International Journal of Molecular Sciences

Efficient in vitro regeneration remains a major constraint in the genetic transformation, genome editing, and molecular breeding of wheat (Triticum aestivum L.), largely due to strong genotype-dependent recalcitrance and limited activation of developmental programs required for somatic embryogenesis. Plant regeneration relies on extensive transcriptional reprogramming and epigenetic remodeling orchestrated by morphogenic regulators that modulate meristem identity, as well as cellular pluri- and totipotency. In this review, we synthesize current molecular knowledge on key transcription factors (BBM, WUS/WUS2, GRF-GIF, WOX, LAX1, SERK, WIND1/ERF115) and signaling peptides (CLE/CLV-WUS module, phytosulfokine/PSK) that regulate embryogenic competence in monocot cereals, with emphasis on their orthologs and functional relevance in wheat. We highlight how controlled expression of these morphogenic genes, promoter engineering, and transient or excisable induction systems can significantly enhance regeneration capacity, reduce chimerism in CRISPR-Cas-edited plants, and facilitate genotype-independent transformation. We also discuss epigenetic and metabolic constraints underlying wheat recalcitrance and their potential modulation to improve culture responsiveness. By integrating evidence from wheat, rice, maize, and barley, we outline conserved gene-regulatory networks that reinitiate totipotency and propose strategies to accelerate doubled haploid production and speed-breeding pipelines. Collectively, morphogenic factors emerge as central molecular tools for overcoming regeneration bottlenecks and enabling next-generation wheat improvement. The objective of this review is to synthesize and critically evaluate current molecular knowledge on morphogenic regulators controlling in vitro regeneration in wheat (Triticum aestivum L.), with particular emphasis on their roles in genetic transformation and genome editing.

Hericium erinaceus (H. erinaceus), a medicinal mushroom, is a source of bioactive compounds with demonstrated neuroprotective potential. This activity is primarily attributed to two distinct classes of compounds: erinacines from the mycelium, which potently induce the synthesis of neurotrophins, protein growth factors essential for neuronal survival and health, and hericenones from the fruiting body, which subsequently appear to enhance or potentiate neurotrophin-activated signaling pathways. Preclinical evidence substantiates their ability to enhance neurotrophin levels, particularly Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), and activate their cognate Trk receptors. Activation of these pathways, including PI3K/AKT/mTOR and MAPK/ERK, converges on transcription factors such as CREB, promoting neuronal survival, neurite outgrowth, and synaptic plasticity. However, the precise molecular mechanisms linking these small molecules to the complex orchestration of neurotrophic gene expression remain incompletely defined. This review synthesizes current knowledge of the neurotrophic pharmacology of H. erinaceus bioactives and proposes a novel framework suggesting that non-coding RNAs (ncRNAs) play a key regulatory role. We hypothesize that hericenones and erinacines modulate key transcriptional hubs, such as CREB, Nrf2, and NF-κB, which in turn regulate the expression of specific ncRNAs (e.g., miR-132, miR-146a) known to control neurogenesis, synaptogenesis, oxidative stress, and neuroinflammation. This ncRNA-mediated mechanism may represent an un-explored axis that explains the pleiotropic neuroprotective effects of these compounds. We critically appraise the existing preclinical evidence, identify significant methodological limitations and translational gaps, and propose a structured research roadmap to test these ncRNA-centric hypotheses, aiming to accelerate the rational development of H. erinaceus-derived compounds for neurodegenerative diseases.

Diabetes mellitus (DM) is recognized as a major contributor to impaired testicular function and compromised male fertility. In the present study, the protective effects of the natural flavonoid diosmin (Dios) against diabetes-induced testicular injury were investigated using a rat model of streptozotocin (STZ)-induced diabetes. Diabetes was induced in rats via a single intraperitoneal injection of STZ at a dose of 50 mg/kg body weight. Dios was administered at doses of 25 and 50 mg/kg body weight for eight weeks. Diabetic rats displayed marked testicular dysfunction, evidenced by reduced serum testosterone levels, deteriorated sperm parameters, and pronounced histopathological alterations in testicular tissues. Biochemical analysis revealed elevated levels of oxidative stress markers, including malondialdehyde and protein carbonyls, along with decreased levels of reduced glutathione and diminished activities of catalase and superoxide dismutase in the testicular tissues. Furthermore, diabetes exacerbated testicular inflammation, as indicated by increased immunoexpression of NF-κB p65 and levels of pro-inflammatory cytokines. Likewise, diabetes induced testicular apoptosis, demonstrated by increased Bax and caspase-3 levels and decreased Bcl-2 levels. Treatment of diabetic rats with Dios significantly attenuated sperm parameters and testicular architecture and mitigated oxidative stress, inflammatory responses, and apoptotic cell death. Additionally, Dios enhanced antioxidant defense mechanisms and restored the Sirt1/Nrf2/HO-1 signaling pathway in the testicular tissues of diabetic rats. These results suggest that Dios may serve as an adjuvant therapeutic agent for diabetes-associated testicular dysfunction.