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.

Bunium persicum Boiss. Fedtsch., a highly valued spice crop from the Apiaceae family, is renowned for its rich phytochemical profile, including compounds such as cuminaldehyde, α-terpinene-7-al, γ-terpinene-7-al, γ-terpinene, p-cymene, and β-pinene. These bioactive constituents contribute to its diverse therapeutic properties, including antioxidant, antimicrobial, anti-inflammatory, lipid and glucose-lowering, and anti-carcinogenic activities. Due to its limited growth in specific wild regions and over-exploitation, B. persicum faces significant conservation challenges, both in vitro and in situ. In India, its primary hotspots are in Jammu and Kashmir, Himachal Pradesh, and Uttarakhand. This review provides a comprehensive examination of B. persicum’s functional properties, with a focus on its traditional uses, phytochemistry, and pharmacological activities, highlighting the need for its conservation and sustainable use.

Protein phosphorylation is a fundamental regulatory mechanism governing a broad spectrum of cellular processes. In the nervous system, it is critical for modulating neurotransmitter release, synaptic plasticity, neuronal excitability, and cell survival. Dysregulation of protein kinase activity is closely linked to the pathogenesis of various neurological and psychiatric disorders, positioning several kinases as promising therapeutic targets. Although protein kinase inhibitors (PKIs), a major class of compounds that modulate kinase activity, have shown considerable therapeutic success in oncology, their application in neurological diseases remains in the early stages of exploration. Of the 82 PKIs approved by the Food and Drug Administration (FDA), 37 are now in various preclinical and clinical trials for neurological conditions, primarily targeting signaling pathways mediated by key protein kinases implicated in these diseases. This review examines the roles of critical protein kinases and the therapeutic effects of their inhibitors in neurodegenerative, psychiatric, and selected neurological disorders, such as autism spectrum disorders (ASD) and epilepsy. We focus on Abelson kinase I (ABL1), calmodulin-dependent kinase II (CaMKII), casein kinase 1δ (CK1δ), c-Jun N-terminal kinase (JNK), cyclin-dependent kinase 5 (CDK5), dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A), leucine-rich repeat kinase 2 (LRRK2), extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase 3β (GSK3β), mammalian target of rapamycin (mTOR), p38 mitogen-activated protein kinase, and protein kinase C (PKC) in neurodegenerative diseases. Additionally, we discuss CaMKII, CDK5, ERK1/2, PI3K/AKT/GSK3, protein kinase A (PKA), and PKC in psychiatric disorders, focusing on schizophrenia and mood disorders, and analyze GSK3β, ERK1/2, and mTOR in ASD and epilepsy. This review underscores the therapeutic potential of PKIs in neurological disorders while highlighting ongoing challenges and the need for further research to refine kinase-targeted therapies.

Ischemic stroke (IS) is a leading cause of death globally. IS occurs due to a blockage of cerebral arteries, leading to neuronal injury, tissue death, and brain infarcts. This induces lack of oxygenation to the brain which induces neuroinflammation, characterised by interactions involving molecules which can exacerbate brain damage but also aid recovery through processes like microglial phagocytosis. Post-stroke depression (PSD) affects 30–33% of stroke survivors, complicating recovery with various symptoms. The pathophysiology of PSD involves disruptions in the glutamatergic and monoaminergic systems, the gut-brain axis, and neuroinflammation. Agomelatine, an atypical antidepressant, can potentially treat both IS and PSD. It acts as a melatonin receptor agonist and a serotonin receptor antagonist, enhancing dopamine and norepinephrine availability in the prefrontal cortex. Agomelatine’s neuroprotective, anti-inflammatory, antioxidative, and antiapoptotic properties have been demonstrated in research, where it reduces reactive oxygen species (ROS) levels and activates the Nrf2 pathway, promoting antioxidative enzyme expression. Additionally, it prevents microglial activation by inhibiting the toll-like receptor 4 (TLR4)/nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) pathway, thus reducing inflammation. This review examines the pathophysiology of IS and PSD, highlighting agomelatine’s multifaceted therapeutic potential. Agomelatine’s distinct pharmacological profile and minimal side effects make it a compelling candidate for IS and PSD treatment, necessitating further exploration to optimise stroke management and improve patient outcomes.

Over the last 60 years, only four new classes of antibiotics have been introduced, while the prevalence of antibiotic-resistant Gram-positive and Gram-negative bacteria has risen. This underscores the urgent need for new antibacterial therapeutics. This commentary leverages the recent exploration of γ-substituted-N-acylated-N-aminoethyl amino acid peptides (γ-AApeptides) to mimic the structures and function of natural antimicrobial peptides (AMPs), highlighting the promise and limitations for developing a new, effective treatment for antibiotic-resistant bacteria.

Antibiotic resistance is a significant threat to public health and drug development, driven largely by the overuse and misuse of antibiotics in medical and agricultural settings. As bacteria adapt to evade current drugs, managing bacterial infections has become increasingly challenging, leading to prolonged illnesses, higher healthcare costs, and increased mortality. This review explores the critical role of antibiotics in fighting infections and the mechanisms that enable bacteria to resist them. Key antibiotics discussed include carvacrol, dalbavancin, quinolones, fluoroquinolones, and zoliflodacin, each with unique actions against bacterial pathogens. Bacteria have evolved complex resistance strategies, such as enzyme production to neutralize drugs, modifying drug targets, and using efflux pumps to remove antibiotics, significantly reducing drug efficacy. Additionally, the review examines the challenges in antibiotic development, including a declining discovery rate of novel drugs due to high costs and regulatory complexities. Innovative approaches, such as structure-based drug design, combination therapies, and new delivery systems, are highlighted for their potential to create compounds with enhanced action against resistant strains. This review provides valuable insights for researchers and developers aiming to combat antibiotic resistance and advance the development of robust antibacterial therapies for future health security.

Lutein, a natural dihydroxy carotenoid and a member of the non-vitamin A carotenoids family, is abundant in yellow-colored fruits and green leafy vegetables such as spinach and lettuce. As the second most common type of carotenoid found in human serum, lutein offers a plethora of medicinal benefits, including anti-cancer, anti-inflammatory, and anti-oxidative properties. It is well-absorbed and systemically localized to the liver, lung, and retina, where it can cross the blood-retina barrier and accumulate in the macular pigment. Due to its anti-oxidative and singlet oxygen quenching properties, lutein is reported to reduce the risk of age-related macular degeneration (AMD). Higher concentrations of fasting plasma carotenoids and enhanced skin yellowing after lutein consumption indicate its presence in various regions of the human body, including the skin, breast, brain, and cervix. Lutein has remarkable benefits for neurodegenerative diseases, cardiovascular health, liver protection, and bone disease prevention. In the central nervous system (CNS), lutein supports brain homeostasis through its antioxidant and anti-inflammatory properties, increasing interleukin-10 (IL-10) and reducing tumor necrosis factor-α (TNF-α). It reduces the risk of coronary artery disease and exerts anti-inflammatory effects on peripheral blood mononuclear cells (PBMCs). Lutein protects against alcohol-induced liver damage by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Additionally, lutein promotes bone health by enhancing mineralized bone nodule development and inhibiting osteoclast production, reducing bone resorption, and suppressing soluble receptor activator of nuclear factor kappa B ligand (RANKL). These multifaceted benefits make lutein a valuable agent in disease prevention and health promotion. This review discusses the comprehensive profile of lutein as a phytochemical activity, including anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, neurological, and cardioprotective effects. Additionally, it discusses lutein’s beneficial impact on macular degeneration and eye diseases, showcasing its potential as a natural, plant-based therapeutic agent.

Microbial biotransformations are valuable tools from “green chemistry” and involve converting parental molecules into new daughter ones with unique physical, chemical, or pharmacological properties. These reactions are often carried out by cells grown under a planktonic phenotype. However, microbial cells grown under a phenotype of biofilm can improve biotransformation bioprocesses once they form more biomass per volume, are more resistant to extreme conditions (pH, temperature, and toxic substances), remain active for extended periods, are less prone to cell washouts, and reduce re-inoculation demands, leading to increased production rates due to their unique physiological features. In addition, experience has shown that biofilms may furnish a broader array of new daughter molecules. This review highlighted the benefits of using biofilms in microbial biotransformations to obtain a variety of bioactives.

The integration between the tumor-suppressive and oncogenic signaling pathways controls various cellular activities of cancer cells, including cell growth and apoptosis. While the activation of oncogenes fuels cancer progression and escape mechanisms, tumor suppressors regulate and counterbalance the negative effects of oncogenic signaling. Notably, phosphatase and tensin homolog (PTEN) constitute one of the important family members of tumor suppressor genes, which play critical roles in regulating the activities of tumor cells. Thus, an impaired, mutated, or loss of PTEN is associated with low survival or high tumor recurrence rates in cancer patients. Importantly, high tumor expression of a G-protein coupled platelet-activating factor-receptor (PAFR) is associated with increased tumor progression as well as decreased overall survival and poor prognosis in malignancies such as non-small cell lung cancer (NSCLC). Along similar lines, overactivation or mutations in epidermal growth factor receptor (EGFR) signaling are detected in various human malignancies and associated with poor prognosis. The goal of the current minireview was to highlight the significance of the mechanistic insights between the PTEN and PAFR as well as the PAFR and EGFR pathways in impacting cancer growth and/or efficacy of therapeutic agents in experimental model systems.