{"title":"Aromatic-Turmerone Analogs Activate Chaperone-Mediated Autophagy and Ameliorate Dendritic Shrinkage in Purkinje Cell Models of Spinocerebellar Ataxia.","authors":"Kensuke Motomura, Erika Ueda-Ishizaka, Alex Boateng, Masaharu Sugiura, Ayumu Konno, Yasushi Yabuki, Natsuko Hitora-Imamura, Yuki Kurauchi, Norifumi Shioda, Satohiro Masuda, Hirokazu Hirai, Hiroshi Katsuki, Takahiro Seki","doi":"10.1248/bpb.b26-00103","DOIUrl":"10.1248/bpb.b26-00103","url":null,"abstract":"<p><p>We recently demonstrated that aromatic (ar)-turmerone analogs ((E)-5-methyl-1-(p-tolyl)hexa-1,4-dien-3-one [A2] and (E)-1-(4-methoxyphenyl)-5-methylhexa-1,4-dien-3-one [A4]) activate chaperone-mediated autophagy (CMA), a pathway in the autophagy-lysosome protein degradation system, in SH-SY5Y cells. Our previous studies revealed that the impairment of CMA and microautophagy (mA), another autophagy-related pathway, and dendritic shrinkage were observed in primary cultured Purkinje cells (PCs) expressing causal proteins of spinocerebellar ataxia (SCA), an autosomal dominant neurodegenerative disease. In the present study, we first investigated the effects of A2 and A4 on lysosomal protein degradation and dendritic morphology in cerebellar primary cultured PCs. Both compounds enhanced dendritic development and activated CMA in cultured PCs. These effects were significantly suppressed by the inhibitors of nuclear factor erythroid 2-related factor 2 and p38. We next examined the effects of A2 and A4 on PCs expressing several types of SCA-causing proteins (SCA model PCs). Both chemicals ameliorated the dendritic shrinkage and restored the decreased CMA/mA activity in several SCA model PCs. These findings suggest that the ar-turmerone analogs A2 and A4 improve the in vitro phenotype of SCA model PCs through CMA activation, highlighting the therapeutic potential of these analogs for various types of SCAs.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 5","pages":"852-862"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tramadol Eye Drop Reduces Ocular Nocifensive Behavior Not Primarily Mediated by μ-Opioid Receptor Activation in a Rat Dry Eye Model.","authors":"Shogo Nagaoka, Yoshihiro Takai, Takeshi Kiyoi, Takayoshi Masuoka","doi":"10.1248/bpb.b26-00041","DOIUrl":"10.1248/bpb.b26-00041","url":null,"abstract":"<p><p>This study aimed to explore the possibility of using a novel eye drop for ocular pain in dry eyes by examining the effect of tramadol eye drops on nocifensive behavior in normal and dry eye rats. Dry eye model rats were generated by the unilateral surgical excision of the extraorbital lacrimal glands. The effect of tramadol eye drops on ocular pain in normal and dry eye model rats was assessed using the eye closure time induced by a hyperosmolar (5 M NaCl) solution and the transient receptor potential vanilloid 1 (TRPV1) agonist (1 mM capsaicin). The current response induced by 1 μM capsaicin in the primary sensory neurons was measured by whole-cell recording using cultured trigeminal ganglion neurons. Extraorbital lacrimal gland excision (LGE) significantly enhanced the ocular nocifensive response induced by a 5 M NaCl solution. Pretreatment with tramadol eye drops transiently suppressed nocifensive behavior on the ocular surface in sham-operated and dry eye rats. The suppressive effect of tramadol was only effective on the ipsilateral eye and was not canceled by a μ-opioid receptor antagonist. Furthermore, the capsaicin-induced nocifensive behavior and current responses in primary sensory neurons were suppressed by tramadol treatment. Tramadol eye drops have been shown to temporarily relieve ocular pain in normal and hyperalgesic conditions, such as dry eye. The underlying mechanism may be a decrease in TRPV1-mediated responses at the peripheral sensory nerves on the ocular surface, not primarily mediated by μ-opioid receptor activation.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 5","pages":"794-801"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxaliplatin-Induced Liver Toxicity: Hepatic Transglutaminase 7 Upregulation Associates with Oxidative Stress, Inflammation, and Apoptosis.","authors":"Husah M Alowss, Ibtesam S Almami, Heba F Gomaa","doi":"10.1248/bpb.b25-00689","DOIUrl":"10.1248/bpb.b25-00689","url":null,"abstract":"<p><p>Transglutaminases (TGs) are calcium-dependent enzymes that cross-link proteins, contributing to apoptosis, extracellular matrix (ECM) stabilization, and inflammation. While TG2 has been extensively studied in hepatic injury, the role of TG7 in oxaliplatin-induced liver responses remains unclear. Oxaliplatin, a third-generation platinum chemotherapeutic, effectively treats solid tumors but can induce hepatic stress through oxidative and pro-inflammatory signaling. Adult rats received intraperitoneal oxaliplatin (10 mg/kg weekly) for 6 weeks. qRT-PCR, immunohistochemistry (IHC), immunofluorescence (IF), and a TG activity assay assessed hepatic TG7 expression, localization, and activity. Oxidative stress indicators (serum malondialdehyde [MDA] and reduced glutathione [GSH]) and pro-inflammatory cytokine transcription (CASP3, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α)) were evaluated. Oxaliplatin exposure markedly increased TG7 mRNA and protein levels, elevated TG enzymatic activity, raised MDA (+49.4%), depleted GSH (-18.6%), and upregulated CASP3, IL-6, and TNF-α. DNA fragmentation and microscopic observations from IHC- and IF-processed sections were consistent with apoptosis-associated DNA degradation and subtle stress-related structural variations. Immunostaining revealed altered TG7 distribution within hepatocytes and sinusoidal regions. In this oxaliplatin-exposed rat liver model, TG7 upregulation and increased TG activity were associated with oxidative stress, inflammatory cytokine induction, and apoptotic signaling. These findings identify TG7 as a stress-associated marker during oxaliplatin exposure and support further studies to clarify its mechanistic role and evaluate its potential as utility as a biomarker under chemotherapy-associated hepatic stress conditions.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"316-326"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of Readthrough Efficiency of Negamycin Derivatives against Nonsense Mutations in Muscular Dystrophy Genes.","authors":"Noriko Omura, Akihiro Taguchi, Keisuke Hamada, Sho Konno, Atsuhiko Taniguchi, Yoshio Hayashi","doi":"10.1248/bpb.b25-00728","DOIUrl":"10.1248/bpb.b25-00728","url":null,"abstract":"<p><p>Recently, \"readthrough compounds\" have attracted attention as a promising approach to treat human hereditary diseases caused by nonsense mutations. These compounds enable ribosomes to bypass a premature termination codon (PTC) introduced into mRNA by a nonsense mutation, thereby restoring the expression of full-length functional proteins. We performed a structure-activity relationship study focusing on (+)-negamycin, a known readthrough compound, and identified potent derivatives, TCP-304 and TCP-306, featuring a cyclopropane moiety. In this study, we investigated how the nature of PTCs and their surrounding nucleotide sequences influence the readthrough activity of these negamycin derivatives, using nonsense mutation sequences derived from Duchenne muscular dystrophy and congenital muscular dystrophy genes. In cell-based reporter assay systems, TCP-306 exhibited potent readthrough efficiency against several nonsense mutation sequences containing the TGA-A. Moreover, its sequence preference differed from that of the aminoglycoside G418, a representative readthrough compound that preferentially induces readthrough at TGA-C sequences, suggesting that TCP-306 may serve as an alternative therapeutic option for muscular dystrophies associated with TGA-A nonsense mutations. Overall, this study provides valuable insights for the development of readthrough drugs for hereditary diseases such as muscular dystrophy caused by nonsense mutations.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"346-354"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolution of Pharmacy Education and Pharmacist Competency Development in Japan in Response to Changing Healthcare Demands.","authors":"Kayoko Takeda Mamiya","doi":"10.1248/bpb.b26-00181","DOIUrl":"https://doi.org/10.1248/bpb.b26-00181","url":null,"abstract":"<p><p>This article reviews the historical development and current challenges of pharmacy education in Japan, focusing on structural reform and the shift toward competency-based education. The 1992 revision of the Medical Care Act and the 1993 sorivudine incident heightened awareness of medication safety and accelerated expansion of pharmacists' clinical responsibilities, prompting educational reform. In 2006, a six-year pharmacy education program (6-YP) was introduced as the primary pathway to pharmacist licensure, while a four-year program (4-YP) was retained for research-oriented training. The Model Core Curriculum (MCC) standardized pharmacy education nationwide. The 2013 revision defined ten graduation-level competencies, reflecting an outcome-based framework. The 2022 MCC further reconceptualized competencies as capabilities that develop longitudinally across the professional lifespan and strengthened alignment with medical and dental education, public health perspectives, research literacy, and digital competencies. Pharmacist licensure in Japan is granted for life, and continuing education is not legally mandated. Although multiple voluntary certification systems promote advanced practice, variability among programs has raised concerns regarding transparency and standardization. Establishing a nationally coordinated continuing professional development framework and promoting lifelong competency development remain key priorities in response to technological innovation and evolving healthcare needs.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 8","pages":"1226-1231"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment of Irinotecan-Induced Oral Mucositis Hamster Model and Evaluation of Therapeutic Agents.","authors":"Shinichi Watanabe, Natsumi Mori, Sakura Toyooka, Kaede Utsunomiya, Yukiro Kurokawa, Yasuhiro Nakagami, Takumi Yamaguchi","doi":"10.1248/bpb.b26-00018","DOIUrl":"10.1248/bpb.b26-00018","url":null,"abstract":"<p><p>Chemotherapy-induced oral mucositis is a frequent and debilitating adverse effect that impairs nutritional status and interrupts cancer therapy. Although 5-fluorouracil-induced animal models of oral mucositis are well established, irinotecan, widely used for colorectal, lung, and pancreatic cancers, has also been associated with oral mucosal injury; however, no standardized preclinical model exists. This study aimed to establish a reproducible hamster model of irinotecan-induced oral mucositis and evaluate the prophylactic and therapeutic efficacy of topical hangeshashinto (HST) compared with dexamethasone. Male Syrian hamsters received intraperitoneal irinotecan (100, 150, or 200 mg/kg) on Day 0, followed by localized mucosal injury induced by 50% acetic acid. Ulcer area, body weight, histopathology, peripheral blood count, and myeloperoxidase (MPO) activity were evaluated. HST (10% aqueous solution) or dexamethasone (0.01% elixir) was administered topically once daily either prophylactically (Days -3 to 0) or therapeutically (from Day 0 onward). Ulcer area increased in a dose-dependent manner, peaking on Day 4. The 200 mg/kg dose yielded consistent lesion formation with transient weight loss. Histopathological examination revealed dense neutrophilic infiltration and epithelial disruption. MPO activity was significantly elevated on Days 4 and 7. Prophylactic HST significantly reduced the peak and cumulative ulcer areas, whereas dexamethasone delayed healing. The 200 mg/kg irinotecan plus acetic acid hamster model thus provides a reliable platform for investigating oral mucositis. HST, particularly when administered prophylactically, exhibited better efficacy than dexamethasone, potentially through modulation of inflammatory responses and attenuation of oxidative stress. This model may facilitate further mechanistic studies and the development of preventive strategies for chemotherapy-induced oral mucositis.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 3","pages":"572-577"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigation of the Effects of Calcium Alginate on Blood Sodium Concentration and the Suppression of Blood Pressure Elevation in Rats.","authors":"Yusuke Namiki, Kenji Ida, Yoko Homma, Namino Tomimori, Ken Sato, Chihaya Kakinuma, Hidehisa Tachiki, Takuo Ogihara","doi":"10.1248/bpb.b25-00592","DOIUrl":"10.1248/bpb.b25-00592","url":null,"abstract":"<p><p>The effects of calcium alginate (Ca-Alg) on the suppression of blood sodium (Na<sup>+</sup>) concentration and blood pressure elevation in rats were investigated. In a single-dose administration test, oral administration of a 0.3% sodium chloride (NaCl) solution (5 mg/kg) resulted in a significant increase in the difference in the area under the blood Na<sup>+</sup> concentration-time curve (ΔAUC). When the finest Ca-Alg particles (8 mg/body, 270 mesh) were simultaneously administered orally under the same conditions, a significant decrease in ΔAUC and a tendency for a decrease in the maximum blood concentration difference (ΔC<sub>max</sub>) were observed. In a repeated administration test, rats were allowed to freely ingest a 3.0% Ca-Alg-containing feed for 5 weeks, and an increase in Na<sup>+</sup> excretion in feces was observed. Furthermore, in spontaneously hypertensive rats (SHR), when the same Ca-Alg-containing feed was freely consumed for 15 weeks, a significant inhibition of blood pressure elevation was observed after 10 weeks. Additionally, blood biochemical tests and renal histopathological examination of these rats confirmed the safety of Ca-Alg. Based on these results, it was concluded that Ca-Alg suppresses Na<sup>+</sup> absorption and blood pressure elevation in rats.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 3","pages":"564-571"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyu Hou, Ziyi Chen, Jie Wang, Huailong Yu, Biyao Liu, Yue Zhang, Huarong Shao, Fei Liu
{"title":"Mechanisms of Skin Aging and the Interventional Effects of Plant Polysaccharides: A Review Based on Signaling Pathways.","authors":"Xinyu Hou, Ziyi Chen, Jie Wang, Huailong Yu, Biyao Liu, Yue Zhang, Huarong Shao, Fei Liu","doi":"10.1248/bpb.b25-00733","DOIUrl":"10.1248/bpb.b25-00733","url":null,"abstract":"<p><p>Skin aging is a complex physiological process driven by both endogenous and exogenous factors, involving various mechanisms such as oxidative stress, inflammatory responses, and cellular senescence. As natural bioactive macromolecules, plant polysaccharides possess properties including antioxidant, anti-inflammatory, and free radical scavenging abilities, and have recently shown significant potential in anti-skin aging research. This article systematically reviews the molecular mechanisms of skin aging, with a focus on elucidating how plant polysaccharides exert anti-aging effects by regulating key signaling pathways. Additionally, it summarizes strategies for the extraction, purification, and structural modification of plant polysaccharides, as well as their structure-activity relationships. The aim is to provide a theoretical foundation and research directions for both fundamental studies and product development of plant polysaccharides in the field of anti-skin aging.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 4","pages":"625-635"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wakaba Idehara, Yuya Haga, Mii Hokaku, Phyo Bo Bo Aung, Yuto Motoyama, Ayaha Mori, Kazuma Higashisaka, Yasuo Tsutsumi
{"title":"Surface-Oxidized Nanoplastics Exhibit Increased Interaction with THP-1 Cells.","authors":"Wakaba Idehara, Yuya Haga, Mii Hokaku, Phyo Bo Bo Aung, Yuto Motoyama, Ayaha Mori, Kazuma Higashisaka, Yasuo Tsutsumi","doi":"10.1248/bpb.b26-00249","DOIUrl":"https://doi.org/10.1248/bpb.b26-00249","url":null,"abstract":"<p><p>The environmental and human health implications of microplastics (MPs) and nanoplastics (NPs) have become a growing concern, particularly as increasing evidence demonstrates their accumulation in human tissues and association with disease. However, most toxicological studies rely on spherical polystyrene particles, which poorly represent environmentally relevant MPs and NPs that exhibit irregular morphologies and undergo surface oxidative degradation. In this study, we developed fragmented polyethylene NPs (PE-NPs) with physicochemical properties that better mimic environmental particles. PE-NPs were synthesized via a precipitation-based method and subsequently subjected to vacuum UV irradiation to induce surface oxidation and generate degraded PE-NPs (dPE-NPs). Structural and chemical characterizations confirmed the irregular morphology and successful introduction of carbonyl functional groups without altering the particle shape. Fluorescent labeling using Nile Red enabled the visualization of PE-NPs and revealed oxidation-dependent shifts in fluorescence properties. Using phorbol 12-myristate 13-acetate-differentiated THP-1 macrophage-like cells, we investigated cellular interaction behavior, including particle uptake and particles localized near the cell membrane. Confocal microscopy demonstrated a significantly enhanced cellular interaction of dPE-NPs, including both uptake and particle-associated signals localized near the cell membrane. Quantitative analysis confirmed that surface oxidation markedly increased the particle-associated area per cell. These findings highlight the critical role of surface oxidative modification in governing NP-cell interactions and uptake kinetics. Our results emphasize that physicochemical properties, particularly environmentally induced surface changes, must be considered for realistic risk assessment of NPs. This study provides an environmentally relevant experimental framework and advances our understanding of how NP aging influences biological behavior and potential health risks.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 7","pages":"1132-1139"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ependymal Cells and Hydrocephalus: Recent Advances in Molecular Mechanisms.","authors":"Shinya Ohata, Maki Takagishi","doi":"10.1248/bpb.b26-00284","DOIUrl":"https://doi.org/10.1248/bpb.b26-00284","url":null,"abstract":"<p><p>Ependymal cells are specialized multiciliated epithelial cells that line the brain ventricles. Their coordinated ciliary beating contributes to cerebrospinal fluid circulation and neural homeostasis. Hydrocephalus, a severe neurological condition affecting ∼1-3 per 1000 births worldwide, can arise from defects in ciliary motility, ependymal cell differentiation, planar cell polarity (PCP), and cytoskeletal organization. Mutations in genes that regulate these processes have been identified in patients with congenital hydrocephalus and related ciliopathies, establishing the clinical relevance of these pathways. This review summarizes the recent advances in the molecular mechanisms underlying ependymal cell biology. We describe the structural and functional organization of the ependymal cilia and discuss how ciliary defects range from severe developmental disruptions causing neonatal hydrocephalus to subtle maintenance defects underlying late-onset forms of the disease. We then examine the hierarchical transcriptional programs controlling ependymal differentiation, from master regulators such as GemC1 and Multicilin to downstream effectors, including FoxJ1 and Regulatory Factor X proteins. The core PCP pathway, comprising Vangl, Celsr, Frizzled, and Dishevelled proteins, coordinates tissue-wide ciliary orientation. Recent cryo-electron microscopy studies have provided structural insights into core components. Finally, we discuss the role of cytoskeletal networks in ependymal maintenance. Actin networks support structural integrity through mechanosensitive feedback loops and transduce mechanical forces into transcriptional activation of multiciliogenesis. In parallel, microtubule-based systems coordinate the planar polarized ciliary orientation via the Daple-dynein axis. Taken together, these molecular insights advance our understanding of the pathogenesis of hydrocephalus and may inform future diagnostic and therapeutic strategies.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1382-1394"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}