Search Results (170)

Background: Early feeding practices are among the most influential determinants of the infant oral microbiota during the first years of life. Breastfeeding provides bioactive components—immunoglobulins, human milk oligosaccharides (HMOs), and commensal bacteria—that may shape microbial colonisation patterns with long-term implications for oral health. However, the nature, magnitude, and clinical relevance of these effects remain poorly characterised, particularly with regard to early childhood caries (ECC) risk. Objectives: The primary objective was to evaluate the association between early feeding practices and oral microbiota composition during infancy. A secondary exploratory objective was to assess whether feeding-associated microbiota differences had been linked to subsequent dental caries outcomes. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed, Scopus, Web of Science, and Embase were searched from January 2010 to June 2026. Eligible studies compared at least two feeding groups and measured oral microbiota directly using culture-independent methods (16S rRNA gene sequencing, metagenomics, or quantitative PCR targeting multiple taxa). Study selection, data extraction, and risk of bias assessment using the ROBINS-E tool were performed independently. Qualitative synthesis was conducted given clinical and methodological heterogeneity. Results: Of 8582 records identified, 12 studies met the inclusion criteria (sample size range: 12–448 participants; age range at microbiota assessment: 2 days–14 years, although eligibility was based on feeding exposure during infancy; six countries). Most included studies reported differences in oral microbiota composition associated with feeding type. During the first months of life, breastfed infants generally showed lower oral microbial diversity and higher abundance of Lactobacillus, the Streptococcus mitis group and Bifidobacterium compared with formula-fed infants, who exhibited greater alpha diversity, higher transmission of maternal oral bacteria, and higher abundance of Prevotella and Actinomyces. Effects were most pronounced in the first three months of life and attenuated by 12 months in most cohorts. Only one study reported subsequent dental caries outcomes after early-life microbiota assessment, finding that Streptococcus cristatus abundance at three months was associated with dental caries at nine years of age, and that longer breastfeeding duration (≥12 months) was associated with a distinct microbiota profile and lower caries rates in this single available longitudinal study. Risk of bias was low in two studies, moderate in six, and high in four. Publication bias could not be formally evaluated. Conclusions: Early feeding practices are associated with measurable differences in oral microbiota composition during infancy, particularly during the first months of life. However, evidence linking these microbiota differences to subsequent dental caries outcomes remains extremely limited, with only one included study assessing later caries development. Therefore, the clinical significance of feeding-associated microbiota profiles remains uncertain and should be investigated through well-designed prospective longitudinal studies. Full article

This review describes a novel method for increasing the effectiveness of inactivated enveloped whole-virus vaccines by targeting them for extensive uptake by antigen-presenting cells (APCs). Several inactivated whole-virus vaccines with dense glycan shields display suboptimal effectiveness because the multiple carbohydrate chains (glycans) on the virus mask immunogenic peptides and surround the virus with a negative electrostatic charge that decreases uptake by APCs. It is postulated that engineering such vaccinating viruses to present the carbohydrate antigen “α-gal epitope” on the glycan shields will immunocomplex them with the anti-Gal antibody; thus, it will target them for robust uptake by APCs. Anti-Gal is an abundant natural antibody in humans, constituting ~1% of human circulating immunoglobulins. The ligand of anti-Gal is the α-gal epitope, which is naturally synthesized in non-primate mammals and New World monkeys by the glycosylation enzyme α1,3galactosyltransferase. This enzyme is encoded by the GGTA1-gene. Viral vaccines presenting multiple α-gal epitopes on their glycan shield bind anti-Gal and activate the complement system to produce complement chemotactic cleavage peptides C5a and C3a that induce extensive recruitment of APCs to vaccine injection sites. The virion-bound anti-Gal further targets the viral vaccine for robust uptake by APCs, following binding of its Fc “tail” to Fcγ-receptors on APCs. The efficacy of this method was studied in anti-Gal-producing mice with α-gal presenting inactivated influenza virus vaccine and with gp120 of HIV presenting this epitope. These studies indicated that virus vaccines engineered to present α-gal epitopes increase anti-virus antibody production and virus-specific T-cell activation by 15- to 100-fold in comparison to the same vaccines lacking α-gal epitopes. It is suggested that α-gal presenting inactivated SARS-CoV-2 virus vaccines can induce a similar protective long-term immune memory against S- M-, E-, and N-viral proteins. Furthermore, immune-escaping variants of the mutated S-protein may be destroyed by antibodies to M and E proteins, and cells infected with such variants may be killed by cytotoxic T cells specific to peptides of the N-protein. Such an anti-M-, E-, and N-protein immune protection may prevent expansion of these variants and thus may avoid the need for immunization with COVID-19 vaccines every 6 months or following the appearance of new variants. A similar potent immunization may be achieved with an inactivated Ebolavirus vaccine engineered to present α-gal epitopes on the glycan shield. The resulting immune response to the various Ebolavirus proteins also may contribute to cross-reactive protection against other Ebolavirus species containing proteins with evolutionarily conserved structures. An effective method for the preparation of a whole-virus vaccine presenting α-gal epitopes is by arming it with the GGTA1-gene inserted into the viral genome. Such virions will present multiple α-gal epitopes on their glycan shield, which will amplify their immunogenicity instead of reducing it in the wild-type virus. Full article

Pediatric acute liver failure (PALF) is a rare but life-threatening condition characterized by rapid clinical deterioration and high mortality. Viral infections represent a major etiology of PALF, although the causative agent remains unidentified in a substantial proportion of cases. Human Enteroviruses (EVs) are typically associated with self-limiting illnesses; however, they may rarely cause severe systemic disease, including fulminant hepatitis, particularly in neonates and young children. We describe the case of a 4-year-old previously healthy male who presented with acute fulminant hepatitis secondary to systemic Echovirus 25 (E25) infection, with concomitant Epstein–Barr virus (EBV) co-infection of recent onset. The diagnosis was established through multiplex PCR on cerebrospinal fluid, blood, stool, and nasopharyngeal aspirate, with serotype confirmation by the Italian National Institute of Health. The patient required intensive supportive care including therapeutic plasma exchange (TPE), continuous kidney replacement therapy (CKRT), and intravenous immunoglobulins (IGIV). Despite initial clinical deterioration and placement on the liver transplant list, the patient achieved complete hepatic recovery and was discharged after fourteen days of hospitalization without requiring transplantation. This case highlights the importance of prompt virological workup including enterovirus PCR in children presenting with acute liver failure of undetermined etiology and supports the use of extracorporeal therapies as a bridge to recovery. Full article

Background/Objectives: Excessive dietary inorganic phosphate (Pi) as a food additive poses potential health risks. Methods: This study investigated the impact of excessive dietary inorganic phosphate on intestinal and immune homeostasis in mice using gradient Pi exposure combined with an inflammatory model. Results: Pi overload induced atrophy in the thymus, spleen, and kidney; damaged the intestinal barrier; reduced the villus height-to-crypt-depth ratio; and decreased goblet cell numbers. Altered levels of serum sIgA and IgE, as well as intestinal IgA, IgG, IgE, and IgM, together with decreased IFN-α, indicated altered levels of immunoglobulins and cytokines under Pi treatment. Proteomic analysis revealed differential expression of key proteins, including CNTFR and Bcl2l1 in the JAK/STAT pathway and metabolic regulators CPT1α and IDH1, when comparing Pi-treated mice with the control group. Conclusions: These preliminary findings suggest that Pi may affect intestinal mucosal barrier function and systemic immune response through immune regulation and mitochondrial metabolic pathways, providing preliminary insight into the potential health implications of Pi overconsumption in humans. Full article

Background and objectives: The PWWP domain of lens epithelium-derived growth factor p75 (LEDGF/p75) mediates chromatin engagement through recognition of histone H3 lysine 36 di- and trimethylation (H3K36me2/3) and nucleosomal DNA. LEDGF/p75 plays a role in multiple human diseases. In particular, its interaction with HIV-1 integrase enables viral genome integration. However, the LEDGF PWWP domain remains difficult to target with small molecules as it lacks optimally shaped binding pockets. Here, we report the generation of high-affinity nanobodies (Nbs) to investigate the structure and function of this domain. Methods: Camelids were immunized with recombinant LEDGF PWWP domain, and immune phage display libraries were screened for affinity. Selected Nbs were recombinantly expressed in E. coli and purified. Their interaction with the PWWP domain of LEDGF and its close homolog HRP-2 was characterized using size-exclusion chromatography and surface plasmon resonance. Structural characterization of the Nbs was performed using X-ray crystallography. Functional effects on chromatin engagement were evaluated using an AlphaScreen assay. Results: Nine sequence-distinct Nbs were identified, seven of which were confirmed to bind the LEDGF PWWP domain with nanomolar affinities. Five Nbs also bound the HRP-2 domain, consistent with conserved functional surfaces, while two showed reduced affinity. The crystal structures of two Nbs (NbC03 and NbH10) confirmed there were canonical immunoglobulin folds, while the latter additionally revealed a domain-swapped dimer. Moreover, NbH10 dose-dependently inhibited the interaction between full-length LEDGF/p75 and H3K36me3-modified nucleosomes in vitro. Conclusions: This work establishes a validated panel of Nbs targeting the LEDGF PWWP domain and identifies one Nb capable of functionally disrupting the LEDGF–chromatin interaction. These Nbs serve as valuable tools for functional studies and structure-based drug design. Full article

Background: Presence of milk, fruits, eggs, fish, nuts and wheat antigens in the amniotic fluid is described in the literature. Studies show a contradictory relationship between maternal exposure to allergens and early sensitization of the fetus to allergens. Hemochorionic type of the human placenta allows for easier transfer of nutrients and antibodies from the mother’s blood to the fetal circulation through the direct contact of maternal blood with the fetal chorion. During the third trimester of pregnancy, immunoglobulin G (IgG) is actively transferred through the placenta into the fetal via neonatal FcRN receptor (FcRN). In addition, monomeric immunoglobulin E (IgE) cannot cross the placenta Aim: The objective of our study is to track intrauterine sensitization to essential food proteins at birth in umbilical cord blood in mothers with established peripheral blood eosinophilia and in their infants using allergen-specific IgE and IgG. Methods: An observational study was carried out in a cohort of 22 mothers with eosinophilia and their babies. Differences in expression between groups were assessed. Blood samples were collected to determine serum IgE and IgG specific to a set of inhalant and food allergens. Results: We did not find a significant correlation between specific IgE to cow’s milk (p = 0.857), egg white (p = 0.926) and egg yolk (p = 0.096) in umbilical cord blood and maternal blood samples taken immediately before birth. Spearman’s correlation of the specific IgE and IgG in umbilical cord blood showed no dependence between the two variables. In contrast, statistical analysis showed that maternal eosinophilia in peripheral blood could be a risk factor for the development of allergy in the offspring (χ², p = 0.0347). However, given the small number of patients, this claim needs to be confirmed with further studies. Conclusions: Due to the functional immaturity of the developing immune system of the fetus, the generation and maintenance of an independent immune response to allergens are incomplete. Maternal IgG (specific) passes to the baby and high maternal IG to a specific allergen reduces babies IgE production. In addition, low maternal specific IgG may promote IgE production in the baby under the influence of microenvironmental factors (cytokine background). The main limitation of our study is the small number of patients. Further research is needed in this direction to clarify the mechanisms and risk factors for early sensitization in newborns. Full article

There are no FDA-approved antiviral treatments for measles virus (MeV). Management is mainly supportive care. MeV treatments may include vitamin A, ribavirin, the MeV vaccine, or human immunoglobulin for pregnant patients exposed to MeV but lacking immunity. The Edmonston strain of MeV serves as the basis for the MeV vaccine and remains a component of the measles-mumps-rubella (MMR) vaccine. We previously showed that probenecid can be used therapeutically to prevent the replication of several key respiratory viruses. This study indicates that pre-treatment with probenecid (prophylaxis) can inhibit the replication of the Edmonston MeV strain in VeroE6 cells (1.12 μM) and Vero-SLAM cells (1.03 μM), while treatment (1 h post-infection, hpi) inhibits replication in VeroE6 cells (1.32 μM) and Vero-SLAM cells (8.66 μM). These results suggest that probenecid is an effective, host-directed antiviral drug against MeV replication in vitro. Full article

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite responsible for toxoplasmosis, a disease with significant health implications for humans and animals. The surface antigen 1 (SAG1) of T. gondii is a major immunodominant protein that facilitates host cell invasion, making it an ideal target for diagnostic and therapeutic interventions. Immunoglobulin Y (IgY), the primary antibody in avian species, offers unique advantages over mammalian IgG, including easier animal care, lower costs, high-yield production, and potential passive immunization. Objectives: This study aimed to induce, purify, and characterize IgY antibodies targeting T. gondii SAG1 from hen egg yolks. Methods: The coding region of the mature portion of T. gondii SAG1 was amplified by PCR, cloned into the pET32a(+) vector for heterologous expression in E. coli. The recombinant SAG1 (rSAG1) was purified by affinity chromatography and used to immunize hens. IgY was extracted from egg yolks using PEG. SDS-PAGE and spectrophotometry were used to evaluate purity and concentration. By ELISA, Western blot, and flow cytometry, the specificity of IgY was assessed against recombinant and endogenous, native, and denatured SAG1. Results: Purified IgY demonstrated strong recognition of both recombinant and native SAG1 in ELISA and Western blot, and against T. gondii tachyzoites by flow cytometry. Conclusions: SAG1-specific IgY was produced in a pure form; it could be helpful in research, diagnosis, and treatment at low costs on a larger production scale, with minimal animal harm. Full article

Alveolar echinococcosis (AE) is a zoonotic disease caused by the larval form of the tapeworm Echinococcus multilocularis, which is considered one of the most dangerous parasites for humans. E. multilocularis infections are most frequently observed in forestry workers, farmers, hunters, berry harvesters, and workers employed in animal shelters. The subject of this study was a four-year follow-up profile of cytokines, including tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-4 (IL-4), and interleukin-10 (IL-10), in a patient with advanced liver alveolar echinococcosis and non-optimal antiparasitic treatment. Ultrasound, computed tomography (CT) of the abdomen, X-ray, CT of the chest, and magnetic resonance imaging (MRI) of the head were performed during the observation and treatment of the AE patient. After antiparasitic treatment was initiated, decreased activity of the gamma-glutamyl transpeptidase (GGTP), decreased serum concentrations of immunoglobulin E, C-reactive protein (CRP), and the pro-inflammatory cytokines TNFα, IL-1, and IL-6 were observed, as well as slightly increased levels of the anti-inflammatory cytokines (IL-4 and IL-10). Conclusions. During a four-year follow-up in a patient with advanced hepatic alveolar echinococcosis and non-optimal antiparasitic treatment, a decrease in proinflammatory cytokines (TNFα, IL-1β, IL-6) and a slight increase in anti-inflammatory cytokines (IL-4, IL-10) were detected. A better understanding of cytokine regulation in infectious diseases may be important to the development of new therapeutic strategies aimed at antiparasitic treatment. We suggest that broad initiatives (preferably at the local community level) should be implemented to raise awareness of the threat of alveolar echinococcosis and methods for avoiding E. multilocularis infection. Full article

Donor-specific anti-HLA antibodies (DSAs) bind to donor vascular endothelial cells and mediate allograft rejection (AMR), but a clinical challenge for which targeted therapeutic options remain limited. We used a multiplexed single-antigen bead (SAB) assay to detect anti-human leukocyte antigen (HLA) antibodies. Based on the antigens which patient’s antibodies aganist to, we developed bivalent HLA-Fc fusion proteins composed of HLA-derived antigenic domains and human IgG1-Fc effector regions (rA24-Fc and rB13-Fc). Specific binding and functional activity of the HLA-Fc proteins were further validated by flow cytometry, ELISA, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) assays. Our findings demonstrate that the fusion proteins rA24-Fc and rB13-Fc significantly reduced HLA-specific antibody reactivity in vitro. Notably, rA24-Fc and rB13-Fc selectively bound to B-cell hybridomas (e.g., mouse W6/32 cells) expressing membrane immunoglobulins (BCR) which bound to the most HLA class I antigens. Importantly, rA24-Fc and rB13-Fc elicited antigen-specific, Fc-dependent elimination of the specific B-cell hybridomas. This study highlights HLA-Fc fusion proteins as a promising therapeutic strategy for the antigen-specific suppression of depletion of alloreactive B cells through dual cytotoxic mechanisms. This precision targeted to BCR of B cells approach is used to apply to the treatment of antibody-mediated rejection. Full article

The aim of this systematic review was to evaluate the current evidence for the involvement of epithelial-derived extracellular vesicles (EVs) in Immunoglobulin E (IgE)-mediated allergic sensitisation. Original clinical and research studies specifically examining the effect of epithelial-derived EVs in IgE-mediated allergic sensitisation were included. Non-IgE mediated allergies, abstracts and review articles were excluded. A total of 18 publications were identified from three databases (EMBASE, Web of Science and PubMed) that indicate epithelial-derived EVs have the potential to promote tolerance or allergic sensitisation. For example, epithelial-derived EVs have the potential to promote IgE-mediated allergic sensitisation by delivering mRNAs that promote T helper 2 (Th2) polarisation and cytokine secretion, or promote tolerance through the induction of T regulatory (Treg) cells. The results also indicate that the potential role of epithelial-derived EVs in IgE-mediated allergic sensitisation may be dependent on the barrier, with all publications related to intestinal epithelium driving tolerance, but publications on nasal and bronchial/alveolar epithelia gaving mixed effects. No publications were found on cutaneous epithelia. Taken together, the literature suggests that epithelial-derived EVs play a key role in influencing IgE-mediated allergic sensitisation. Further research examining all epithelial barriers, using both robust human in vitro models that give more biologically relevant information, as well as clinical studies, are required to further characterise the role of epithelial-derived EVs in IgE-mediated allergic sensitisation. Full article

Respiratory viruses continue to present serious health challenges to human wellness. Growing evidence suggests that the more severe and damaging effects and symptoms of influenza, rhinovirus (RV), respiratory syncytial virus (RSV), and COVID-19 may primarily result from their common ability to disorganize the body’s healthy immune response. The simultaneous over-stimulation of several reactive oxygen species (ROS) pathways and concurrent suppression of bioavailable Nitic Oxide (NO) contribute to an immune disbalance that can lead to cellular oxidative distress and an excessive inflammatory response. This study evaluated the real-time, acute ability of a single, orally administered 50 mg encapsulated dose of a plant-based dietary supplement (“PB-Blend”), compared to 1000 mg of Vitamin C as a positive control, to modulate multiple ROS associated with a dampened immune response, as well as NO and other markers of inflammation, in a cohort recovering from a moderate course of COVID-19. This randomized, double-blind study was performed on 28 individuals 18–24 days after a moderate COVID-19 infection. Participants were orally supplemented with a single encapsulated dose of either 50 mg of PB-Blend or 1000 mg Vitamin C as a positive control. Changes in the levels of bioavailable NO (measured as circulating NOHb) were assessed, as well as the ex vivo cellular formation of mitochondrial, NOX2-, iNOS-, and TNFα-dependent ROS. All parameters were measured in real time before ingestion (baseline), and then at 30, 60, 120, and 180 min after administration. ROS were measured using a portable electron paramagnetic resonance (EPR) spectrometer. Inflammatory, immunity (hsCRP and TNFα plasma levels), interleukin (IL1, IL6, IL8, and IL10), cytokine (IFNγ, TNFα, and NF-κB), and immunoglobulin (IgA, IgM, IgG, and IgE) profiles were also followed. In addition to laboratory and cell function investigations, we performed clinical cardio ergometry, blood O₂ saturation, and respirometry examinations. As hypothesized, the collected baseline data from this study group confirmed that mitochondrial, NOX2, and iNOS enzymatic systems were strongly involved in the generation of ROS at 18–24 days following a positive COVID-19 PCR test. Acute single-dose supplementation of 50 mg PB-Blend had a multifunctional impact on ROS and significantly inhibited the following: (a.) mitochondrial ROS levels by up to 56%; (b.) iNOS by up to 60%; and (c.) NOX2-dependent ROS generation by up to 49%. Moreover, 1000 mg Vitamin C supplementation exhibited narrower ROS-mitigating activity by solely inhibiting NOX2-dependent ROS generation by 45%. Circulating NOHb levels were significantly increased after PB-Blend administration (33%), but not after Vitamin C administration. PB-Blend and Vitamin C exhibited similar potential to reduce ex vivo high dose TNFα (200 ng/mL)-induced H₂O₂ formation. These results suggest that 50 mg of PB-Blend has the potential to modulate disbalanced mitochondria, iNOS, and NOX2 enzymatic systems that can be engendered during respiratory viral infection and subsequent recovery. Moreover, PB-Blend, but not Vitamin C, showed potential to upregulate bioavailable NO, which is known to decline under these conditions. Based upon these observations, PB-Blend could be considered an alternative to, or to be used in tandem with Vitamin C in applications that promote immune support and recovery during seasons of heightened respiratory viral risk (e.g., “flu season”). Full article

Atopic Dermatitis (AD) is a common inflammatory skin disease characterized primarily by its chronic and recurrent nature. This has a significant impact on productivity and human longevity. Dysbiosis of gut flora has been demonstrated to be significantly associated with the progression of AD. In our previous research, it was shown that Lactobacillus rhamnosus RL5-H3-005 (RL) and Pediococcus acidilactici RP-H3-006 (RP) have the ability to reduce the risk of disease in AD mice through the gut–mammary axis. Based on our previous work, this study aims to further investigate the effects of kynurenine (KYN), a metabolite of RL and RP, on AD mice induced by 2, 4-dinitrofluorobenzene (DNFB). In this study, we found that supplementing KYN in AD mice effectively alleviates the pathological symptoms of atopic dermatitis and further improves the levels of SCFAs in their intestines. Further research indicates that KYN’s therapeutic effects on AD are primarily manifested in the reduction of secretory immunoglobulin A (sIgA), immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13, and thymic stromal lymphopoietin (TSLP) levels in mice, while also repairing the intestinal barrier function of AD mice. Overall, the metabolites KYN of probiotics RL and RP can regulate the levels of SCFAs of mice, potentially improving the symptoms of AD mice through the gut–skin axis. Full article

Understanding the biochemical relationship between serum and dermal interstitial fluid (dISF) is critical for advancing minimally invasive diagnostics with wearables and point of care devices focusing on most relevant biomarkers accessible in the ISF. This work compares the composition of dISF and serum using Xsensio’s microneedle-based collector, which yields an average of 3.4 $\mathsf{\mu }$L/h. In the first study, total protein content, human serum albumin (HSA), and immunoglobulin G (IgG) are quantified in twelve volunteers. A second study is dedicated to screening 50 inflammation-related protein biomarkers across twenty volunteers. The results demonstrate that dISF closely resembles serum in its major protein constituents but at reduced concentrations (e.g., 57% for total protein). Strong correlations are observed between dISF and serum for CRP and SAA ($R^2>0.87$), primarily driven by a subject with pathological levels, demonstrating the ability of dISF to reflect systemic inflammation. This study originally reports NT-proBNP detection at comparable levels in both fluids, suggesting that dISF could serve as a reliable proxy for blood NT-proBNP in the non-invasive diagnosis of cardiac failure. Cytokine profiling reveals 36 detectable cytokines, including several unique to dISF. Notably, interleukin concentrations are found to be highly similar between the two fluids. These experimental findings support dISF as a promising diagnostic medium for monitoring both localized and systemic biomarkers in clinical applications. Full article

Immunoglobulin G4 (IgG4), a unique subclass of IgG antibodies, plays diverse roles in human health and disease. Its distinct features, such as Fab-arm exchange and specific mutations, confer reduced effector functions compared to other IgG subclasses. In health, IgG4 responses contribute to immune tolerance, particularly in the context of allergen-specific immunotherapy (AIT), where they can mediate tolerance to environmental antigens, inhibit IgE-dependent mast cell degranulation, and compete with IgE for allergen binding. This helps in attenuating allergic symptoms and is associated with increased levels of allergen-specific IgG4. However, in disease scenarios, the role of IgG4 is complex. IgG4 lacks complement fixation and, thus, shows a reduced ability to activate immune effector pathways, it was initially thought to be protective against autoimmune diseases. However, emerging evidence suggests that it can contribute to pathology. For instance, IgG4 autoantibodies against specific antigens can aggravate conditions in certain autoimmune disorders. In some cancers, it may play a role in immune evasion, with higher levels correlating with poor patient survival, albeit in others, its exact function remains elusive. Overall, understanding the precise role of IgG4 in various physiological and pathological conditions is crucial for developing targeted therapeutic strategies and improving patient outcomes. Full article