1.Clinical Application Advances of Antipsychotic Drugs in Female Schizophrenic Patients
Haoran XING ; Xi ZHANG ; Wenjing DING ; Yingying ZHANG ; Tianhao BAO
Herald of Medicine 2023;42(12):1808-1812
Female patients with schizophrenia exhibit a slower rate of absorption and excretion,leading to higher blood levels of antipsychotic drugs in their bodies and consequently causing more drug side effects.Women also have different levels of estrogen at different stages of life,and estrogen improves the efficacy of antipsychotic drugs by increasing dopamine D2receptor sensitivity.It is necessary to adjust the dosage of antipsychotic medication based on the level of estrogen,while also monitoring indicators such as blood glucose,triglycerides,cholesterol,and prolactin to minimize medication side effects.Nevertheless,the current literatures do not provide specific treatment plans for schizophrenia tailored to different genders,which is not the optimal treatment strategy for female patients.This review aims to summarize and categorize the differences in prescription,pharmacokinetics,pharmacodynamics,efficacy,and side effects in female patients with schizophrenia,and to provide scientific recommendations for drug treatment strategies in different stages of a woman's life(premenopausal,pregnancy,lactation,postmenopausal).
2.mIgM-mediated splenic marginal zone B cells targeting of folic acid for immunological evasion.
Huan WANG ; Zhuxuan JIANG ; Zhiwei GUO ; Gan LUO ; Tianhao DING ; Changyou ZHAN
Acta Pharmaceutica Sinica B 2024;14(2):808-820
Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.
3.Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement.
Liyuan CHEN ; Huajie YU ; Zixin LI ; Yu WANG ; Shanshan JIN ; Min YU ; Lisha ZHU ; Chengye DING ; Xiaolan WU ; Tianhao WU ; Chunlei XUN ; Yanheng ZHOU ; Danqing HE ; Yan LIU
International Journal of Oral Science 2024;16(1):3-3
Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals
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Humans
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Mice
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Rats
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Bone Remodeling/physiology*
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Caspase 1
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Periodontal Ligament
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Pyroptosis
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Tooth Movement Techniques