Abstract: Background: The escalating global burden of complex chronic diseases and severe mental health challenges represents a significant limitation of reductionist healthcare paradigms. We propose that health is not merely the absence of disease, but rather a dynamic state of coherence across three integrated domains: biological, psychological, and noetic (consciousness-related). This review evaluates emerging technologies and interventions designed to restore this tripartite coherence. Objective: To systematically synthesize and critically evaluate the scientific evidence for technologies and interventions aligned with the ReGEN framework's seven pillars: Light, Water, Frequency, Energy, Breath, Intention, and Food. Methods: Following PRISMA guidelines, we conducted a systematic literature search across PubMed, IEEE Xplore, PsycINFO, and Cochrane Library (2010-2024). Included studies were evaluated against five criteria: biophysical plausibility, evidence quality, biomarker correlates, safety profile, and transdisciplinary alignment. Technologies were graded (A-D) based on evidence strength. Results: From 2,148 identified records, 215 studies met inclusion criteria after systematic screening. Our analysis identified a "Foundational Triad" of interventions with the strongest mechanistic plausibility and evidence base: Photobiomodulation (Light Pillar, Grade A), Coherent Breathing (Breath Pillar, Grade A), and Focused Intention (Intention Pillar, Grade B). These pillars demonstrate significant combined potential for initiating systemic healing cascades. Technologies targeting the Frequency and Energy pillars showed more preliminary evidence (Grade B-C), requiring further rigorous validation. Conclusion: The ReGEN framework provides a thorough transdisciplinary taxonomy for classifying and evaluating coherence-enhancing technologies. Convergent evidence across multiple scientific disciplines supports the complementary application of photobiomodulation, coherent breathing, and focused intention as a potent, non-invasive approach for restoring systemic coherence. This synthesis outlines a verification protocol via a Tripartite Coherence Index and identifies critical research priorities for advancing this emerging paradigm.

Abstract: We propose the Informational Field Consciousness Theory (IFCT), an integrative framework combining information physics, quantum biology, and neuroscience to address the Hard Problem of Consciousness. Central to our thesis is the hypothesis that DNA functions as a fractal antenna capable of coupling with a fundamental informational field (IF), with neural networks serving as processors that filter and render conscious experience. We present empirical evidence from recent studies on DNA’s electromagnetic properties, biophoton emission, and quantum coherence in biological systems. Critically, we argue that the inability of synthetic biology to design functional DNA de novo - despite successfully replicating existing sequences - suggests undiscovered principles governing DNA’s role beyond genetic information storage, potentially including antenna/receiver properties optimized through evolution. We propose testable experimental protocols to distinguish our framework from purely materialist emergence theories and discuss implications for artificial consciousness, ethics, and the nature of life itself.

Abstract: The current manuscript is meant to introduce how piezo2 channelopathy may play a critical role in (epi)genetics, when it comes to development, growth and aging initiation from a neurocentric view. Accordingly, it demonstrates how the principality of excitatory Piezo2 ion channel may not only reflected in Piezo cross-frequency coupling, transcription activation, ultradian event sensing and modulation, but might also fine-modulates emergent entropic force from gravity and (epi)genetics, hence underscoring its principality not only in proprioception. The implicated Piezo ion channels, especially Piezo2, have cellular, inter-cellular, compartmental and systemic effect through a Piezo system, however the underlying backbone ultrafast (glutamatergic proprioceptive Piezo2) system may carry the principality. Syndecans as co-functioning accessory ligand of Piezo2 may serve the non-linear dynamics of the ultrafast non-linear time-delay system in order to quantum tunnel/synchronize protons in an ultrafast fashion into the suggested anticipatory coupled hippocampal chaotic system. The co-function of the intrinsically disordered intracellular domain of Piezo2 and the intrinsically disordered ectodomain of syndecans may posit the critical structure in this proposed ultrafast non-linear dynamics that may be impaired due to Piezo2 channeloapthy, leading to altered response to postural perturbations, consequently might cause an increased the risk of non-contact injuries. Proton affinity switch on proprioceptive glutamatergic terminals may not only induce acquired Piezo2 channeloapthy and resultant switch to glutamate-based signaling, but may miswire protons as well through the lipoxygenase pathway. This proton miswiring may also inhibit fine-regulation of excitatory AMPA information processing in neuronal synapsis. After all, acquired Piezo2 channelopathy may posit such an initiatingcritical primary damage that impacts development, growth and aging through (epi)genetics, however quantum (gravity) theory is needed for translation.

Abstract: Background/Objectives: Neutrophils express the receptor for advanced glycation end products (RAGE), but its role in the responses of neutrophils to bacteria is not well understood. Methods: Human peripheral neutrophils were isolated from blood of healthy donors. Fluorescent-based techniques and spectroscopy were used to assess calcium flux, ROS/RNS formation and phagocytic activity. Cellular expression of the PAGE-antigen was studied using immunofluorescence microscopy and flow cytometry. ELISA was used to quantify sRAGE in the culture medium. Results: We studied human peripheral neutrophils interacting with gram-negative bacteria S. typhimurium and asked how RAGE controls the neutrophil cellular responses. Blocking RAGE with the specific inhibitor FPS-ZM1 reduced bacteria-induced calcium signals, reactive oxygen species, nitric oxide production, and phagocytosis. We also found that neutrophil adhesion and stimulation by bacteria, lipopolysaccharide, or fMLP caused rapid release of soluble RAGE (sRAGE) into the cell environment. Immunofluorescence and flow cytometry showed low RAGE at the plasma membrane but abundant intracellular RAGE, which decreased on activation. Conclusions: Our data support a dual role of RAGE in neutrophils as both a membrane sensor and a secreted regulator.

Abstract: Pathological USH2A mutations cause Usher Syndrome type II, characterized by progres-sive retinitis pigmentosa and hearing and balance impairment. This study aims to inves-tigate the cellular mechanisms underlying USH2A-related retinal degeneration using hu-man induced pluripotent stem cell (hiPSC)-derived retinal organoids. The introduction of a homozygous nonsense mutation in the USH2A hotspot exon-13 resulted in normal photoreceptor development, but loss of ciliary localization of usherin long form B and its interacting proteins, ADGRV1 and whirlin. Notably, single-cell RNA sequencing revealed unexpected significant changes in Müller glial cells (MGCs), with disruptions in the translation, innate immune response, and endolysosomal system. These findings suggest that, while photoreceptor cells are mildly affected by the exon-13 USH2A mutation, MGCs exhibit major dysfunction, potentially contributing to the disease progression and there-fore shedding light on potential alternative therapeutic targets.

Abstract: The growing use of computed tomography (CT) in medicine requires a better understanding of how low-dose radiation affects human stem cells. This study investigated the long-term consequences of CT-level radiation on the secretory profile of human adipose-derived mesenchymal stem cells (AD-MSCs). AD-MSCs were exposed to radiation regimens simulating a single or multiple head CT scans, or to a single 2 Gy therapeutic dose, and their secretion of 41 cytokines, chemokines, and growth factors was monitored during long-term culture. At the early passage, AD-MSCs receiving a single 2 Gy dose showed a coordinated increase in several lymphocyte-regulating cytokines compared to cells exposed to multiple CT scans. However, these initial differences were not sustained. Long-term culturing led to a progressive and widespread decrease in the secretion of 26 cytokines, chemokines, and growth factors across all groups. By the latest passage, all irradiated cells showed a generalized reduction in secretory function compared to non-irradiated controls. These findings demonstrate that while different radiation regimens trigger distinct immediate responses, long-term culture results in a broad decline of the AD-MSCs secretome, which is accentuated by prior radiation exposure. This underscores the importance of assessing long-term consequences to fully evaluate the functional impact of diagnostic radiation on stem cells.

Abstract: This study examined how ultrasonic frequency changes droplet size and affects the delivery of nanoparticles through airway mucus. A simple nebulizer system was tested at 1.7 MHz and 2.5 MHz using fluorescent nanoparticles in a mouse model. At 2.5 MHz, the average droplet size decreased from 4.5 µm to 2.1 µm, which increased total lung deposition by 38% and extended mucus penetration by about 25 µm. Fluorescence imaging showed that the higher frequency produced a more uniform spread and higher drug level in the alveolar region. These findings show that adjusting ultrasonic frequency can improve droplet control and nanoparticle movement in the lungs. This approach offers a useful way to improve inhaled drug delivery and may also support future aerosol treatments for long-term lung diseases.

Abstract: This study used a PDMS microfluidic chip to study how nanoparticle size and surface wettability affect their movement in airway mucus. Artificial mucus with 3% mucin was used to test nanoparticles ranging from 50 nm to 300 nm in size and with contact angles between 40° and 90°. When the particle size was smaller than 150 nm and the contact angle was below 60°, the diffusion coefficient increased about 2.7 times, and the retention time in mucus dropped by nearly 45%. A simple regression model combining particle size and contact angle showed strong agreement with experimental data ( ), allowing clear prediction of transport efficiency. Unlike earlier static or single-factor tests, this microfluidic system provided a stable and repeatable environment close to airway conditions. The results offer practical guidance for designing nanoparticles that can cross mucus barriers and improve inhaled drug delivery. Future work should test real human mucus and include ciliary movement to verify the model under physiological conditions.

Abstract: The purpose of our study is to directly convert mouse fibroblasts into photoreceptor-like cells through an adenoviral gene delivery system. The mouse cDNAs of Ascl, Crx, Ngn1, Nrl, and Otx2 were cloned into a modified commercial adenoviral vector. Mouse embryonic fibroblasts (MEFs) were isolated from E13.5 embryos, and mouse postnatal fibroblasts (MPFs) were isolated from three-day-old mice. A pool of adenoviruses containing five genes was prepared to infect MEFs once daily for two days. Next, half of the neural medium supplemented with forskolin was changed every two days. After 7 or 14 days, the photoreceptor-like cells were assayed via immunofluorescence or polymerase chain reaction with reverse transcription (RT–PCR). The photoreceptor-like cells were then transplanted into adult C57BL/6 mouse retina and were assessed by immunofluorescence 14 days following transplantation. Screening from a pool of five candidate genes, we reported that a combination of only three factors—Crx, Nrl, and Otx2—was sufficient to convert mouse embryonic and postnatal fibroblasts into functional photoreceptors. The induced photoreceptor-like cells ex-pressed photoreceptor-specific proteins such as Recoverin, Rhodopsin, and Opsin and integrated into the outer nuclear layer of the retina following transplantation. This study demonstrates that the photoreceptor-like cells converted by defined factors from fibroblasts can provide a source of photoreceptor transplantation and feasible future treatment for retinal repair.

Abstract: Precision oncology has progressed through three eras: the genomic era, which identified mutations and molecular circuits; the archetype era, which revealed recurring tumor ecosystems; and now the emerging engineering era, enabled by AI and spatial modeling, which allows the rational reprogramming of tissue architecture. We define Spatial Engineering as a framework that integrates cellular composition, topology, physical context, and clonality into a multidimensional control space, describing how architecture can be perturbed to destabilize malignancy or restore homeostasis. Many breakthrough therapies, including checkpoint inhibitors, anti-angiogenics, CAR-T cells, and bispecific antibodies, already act through spatial mechanisms, yet most were discovered empirically. Spatial Engineering reframes them within a predictive logic of tissue design: measure architecture, model stability, intervene with intent, and adapt in real time. Early clinical trials are beginning to use spatial archetypes to assign therapy; the next leap is AI-guided simulation of drug sequences and therapeutic windows to steer malignant equilibria toward collapse. Together, these advances complete oncology’s transition from mapping tumors to designing their cure.

Abstract: Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and intellectual disability (ID), arise from disruptions of tightly orchestrated molecular programmes that govern neurogenesis, synaptogenesis and circuit maturation. Although large-scale genomic analyses have identified numerous susceptibility loci, DNA variation alone explains only a fraction of disease heritability, highlighting the pivotal contribution of post-transcriptional and epigenetic regulation. Among these regulatory layers, non-coding RNAs (ncRNAs)—encompassing microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs) and transfer-RNA-derived small RNAs (tsRNAs)—have emerged as key modulators of neural differentiation, synaptic plasticity and intercellular communication. Multi-omics studies reveal that ncRNAs fine-tune chromatin accessibility, transcriptional output and translation through complex competing-endogenous-RNA (ceRNA) and ribonucleoprotein networks. While miRNAs sculpt neurogenesis and circuit remodelling, lncRNAs and circRNAs integrate chromatin and transcriptional control with exquisite spatial and temporal precision. Newly characterized small RNAs such as tsRNAs and piRNAs extend this regulatory repertoire by linking translational reprogramming, epigenetic memory and even intergenerational inheritance. Advances in single-cell and spatial transcriptomics have further mapped ncRNA expression to discrete neuronal and glial populations, revealing cell-type-specific vulnerability signatures across cortical and subcortical regions. Clinically, circulating ncRNAs—particularly those encapsulated within plasma or extracellular vesicles—exhibit robust and disease-specific expression patterns, supporting their promise as non-invasive biomarkers for early diagnosis and patient stratification. In parallel, innovations in RNA interference, antisense oligonucleotides, CRISPR-based editing and exosome-mediated delivery are transforming ncRNAs from molecular indicators into therapeutic instruments capable of restoring transcriptional and epigenetic equilibrium. Together, these converging insights position ncRNAs as both mechanistic determinants and translational targets in neurodevelopmental pathology. The emerging ncRNA landscape redefines the molecular architecture of brain development, offering a unifying framework that links genome regulation, environmental responsiveness and neural plasticity. Decoding this multilayered RNA circuitry will be pivotal for the development of next-generation diagnostics and RNA-guided therapies for neurodevelopmental disorders.

Abstract: Melatonin, an ancient and conserved indolamine, has always attracted attention for its multifunctional roles in redox balance. More recently, it has been studied in relation to immune regulation and cancer biology. Beyond its well-known circadian function, melatonin modulates oxidative stress by directly scavenging reactive oxygen and nitrogen species and by upregulating antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. At the same time, it exerts wide-ranging immunomodulatory functions by influencing both the innate and adaptive immune responses. All these actions converge in the tumor microenvironment, where oxidative stress and immune suppression drive cancer progression. Notably, melatonin influences macrophage polarization, favoring antitumor M1 phenotypes over pro-tumoral M2 states, while attenuating chronic inflammation and restoring mitochondrial function. This review summarizes current knowledge on melatonin’s antioxidant and immunoregulatory mechanisms, highlighting its impact on the tumor immune microenvironment and its potential use as an adjuvant in cancer prevention and treatment.

Abstract: The Maternal Embryonic Leucine Zipper Kinase (MELK) gene is a part of the Snf1/AMPK of serine/threonine kinase family. MELK has recently attracted considerable interest in the fields of stem cell and cancer biology. Furthermore, MELK is expressed normally during embryogenesis and in proliferative tissues; however, its aberrant overexpression has been observed in various malignancies, including glioma, breast, lung, colorectal, gastric, and hematological cancers. Higher MELK levels are often correlated with unfavorable prognosis, aggressive tumor manifestations, resistance to treatment, and stem-like tumor morphologies. Preclinical studies utilizing RNA interference and small-molecule inhibitors such as OTSSP167 demonstrate that MELK promotes cancer cell proliferation, survival, and metastasis. However, contrasting evidence from CRISPR/Cas9-based knockout studies indicates that MELK may not be essential for tumor growth, raising concerns that the observed anti-tumor effects of MELK inhibitors could partly result from off-target activity. This review aims to summarize the current understanding of MELK biology, including its functions in cell cycle regulation, apoptosis, oncogenic signaling pathways, and tumor stemness. In this review, we discuss the therapeutic potential and limitations of MELK inhibitors, the controversy regarding MELK dependency, and the implications for cancer diagnosis and treatment. MELK may not be a universal driver oncogene; nonetheless, it is consistently linked to aggressive disease, underscoring its potential as a prognostic biomarker and a candidate for therapeutic co-targeting in combination treatments.

Abstract: A critical obstacle in cardiac cell therapy is the unpredictable and poorly understood initial electrophysiological integration of grafted cardiomyocytes into the host tissue, a process that dictates therapeutic success and arrhythmic risk. Current models fail to capture the earliest stages of functional coupling formation. Here, we employed a tailored bioengineering platform, where single cardiomyocytes were stabilized on minimalist electrospun polycaprolactone (PCL) nanofibers, to model the "graft-host" interface and study the dynamics of excitation wave transmission in real-time. Using high-speed optical mapping enhanced by a custom SUPPORT neural network, we achieved the first quantitative insights into the efficiency of nascent intercellular contacts. We determined that within the first 3 hours, these initial connections are 39-44 times less effective at conducting excitation than mature contacts within the native monolayer, explaining the observed partial (46%) synchronization of grafted cells. This work provides the first direct measurement of the functional deficit during the initial minutes and hours of graft integration. It establishes that simple, inert polymer fibers can act as a catalytic scaffold to enable this fundamental biological process, offering a powerful strategy to deconstruct and ultimately control the integration of engineered tissues (or cells) for safer cell therapies.

Abstract: Glycation-induced modifications of extracellular matrix (ECM) proteins, including collagen, are increasingly recognised as critical modulators of cellular behaviour, particularly in pathophysiological contexts such as ageing and diabetes. While their impact on general cell adhesion has been explored, the specific consequences for mesenchymal stem cell (MSC) mechanotransduction remain poorly defined. In this study, we investigated the temporal and mechanistic aspects of adhesion and mechanosensitive signalling in adipose-derived MSCs (ADMSCs) cultured on native versus glycated collagen substrates. Our findings identify two temporally distinct adhesion mechanisms: an initial pathway mediated by the receptor for advanced glycation end-products (RAGE), which is activated within the first 30 minutes following substrate engagement, and a later-stage adhesion process predominantly governed by integrins. Immunofluorescence analysis demonstrated maximal nuclear localisation of YAP/TAZ transcriptional regulators during the initial adhesion phase, coinciding with RAGE engagement. This nuclear enrichment was progressively attenuated as integrin-mediated focal adhesions matured, suggesting a dynamic shift in receptor usage and mechano-transductive signalling. Interestingly, glycated collagen substrates accelerated early cell attachment but impaired focal adhesion maturation, suggesting a disruption in integrin engagement. Endogenous collagen synthesis was consistently detected at all examined time points (30 minutes, 2 hours, and 5 hours), suggesting a constitutive biosynthetic activity that remains sensitive to the glycation state of the substrate. Atomic force microscopy (AFM) demonstrated that glycation disrupts collagen fibrillogenesis: while native collagen forms a well-organised network of long, interconnected fibrils, GL-1 substrates (glycated for 1 day) displayed sparse and disordered fibrillary structures, whereas GL-5 substrates (5-day glycation) exhibited partial restoration of fibrillar organisation. These matrix alterations were closely associated with changes in adhesion kinetics and mechanotransduction profiles. Taken together, our findings demonstrate that collagen glycation modulates both MSC adhesion dynamics and mechanosensitive signalling through a dual-receptor mechanism. These insights have significant implications for the design of regenerative therapies targeting aged or metabolically compromised tissues, where ECM glycation is prevalent.

Abstract: Background: Neonatal neuroinflammation, driven by microglial activation and cytokine signaling, contributes to brain injury and adverse neurodevelopment outcomes. Perinatal inflammatory mediators, including IL-6, COX-2, and IL-17, prime microglia and influence circuit vulnerability. This study investigated whether oxytocin (OT) pretreatment attenuates lipopolysaccharide (LPS)-induced inflammatory priming in BV-2 microglial cells. Methods: BV-2 microglia were preincubated with OT (33ng/mL) for 2 hours, followed by LPS (0.5 µg/mL) for 2 hours. Expression of IBA1, a microglia marker, in BV-2 was assessed by immunofluorescence. After LPS treatment, the gene expression of BV-2 cells was assayed 2 and 6 hours post-LPS stimulation by RT-qPCR and RNA-seq. Functional characterization of gene expression profile was performed with KEGG and GO analyses. Results: Analyses of gene expression profile of BV-2 cells by RT-qPCR and RNA-seq revealed that OT pretreatment attenuated LPS-induced transcriptional activation, including IL-6 and COX-2 upregulation. KEGG pathway enrichment analyses suggested that OT-responsive genes were linked to the IL-17 signaling pathway. GO analyses showed enrichment for genes related to cytokine production, membrane raft, and chemokine activity. Conclusions: OT pretreatment mitigates LPS-induced microglial activation by modulating the IL-17–IL-6/COX-2 axis, suggesting its potential role for OT as an endogenous modulator of neuroinflammation during early brain development.

Abstract: Background: The combination of manganese porphyrins (MnPs) and ascorbate (ASC) represents a promising redox-based therapeutic approach for selectively targeting cancer cells. In this study, we investigated the cytotoxic effects of two structurally distinct MnPs (MnTPPS and MnF₂BMet) with differing lipophilicity and potential membrane permeability in combination with ASC. Methods: Human cancer cell lines (MCF-7, PANC-1, U87, T98G, AT-2), and normal human dermal fibroblasts (HDF), were treated with MnTPPS and MnF₂BMet in the absence or presence of ASC. Their viability and invasive potential were then assessed with single-cell methods along with the analyses of intracellular oxidative stress. Results: MnPs alone exhibited no intrinsic cytostatic or cytotoxic activity, as confirmed by proliferation, viability, and motility assays. When combined with ASC, both MnTPPS and MnF₂BMet significantly enhanced ASC-induced oxidative stress, leading to lipid peroxidation, glutathione depletion, mitochondrial dysfunction, and cell membrane disruption. Time-lapse microscopy revealed rapid necrotic cell death under co-treatment. The cytotoxic effect was completely abolished by catalase, indicating the essential role of hydrogen peroxide. In contrast, dehydroascorbate (DHA), which increases intracellular ASC levels, did not reproduce the same toxicity, suggesting that extracellular ROS gener ation contributes predominantly to the observed effects. Normal fibroblasts were minimally affected, supporting the selectivity of the MnPs–ASC system toward cancer cells. Conclusions: The results indicate that MnTPPS and MnF₂BMet enhance extracellular oxidation of ascorbate and subsequent ROS production, leading to selective oxidative stressmediated cancer cell death. This study supports the potential of MnPs–ASC redox catalysis as a complementary oxidative stress–based anticancer strategy and highlights the need for further mechanistic and structure–activity investigations.

Abstract: Osteoarthritis (OA) is a chronic degenerative disease characterized predominantly by cartilage degradation, wherein extracellular matrix (ECM) proteins play pivotal roles in its pathogenesis. Proteins such as Asporin (ASPN), Cartilage Intermediate Layer Protein (CILP), Chondroadherin (CHAD), Fibulin-3 (EFEMP1), Pannexin 3 (PANX3), and C-terminal cross-linking telopeptide of type II collagen (CTX-II) exhibit aberrant expression patterns in OA cartilage, influencing chondrocyte metabolism, signaling pathways, and matrix homeostasis. This review provides a comprehensive overview of the altered expression and molecular functions of these ECM-related proteins in OA, emphasizing their interactions with key signaling cascades including TGF-β, Wnt, and BMP pathways. Incorporating recent advances from single-cell sequencing and gene editing technologies, we explore how these proteins serve as potential biomarkers and therapeutic targets. Furthermore, the review delves into the impact of post-translational modifications of ECM proteins on OA pathology, aiming to elucidate mechanisms that underpin precise diagnosis and targeted treatment strategies. By synthesizing current findings, this article seeks to advance understanding of ECM protein-mediated regulatory networks in OA and foster the development of innovative interventions for cartilage preservation and repair.

Abstract: BAG1 (Bcl-2-associated athanogene 1) is a versatile protein that plays a crucial role in various cellular functions, such as the regulation of cell survival, apoptosis, and protein quality management. Unusual BAG1 expression levels have been observed in multiple cancer types. This atypical expression grants cancer cells the capability to evade cell death via both cellular processes and cancer treatments. Focusing on inhibition of BAG1 with natural compounds presents a hopeful treatment strategy. This study investigates the inhibitory potential of phytochemicals derived from Nigella sativa against BAG1 using molecular docking techniques. Initially, a comprehensive insilico screening of Nigella sativa phytochemicals was conducted to evaluate their binding affinities against BAG1. The compound exhibiting the lowest binding energy was identified as the most promising candidate, demonstrating greater selectivity for BAG1 and inhibiting its aberrant activity in the natural pathway. The most promising phytochemical was further analysed by docking its structural and functional homologues against BAG1 to assess their potential as inhibitors, aiming to identify the most suitable BAG1 inhibitor. The results revealed five compounds that can inhibit the activity of BAG1 and have a higher binding affinity towards BAG1 than its natural bound inhibitor 3F5. This study provides valuable insights into the potential of Nigella sativa-derived compounds as BAG1 inhibitors, contributing to the development of novel cancer therapeutics.

Abstract: Neurodevelopmental disorders (NDDs), including autism spectrum disorder, intellectual disability, and attention deficit hyperactivity disorder, are increasingly recognized as disorders of early brain construction arising from defects in neural stem and progenitor cell (NSPC) proliferation. NSPCs are responsible for generating the diverse neuronal and glial lineages that establish cortical architecture and neural circuitry; thus, their expansion must be tightly coordinated by intrinsic cell cycle regulators and extrinsic niche-derived cues. Disruption of these mechanisms—through genetic mutations, epigenetic dysregulation, or environmental insults—can perturb the balance between NSPC self-renewal and differentiation, resulting in aberrant brain size and connectivity. Recent advances using animal models and human pluripotent stem cell–derived brain organoids have identified key signaling pathways, including Notch, Wnt, SHH, and PI3K–mTOR, as central hubs integrating proliferative cues, while transcriptional and chromatin regulators such as PAX6, CHD8, SETD5, and ANKRD11 govern gene expression essential for proper NSPC cycling. Furthermore, prenatal exposure to teratogens such as Zika virus infection, valproic acid, or metabolic stress in phenylketonuria can recapitulate proliferation defects and microcephaly, underscoring the vulnerability of NSPCs to environmental perturbation. This review summarizes emerging insights into the molecular and cellular mechanisms by which defective NSPC proliferation contributes to NDD pathogenesis, highlighting convergence among genetic and environmental factors on cell cycle control. A deeper understanding of these pathways may uncover shared therapeutic targets to restore neurodevelopmental trajectories and mitigate disease burden.