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Zhuangyao Jianshen pill(壮腰健肾丸) ameliorates testosterone-induced benign postatic hyperplasia in rats

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Journal of Traditional Chinese Medicine 2024年第4期44卷 694-702页

作者： ZHENG Jingrui CHEN Weijian YE Binbin MO Ziyao DU Qunqun QIN Renan NIE Ke School of Chinese Materia Medica Guangdong Pharmaceutical University Modern Chinese Medicine research institute Guangzhou Baiyunshan Chenliji Pharmaceutical Factory Co.Ltd.

OBJECTIVE: To determine the therapeutic effects of the Zhuangyao Jianshen pill(壮腰健肾丸, ZYJSP) against benign prostatic hyperplasia(BPH) and investigate the underlying mechanism. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into six groups: Control group, BPH model group, finasteride-treated group, ZYJSP low, medium and high dose groups. Except for the control group, 40 rats were castrated and injected with testosterone propionate(TP) for 28 consecutive day to induce BPH. Meanwhile, the corresponding drugs were administered by gavage. The prostate wet weight, prostate index(PI), and the histopathological changes in the prostate were measured as the basis for examining the efficacy of ZYJSP against BPH. Levels of the serum sex hormones, oxidative stress markers, inflammatory markers, renal function markers, growth factors, and Cyclin D1 expression in prostate were measured to characterize the therapeutic mechanism of ZYJSP against BPH. RESULTS: ZYJSP administration significantly reduced prostate wet weight and PI and ameliorated histological changes of the prostate in TP-treated castrated rats. TP markedly increased the levels of creatinine, blood urea nitrogen and growth factors in the serum as well as the expression of the Cyclin D1 in the prostate. Most of these markers were significantly decreased by ZYJSP. ZYJSP significantly restored the dysregulation of testosterone, estradiol, and dihydrotestosterone caused by TP. Furthermore, ZYJSP relieved TP-induced prostate injury and exhibited both anti-inflammatory and anti-oxidant activity by decreasing interleukin-6, interleukin-8, and malondialdehyde levels and increasing the activity of superoxide dismutase in the serum. CONCLUSION: These findings indicate that ZYJSP can effectively ameliorate BPH induced by TP in castrated rats, and the underlying mechanism might be related to regulating sex hormone balance, reducing oxidative stress, and inhibiting the inflammatory response.

关键词： Zhuangyao Jianshen pill prostatic hyperplasia rat testosterone propionate

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Untoward immune effects of modern medication

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The Journal of Biomedical research 2024年第1期38卷 17-23页

作者： Daohong Chen research institute Changshan Biochemical PharmaceuticalShijiazhuangHebei 050800China.

Immune-related adverse events(irAEs)represent an increasingly concerning challenge in the assessment of biopharmaceutical *** contrast to historically rare allergic reactions associated with small chemical drugs,contemporary biotherapeutics exhibit a significantly higher morbidity of irAEs,because of their complex structure and comprehensive mechanisms of *** the immunogenicity of protein-based compounds is associated with the induction of anti-drug antibodies,the pathogenesis of irAEs in advanced biologics,such as cell and gene therapy,remains to be further *** the current study,I present an updated profile regarding the untoward immune effects of medications,covering various material categories systematically,with the underlying mechanisms to inspire risk mitigation in biopharmaceutical development and application.

关键词： immunotoxicology immune-related adverse events anti-drug antibody

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Complications and comorbidities associated with antineoplastic chemotherapy:Rethinking drug design and delivery for anticancer therapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2901-2926页

作者： Xiaoman Mao Shuang Wu Dandan Huang Chong Li College of pharmaceutical Sciences Southwest UniversityChongqing 400715China Medical research institute Southwest UniversityChongqing 400715China School of pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China

Despite the considerable advancements in chemotherapy as a cornerstone modality in cancer treatment,the prevalence of complications and pre-existing diseases is on the rise among cancer patients along with prolonged survival and aging *** relationships between these disorders and cancer are intricate,bearing significant influence on the survival and quality of life of individuals with cancer and presenting challenges for the prognosis and outcomes of ***,we review the prevailing complications and comorbidities that often accompany chemotherapy and summarize the lessons to learn from inadequate research and management of this scenario,with an emphasis on possible strategies for reducing potential complications and alleviating comorbidities,as well as an overview of current preclinical cancer models and practical advice for establishing bio-faithful preclinical models in such complex context.

关键词： Complications Comorbidities Chemotherapy Preclinical cancer models Drug design Drug delivery

Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1742-1758页

作者： Renming Fan Ruizhuo Lin Shuo Zhang Aohua Deng Yongrui Hai Junyan Zhuang Yang Liu Maosheng Cheng Gaofei Wei institute of Medical research Northwestern Polytechnical UniversityXi'an 710072China research&Development institute of Northwestern Polytechnical University in Shenzhen Shenzhen 518057China Key Laboratory of Structure-Based Drug Design and Discovery Ministry of EducationSchool of Pharmaceutical EngineeringShenyang Pharmaceutical UniversityShenyang 110016China

Mitochondrial membrane remodeling can trigger the release of mitochondrial DNA (mtDNA), leading to the activation of cellular oxidative stress and immune responses. While the role of mitochondrial membrane remodeling in promoting inflammation in hepatocytes is well-established, its effects on tumors have remained unclear. In this study, we designed a novel Pt(IV) complex, OAP2, which is composed of oxaliplatin (Oxa) and acetaminophen (APAP), to enhance its anti-tumor effects and amplify the immune response. Our findings demonstrate that OAP2 induces nuclear DNA damage, resulting in the production of nuclear DNA. Additionally, OAP2 downregulates the expression of mitochondrial Sam50, to promote mitochondrial membrane remodeling and trigger mtDNA secretion, leading to double-stranded DNA accumulation and ultimately synergistically activating the intracellular cGAS-STING pathway. The mitochondrial membrane remodeling induced by OAP2 overcomes the limitations of Oxa in activating the STING pathway and simultaneously promotes gasdermin-D-mediated cell pyroptosis. OAP2 also promotes dendritic cell maturation and enhances the quantity and efficacy of cytotoxic T cells, thereby inhibiting cancer cell proliferation and metastasis. Briefly, our study introduces the first novel small-molecule inhibitor that regulates mitochondrial membrane remodeling for active immunotherapy in anti-tumor research, which may provide a creative idea for targeting organelle in anti-tumor therapy.

关键词： Anti-tumor drug Prodrug Platinum Chemo-immunotherapy Mitochondrial membrane modeling STING Pyroptosis mtDNA

Cellular interplay to 3D in vitro microphysiological disease model:cell patterning microbiota-gut-brain axis

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Bio-Design and Manufacturing 2024年第3期7卷 320-357页

作者： Kamare Alam Lakshmi Nair Souvik Mukherjee Kulwinder Kaur Manjari Singh Santanu Kaity Velayutham Ravichandiran Sugato Banerjee Subhadeep Roy Department of Pharmacology and Toxicology National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of pharmaceutical Sciences Assam UniversitySilchar 788011India Department of pharmaceutical Sciences Guru Ghasidas UniversityKoniBilaspur 495009C.G.India School of Pharmacy and Biomolecular Sciences RCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Tissue Engineering research Group Department of Anatomy and Regenerative MedicineRCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Department of Pharmaceutics National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of Natural Products National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India

The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the *** between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological *** most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune ***,each pathway is intertwined with a complex *** the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative *** paper briefly retraces the possible communication pathways between the gut microbiome and the *** further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the *** diseases also decrease patients’quality of ***,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the *** of MGBA in the laboratory uses many molecular technologies and biomaterial *** and organoids provide a more realistic picture of the cell and tissue structure than *** them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between ***-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

关键词： Microbiota-gut-brain axis Neurodegeneration 3D disease model Organoid Transwell system

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New phenylbutenoids and terpene glycosides from Ginkgo biloba leaves

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Chinese Journal of Natural Medicines 2024年第2期22卷 161-170页

作者： SUN Zeshi LIN Shan WU Zhi-Li DONG Hong-Yuan XU Xi-Ke LI Hui-Liang WANG Jinxin School of Pharmacy Second Military Medical UniversityShanghai 200433China State Key Laboratory of New Drug and pharmaceutical Process Shanghai Institute of Pharmaceutical IndustryChina State Institute of Pharmaceutical IndustryShanghai 201203China

Our continued works on the chemical constituents of Ginkgo biloba(***)leaves has led to the isolation of two novel phenylbutenoids(1,2),along with five previously unidentified terpene glycosides(3−7).Among them,compounds 1 and 2 represent unique(Z)-phenylbutenoids,3−6 are megastigmane glycosides,and 7 is identified as a rare bilobanone glycoside(Fig.1).This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from *** chemical structures of these compounds were elucidated through extensive spectroscopic analysis,including HR-ESI-MS and various 1D and 2D NMR ***,the absolute configurations of these molecules were determined using Mosher’s method,ECD experiments,and Cu-KαX-ray crystallographic analyses.

关键词： Ginkgo biloba Phenylbutenoid Megastigmane glycoside Bilobanone glycoside

Real-time model correction using Kalman filter for Raman-controlled cell culture processes

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Chinese Journal of Chemical Engineering 2024年第6期70卷 251-260页

作者： Xiaoxiao Dong Zhuohong He Xu Yan Dong Gao Jingyu Jiao Yan Sun Haibin Wang Haibin Qu pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Hisun Biopharmaceutical Co.Ltd. Hangzhou 311404China

Raman spectroscopy has found extensive use in monitoring and controlling cell culture *** this context,the prediction accuracy of Raman-based models is of paramount ***,models established with data from manually fed-batch cultures often exhibit poor performance in Raman-controlled ***,there is a need for effective methods to rectify these *** objective of this paper is to investigate the efficacy of Kalman filter(KF)algorithm in correcting Raman-based models during cell ***,partial least squares(PLS)models for different components were constructed using data from manually fed-batch cultures,and the predictive performance of these models was ***,various correction methods including the PLS-KF-KF method proposed in this study were employed to refine the PLS ***,a case study involving the auto-control of glucose concentration demonstrated the application of optimal model correction *** results indicated that the original PLS models exhibited differential performance between manually fed-batch cultures and Raman-controlled *** glucose,the root mean square error of prediction(RMSEP)of manually fed-batch culture and Raman-controlled culture was 0.23 and 0.40 g·L^(-1).With the implementation of model correction methods,there was a significant improvement in model performance within Raman-controlled *** RMSEP for glucose from updating-PLS,KF-PLS,and PLS-KF-KF was 0.38,0.36 and 0.17 g·L^(-1),***,the proposed PLS-KF-KF model correction method was found to be more effective and stable,playing a vital role in the automated nutrient feeding of cell cultures.

关键词： Raman spectroscopy Model correction Algorithm Model-predictive control Bioprocess

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Targeting brain tumors with innovative nanocarriers:bridging the gap through the blood-brain barrier

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Oncology research 2024年第5期32卷 877-897页

作者： KARAN WADHWA PAYAL CHAUHAN SHOBHIT KUMAR RAKESH PAHWA RAVINDER VERMA RAJAT GOYAL GOVIND SINGH ARCHANA SHARMA NEHA RAO DEEPAK KAUSHIK Department of pharmaceutical Sciences Maharshi Dayanand UniversityRohtak124001India Department of pharmaceutical Technology Meerut Institute of Engineering and Technology(MIET)NH-58Delhi-Roorkee HighwayMeerut250005India institute of pharmaceutical Sciences Kurukshetra UniversityKurukshetra136119India Department of pharmaceutical Sciences Chaudhary Bansi Lal UniversityBhiwani127021India MM College of Pharmacy Maharishi Markandeshwar(Deemed to be University)Mullana-AmbalaHaryana133207India Delhi pharmaceutical Sciences and research University(DIPSAR) Delhi Pharmaceutical Sciences and Research UniversityNew Delhi110017India

Background:Glioblastoma multiforme(GBM)is recognized as the most lethal and most highly invasive *** high likelihood of treatment failure arises fromthe presence of the blood-brain barrier(BBB)and stemcells around GBM,which avert the entry of chemotherapeutic drugs into the ***:Recently,several researchers have designed novel nanocarrier systems like liposomes,dendrimers,metallic nanoparticles,nanodiamonds,and nanorobot approaches,allowing drugs to infiltrate the BBB more efficiently,opening up innovative avenues to prevail over therapy problems and radiation ***:Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases,for example,PubMed,Science Direct,Google Scholar,and others,using specific keyword combinations,including“glioblastoma,”“brain tumor,”“nanocarriers,”and several ***:This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM *** of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

关键词： Glioblastoma Brain tumor Blood-brain barrier Liposomes Metallic nanoparticles Nanocarriers

Design and optimization of a greener sinomenine hydrochloride preparation process considering variations among different batches of the medicinal herb

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Chinese Journal of Chemical Engineering 2024年第7期71卷 77-90页

作者： Dandan Ren Jiale Xie Tianle Chen Haibin Qu Xingchu Gong pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China National Key Laboratory of Chinese Medicine Modernization Zhejiang UniversityHangzhou 310058China Jinhua institute of Zhejiang University Jinhua 321016China

The current methods used to industrially produce sinomenine hydrochloride involve several issues,including high solvent toxicity,long process flow,and low atomic utilization efficiency,and the greenness scores of the processes are below 65 *** solve these problems,a new process using anisole as the extractant was *** exhibits high selectivity for sinomenine and can be connected to the subsequent water-washing *** alkalization of the medicinal material,heating extraction,water washing,and acidification crystallization were carried *** process was modeled and *** design space was *** recommended operating ranges for the critical process parameters were 3.0–4.0 h for alkalization time,60.0–80.0℃ for extraction temperature,2.0–3.0(volume ratio)for washing solution amount,and 2.0–2.4 mol·L^(-1) for hydrochloric acid *** new process shows good robustness because different batches of medicinal materials did not greatly impact crystal purity or sinomenine transfer *** sinomenine transfer rate was about 20%higher than that of industrial *** greenness score increased to 90 points since the novel process proposed in this research solves the problems of long process flow,high solvent toxicity,and poor atomic economy,better aligning with the concept of green chemistry.

关键词： Sinomenine hydrochloride Process optimization Anisole