Biological & pharmaceutical bulletin最新文献

{"title":"Molecular Mechanisms of Natural Saponins in Treating Acute Lung Injury: Systemic Regulatory Roles Involving Multiple Cell Types and Signaling Pathways.","authors":"Zicheng Mei, Yuji Pan, Changshun Chen, Huijun Guo, Chao Zhong, Yanyun Fang, Yanfei Xie, Jun Yu, Wenli Lyu","doi":"10.1248/bpb.b26-00161","DOIUrl":"https://doi.org/10.1248/bpb.b26-00161","url":null,"abstract":"<p><p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions characterized by severe pulmonary dysfunction, with persistently high global incidence and mortality. Although glucocorticoids, the standard pharmacotherapy for ALI/ARDS, have been reported to reduce short-term mortality and improve outcomes, their clinical benefit is limited by dose- and duration-dependent adverse effects, thereby driving the exploration of complementary or alternative approaches. Natural saponins, a structurally diverse group of glycosides widely distributed in medicinal plants, have gained considerable interest owing to their multitarget anti-inflammatory, antioxidant, and antiapoptotic activities demonstrated in various in vitro and in vivo ALI models. Here, we systematically review the protective mechanisms of natural saponins from the perspectives of cellular regulation and signaling pathways, highlighting their modulatory effects on macrophages, neutrophils, and other effector cells, as well as their actions through key pathways related to inflammation, oxidative stress, and apoptosis. We further discuss current strategies to overcome the major translational barriers of saponins, particularly structural modifications and formulation approaches aimed at improving oral bioavailability and reducing hemolytic activity. This review consolidates the pharmacological basis for saponin-based ALI therapy and provides a forward-looking perspective on addressing their limitations to facilitate clinical translation.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1352-1369"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878912","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":"Nuclear Bodies and RNA Regulation in Psychiatric Disorders: Current Perspectives and Therapeutic Alternatives.","authors":"Hidefumi Fukumitsu, Hitomi Soumiya","doi":"10.1248/bpb.b26-00308","DOIUrl":"https://doi.org/10.1248/bpb.b26-00308","url":null,"abstract":"<p><p>Nuclear bodies are membrane-less compartments formed via liquid-liquid phase separation (LLPS) and serve as \"dynamic information-processing hubs\" for key molecular processes, including transcription and RNA metabolism. In the nervous system, these functional condensates provide a physical substrate for the formation of diverse splicing isoforms, which are essential for maintaining the complexity of the human brain. Recent findings suggest that the collapse of this \"nuclear infrastructure\" is the underlying cause of several psychiatric disorders. This collapse is due to an aberrant phase transition, where the nuclear environment shifts from a reversible, dynamic state to an irreversible, rigid state-a disruption of the homeostatic mechanism known as \"Interstasis.\" This review discusses how this physical transition leads to systemic splicing failure and explores next-generation therapeutic strategies, such as antisense oligonucleotides (ASOs) and small-molecule modifiers, to restore nuclear integrity. This review is structured as follows to systematically explore the nexus between subnuclear architecture and neuropsychiatric pathogenesis. Section 1 establishes the biophysical foundations of nuclear bodies, highlighting LLPS and homeostatic mechanisms like interstasis. Section 2 addresses the advanced diversity and spatiotemporal regulation of alternative splicing in the nervous system, with a particular focus on the neuron-specific long non-coding RNA Gomafu. Section 3 comprehensively dissects the molecular mechanisms of nuclear infrastructure collapse-encompassing aberrant phase transitions, microexon/novel exon dysregulation, and 3D genome and transport deficits-in neurodevelopmental disorders and schizophrenia. Finally, Section 4 outlines next-generation drug discovery strategies, focusing on therapeutic modalities such as ASOs and small molecules capable of modulating network-level analog states.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1395-1403"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879059","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":"Vitamin D3 Attenuates Delirium-Like Cognitive Impairment in a Postoperative Mouse Model.","authors":"Kyoka Nakatomi, Koki Okawa, Yuki Shigetsura, Natsuki Imayoshi, Yukiko Miyoshi, Hirotsugu Kawashima, Hiromichi Inaba, Shimpei Yamasaki, Keisuke Umemura, Keiko Ikuta, Yurie Katsube, Daiki Hira, Shunsaku Nakagawa, Masahiro Tsuda, Tomohiro Terada","doi":"10.1248/bpb.b26-00245","DOIUrl":"https://doi.org/10.1248/bpb.b26-00245","url":null,"abstract":"<p><p>Delirium is an acute neurocognitive impairment triggered by physiological stressors such as medical illness, surgery, or medication use. Although often transient, it is associated with adverse clinical outcomes. Current management primarily relies on nonpharmacological or symptomatic approaches; however, their effectiveness remains limited. Therefore, strategies that target the underlying pathophysiological mechanisms of delirium are of considerable clinical interest. Neuroinflammation has been proposed as a key mechanism in the development of delirium, with inflammatory cytokines produced during systemic inflammation impairing neuronal function. Vitamin D3 (VD3) exerts neuroprotective effects by suppressing the production of inflammatory cytokines. In this study, we hypothesized that VD3 reduces the risk of delirium. To test this hypothesis, a mouse model of postoperative delirium was established using anesthesia and surgery (AS). Cognitive function was assessed using behavioral tests, including the novel object recognition test. Mice subjected to AS exhibited impaired cognitive function, whereas VD3 administration attenuated this impairment. Serum interleukin-6 levels were elevated in the AS group but were reduced following VD3 treatment, consistent with the behavioral findings. These findings suggest that VD3 attenuates cognitive impairment in this postoperative delirium-like mouse model and is associated with reduced serum IL-6 levels. Further studies are required to clarify the underlying mechanisms and the relationship between peripheral and central inflammatory responses.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1444-1451"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900365","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":"Association of Pretreatment Hepatic Function Markers with Clazosentan-Associated Fluid Retention in Patients with Subarachnoid Hemorrhage.","authors":"Kinuka Oguni, Rintaro Sogawa, Yuki Nakano, Shuko Tobita, Atsushi Ogata, Tatsuya Abe, Chisato Shimanoe","doi":"10.1248/bpb.b26-00344","DOIUrl":"https://doi.org/10.1248/bpb.b26-00344","url":null,"abstract":"<p><p>Clazosentan is used to prevent cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH), but it is often associated with fluid retention-related adverse events. This retrospective study investigated the relationship between the pretreatment Albumin-Bilirubin (ALBI) score and clazosentan-associated fluid retention in patients with SAH. Patients who newly initiated clazosentan treatment at Saga University Hospital between April 2022 and March 2026 were enrolled. Clinical characteristics and laboratory data were retrospectively obtained from electronic medical records. Patients were divided into fluid retention and non-fluid retention groups, and factors associated with fluid retention were analyzed. A total of 61 patients were included, with clazosentan-associated fluid retention observed in 32 patients (52.5%). The ALBI score was significantly higher (i.e., less negative) in the fluid retention group than in the non-fluid retention group (median: -2.62 vs. -2.94, p = 0.007). Multivariate logistic regression analysis revealed that an elevated ALBI score was independently associated with fluid retention (odds ratio per 0.1-point increase: 1.17; 95% confidence interval: 1.01-1.37; p = 0.03). Additionally, patients requiring loop diuretics for fluid management had significantly higher ALBI scores than those not requiring them (median: -2.61 vs. -2.91; p = 0.006). These findings suggest that an elevated pretreatment ALBI score may be linked to an increased risk of clazosentan-associated fluid retention. Further validation in patients with varying degrees of hepatic function is warranted to establish its clinical utility.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 8","pages":"1329-1333"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860476","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":"Cardioprotective Role of Neuregulin1-ErbB2 Signaling Pathway: Its Physiological and Onco-Cardiological Roles in the Heart.","authors":"Yoshinori Mikami, Satomi Adachi-Akahane","doi":"10.1248/bpb.b25-00481","DOIUrl":"https://doi.org/10.1248/bpb.b25-00481","url":null,"abstract":"<p><p>Neuregulin 1 (NRG1), a member of the epidermal growth factor (EGF) family, regulates the development, differentiation, proliferation, and plasticity in multiple tissues through its binding to ErbB3 and ErbB4 receptors. In the cardiovascular system, NRG1 plays a crucial role in cardiac development, physiological function, and cell survival. Since NRG1 exerts cardioprotective effects through its interaction with ErbB2/ErbB4 and ErbB4 homodimers on cardiomyocytes, the administration of recombinant human NRG1 has the potential for the treatment of heart failure. ErbB2 is known as human epidermal growth factor receptor 2 (HER2), which is overexpressed in approximately 20% of breast cancers. Trastuzumab (TRZ), a humanized monoclonal antibody targeting ErbB2/HER2, is used for the therapy of HER2-positive breast cancer. However, cardiotoxicity has been observed in approximately 5-10% of patients treated with TRZ. Risk factors for the onset of cardiotoxicity include the use of anthracyclines, hypertension, and diabetes. However, the mechanism linking diabetes and TRZ-induced cardiotoxicity remains unclear. Recently, we reported that the serum levels of NRG1 were elevated in the mouse model of diabetic cardiomyopathy. We found that the up-regulated NRG1 compensates for insulin deficiency to maintain systolic function in the early stage of diabetic cardiomyopathy. This review aims to discuss the physiological roles of NRG1-ErbB2 signaling in the cardiovascular system, the cardioprotective effects of NRG1 and its clinical applications, and the molecular mechanisms of TRZ-induced cardiotoxicity through the blockade of the NRG1-ErbB2 signaling pathway.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"24-29"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899243","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":"Hydrophobic Compounds in the Paeonia suffruticosa Root Cortex Reduce Lipid Accumulation in Adipocytes and the Livers of Obese ob/ob Mice.","authors":"Tatsuki Sato, Airi Fujii, Satsuki Kato, Mufidah Afiyanti, Saki Shirako, Yuto Nishidono, Tetsuya Okuyama, Richi Nakatake, Yukinobu Ikeya, Mikio Nishizawa","doi":"10.1248/bpb.b25-00806","DOIUrl":"https://doi.org/10.1248/bpb.b25-00806","url":null,"abstract":"<p><p>Insulin plays a critical role in the regulation of lipid and carbohydrate metabolism in the liver, muscle, and adipose tissue via its receptor. The root cortex of Paeonia suffruticosa (Paeoniaceae) has been used as a crude drug, Botanpi, in several formulae of traditional Japanese (Kampo) medicines, such as Hachimijiogan, to treat type 2 diabetes mellitus (DM). We previously isolated constituents from the P. suffruticosa root cortex and found that 1,2,3,4,6-pentagalloyl-β-d-glucose (β-PGG), methyl gallate, and paeonol, but not paeoniflorin, suppressed the production of the proinflammatory mediator nitric oxide in interleukin (IL)-1β-treated hepatocytes. Here, we selected three crude drugs that are often used for patients with obesity and DM (i.e., P. suffruticosa root cortex, P. lactiflora roots, and Alisma orientale roots). Among their extracts, P. suffruticosa root cortex extract and its ethyl acetate (EtOAc)-soluble fraction significantly decreased the triglyceride content in insulin-treated rat adipocytes. Additionally, β-PGG, a constituent of this fraction, efficiently reduced the triglyceride content. When the EtOAc-soluble fraction of the P. suffruticosa root cortex was administered to leptin-deficient (ob/ob) mice, a DM model, it markedly improved hepatic lipid accumulation compared with that in the non-treated mice. Furthermore, the blood glucose level and body weight of ob/ob mice administered the EtOAc-soluble fraction were significantly decreased. In hepatocytes, β-PGG reduced mRNA levels encoding glucose transporter 2, AMP-activated protein kinase, and forkhead box O1 transcription factor in the absence of IL-1β. Overall, hydrophobic constituents, including β-PGG and paeonol, may be involved in the antidiabetic effects of P. suffruticosa root cortex on ob/ob mice.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1471-1481"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918521","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":"Errata for Biological and Pharmaceutical Bulletin.","authors":"","doi":"10.1248/bpb.b26-e4909","DOIUrl":"https://doi.org/10.1248/bpb.b26-e4909","url":null,"abstract":"","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1578"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103671","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":"Sex Differences in Sentiment-Scored Vocabulary Patterns in VAERS Free-Text Narratives of Four Major Vaccine Categories.","authors":"Kae Matsumura, Megumi Horibe, Yoko Ino, Kana Sugishita, Tomofumi Yamazaki, Moe Maeno, Koichi Kageyama, Seiichiro Ito, Mugita Sato, Mahiro Chikahisa, Mayumi Kitamura, Mari Iwata, Kazuhiro Iguchi, Mitsuhiro Nakamura","doi":"10.1248/bpb.b26-00304","DOIUrl":"https://doi.org/10.1248/bpb.b26-00304","url":null,"abstract":"<p><p>Free-text narratives in vaccine adverse event reports contain symptom descriptions and contextual wording that can be characterized using text mining. However, lexicon-based sentiment scores in medical narratives should be interpreted as vocabulary patterns rather than direct measures of patients' emotional states. We evaluated sex-specific and vaccine-specific patterns in sentiment-scored and emotion-category assignment vocabulary in Vaccine Adverse Event Reporting System (VAERS) narratives for coronavirus disease 2019 (COVID-19), influenza, human papillomavirus (HPV), and measles-mumps-rubella (MMR) vaccines. Public VAERS reports received from 2010 to 2024 were analyzed. VAERSDATA, VAERSVAX, and VAERSSYMPTOMS were linked by VAERS_ID, with duplicate records removed. Report-level AFINN scores were normalized per 100 words. Sensitivity analyses excluded common clinical and symptom-related terms. Effect sizes, 95% confidence intervals, adjusted linear regression models with HC3 robust standard errors, and NRC emotion-category assignment profiles were evaluated. After duplicate handling, 1022460 COVID-19, 148489 influenza, 41212 HPV, and 47459 MMR reports were analyzed. Female-associated reports generally showed slightly lower primary AFINN scores than male-associated reports, although effect sizes were negligible. Excluding clinical and symptom-related terms attenuated or reversed these differences. Adjusted regression models showed only small associations between sex and AFINN scores. NRC analyses demonstrated clearer vaccine-specific than sex-specific vocabulary patterns. VAERS narratives showed only small sex-related differences but distinct vaccine-specific patterns in sentiment-scored and emotion-category assignment vocabulary. These findings should be interpreted as lexicon-derived vocabulary patterns rather than direct measures of psychological responses, vaccine perceptions, or clinical outcomes.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1561-1569"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069198","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":"Albumin Quality in Oxidative and Ischemic Stress: Implications for Drug Binding and Clinical Pharmacokinetics.","authors":"Shota Ichimizu, Kosuke Doki, Masato Homma","doi":"10.1248/bpb.b26-00232","DOIUrl":"https://doi.org/10.1248/bpb.b26-00232","url":null,"abstract":"<p><p>Human serum albumin (HSA), the most abundant plasma protein, plays a critical role in transporting endogenous and exogenous ligands and drugs. Oxidative stress and ischemia induce structural modifications in HSA, including S-cysteinylation, sulfenylation, sulfinylation, and sulfonylation. These changes affect the Sudlow's sites and fatty acid-binding pockets, leading to altered drug affinity and pharmacokinetics. In patients with systemic inflammation or metabolic dysfunction, including sepsis, diabetes, liver disease, and cardiovascular disease, a substantial proportion-often exceeding 50%-of circulating albumin may be structurally modified. Ischemic injury produces ischemia-modified albumin via N-terminal damage, offering a rapid and reversible biomarker for hypoxia. Experimental and clinical evidence suggests that oxidative modification of HSA can either diminish or enhance drug binding, as observed with aripiprazole and methotrexate, respectively, resulting in significant interindividual variability in pharmacodynamic responses. Reduced drug-binding capacity in patients with cirrhosis and sepsis underscores the importance of evaluating albumin quality, in addition to its quantity, when optimizing drug dosing. Future work should clarify how modified HSA affects clearance pathways and whether exogenous albumin is similarly oxidized in vivo. Understanding these qualitative alterations may improve pharmacotherapy in critically ill and chronically inflamed patients.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 10","pages":"1579-1586"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103649","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":"An Improved Brain-Penetrating Nanoformulation of the VIPR2 Antagonist Peptide KS-133 for Treating Cognitive Impairment in Schizophrenia.","authors":"Kotaro Sakamoto, Zihao Jin, Daichi Koan, Runa Fujimoto, Rei Yokoyama, Satoshi Asano, Rika Ishimura, Kazuto Nunomura, Bangzhong Lin, Daisuke Sugiyama, Hideki Shiba, Naoki Nishizawa, Shinsaku Nakagawa, Yukio Ago","doi":"10.1248/bpb.b26-00222","DOIUrl":"https://doi.org/10.1248/bpb.b26-00222","url":null,"abstract":"<p><p>In 2024, we reported a brain-penetrant formulation of the vasoactive intestinal peptide receptor 2 (VIPR2) antagonist peptide KS-133 that mitigated cognitive dysfunction in the VIPR2 hyperactivation mouse model of schizophrenia. In this formulation, KS-133 was encapsulated in the hydrophobic core of nanoparticles (NPs) coated with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-KS-487 (DPPE-KS-487), a conjugate of the cyclic peptide KS-487 and DPPE produced by a click reaction that binds low-density lipoprotein-related protein 1, enabling blood-brain barrier penetration upon subcutaneous injection. However, the click reaction generated multiple positional isomers and manufacturing required repetitive cycles of ultrasonication at high and low temperatures, posing challenges for industrial scalability. In the current study, we coated KS-133-containing NPs with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-KS-487 (DSPE-KS-487), a novel conjugate of KS-487 with DSPE produced through a non-click method, thus eliminating positional isomers, and also established a simplified manufacturing process allowing a unidirectional transition from ultrasonication at high to low temperatures. This formulation remained physically and chemically stable for at least 12 months under refrigeration, with no changes in particle size, zeta potential, KS-133 content, or KS-487 presentation level. The formulation also exhibited brain penetration and therapeutic efficacy against VIPR2 agonist-induced novel object recognition impairment in mice comparable to those of DPPE-KS-487 NPs. Furthermore, no systemic side effects of hematologic, brain, heart, liver, and lung toxicity were detected following daily injections to mice for two weeks at five times the effective dose. This new KS-133 formulation incorporating DSPE-KS-487 as a brain-penetrant shuttle is a promising drug candidate for the treatment of cognitive dysfunction in schizophrenia.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 6","pages":"1023-1037"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343875","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}