keyword
https://read.qxmd.com/read/38496966/synthesis-of-triphenylphosphonium-linked-derivative-of-3-5-di-tert-butyl-4-hydroxybenzylidene-malononitrile-sf6847-via-knoevenagel-reaction-yields-an-effective-mitochondria-targeted-protonophoric-uncoupler
#1
JOURNAL ARTICLE
Roman S Kirsanov, Ljudmila S Khailova, Tatyana I Rokitskaya, Konstantin G Lyamzaev, Alisa A Panteleeva, Pavel A Nazarov, Alexander M Firsov, Iliuza R Iaubasarova, Galina A Korshunova, Elena A Kotova, Yuri N Antonenko
Mitochondrial uncouplers are actively sought as potential therapeutics. Here, we report the first successful synthesis of mitochondria-targeted derivatives of the highly potent uncoupler 3,5-di tert -butyl-4-hydroxybenzylidene-malononitrile (SF6847), bearing a cationic alkyl(triphenyl)phosphonium (TPP) group. As a key step of the synthesis, we used condensation of a ketophenol with malononitrile via the Knoevenagel reaction. SF-C5 -TPP with a pentamethylene linker between SF6847 and TPP, stimulating respiration and collapsing membrane potential of rat liver mitochondria at submicromolar concentrations, proved to be the most effective uncoupler of the series...
March 12, 2024: ACS Omega
https://read.qxmd.com/read/38496964/targeted-delivery-of-gemcitabine-for-precision-therapy-of-cholangiocarcinoma-using-hyaluronic-acid-modified-metal-organic-framework-nanoparticles
#2
JOURNAL ARTICLE
Chuan Long, Han Peng, Wei Yang, Min Wang, Bo Luo, Jie Hao, Yan Dong, Wenwei Zuo
Chemotherapy is widely recognized as an important approach for the treatment of cholangiocarcinoma. Gemcitabine (GEM) has been considered a first-line drug for treating cholangiocarcinoma due to its ability to effectively inhibit the proliferation, migration, and invasion of liver cancer cells. However, the systemic toxicity, premature degradation, and lack of tumor-targeting properties of GEM limit its application in cholangiocarcinoma chemotherapy. Additionally, precise targeted delivery of GEM is necessary to align with the current concept of precision medicine...
March 12, 2024: ACS Omega
https://read.qxmd.com/read/38495473/sub-chronic-oral-toxicity-study-of-the-alkaloid-rich-fraction-from-luffa-cylindrica-fruit-in-sprague-dawley-rats
#3
JOURNAL ARTICLE
Ankul Singh S, Chitra Vellapandian
The loofah/sponge gourd Luffa cylindrica (L.), a member of the Cucurbitaceae family, is one of the neglected medicinal plants. Traditionally, Luffa cylindrica is prescribed for inducing labor. It has a long history of use in China for the treatment of fever, diabetes, dyspnea, and dysentery. This study investigated the toxicity profile of the alkaloid-rich fraction of Luffa cylindrica (ARF-LC) for the first time in Sprague Dawley rats. A total of 80 rats (40 male and 40 female rats) aged 13 weeks old and weighing 200-220 g were selected for this study...
June 2024: Toxicology Reports
https://read.qxmd.com/read/38495462/rejection-in-liver-transplantation-recipients
#4
JOURNAL ARTICLE
Haripriya Maddur, Nicole Wilson, Pallavi Patil, Sumeet Asrani
Rejection following liver transplantation continues to impact transplant recipients although rates have decreased over time with advances in immunosuppression management. The diagnosis of rejection remains challenging with liver biopsy remaining the reference standard for diagnosis. Proper classification of rejection type and severity is imperative as this guides management and ultimately graft preservation. Future areas of promise include non-invasive testing for detection of rejection to reduce the morbidity associated with invasive testing and further advances in immunosuppression management to reduce toxicities associated with immunosuppression while minimizing rejection related morbidity...
2024: Journal of Clinical and Experimental Hepatology
https://read.qxmd.com/read/38495266/immunoembolization-for-the-treatment-of-uveal-melanoma-hepatic-metastases
#5
REVIEW
Carin F Gonsalves
Uveal melanoma is the most common primary intraocular tumor in adults. Approximately 50% of patients develop metastatic disease despite successful treatment of the primary eye tumor. The liver is the most common site of metastatic disease occurring in more than 90% of patients. Clinical prognosis is dependent on the ability to control the growth of liver tumors. Locoregional therapies play an important role in stabilizing liver metastases, prolonging survival for patients with metastatic uveal melanoma. As overall survival is prolonged, the development of extrahepatic disease becomes more common...
February 2024: Seminars in Interventional Radiology
https://read.qxmd.com/read/38495259/sbrt-for-liver-tumors-what-the-interventional-radiologist-needs-to-know
#6
REVIEW
Michael J Gutman, Lucas M Serra, Matthew Koshy, Rohan R Katipally
This review summarizes the clinical evidence supporting the utilization of stereotactic body radiotherapy (SBRT) for liver tumors, including hepatocellular carcinoma, liver metastases, and cholangiocarcinoma. Emerging prospective evidence has demonstrated the benefit and low rates of toxicity across a broad range of clinical contexts. We provide an introduction for the interventional radiologist, with a discussion of underlying themes such as tumor dose-response, mitigation of liver toxicity, and the technical considerations relevant to performing liver SBRT...
February 2024: Seminars in Interventional Radiology
https://read.qxmd.com/read/38495096/research-progress-on-arsenic-arsenic-containing-medicinal-materials-and-arsenic-containing-preparations-clinical-application-pharmacological-effects-and-toxicity
#7
REVIEW
Yichu Yang, Yiye Li, Ran Li, Zhang Wang
Introduction: The toxicity of arsenic is widely recognized globally, mainly harming human health by polluting water, soil, and food. However, its formulations can also be used for the clinical treatment of diseases such as leukemia and tumors. Arsenic has been used as a drug in China for over 2,400 years, with examples such as the arsenic-containing drug realgar mentioned in Shennong's Herbal Classic. We have reviewed references on arsenic over the past thirty years and found that research has mainly focused on clinical, pharmacological, and toxicological aspects...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38494922/first-in-human-study-of-jnj-67571244-a-cd33-%C3%A3-cd3-bispecific-antibody-in-relapsed-refractory-acute-myeloid-leukemia-and-myelodysplastic-syndrome
#8
JOURNAL ARTICLE
Rupa Narayan, Ana Alfonso Piérola, William B Donnellan, Antonieta Molero Yordi, Maher Abdul-Hay, Uwe Platzbecker, Marion Subklewe, Tapan Mahendra Kadia, Juan Manuel Alonso-Domínguez, James McCloskey, Kathryn Bradford, Martin Curtis, Nikki Daskalakis, Christina Guttke, Karim Safer, Brett Hiebert, Joseph Murphy, Xiang Li, Ken Duchin, Daniel Esteban
Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ-67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS. This first-in-human, open-label, phase I, dose-escalation/dose-expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options...
March 2024: Clinical and Translational Science
https://read.qxmd.com/read/38494025/exposure-to-the-environmental-pollutant-chlorpyrifos-induces-hepatic-toxicity-through-activation-of-the-jak-stat-and-mapk-pathways
#9
JOURNAL ARTICLE
Huiyang Fu, Yao Ge, Xiyuan Liu, Siwei Deng, Jun Li, Peng Tan, Ying Yang, Zhenlong Wu
Chlorpyrifos (CHP) is an inexpensive highly effective organophosphate insecticide used worldwide. The unguided and excessive use of CHP by farmers has led to its significant accumulation in crops as well as contamination of water sources, causing health problems for humans and animals. Therefore, this study evaluated the toxicological effects of exposure to the environmental pollutant CHP at low, medium, and high (2.5, 5, and 10 mg·kg-1 BW) levels on rat liver by examining antioxidant levels, inflammation, and apoptosis based on the no observed adverse effect levels (NOAEL) (1 mg·kg-1 BW) and the CHP dose that does not cause any visual symptoms (5 mg·kg-1 BW)...
March 15, 2024: Science of the Total Environment
https://read.qxmd.com/read/38493905/in-silico-and-in-vivo-study-of-anti-inflammatory-activity-of-morinda-longissima-rubiaceae-extract-and-phytochemicals-for-treatment-of-inflammation-mediated-diseases
#10
JOURNAL ARTICLE
Hafidha Mehallah, Noureddine Djebli, Pham Ngoc Khanh, Nguyen Xuan Ha, Vu Thi Ha, Tran Thu Huong, Do Dinh Tung, Nguyen Manh Cuong
ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the plant Morinda longissima Y.Z.Ruan (Rubiaceae) is used by ethnic people in Vietnam for the treatment of liver diseases and hepatitis. AIM OF THE STUDY: The study was designed to assess the efficacy of the 95% ethanolic extract of Morinda longissima roots (MLE) in experimental immune inflammation. The phytochemical variation of root extract and the chemical structures of natural compounds were also investigated using HPLC-DAD-HR-MS analysis...
March 15, 2024: Journal of Ethnopharmacology
https://read.qxmd.com/read/38493717/jiagasongtang-improves-chronic-cholestasis-via-enhancing-fxr-mediated-bile-acid-metabolism
#11
JOURNAL ARTICLE
Xiaoliang He, Yingya Zhou, Jingtao Yu, Qinpo Huang, Zhengyuan Chen, Ru Xiao, Changhui Liu, Shuhua Gui, Tianqin Xiong
BACKGROUND: Bile acid (BA) enterohepatic circulation disorders are a main feature of chronic cholestatic diseases. Promoting BA metabolism is thus a potential method of improving enterohepatic circulation disorders, and treat enterohepatic inflammation, oxidative stress and fibrosis due to cholestasis. PURPOSE: To investigate the effect of JiaGaSongTang (JGST) and its blood-absorbed ingredient 6-gingerol on α-naphthylisothiocyanate (ANIT)-induced chronic cholestasis, as well as elucidate the underlying regulatory mechanism...
January 8, 2024: Phytomedicine
https://read.qxmd.com/read/38493406/bmscs-driven-graphite-oxide-grafted-carbon-fibers-reinforced-polyetheretherketone-composites-as-functional-implants-in-vivo-biosafety-and-osteogenesis
#12
JOURNAL ARTICLE
Wen Qin, Tong Xing, Shengnan Qin, Bin Tang, Weiyi Chen
Mesenchymal stem cells (MSCs) are increasingly becoming a potential treatment approach for bone injuries due to the multi-lineage differentiation potential, ability to recognize damaged tissue sites and secrete bioactive factors that can enhance tissue repair. The aim of this work was to improve osteogenesis of carbon fibers reinforced polyetheretherketone (CF/PEEK) implants through bone marrow mesenchymal stem cells (BMSCs)-based therapy. Moreover, bioactive graphene oxide (GO) was introduced into CF/PEEK by grafting GO onto CF to boost the osteogenic efficiency of BMSCs...
March 17, 2024: Journal of Biomaterials Science. Polymer Edition
https://read.qxmd.com/read/38492862/tumor-activated-il-2-mrna-delivered-by-lipid-nanoparticles-for-cancer-immunotherapy
#13
JOURNAL ARTICLE
Yuhao Jiang, Yanhao Zhang, Chao Liu, Jinyu Liu, Wenliang Xue, Zihao Wang, Xinsong Li
Interleukin-2 (IL-2) exhibits the unique capacity to modulate immune functions, potentially exerting antitumor effects by stimulating immune responses, making it highly promising for immunotherapy. However, the clinical use of recombinant IL-2 protein faces significant limitations due to its short half-life and systemic toxicity. To overcome these challenges and fully exploit IL-2's potential in tumor immunotherapy, this study reports the development of a tumor-activated IL-2 mRNA, delivered via lipid nanoparticles (LNPs)...
March 14, 2024: Journal of Controlled Release
https://read.qxmd.com/read/38492781/role-of-carboxylesterase-and-arylacetamide-deacetylase-in-drug-metabolism-physiology-and-pathology
#14
REVIEW
Mai Nagaoka, Yoshiyuki Sakai, Miki Nakajima, Tatsuki Fukami
Carboxylesterases (CES1 and CES2) and arylacetamide deacetylase (AADAC), which are expressed primarily in the liver and/or gastrointestinal tract, hydrolyze drugs containing ester and amide bonds in their chemical structure. These enzymes often catalyze the conversion of prodrugs, including the COVID-19 drugs remdesivir and molnupiravir, to their pharmacologically active forms. Information on the substrate specificity and inhibitory properties of these enzymes, which would be useful for drug development and toxicity avoidance, has accumulated...
March 14, 2024: Biochemical Pharmacology
https://read.qxmd.com/read/38492435/development-of-a-c-met-x-cd137-bispecific-antibody-for-targeted-immune-agonism-in-cancer-immunotherapy
#15
JOURNAL ARTICLE
Hong Zhang, Qun Wang, Sireesha Yalavarthi, Lukas Pekar, Steven Shamnoski, Liufang Hu, Laura Helming, Stefan Zielonka, Chunxiao Xu
BACKGROUND: Targeting the costimulatory receptor CD137 has shown promise as a therapeutic approach for cancer immunotherapy, resulting in anti-tumor efficacy demonstrated in clinical trials. However, the initial CD137 agonistic antibodies, urelumab and utomilumab, faced challenges in clinical trials due to the liver toxicity or lack of efficacy, respectively. Concurrently, c-MET has been identified as a highly expressed tumor-associated antigen (TAA) in various solid and soft tumors. METHODS: In this study, we aimed to develop a bispecific antibody (BsAb) that targets both c-MET and CD137, optimizing the BsAb format and CD137 binder for efficient delivery of the CD137 agonist to the tumor microenvironment (TME)...
March 8, 2024: Cancer Treatment and Research Communications
https://read.qxmd.com/read/38491482/construction-of-in-vitro-liver-on-a-chip-models-and-application-progress
#16
REVIEW
Jie Liu, Yimei Du, Xinxin Xiao, Daopeng Tan, Yuqi He, Lin Qin
The liver is the largest internal organ of the human body. It has a complex structure and function and plays a vital role in drug metabolism. In recent decades, extensive research has aimed to develop in vitro models that can simulate liver function to demonstrate changes in the physiological and pathological environment of the liver. Animal models and in vitro cell models are common, but the data obtained from animal models lack relevance when applied to humans, while cell models have limited predictive ability for metabolism and toxicity in humans...
March 15, 2024: Biomedical Engineering Online
https://read.qxmd.com/read/38490808/components-from-curcuma-longa-turmeric-against-hepatobiliary-diseases-based-on-gut-liver-axis-pharmacotherapeutic-properties-and-potential-clinical-applications
#17
JOURNAL ARTICLE
Tianhui Gao, Shuyi Wang, Zongping Zhu, Liting Lin, Yirong Luo, Meigui Lu, Wan Liao
Turmeric is widely used worldwide, and there are many examples of its use in treating hepatobiliary diseases. The gut-liver axis is a bidirectional relationship between gut microorganisms and the liver that is closely related to the pathogenesis of hepatobiliary diseases. This review systematically summarizes the components of turmeric. It links the studies on turmeric affecting gut microorganisms to its effects on liver and biliary diseases to explain the potential mechanism of turmeric's regulation of the gut-liver axis...
March 16, 2024: American Journal of Chinese Medicine
https://read.qxmd.com/read/38490420/mechanistic-interplay-of-dual-environmental-stressors-bisphenol-a-and-cadmium-induced-ovarian-follicular-damage-and-hepatocyte-dysfunction-in-vivo
#18
JOURNAL ARTICLE
Gokul Sudhakaran, P Snega Priya, B Haridevamuthu, Raghul Murugan, Jagan Kannan, Mikhlid H Almutairi, Bader O Almutairi, Ajay Guru, Jesu Arockiaraj
This study investigates the individual and combined toxic effects of Bisphenol A (BPA) and Cadmium (Cd) in zebrafish, recognizing the complex mixture of pollutants organisms encounter in their natural environment. Examining developmental, neurobehavioral, reproductive, and physiological aspects, the study reveals significant adverse effects, particularly in combined exposures. Zebrafish embryos exposed to BPA + Cd exhibit synergistically increased mortality, delayed hatching, and morphological abnormalities, emphasizing the heightened toxicity of the combination...
March 13, 2024: Science of the Total Environment
https://read.qxmd.com/read/38490395/attenuation-effect-of-a-polysaccharide-from-large-leaf-yellow-tea-by-activating-autophagy
#19
JOURNAL ARTICLE
Hao Chen, Zhuang Wang, Lei Gong, Jielin Chen, Yuzhe Huang, Wenqiang Guo, Zhang Qiang, Yong Li, Guanhu Bao, Daxiang Li, Yan Chen
Chemotherapy, the most common class of anticancer drugs, is considerably limited owing to its adverse side effects. In this study, we aimed to evaluate the protective effect and mechanism of action of large-leaf yellow tea polysaccharides (ULYTP-1, 1.29 × 104  Da) against chemotherapeutic 5-fluorouracil (5-Fu). Structural characterisation revealed that ULYTP-1 was a β-galactopyranouronic acid. Furthermore, ULYTP-1 promoted autolysosome formation, activating autophagy and reducing the oxidative stress and inflammation caused by 5-Fu...
March 13, 2024: International Journal of Biological Macromolecules
https://read.qxmd.com/read/38490394/pharmacokinetics-tissue-distribution-and-subacute-toxicity-of-oral-carrageenan-in-mice
#20
JOURNAL ARTICLE
Jiahui Wang, Kehan Zhu, Miaomiao Zhang, Qian Zhou, Wen Ji, Zhen Yao, Duxin Li
Carrageenan (CGN) is a typical sulfated polysaccharide widely applied in the food and pharmaceutical industries. Its in vivo behavior plays vital roles in understanding structural and biological functional relationships. The lack of UV chromophores in highly sulfated polysaccharides presents a challenge for their in vivo behavior studies. Therefore, this study aimed to develop a fast and effective quantitative fluorescence method for investigating the pharmacokinetics and tissue distribution of CGN. Fluorescence isothiocyanate labeling of CGN (FCGN) and microplate reader-based measurements were developed and validated to study its pharmacokinetics...
March 13, 2024: International Journal of Biological Macromolecules
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