Background/Objective: Melanoma is the most aggressive form of skin cancer and most common among fair-skinned people, and about 80% of fatalities are from skin lesions. The rise in deaths from melanoma worldwide has been related to a lack of access to healthcare, mostly in low-income nations. Melanoma therapy using current treatments, such as cisplatin, has been beneficial. However, it has been linked to irreversible DNA damage, whereas most current treatments are either ineffective or have intolerable side effects. This study investigated the cytotoxic effects of Leptospermum petersonii extracts on A375 melanoma cells and aimed to identify at least one putative bioactive compound. L. petersonii is a well-established medicinal plant for its antimicrobial activities, and its leaves are reported to contain essential oils that suppress fungus development. However, no previous research on the effects of this herb on cancer has been reported. Methods: The sequential extraction was conducted by soaking the leaves in hexane, ethyl acetate, and methanol. The chemical 6-methyltectochrysin was effectively isolated from L. petersonii and showed cytotoxicity against melanoma cancer cells. Caspase Glo 3/7 and Annexin V-FITC–PI apoptotic tests were performed following 6-methyltectochrysin administration. Results: The findings showed cytotoxicity and possible apoptosis induction in A375 cells, and further examination using relative expression analysis revealed an increase in the pro-apoptotic Bax and a decrease in the anti-apoptotic Bcl-2 gene. Conclusions: Further research is needed to identify molecular pathways and targets of the compound 6-methyltectochrysin in melanoma cancer cells.
Background: D-amino acids are increasingly recognized as bioactive molecules with diverse physiological and pathological roles in humans, particularly in the gut, kidneys, and nervous system. Advances in analytical techniques have revealed their widespread presence in biological fluids, including plasma, urine, cerebrospinal fluid, amniotic fluid, and saliva, challenging the long-standing assumption that D-amino acids are absent or biologically insignificant in mammals. Scope: This review systematically summarizes the current knowledge on D-amino acid sources, distribution, metabolic regulation, and biological functions, with emphasis on their roles in human physiology and disease. Key findings: Accumulating evidence indicates that major D-amino acids, including D-serine, D-aspartate, and D-alanine, are derived from multiple sources such as diet, intestinal microbiota, and endogenous racemization processes. Rather than being passive metabolic byproducts, D-amino acids are now understood to participate in host–microbe interactions, neurotransmission, and renal physiology. Importantly, a consistent trend across studies is their dual and concentration-dependent nature, exhibiting beneficial effects under physiological conditions but potential cytotoxic effects at elevated levels. Conclusions and perspectives: Overall, D-amino acids represent multifunctional biomolecules with tightly regulated physiological roles and context-dependent pathological implications. However, major gaps remain in understanding their quantitative dynamics, tissue-specific regulation, and microbiota-dependent metabolism. Future studies addressing these mechanisms will be essential for establishing their clinical utility as biomarkers and for developing D-amino acid-based therapeutic and nutritional strategies.
Background: Tandem leucine-rich repeats (LRRs) are typically classified into eleven types; however, several variant motifs have also been reported. Here, we identified new LRR variants that exhibit dual characteristics of two distinct types. We investigated how the dual characteristics influence the structure and function of LRRs. Methods: We conducted sequence similarity searches using the protein database and analyzed sequence features. We also characterized the structural features of these LRR variant motifs using solved structures and AlphaFold models and investigated their potential biological functions through domain analysis. Results: Of the identified 3222 proteins, approximately 60% originate from the bacterial PVC superphylum. The variants were classified into two groups: one defined by the consensus sequence LxxLxLxx(C/T)xzI TDxxLxx(L/F)xx(L/C)xx, and the other by LxxLxLxxCxxI TDxxLxxLxxLP (where “z” denotes a deletion). The LRRs highly similar to the variants are occasionally observed in solved structures and comprise three types of super-secondary structures (SSSs): β-strand–α-helix adjoining a 3(10)-helix–β-strand, β-strand–3(10)-helix–β-strand, and β-strand–3(10)-helix adjoining an α-helix–β-strand. The AlphaFold models adopt these SSSs and, in addition, include the SSS of the β–α–β motif. Functional annotation identified kinase and F-box domains in a subset of these LRR proteins. Conclusions: The coexistence of these four SSSs and the high frequency of the first SSS appear to reflect the dual characteristics of the LRR variants. The LRR variant-containing proteins suggest potential roles in bacterial immunity and ubiquitination. The present findings expand the structural diversity of LRR proteins and provide new insights into their functional roles.
Voltage-gated sodium channels are central to electrical excitability, and Nav1.7 is a major therapeutic target implicated in pain disorders and sensory signaling. Within the channel pore, permeating Na+ ions experience dynamically fluctuating hydration and coordination environments that may influence local ion-protein interactions. Identifying chemically distinct coordination states from molecular dynamics (MD) simulations is an important prerequisite for future higher-level electronic structure investigations. In this study, we present a reproducible workflow for identifying and classifying Na+ hydration-coordination microstates in the Nav1.7 pore using explicit-solvent molecular dynamics simulations. A geometrically defined pore region was used to quantify pore hydration and Na+ inner-shell coordination based on a 3.2 & Aring; Na-O distance criterion. Na+ configurations were classified according to ligand identity into water-only (W), mixed protein-water (PW), and protein-only (P) microstates. Analysis of a 2 ns proof-of-principle simulation revealed a persistently hydrated pore environment, with Na+ coordination dominated by water-rich states and a smaller but distinct population of protein-contact configurations. These observations demonstrate that local coordination environments are chemically heterogeneous and cannot be fully described by hydration number alone. Representative structures from each microstate class were extracted to provide candidate configurations for future quantum mechanical, Quantum Mechanics/Molecular Mechanics (QM/MM), or density functional theory investigations of ion-ligand interactions in confined pore environments. The present work establishes a transparent and reproducible microstate-selection framework and does not report quantum mechanical energies, free-energy landscapes, or converged microstate populations. More broadly, the workflow provides a practical strategy for reducing complex MD ensembles into chemically interpretable coordination states suitable for subsequent higher-level analysis.
As mentioned in the Editorial of the first edition of the Special Issue on “Feature Papers in BioChem”, biochemistry acts as a key cog in the “clock of the knowledge, permitting that wheels from several science areas move each other” [...]
To improve the visible-light response and antibacterial performance of titanium dioxide, a TiO2/GO/CdS mesoporous nanocomposite was prepared via an ultrasound-assisted sol-gel method in this study. Systematic characterizations including XRD, XPS, SEM, TEM, BET, UV-Vis DRS and FTIR were carried out to analyze the structure, morphology and optical properties of the material. The results show that the composite exhibits a typical mesoporous structure with a specific surface area of 197.0962 m(2)/g and a pore size distribution of 2-14 nm. CdS is successfully doped into the TiO2 matrix and forms a heterostructure with GO. UV-Vis diffuse reflectance spectra indicate that the synergistic effect of CdS and GO significantly broadens the visible-light absorption range of TiO2 and suppresses the recombination of photogenerated carriers. Antibacterial tests using Escherichia coli as the target strain demonstrate that the TiO2/GO/CdS composite exhibits remarkably better visible-light photocatalytic bactericidal activity than pure TiO2 and the TiO2/GO composite. This work provides a new strategy for the modification of TiO2-based photocatalytic antibacterial materials, and the as-prepared composite shows promising application prospects in the antibacterial field.
This study addresses two key challenges in computational pharmacology: identifying novel therapeutic uses for existing drugs and modeling drug safety-related characteristics. We propose a multi-relational biomedical knowledge graph that integrates gene, drug, and disease associations with adverse effect data, enabling joint modeling of therapeutic and safety-related properties. A Relational Graph Convolutional Network (R-GCN) is employed to learn relationally aware embeddings that capture complex biological interactions across heterogeneous entities. The framework is evaluated on two tasks: (1) drug-disease link prediction for drug repurposing and (2) prediction of drug side-effect burden based on adverse event patterns. The experimental results demonstrate that the R-GCN model outperforms baseline methods, achieving 94.63% accuracy in drug-disease link prediction, while embedding-based classifiers attain up to 97.14% F1-score in side-effect burden classification. Additionally, multi-hop relational reasoning enables the discovery of biologically plausible connections between drugs, genes, and diseases. These findings highlight the effectiveness of knowledge graph-based representation learning in jointly supporting therapeutic discovery and safety-related analysis. While side-effect burden is used as a surrogate measure rather than a direct indicator of drug quality, the proposed framework provides a scalable foundation for integrating real-world pharmacovigilance and regulatory data in future studies.
Following the discovery of therapeutic molecules and the identification of specific biological targets, preparation of regulatory dossiers entails extensive product development and characterization to support their safety, efficacy, and stability. We have examined the drug development and relevant regulatory considerations related to inhaled biological proteins in the accompanying article. This review focuses on the characterization of locally acting inhaled biological proteins. Drug product characterization is a regulatory requirement, and it ensures drug product safety, efficacy, stability, and usability by the target populations. Together, these two articles provide a comprehensive discussion based on our review and analysis of the available open literature. We have attempted to fill gaps and simulate discussion of challenges following sound scientific pathways. This approach has the prospect of addressing regulatory expectations leading to rapid solutions to unmet medical needs. The robustness of characterization strategies and the development of analytical methods used in the in vitro testing for the evaluation of drug product attributes is assured through application of the Design-of-Experiment (DOE) and Quality-by-Design (QBD) approaches. Drug product characterization entails a variety of in vitro studies evaluating drug products for purity and contamination, and determination of drug delivery by the intended route of administration. Measurement of the proportion of the labeled amount per dose and the form suitable for delivery to the intended target sites is central to this assessment. For respiratory Drug–Device combination products, the testing may vary with the product designs. However, determination of the single-dose content, delivered-dose uniformity, aerodynamic particle size distribution, and device robustness when used by the target populations is common to all combination products. Characterization of aerosol plumes is limited to inhalation aerosols that produce specific aerosol clouds upon actuation. The flow rate dependency of devices is also examined. Product characterization also includes safety-related product attributes such as degradation products and leachables. For inhaled biological proteins, safety-related in vitro testing includes additional testing to assure maintenance of the three-dimensional structural integrity and the sustained biological activity of the drug substance in the formulation, during aerosolization and upon deposition. This article discusses various tests employed for regulatory-compliant product characterization. In addition, the stability testing and handling of possible changes during product development and post-approval are discussed.
The pharmaceutical industry faces a broken drug development pipeline, characterized by high costs, slow timelines and is prone to high failure rates. The convergence of Artificial Intelligence (AI) and quantum technologies is poised to fundamentally transform this landscape. AI excels in interpreting complex data, optimizing processes and designing drug candidates, while quantum systems enable unprecedented molecular simulation, ultra-sensitive sensing and precise physical control. This convergence establishes an integrated, self-learning ecosystem for the discovery, development, and delivery of therapeutics. This framework co-designs strategies from molecular targeting to formulation stability, compressing timelines and enhancing precision, which may enable safer, faster, and more adaptive medicines.
Background/Objectives: Lactic acid bacteria have long been recognized as pivotal microorganisms in food fermentation and health promotion. However, their significance has recently grown due to innovative applications in various fields, particularly at the intersection of biotechnology and nanotechnology. This study aimed to provide a comprehensive overview of these emerging applications. Methods: The latest scientific literature was drawn from online databases and thoroughly reviewed. The new nomenclature system based on the post-2020 reclassification was used for reports. Results: The current study highlighted the evolving role of lactic acid bacteria, beyond their traditional use as starter cultures for food fermentation, in newer challenges, including the production of high-value bioactive compounds through bioprocessing under optimal conditions to enhance the yield, underlining the involved genes and pathways. Furthermore, this review addressed the beneficial effects of lactic acid bacteria as probiotics, postbiotics, and paraprobiotics in the treatment of various diseases and disorders, their application in the production of functional foods, and the encapsulation of their bioproducts to produce advanced health-promoting functional ingredients. The potential use of lactic acid bacteria to synthesize metallic nanoparticles, minicells, and carbon dots was also explored, promising significant advancements in nanomedicine. Conclusions: This review could open a new horizon for leveraging the potential of lactic acid bacteria in biotechnology, food science, and nanomedicine. The multilateral perspective offered here would provide a foundation for future research and development to exploit the capabilities of lactic acid bacteria across these innovative fields.
Background: COVID-19 severity shows marked interindividual variability, suggesting a role for host genetic factors. Polymorphisms in genes involved in the renin-angiotensin system and inflammatory response, such as the angiotensin-converting enzyme (ACE) and the tumor necrosis factor-alpha (TNF-alpha), have been proposed as potential modulators of disease severity. Objectives: To evaluate the association between the ACE I/D (rs4646994) and TNF-alpha-308 G/A (rs1800629) polymorphisms and COVID-19 severity in a Mexican population. Methods: A total of 235 individuals with RT-PCR-confirmed SARS-CoV-2 infection were included. Patients were classified as hospitalized (severe, n = 155) or non-hospitalized (asymptomatic-mild, n = 80). Genotyping was performed by PCR-RFLP. Genotype distributions were analyzed using chi 2 tests under dominant and recessive genetic models, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: The ACE I/D polymorphism showed a significant association with COVID-19 severity. Carriers of the I allele (ID + II) had a higher risk of hospitalization compared with DD homozygotes (OR = 2.78, 95% CI: 1.53-5.06, p = 0.001). After adjustment for sex, the association remained significant (adjusted OR = 2.55, 95% CI: 1.38-4.70, p = 0.003). Sex-stratified analysis revealed that this association was significant only in male patients. The DD genotype was more frequent among non-hospitalized individuals, suggesting a potential protective effect in this population. No significant association was observed between the TNF-alpha-308 G/A polymorphism. Conclusions: The ACE I/D polymorphism is associated with COVID-19 severity in a Mexican population, with a stronger association observed in males. These findings highlight the potential role of host genetic background and sex-specific effects in COVID-19 outcomes.
Paediatric ovarian neoplasms are rare and histologically diverse tumours with distinct clinical behaviour and prognosis compared to their adult counterparts. This review synthesises current knowledge from an anatomical pathology perspective, emphasising diagnostic and therapeutic strategies. Paediatric ovarian tumours are classified into three main categories: germ cell tumours, sex cord-stromal tumours, and epithelial neoplasms. Germ cell tumours, the most frequent in children, include dysgerminoma, mature and immature teratoma, yolk sac tumour, and choriocarcinoma. Sex cord-stromal tumours encompass Sertoli-Leydig cell tumours, juvenile granulosa cell tumours, and adrenal-like stromal tumours, while epithelial tumours, rare in paediatric patients, include serous and mucinous adenocarcinomas or cystadenomas. Clinical presentation is often nonspecific, with abdominal pain, pelvic mass, or endocrine abnormalities. Diagnosis integrates imaging, serum tumour markers, and histopathology supported by immunohistochemistry. Treatment prioritises fertility-sparing surgery, with selective adjuvant chemotherapy based on histotype and stage. Despite generally favourable outcomes, the rarity of these tumours limits high-quality evidence, highlighting the need for referral centres and multicenter studies. Standardised diagnostic protocols and personalised therapeutic approaches are essential to optimising clinical outcomes and preserve long-term reproductive function.
The majority of approved drug products comprise formulations of either chemically synthesized small molecules or large molecular entities derived from living cells, commonly referred to as biologics. Over the past two decades, there has been remarkable growth in the approval of biologics for a variety of disorders, including respiratory diseases. The preference for biologics stems from their high target specificity, strong binding affinity, and favorable safety profiles. Most approved biologics are peptides or proteins, which are unsuitable for oral administration due to negligible bioavailability, resulting from their large molecular size, polarity, and susceptibility to enzymatic degradation in the gastrointestinal tract. Consequently, the majority of biologics are administered parenterally, delivering the drug systemically to reach target sites. However, achieving therapeutic concentrations of locally acting respiratory drugs in the lungs via systemic delivery often requires high doses, which increases the risk of adverse effects. For respiratory disorders, nasal and pulmonary drug deliveries are the preferred noninvasive routes. These routes bypass gastrointestinal and first-pass metabolism and deliver therapeutic agents directly to their local site of action. This approach enables a faster onset of action, reduces the required dose by orders of magnitude, and significantly lowers the risk of systemic adverse effects. These advantages have driven the successful development of inhaled formulations for certain rescue and maintenance medications that were originally administered orally or parenterally. Despite this, treatment options for respiratory diseases remain largely limited to small molecules, with only a single inhaled biologic approved in 1993, even though several parenterally administered biologics have since been approved for pulmonary disorders. The scarcity of inhaled biologics is primarily due to the inherent complexity of these drug substances, which impacts all stages of product development, including manufacturing, characterization, purification, stability, formulation design, delivery, and preclinical and clinical evaluations of safety and efficacy. Additionally, sponsors’ interest in developing inhaled biologics may be tempered by the lack of regulatory guidance addressing the multidisciplinary and intricate nature of their development. This article, together with the accompanying review, addresses both regulatory considerations and scientific challenges in the development of inhaled biologics. To the authors’ knowledge, these works represent seminal efforts to examine available regulatory guidance and the applicable literature across various phases of product development beyond safety and efficacy evaluations. We examined the formal regulatory expectations and summarized the requirements as they apply to inhaled products and inhaled biologic protein therapeutics. In parallel, we explored scientifically relevant considerations in the development of inhalation-specific protein therapeutics for which regulatory guidance remains limited, evolving, or absent. While they should not be considered definitive, it is hoped that these contributions will stimulate scientific and regulatory interest, ultimately promoting the identification and resolution of gaps to advance the development of locally acting biologics and address unmet patient needs.
Background: Competitive sports represent a powerful physiological and psychological stressor capable of modulating neuroendocrine and immune pathways. Water polo, characterized by intense intermittent exertion and frequent physical contact, provides a unique model to investigate competition-related stress biology. Methods: Sixteen male Italian Serie C water polo players were enrolled in the study. Using a within-subject design, saliva samples were collected under controlled circadian conditions. Salivary biomarkers, including cortisol, IgA, and cytokines, were assessed both before and after training sessions and competitive matches. Results: Both training and competition elicited POST-session increases in salivary cortisol and cytokines, alongside reductions in IgA. However, competition produced significantly higher anticipatory and POST-session cortisol concentrations. A larger POST-session decreases in IgA compared with training was observed. Cytokine concentrations increased from PRE- to POST-session in both conditions, with significantly greater induction during competition across the panel. During training, selected cytokines showed positive within-session correlations with cortisol, indicating coordinated hypothalamic–pituitary–adrenal–immune activation under lower psychosocial load. These associations were attenuated and less consistent during competition. Conclusions: Official competition amplifies endocrine and immune responses beyond those observed during match-like training in elite water polo players, despite comparable physical demands. Altered cytokine–cortisol coupling under competitive conditions suggests modulation of neuroendocrine–immune integration by psychosocial stress. Combined salivary profiling of cortisol, cytokines, and IgA represents a feasible, non-invasive approach for monitoring psychophysiological load in elite aquatic team sports.
Background: Diabetes mellitus is a global health challenge associated with chronic complications like diabetic nephropathy and diabetic foot infections. Diabetic nephropathy, mediated by hyperglycemia-induced activation of the polyol pathway, represents a primary cause of end-stage renal disease. Additionally, infections caused by multidrug-resistant bacteria like Enterococcus faecalis lead to amputations and contribute to morbidity in diabetic patients. Methods: In this study, we synthetized nitrogen-doped carbon dots (N-CDs) using succinic acid with either hexamethylenediamine (N-HCD) or ethylenediamine (N-ECD) and evaluated their potential therapeutic applications. Results: Both N-HCD and N-ECD demonstrated a significant reduction in aldose reductase (AR) and sorbitol dehydrogenase (SDH) in vitro, with a substantial reduction in polyol pathway enzymatic activity. Furthermore, these N-CDs exhibited antibacterial activity against E. faecalis in vitro. Conclusions: Taken together, our findings suggest that N-HCD and N-ECD represent promising candidates for addressing diabetes-related complications and warrant further investigation for potential drug delivery applications.
Background: Proper storage of biofluids is critical to preserving their molecular integrity for downstream applications. This study investigates the effect of different storage temperatures on the stability of preservative-free urine samples over a two-year period. Methods: Urine samples were collected, aliquoted, and stored at -80 degrees C, -20 degrees C, 4 degrees C, and in lyophilized form. Samples were retrieved at 0, 6, 12, and 24 months for analysis. DNA, RNA, and protein were isolated and evaluated using agarose and polyacrylamide gel electrophoresis. Nucleic acid quality was assessed using Nanodrop spectrophotometry and Bioanalyzer profiles. Results: A significant increase in pH and a concurrent decline in protein concentration were observed within the first six months at -20 degrees C and 4 degrees C. These changes plateaued after six months. Samples stored at -80 degrees C and in lyophilized form showed minimal variation in pH and retained higher protein stability. DNA quality, based on 260/280 and 260/230 ratios and electrophoretic band integrity, was well-preserved under these two conditions. RNA quality remained stable for up to 12 months but declined thereafter. Conclusions: Storage at -80 degrees C or in lyophilized form offers optimal preservation of protein concentration and nucleic acid quality in preservative-free urine samples over extended storage durations. However, lyophilization offers a cost-effective and logistically practical alternative, as samples can be stored at room temperature without the requirement of ultra-low freezers.
Alzheimer’s disease (AD) signifies a devastating impact on the quality of life of patients and their families. At a biomolecular level, AD is characterized by the deposition of extracellular plaques of β-amyloid (Aβ), affecting language, spatial navigation, recognition abilities and memory. Among the selected 30 articles about polyoxometalates (POMs) and AD published from 2011 to 2025, pure POMs, hybrid POMs and POM nanoparticles can be found. The majority of POMs are polyoxotungstates (62%), the Keggin-type SiW11O39 being the most studied in AD. The main effect described is the inhibition of Aβ aggregates. Other effects include reversing the neurotoxicity induced by Aβ aggregates, decreasing ROS production and neuroinflammation, restoring memory and sequestering Zn2+ and Cu2+, among others, features that are well known to be associated with the pathology of AD. POMs have also shown the ability to induce the disaggregation of Aβ fibrils, particularly after irradiation, and to inhibit acetylcholinesterase activity at an nM range. Putting it all together, this review highlights a predominant trend in the exploration of POMs to act directly at the level of the formation and/or disaggregation of Aβ aggregates in the treatment of AD.
Background/Objectives: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with over 50% of individuals succumbing to the disease annually. This study aimed to assess the correlation between human leukocyte antigen (HLA) genes and acute myeloid leukemia (AML) in an adult Moroccan cohort. We included 60 persons with acute myeloid leukemia (AML) who were eligible for hematopoietic stem cell transplantation and compared them to a control group of 90 healthy adults. Methods: Patients and controls were subjected to HLA class I and II typing utilizing either sequence-specific primers (SSP) or sequence-specific oligonucleotides (SSO) in polymerase chain reaction-based methodologies. Results: The AML categories were predominantly represented by AML2, AML3, and AML4, comprising 36.66%, 30%, and 16.66%, respectively. We identified a notable correlation between HLA-A*11 (p = 0.003) and HLA-B*27 (p = 0.005) with acute myeloid leukemia (AML), and for HLA class II allele groups, we detected an elevated frequency of HLA-DQB1*05 (p = 0.002) in adult AML patients. We identified a notable correlation between AML 2 and the allele groups examined, namely with HLA class I: HLA-A*11 (p = 0.0003) and HLA-B*27 (p = 0.00006). Conclusion: Our study suggests a potential association between specific HLA alleles and the development of AML specifically AML type 2 in adults. Further larger studies are needed to confirm these findings.
Background: Microglial cells are the resident immune cells in the central nervous system (CNS) and constitute the brain’s innate immune system. They are the smallest of the glial cells and are derived from phagocytic white blood cells, fetal monocytes, which migrate from the blood into the brain during development. On the other hand, epilepsy is a chronic condition defined as recurrent unprovoked seizures, with at least two seizures occurring over 24 h apart. Methods: To determine the role of microglial activation in the pathogenesis of drug-resistant epilepsy, we systematically searched published data for biomarkers of microglial activation from main databases including PubMed, PubMed Central, Scopus, Embase, Google Scholar, and Medline. Two research registries were also searched: the Cochrane Registry and clinicaltrial.gov. Data was collected after applying inclusion and exclusion criteria and studies were appraised critically. Both Medical Subject Headings (MeSH) and regular keyword search strategies were employed. Results: Our systematic review shows significant elevation of biomarkers of microglial activation in patients with drug-resistant epilepsy, suggesting its role in the disease’s pathogenesis. Conclusions: Microglia cells are therefore considered as a special type of mononuclear phagocytes found in the CNS that plays important roles in both the brain’s immunity and homeostatic functions. The role of microglial activation in the pathogenesis of drug-resistant epilepsy is an active area of study, with potential therapies for drug-resistant epilepsy that target microglia currently being investigated.
