Larvae of the greater wax moth Galleria mellonella have become an increasingly important in vivo model for biomedical research, providing a practical, ethical, and biologically relevant alternative to vertebrate organisms. Its suitability as a model system lies in its low maintenance cost, ease of handling, and ability to survive at both ambient and mammalian body temperatures. Most importantly, G. mellonella exhibits an innate immune system with functional and structural parallels to that of mammals, allowing meaningful insights into infection dynamics and immune responses. This review summarizes the biological and immunological foundations that underpin the use of G. mellonella in experimental research and examines its expanding range of applications. The model has been successfully employed to study microbial pathogenicity, antimicrobial efficacy, host-pathogen interactions, and toxicological responses. In recent years, its use has extended to emerging fields such as nanomedicine, immunomodulation, and environmental biotechnology, reflecting its growing translational value. The adoption of G. mellonella also aligns with current ethical principles in science, particularly the 3Rs framework (replacement, refinement, and reduction), by minimizing the use of vertebrate animals while maintaining robust experimental outcomes. However, certain challenges persist, including the lack of adaptive immunity and the need for methodological standardization to enhance data reproducibility and comparability across laboratories. Collectively, the growing body of evidence supports G. mellonella as a reliable and versatile experimental model that bridges the gap between invertebrate and mammalian systems. Continued methodological refinement and integration with molecular and omics approaches are expected to further consolidate its role in translational and preclinical research. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC.
Lignocellulosic biomass (LCB) is a plentiful resource, and its effective utilization is essential for mitigating resource scarcity. Xylose, the second most abundant sugar in LCB after glucose, is present in significant quantities. Nevertheless, its current utilization is markedly lower than that of glucose. Although microbial conversion of LCB into high-value products is promising, inefficient xylose metabolism remains a bottleneck. Advances in metabolic engineering and synthetic biology techniques offer powerful tools to improve microbial xylose utilization. In this review, we summarize recent research progress in microbial xylose metabolism, emphasizing xylose metabolic pathways, metabolic engineering strategies, and the production of high-value chemicals derived from xylose. We also discuss future opportunities to overcome key challenges, including efficient xylose extraction from LCB, coutilization of glucose and xylose, and enzyme and pathway optimization. These insights aim to support the development of more efficient bioconversion processes for xylose and contribute to the broader utilization of lignocellulosic feedstocks.
The world's increasing demand for petrochemical, pharmaceutical, and nutraceutical products necessitates the development of new strategies for producing these high-value chemicals. The depletion of the natural fossil reserves and environmental pollution associated with their procurement further compel us to find sustainable, greener, and cost-effective alternatives. In light of this, a shift has been witnessed in deriving these products from fossil-based sources or chemical synthesis to biomanufacturing (production using living systems). However, to fully utilize the potential of biomanufacturing, novel tools and strategies that can function in bacteria, archaea, and eukaryotes, regulate multi-enzyme pathways, offer precise and conditional gene regulation, and possess versatility are highly required. This review presents a comprehensive summary of the latest gene modulation tools and strategies used by metabolic engineers, along with a mechanistic overview and their applications. In addition, we presented the tools that have the potential to be used for pathway optimization but are still less explored. Within this context, we categorized these tools based on their molecular level of gene regulation, i.e., at and beyond the central dogma. We believe that a deeper understanding of the design, development, and application of these tools would be beneficial for metabolic engineers to reprogram biosynthetic pathways by adopting system-specific approaches, as a single strategy cannot be applied to all systems. Lastly, we discussed the challenges and future prospects of developing these gene regulatory tools to further advance the biomanufacturing field.
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Medical science liaisons (MSLs) serve a critical role in pharmaceutical, biotechnology, medical device, diagnostics, and healthcare companies by facilitating scientific exchange with key opinion leaders (KOLs) and health care professionals (HCPs). Despite their growing strategic importance, evaluating MSL impact remains challenging due to the complexity of their responsibilities. This study investigates current practices for assessing MSL impact, explores how their value is defined, and examines the challenges in measuring MSL performance. A cross-sectional online survey was conducted, targeting MSLs, MSL managers/directors, MSL Excellence and Operations, executive management, and other medical affairs professionals. Participants were recruited via professional networks, social media, pharmaceutical industry conferences, online platforms dedicated to medical affairs, and posting on LinkedIn, resulting in a non-probability convenience sample. The survey comprised multiple-choice and Likert-scale questions covering KOL engagement impact scores, definitions of MSL value and impact, and challenges in performance, measurement, and assessment. A total of 1023 respondents participated. Geographically, the majority of respondents were based in the United States (56%), followed by Spain (6%), Brazil (5%), and Canada (5%), with additional contributions from Europe, Latin America, and other regions. Overall, 52% indicated that KOL engagement impact scores should be utilized as a performance metric. MSL value was most often defined as building and maintaining strong KOL relationships (27%), whereas MSL impact was most frequently linked to influencing clinical practice and improving patient care (46%). Key challenges included difficulty defining and measuring the quality of MSL activities (76%) and reliance on quantitative standards that do not reflect MSLs' value (61%). Only 40% reported that their organizations measure MSL impact, and 41% suggested that the assessment should combine individual achievements with team contributions. Furthermore, 67% considered measuring MSL performance "difficult" or "very difficult". This study highlights the challenges of measuring MSLs' impact and value. Many organizations continue to struggle with capturing the quality of MSL activities and their broader strategic contributions.
As an innovative sensing platform, electrochemical biosensors have been extensively developed in academic research for diverse applications: clinical diagnostics, food safety, environmental monitoring, pharmaceutical analysis, etc. These devices convey molecular recognition events to prompt and readable electrical signals for point-of-care and on-side detection of specific target analytes and contaminants with high performance and rapid response often in small sample volume. Considering the limited lifetime, activity and stability of direct immobilization biorecognition molecules, different modification strategies of electrode surface have been developed over the years using nanomaterials, self-assembled monolayers, conducting/anti-fouling/redox polymers and even composite materials of above. This is intended to introduce functional groups and increasing the effective surface area of electrode surface so as to lower the sensor detection limit. In particular, hydrogel-modified electrochemical biosensors with high sensitivity, selectivity, as well as sustained stability represent a rapidly advancing frontier in analytical biotechnology, are combining the unique properties of hydrogels and the specific recognition properties of biomolecules for target molecules with the precision of electrochemical transduction. The main strategies for hydrogel polymer surface immobilization are discussed, comparing non-covalent and covalent attachment of hydrogels. Notably, the covalent immobilization of hydrogel layers with tunable porosity for improved ion diffusion on electrode surface, are interesting since they are forming polymer interface with long-term stability and reducing non-specific interactions. Special attention is then given to the methods for biorecognition element immobilization in/on hydrogel functionalized electrodes, including physical adsorption, encapsulation, affinity binding and covalent binding. For bio-elements covalent coupling, the covalent immobilization within or onto hydrogel matrix enhanced bio-elements retention to give efficient response, prolonged sensor lifetime through providing biocompatible interface and precise orientation of biomolecules, which processes a competitive edge in terms of real water sample detection. Typical examples of hydrogels-based electrochemical biosensors for clinical diagnostics, food safety, environmental monitoring, and pharmaceutical analysis are highlighted with recent breakthroughs. Finally, current challenges are outlined providing a roadmap for next-generation hydrogel biosensor design.
Although tuber polysaccharides of Bletilla striata have been extensively studied, the leaf polysaccharides, which constitute over 25% of the plant's biomass, are frequently discarded as agricultural waste. Given the well-documented bioactivities of plant polysaccharides, this represents significant untapped potential. Current cardioprotective agents exhibit limitations against doxorubicin-induced cardiotoxicity, creating demand for novel natural alternatives. This study thus aimed to isolate and characterize the primary polysaccharide from B. striata leaves and evaluate its antioxidant capacity and cardioprotective effects, thereby converting this agricultural waste into a therapeutic agent. The purified homogeneous polysaccharide BSP-L2-1 (Mw > 500 kDa) was structurally characterized as a highly branched heteropolysaccharide featuring triple-helix conformation, with a mannose:galacturonic acid:glucose:galactose:arabinose molar ratio of 6.02:1.74:2.70:10.00:4.32. In vitro assays demonstrated potent antioxidant activity, with BSP-L2-1 achieving 72.37% inhibition of ABTS radicals at a concentration of 6 mg mL-1. More notably, in a doxorubicin-injured H9c2(2-1) cardiomyocytes model, BSP-L2-1 exhibited significant cardioprotection by suppressing reactive oxygen species and malondialdehyde overproduction, enhancing glutathione and superoxide dismutase activity and concurrently preserving mitochondrial function. Additionally, toxicity assessments in a zebrafish model confirmed no observable adverse effects across a broad concentration range (100-900 μg mL-1). BSP-L2-1, a novel acidic natural polysaccharide isolated from underutilized B. striata leaves, mitigated doxorubicin-induced cardiotoxicity by attenuating oxidative stress and preserving mitochondrial function. These findings support its development as a natural adjuvant to prevent doxorubicin-induced cardiotoxicity, with potential applications ranging from functional foods to pharmaceutical formulations. © 2026 Society of Chemical Industry.
Female reproductive disorders are a leading cause of infertility, affecting millions of women worldwide and resulting in significant emotional and social challenges. Despite advances in medical science, current treatment options are often limited in their ability to restore normal reproductive function, particularly in cases involving hormonal imbalances, complex tissue damage, or unexplained infertility. These limitations highlight the urgent need for innovative and more effective treatment strategies to address the underlying causes of female infertility. Recent advances in regenerative medicine suggest that stem cell-based therapies, particularly those utilizing mesenchymal stem cells, may offer new hope for addressing infertility-related challenges. However, direct cell therapies face significant limitations within the human body. As a result, cell-free approaches, such as the use of secreted factors from mesenchymal stem cells, have gained attention as promising alternatives. The secretome of these stem cells, which includes cytokines, microRNAs, extracellular vesicles, and other bioactive molecules, plays a vital role in regulating key biological processes such as cell growth, migration, and the formation of new blood vessels. These properties are especially relevant for treating conditions like endometriosis and ovarian dysfunction, both of which are closely associated with infertility. This review examines preclinical studies that have evaluated the safety and therapeutic potential of cell-free treatments derived from mesenchymal stem cells for female infertility. Although preclinical findings are promising, there is currently limited clinical evidence supporting the use of cell-free therapies for human infertility, and this evidence is still emerging. This review emphasizes the therapeutic potential of MSC secretome in treating female infertility and underscores the necessity for further well-designed clinical studies to support its integration into standard clinical practice.
Dandelion (Taraxacum officinale) is an edible medicinal herb having an extended history for its traditional usage owing to the health promoting benefits associated with this plant. Nevertheless, traditional extraction methods limit the recovery of bioactive compounds from different parts of dandelion and insufficient research is available on process optimization. Hence, current research developed an effective ultrasound-assisted extraction method for maximum recovery of total phenolics contents (TPC), total flavonoids contents (TFC), antioxidant activities (DPPH, ABTS, FRAP assays), and bioactive compounds (HPLC) from dandelion plant using response surface methodology in combination with Box-Behnken design (BBD). The optimal extraction conditions determined by RSM were as follows: sonication time, 30 min; ultrasound amplitude, 70%, and ultrasound temperature, 40 °C. At these conditions, the recovery of total phenolics and total flavonoids reached 40.77 mg GAE/g and 22.68 mg RE/g, respectively. Moreover, the antioxidant activities determined based on DPPH-scavenging, ABTS+-scavenging and FRAP were reported as 88.55%, 445.39 µM TE/mg, and 30.64 mg TE/g, respectively. Additionally, a total of 11 major bioactive compounds were quantified using HPLC, including 6 phenolic acids and 5 flavonoids. Under optimized conditions major bioactive compounds identified and quantified were chlorogenic acid, quercetin, apigenin, luteolin-7-O-glycoside, luteolin, p-coumaric acid, caffeic acid, ferulic acid, cichoric acid, isoetin, and caftaric acid. Conclusively, results of present study give a comprehensive insight into optimized ultrasound-assisted extraction method for recovery of maximum antioxidants and bioactive compounds from dandelion using a combination of BBD and RSM. Furthermore, this study may provide a reference in utilizing optimized extraction process for dandelion bioactive compounds in food and pharmaceutical industry.
The prevalence of cancers has actually increased during the last few decades, affecting almost all human societies. Despite progress in therapeutic protocols, cancer is still the main cause of global human mortality. Although the advancement of modern immunotherapeutic approaches can increase the survival rate of cancer patients, new modalities are essential for improved therapeutic outcomes. Extracellular vesicles (EVs) are nanosized particles and are used for cell-free approaches instead of direct whole cell-based administration. It has been thought that EVs can reduce the risks and side effects of immunotherapy. Dendritic cells (DCs), belonging to antigen-presenting cells (APCs), are present in different parts of the body with the fundamental activity against tumors and various inflammatory conditions. Due to the existence of reconfigurable contents, DC EVs are valid bioshuttles to transfer immunogenic molecules, process antigens along with co-regulatory factors to other immune cell subsets like T lymphocytes, involved in the control of immune responses in a paracrine manner. Besides, recent technologies have enabled us to produce engineered DC EVs with higher immunotherapeutic potential against the tumor cells. In the current review article, we aimed to discuss recent developments in nanomedicine and biotechnology fields for the application of DC EVs in terms of cancer. The recent data will help the researchers and clinicians to understand the underlying mechanism associated with the tumoricidal properties of DC EVs and the development of a new delivery system in cancer conditions. Besides, the application of sophisticated modalities and technologies can help in the large-scale production of engineered DC EVs for the alleviation of cancer-related pathologies in the clinical setting with high-rate regenerative outcomes.
Parabiotics (also termed paraprobiotics) are defined as non-viable microbial cells or their components, including peptidoglycans, teichoic acids, surface proteins, that confer health benefits without requiring viability which distinguishes them from traditional probiotics. Their non-viable nature eliminates risks such as microbial translocation, bacteremia, and sepsis, making them suitable for vulnerable populations including immunocompromised, critically ill, paediatric and elderly individuals. In addition, parabiotic exhibit improved thermal stability, extended shelf life, and easier incorporation into functional foods, nutraceuticals, and pharmaceutical formulations without cold-chain requirements. Mechanistically, parabiotics retain immunomodulatory, anti-inflammatory and have barrier-enhancing activities through interactions with host pattern recognition receptors, including Toll-like receptors, modulation of cytokine responses, and reinforcement of gut epithelial integrity. Preclinical and clinical studies support their therapeutic potential such as in case of heat-killed Lactobacillus acidophilus LB (L. acidophilus) has shown efficiency in managing acute paediatric diarrhoea, while heat-inactivated Lacticaseibacillus paracasei PS23 (Lcb. paracasei) has demonstrated improvements in muscle strength and inflammatory markers, including reduced C-reactive protein and interleukin-6 and increased interlukin-10 in elderly individuals. Similarly, inactivated Lactiplantibacillus plantarum (Lpb. plantarum) and Bifidobacterium strains have been associated with benefits in irritable bowel syndrome, atopic dermatitis, respiratory infections, visceral fat reduction, and antibiotic-associated dysbiosis. Synergistic combinations with prebiotics, postbiotics and related bioactives further enhance therapeutic outcomes in inflammatory, metabolic and infectious conditions. Advances in metagenomics, next-generation sequencing, proteomics, metabolomics, CRISPR-Cas systems, and synthetic biology are accelerating strain characterization, functional evaluation, and scalable production. Despite ongoing challenges in standardization and regulated harmonization, parabiotics represent a safe and effective approach for microbiome-targeted interventions. This review synthesizes current evidence on their therapeutic applications, technological advancements, and translational potential, highlighting their role in precision health and next-generation functional nutrition.
Cancer remains a leading global health challenge, necessitating continuous advancements in diagnostics and therapeutics to enhance patient outcomes. According to the recent data of the American Cancer Society, an estimated 20 million new cancer cases and 9.7 million cancer deaths occurred globally in 2022, with cases projected to reach 35 million by 2050. Early and accurate diagnosis is critical for effective treatment, and the traditional methods often lack sensitivity and specificity. Advanced analytical techniques, comprising molecular and genomic diagnostics, next-generation sequencing (NGS), and artificial intelligence (AI)-driven imaging, have significantly enhanced early detection and real-time tumor monitoring. In therapeutics, precision oncology has emerged as a transformative approach, integrating immunotherapy, gene editing (CRISPR), matrix-assisted laser desorption/ionization (MALDI), CAR-T cell therapy, and nanotechnology-based delivery for targeted treatment. Dual-purpose tools like NGS, predictive modeling, and molecular profiling bridge both domains, enhancing predictive accuracy via multimodal data fusion as a paradigm-shifting analytical platform revolutionizing traditional approaches. Despite advancements, resistance and accessibility challenges entail continued innovation. These advancements, driven by the convergence of biotechnology, data science, and molecular medicine, substantiate diagnostic accuracy and therapeutic precision. This review critically examines current analytical innovations, including molecular, imaging modalities, biosensors, and therapy-guiding analytics, highlighting their integration within precision oncology frameworks.
Irritable bowel syndrome (IBS) is a highly prevalent disorder of gut-brain interaction characterized by chronic abdominal pain associated with altered bowel habits, including constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), mixed (IBS-M), and unsubtyped forms. The pathophysiology of IBS is believed to be multifactorial as it involves dysregulation of the gut-brain axis, visceral hypersensitivity, serotonergic imbalance, epithelial barrier dysfunction, immune activation, dysbiosis, bile acid alterations, in addition to psychosocial stressors. These interacting mechanisms are known to be involved in the generation of persistent symptoms as well as the widely reported clinical heterogeneity of the disease. Current management strategies include dietary modification, psychological therapies, microbiota-targeted approaches, and pharmacological agents targeting the prevalent symptom subtype. However, treatment responses remain variable, and many patients seek complementary and natural interventions to alleviate their symptoms. Emerging evidence suggests that natural products may exert therapeutic benefits through anti-inflammatory actions, modulation of serotonergic signaling, improvement of intestinal barrier integrity, microbiota regulation, and neuromodulatory effects. Clinical studies demonstrate that certain natural interventions, particularly peppermint oil, STW 5 (Iberogast), psyllium, and several selected probiotics, can provide modest but clinically meaningful symptom improvement, especially for abdominal pain. Nonetheless, heterogeneity in trial design, short durations, small sample sizes, and limited subtype stratification restrict the strength of the resulting recommendations. This review provides a comprehensive overview of IBS pathophysiology, current treatment strategies, and mechanistic and clinical evidence supporting natural products in IBS management, while highlighting critical gaps and future research priorities.
Colorectal cancer (CRC) is one of the most significant global health concerns, necessitating innovative therapeutic strategies for its effective management. Despite advances in treatment therapies, chemotherapy remains the mainstay of CRC treatment, with 5-Fluorouracil (5-FU) as a standard first-line agent. However, its clinical effectiveness is hindered by drug resistance, rapid clearance and systemic toxicity, underscoring the need for innovative drug delivery strategies. In this context, the current work involves engineering of a bioinspired nanocomplex (NX) comprising zein and a biological macromolecule, such as chitosan, using a Quality by Design (QbD) approach. The resulting NX was characterized for particle size (186.13 ± 8.61 nm), polydispersity index (0.194 ± 0.03), and %entrapment of 5-FU (54.39 ± 3.1%) and silibinin (97.44 ± 1.16%), respectively. SEM and TEM analysis revealed the smooth and spherical nature of NX. Thermal analysis was performed using TGA and DSC and XRD was employed for structural characterization. Subsequently, spectroscopic investigations were carried out using FTIR, Raman and fluorescence spectroscopy to examine the potential interactions between the drugs and polymers used in the formulation of the NX system. In vitro studies confirmed controlled drug release with Weibull release kinetic model. The dual-drug-loaded-NX exhibited a significant increase in cytotoxicity compared to individual 5-FU and silibinin, and achieving nearly a 5-fold increase in cytotoxicity compared to silibinin. The NX demonstrated apoptosis induction, S/G2 cell cycle arrest, and improved cellular uptake compared to control group. The current investigation suggests that QbD-engineered zein-chitosan-based-NX could be a promising therapeutic strategy for managing CRC.
Biomarkers play a pivotal role in the prognosis, risk stratification, and management of cardiovascular diseases (CVDs), which remain the foremost cause of morbidity and mortality globally. A comprehensive review explores the various types of biomarkers utilized in the treatment of different CVD conditions, presenting the information clearly and concisely. Additionally, this overview summarizes recent clinical trial findings and advances in biomarker research. Recent advancements in biomarker research have identified a range of circulating biomarkers, including high-sensitivity C-reactive protein (hsCRP), cardiac troponins (cTn) and various microRNAs, that enhance the predictive accuracy for cardiovascular events. These biomarkers are derived from diverse pathophysiological processes such as inflammation, endothelial dysfunction and MI. As versatile tools, biomarkers serve as prognostic indicators, diagnostic markers, intermediate and surrogate endpoints, and safety monitors, making them essential in personalized medicine. In this context, biomarker-guided cardiovascular therapies represent an advanced approach, allowing clinicians to customize treatment choices and track therapeutic effectiveness in real time. In addition, nanobiotechnology-based systems are also pivotal in personalized medicine, offering targeted therapeutic delivery for CVDs, particularly in addressing heart cell death. Moreover, artificial intelligence, which is emerging as a useful tool in biomarker-guided, personalized cardiovascular treatment, is improving patient care and aiding cardiologists. Recent strides in biomarker research suggest that personalized medicine guided by circulating biomarkers could revolutionize CVD management by enhancing risk prediction and tailoring treatments to each patient. Future research should focus on refining these biomarkers and addressing current limitations to optimise their clinical utility in improving cardiovascular health outcomes.
Plant-derived exosome-like nanovesicles (PELNs), as an emerging "green" nanoplatform, exhibit broad pharmacological activities, low immunogenicity, and inherent advantages as natural drug carriers. They show great potential in the pharmaceutical, cosmetic, and health supplement sectors. The clinical application of PELNs is heavily contingent on their safety profile, which is intricately linked to the administration route. This opinion compares the safety implications of the two primary routes: oral administration versus intravenous injection. Current evidence indicates that intravenous administration of PELNs triggers complement activation, immune responses, and hepatorenal toxicity; even surface engineering modifications cannot completely eliminate these risks. In contrast, oral administration of PELNs may achieve superior safety by leveraging the gastrointestinal tract's ability to effectively reduce the immunogenic components. Based on these findings, we advocate for the prioritization of oral delivery in the future development of PELNs, given its superior safety profile for realizing their potential as natural therapeutics and drug delivery systems.
Human carbonic anhydrases (CAs) catalyse the rapid conversion of CO₂ and bicarbonate, supporting pH balance, ion transport and many metabolic processes. All 15 human CA family proteins share a conserved structure, but they differ in activity, localisation and tissue distribution. Several CA isozymes are directly linked to distinct clinical conditions. Although CA-inhibiting drugs have long been clinically used, research across individual isozymes, chemical compound classes, and therapeutic uses has progressed unevenly. This review brings together current structural, biochemical and pharmacological knowledge of human CAs. It summarises catalytic properties, expression patterns and disease associations across the isozyme family. Loss-of-function variants in CA II and CA VA cause well-defined inherited metabolic disorders. At the same time, the strong and selective overexpression of CA IX and CA XII in tumours provides clear targets for cancer therapy. We outline the development of CA-directed drugs, from early non-selective sulphonamides to modern treatments used in ophthalmology, neurology and metabolic medicine. We also review ongoing clinical trials of isozyme-selective small molecules, antibodies, and radiopharmaceuticals, with particular focus on CA IX-targeting agents. Classical sulphonamides inhibit CAs by binding the catalytic zinc ion and displacing the Zn-bound water. Newer inhibitors achieve selectivity by engaging isozyme-specific pockets and surrounding regions. Antibody- and small-molecule-based radiolabelled ligands targeting CA IX are now advancing as promising tools for precision oncology, with several candidates demonstrating excellent clinical trial results and entering late-stage clinical development.
The paper discusses a comprehensive analysis of contemporary approaches to the structural modification of phenolic acids from the benzoic (C6-C1) and cinnamic (C6-C3) series, which have a wide range of biological activity. The main directions of chemical transformation of phenolic compounds that aim to improve their pharmaco-logical potential, stability, and bioavailability are discussed. The given study also makes an accent on the relationship between the structural features and biological effects of various phenolic acid derivatives, including antioxidant, anti-inflammatory, antimicrobial, and antitumor activity. The purpose of this investigation is to systematize current data on strategies for the structural modification of phenolic acids, to identify key areas of their chemical transformation, and to determine the most promising methods for creating biologically active compounds with improved pharmacological properties. The study was aimed at systematizing the accumulated knowledge and identifying promising areas for further research in the field of structural design of phenolic acid derivatives. Based on the analysis of experimental data and literature sources, key trends in the development of new medicinal compounds using the example of natural phenolic acids were characterized, and prospects for their use in medicine and pharmaceutical chemistry were shown.
Parkinson's disease (PD) is a neurological condition that starts with the degeneration of neurons. Neurons play a crucial role in producing dopamine (DA), a type of neurotransmitter that primarily regulates bodily functions such as motor control, posture, motivation, reward, pleasure, cognition, and memory. Other variables that contribute to the disorder include the buildup of Lewy bodies and Lewy neurites, which are composed of increased α-synuclein (α-syn). Depletion of DA in the striatal area and the death of DA-producing neurons are often considered the basis for the mo-tor impairments seen in PD. In addition, both genetic and environmental factors may play a role in PD etiology; specifically, genetic variations and exposure to toxins may contribute to the development of brain lesions. The article aims to outline the current state of knowledge on the dopaminergic pathway and how PD affects DA homeostasis. Various molecular mechanisms are involved in the pathogenesis of PD, including α-syn aggregation, lysosomal and chaperone-mediated autophagy, mitochondrial dysfunction, and abnormal regulation of calcium homeostasis. Intrinsic and extrinsic caspase-mediated apoptosis, autophagic cell death, and ferroptosis are also involved in neurodegen-eration that often leads to PD. The occurrence of PD can be controlled by the inclusion of antioxi-dants, such as mitoquinone, which inhibit mitochondrial oxidative damage, as well as modulation of autophagy, proteostasis, gene therapy, and its editing, and stem cell regeneration. Diverse mechanistic pathogenesis and genetic variations make PD a complicated disease to tackle. Potential treatment approaches, such as modulating autophagy-lysosomal pathways and protecting mitochon-dria, may be better understood with deeper insight into these mechanisms. We conclude by highlighting current and upcoming gene and cell therapies.
Nanobodies (Nbs), the antigen-binding single-domain fragments derived from camelid heavy-chain antibodies (Abs), have rapidly become a focus of biomedical research due to their compact size, high stability, strong antigen affinity, and ease of molecular engineering. This review systematically outlines their structural and functional features, current strategies for acquisition, screening, optimization, and large-scale production, and comprehensively discusses their wide-ranging applications in therapeutics, diagnostics, and basic research. Specifically, Nbs have shown outstanding efficacy in tumor, toxin, infectious, and cardiovascular disease treatments, while serving as versatile tools for molecular imaging, biosensing, protein purification, structural analysis, and intracellular regulation. The challenges of immunogenicity, off-target effects, and industrial-scale manufacturing are also critically examined. Furthermore, the integration of artificial intelligence in structure prediction, de novo design, and immunogenicity assessment has opened powerful new avenues for rational Nb engineering. Combined with emerging technologies such as gene therapy, nanomaterial delivery, and multispecific architectures, these advances promise to accelerate clinical translation. Overall, Nb technology is poised to become a cornerstone of next-generation precision medicine and biotechnology, offering innovative solutions for disease diagnosis, targeted therapy, and molecular discovery.