elicited during natural HPV infection, making them suitable targets for serological detection. In the envelope proteins E1 and E2 from HCV, five hepatocyte- and CD81-positive cell-binding peptides have been identified. The sequences of these peptides contain linear B-cell epitopes recognized by neutralizing antibodies, and some of them have been used to develop serological tests for determining HCV infection. Peptide-based approaches can lead to innovative strategies for the prevention, diagnosis, and treatment of these viral diseases. Additionally, these peptides and their sequences can be used to modulate the immune response and generate tools for cancer theragnostic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes a global epidemic named COVID-19. It still continues to plague humans with severe complications and unique sequelae, causing huge economic losses in the world. Pathophysiological studies showed that important life organs, such as the lungs, brain, kidneys, heart, liver, and immune system, and even reproductive ones are affected directly or indirectly in patients with COVID-19. Classically and newly discovered drugs, concerning antiviral replication, anti-inflammation, blockage of pathogenic processes, alleviation of symptoms, and especially distinctive multi-actions of Traditional Chinese Medicine, were screened out and tested, presenting promising therapeutic effects on the virus before or even though abundant effective vaccines come out. Moreover, other strategies are underway, including the use of plasma therapy, monoclonal neutralizing antibodies, vaccine trials, and emerging drugs with distinct interference mechanisms. This review features the novel progress on the latest-discovered antiviral drugs and the effective Traditional Chinese Medicine, and highlights the advantages and shortages of different therapeutic strategies and the predicted potential targets of the used Traditional Chinese Medicine components, which provides a valuable reference for clinical treatment continuously to combat COVID-19.

Folic acid (FA) residue is a well-known and widely spread targeting ligand, or biovector, used as a component in engineering artificial nanosized and submicron particles (NSPs) to target various cells and treat a variety of diseases that are associated with FA (or folate) receptors (FR) overexpression. A particular place in the list of these diseases is held by various cancer types, for which overexpression of FR on the cell surface is often accompanied by a more severe disease course, increased resistance to the conventional chemotherapy, and poorer prognosis. The incorporation of albumin into NSPs has been shown to enhance their biocompatibility, give high compatibility with drug molecules, prolong their circulation, reduce thrombogenic activity, and improve their colloidal stability. Nowadays albumin-based NSPs with FA residue as a targeting agent are used for chemotherapy, photothermal and photodynamic therapy, combined therapy, visualization, and theranostics (also known as theragnostics) for various types of cancer: breast, cervical, ovarian, prostate, nasopharyngeal, gastric, colorectal, liver cancer, and brain tumors. A limited number of studies have also focused on the use of NSPs in rheumatoid arthritis treatment. In this review, we discuss the ways of FA-albumin conjugation and conjugation of FA to albumin-modified NSPs systems. An application of nanosized and submicron delivery systems on the base of serum albumin and FA for therapy and diagnostics is discussed.

Proteins from the neurotrophin family perform trophic and regulatory functions in the nervous and other body systems. Understanding the mechanisms of neurotrophin action is crucial not only for the evolution of fundamental scientific knowledge but also for developing new treatment strategies targeting neurotrophin signaling regulation. At our center, dimeric dipeptide mimetics of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have been obtained based on the structure of neurotrophins’ individual loops β-turns. These mimetics activated tyrosine kinase (Trk) receptors TrkA, TrkB, or TrkC specific to their respective neurotrophins, but exhibited varied activation patterns in the main post-receptor signaling cascades. Thus, some dipeptides activated all three main phosphoinositide 3-kinase (PI3K)/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phospholipase C-gamma (PLC-γ) pathways, while others triggered only PI3K/Akt and PLC-γ or MAPK/ERK and PLC-γ. Herewith, dipeptides exhibited a specific set of effects (neuroprotective, differentiating, antidepressant-like, anxiolytic, memory-enhancing, analgesic, antidiabetic) within the spectrum of biological activities of their corresponding native neurotrophin. It was revealed that these effects are influenced by both the patterns of post-receptor signaling activation and the nature of progenitor neurotrophin, uncovering significant correlations. This article is dedicated to reviewing the data that has been collected.

4-Aminobenzoic acid (PABA, para-aminobenzoic acid) exhibits multifaceted therapeutic potential in neuropsychiatric disorders through its roles in neurotransmitter modulation, anti-inflammatory action, and antioxidant defense. Experimental and clinical evidence demonstrates that PABA enhances serotonin and dopamine synthesis by activating key enzymes (e.g., tryptophan hydroxylase and tyrosine hydroxylase), thereby stabilizing mood and improving cognitive function. Mechanistically, PABA suppresses neuroinflammation by inhibiting NF-κB signaling and cytokine production (e.g., IL-1β, TNF-α) while scavenging reactive oxygen species (ROS) to mitigate oxidative stress and protect neuronal integrity. Clinical studies indicate that PABA may synergize with traditional antidepressants by targeting serotonin reuptake transporters (SERT) and monoamine oxidase (MAO), offering improved outcomes in major depressive disorder. Despite promising results, further research is needed to optimize dosing regimens, validate long-term safety, and explore pharmacogenomic interactions. Crucially, experimental validation through cellular and animal models is required to substantiate PABA’s proposed mechanisms, particularly its regulation of NF-κB signaling and enzyme activity in neurotransmitter synthesis. This review underscores PABA’s potential as a neuroprotective agent and calls for integrated strategies to translate mechanistic insights into clinical applications for complex neurological conditions.

Multiple drug-resistant Staphylococcus aureus bacterial pathogens are causative agents of serious infectious disease and are responsible for significant morbidity and mortality rates. Of particular concern in the public health domain are strains of methicillin-resistant S. aureus (MRSA), a member of the Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Escherichia coli (ESKAPEE) group of bacterial pathogens, many of which are recalcitrant to effective chemotherapy in the clinical setting due to their resistance to multiple antimicrobial agents. An important mechanism that confers multi-drug resistance in MRSA involves the active efflux of structurally different antimicrobial agents by members of the major facilitator superfamily (MFS) of proteins. The multidrug efflux pumps of the MFS share similar amino acid sequences, protein structures, and a common evolutionary origin. As such, the multidrug efflux pumps of the MFS are thought to operate by a similar solute transport mechanism and, thus, represent suitable targets for modulating their transport activities. This review article addresses MRSA as a serious pathogen, the mechanisms of antimicrobial resistance, and the functional and structural roles of the multidrug efflux pumps of the MFS in conferring pathogenicity.