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Hepatoprotective effect of Holothuria leucospilota methanolic extract on dimethyl nitrosamine-induced hepatotoxicity in rats

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ANIMAL MODELS AND EXPERIMENTAL medICINE 2024年第4期7卷 544-552页

作者： Dejan, Fatemeh Daneshi, Amineh Aslani, Javad Rajabi Ahmadi, Nasrollah Roozbahani, Narges Eskandari Rahmanian, Elaham Behmanesh, Reza Gheisari, Hamid Reza Shiraz univ Sch Vet Med Dept Basic Sci Shiraz Iran Farzanegan High Sch Dept Educ Tehran Kohgiluyeh & Bo Iran Shiraz univ Sch Vet Med Food Hyg Dept Shiraz Iran Shiraz univ Sch Vet Med Dept Pathol Shiraz Iran kermanshah univ med sci Imam Reza Hosp Clin Res Dev Ctr Kermanshah Iran Shiraz univ med sci Mol Dermatol Res Ctr Shiraz Iran Shiraz univ med sci Sch Med Dept Anat Shiraz Iran Islamic Azad univ Fac Vet Med Dept Pathobiol Garmsar Branch Garmsar Iran

Background: Complementary medicine is an interesting field for extracting bioactive compounds from various plant and animal sources. The hepatoprotective effect of the methanolic extract of a species of sea cucumber called Holothuria leucospilota in an animal model of liver cancer caused by dimethyl nitrosamine (DMN) was studied. Methods: Wistar female rats were randomly divided into five groups (n = 12): control (intact), positive control (received 1% DMN [10 mg/kg/week, intraperitoneally] for 12 weeks), and three treatment groups (received 50, 100, and 200 mg/kg/day H. leucospilota extract orally for 12 weeks along with intraperitoneal administration of 1% DMN [10 mg/kg/week]). In all groups, ultrasound was performed on the liver every week to check its density. Blood sampling and liver isolation were performed on three occasions, at 4, 8, and 12 weeks, to check liver enzymes and the histopathological condition of the liver tissue (every week, four animals from each group were randomly selected). Results: Liver density changes were evident from the eighth week onward in the positive control group. Histopathological results indicated pathologic changes in the positive control group after 4 weeks. The increase in liver enzymes in the positive control group was significantly different from that in the treatment and control groups. Conclusions: We demonstrated the hepatoprotective effect of H. leucospilota on DMN-induced liver damage in rats using biochemical and histological parameters and ultrasonography. More additional research (in silico or in vitro) is needed to find the exact mechanism and the main biological compound in H. leucospilota.

关键词： dimethyl nitrosamine hepatotoxicity Holothuria leucospilota sea cucumber SEA-CUCUMBER HEPATOCELLULAR-CARCINOMA TRITERPENE GLYCOSIDES MOLECULAR-IDENTIFICATION STICHOPUS-HORRENS

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Cucurbitacins mitigate vascular neointimal hyperplasia by suppressing cyclin A2 expression and inhibiting VSMC proliferation

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ANIMAL MODELS AND EXPERIMENTAL medICINE 2024年第4期7卷 397-407页

作者： Yuan, Ruqiang Qian, Lei Xu, Hu Yun, Weijing Dalian med univ Adv Inst Med Sci Dalian 116044 Peoples R China East China Normal univ Hlth Sci Ctr Shanghai 200241 Peoples R China

Background: Restenosis frequently occurs after percutaneous angioplasty in patients with vascular occlusion and seriously threatens their health. Substantial evidence has revealed that preventing vascular smooth muscle cell proliferation using a drug-eluting stent is an effective approach to improve restenosis. Cucurbitacins have been demonstrated to exert an anti-proliferation effect in various tumors and a hypotensive effect. This study aims to investigate the role of cucurbitacins extracted from Cucumis melo L. (CuECs) and cucurbitacin B (CuB) on restenosis. Methods: C57BL/6 mice were subjected to left carotid artery ligation and subcutaneously injected with CuECs or CuB for 4 weeks. Hematoxylin-Eosin, immunofluorescence and immunohistochemistry staining were used to evaluate the effect of CuECs and CuB on neointimal hyperplasia. Western blot, real-time PCR, flow cytometry analysis, EdU staining and cellular immunofluorescence assay were employed to measure the effects of CuECs and CuB on cell proliferation and the cell cycle in vitro. The potential interactions of CuECs with cyclin A2 were performed by molecular docking. Results: The results demonstrated that both CuECs and CuB exhibited significant inhibitory effects on neointimal hyperplasia and proliferation of vascular smooth muscle cells. Furthermore, CuECs and CuB mediated cell cycle arrest at the S phase. Autodocking analysis demonstrated that CuB, CuD, CuE and CuI had high binding energy for cyclin A2. Our study also showed that CuECs and CuB dramatically inhibited FBS-induced cyclin A2 expression. Moreover, the expression of cyclin A2 in CuEC- and CuB-treated neointima was downregulated. Conclusions: CuECs, especially CuB, exert an anti-proliferation effect in VSMCs and may be potential drugs to prevent restenosis.

关键词： CuB Cucurbitacin cyclin A2 restenosis vascular smooth muscle cell SMOOTH-MUSCLE-CELLS IN-VITRO GROWTH ACTIVATION TRANSITION MIGRATION STAT3 MAPK

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Developments in the study of Chinese herbal medicine's assessment index and action mechanism for diabetes mellitus

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ANIMAL MODELS AND EXPERIMENTAL medICINE 2024年第4期7卷 433-443页

作者： Liu, Xin-Yue Zheng, Han-Wen Wang, Feng-Zhong Atia, Tul-Wahab Fan, Bei Wang, Qiong Chinese Acad Agr sci Inst Food Sci & Technol Beijing 100193 Peoples R China Southwest med univ Tradit Chinese Med Hosp Sino Portugal TCM Int Cooperat Ctr Luzhou Peoples R China univ Karachi Dr Panjwani Ctr Mol Med & Drug Res Int Ctr Chem & Biol Sci Karachi Pakistan

In traditional Chinese medicine (TCM), based on various pathogenic symptoms and the 'golden chamber' medical text, Huangdi Neijing, diabetes mellitus falls under the category 'collateral disease'. TCM, with its wealth of experience, has been treating diabetes for over two millennia. Different antidiabetic Chinese herbal medicines reduce blood sugar, with their effective ingredients exerting unique advantages. As well as a glucose lowering effect, TCM also regulates bodily functions to prevent diabetes associated complications, with reduced side effects compared to western synthetic drugs. Chinese herbal medicine is usually composed of polysaccharides, saponins, alkaloids, flavonoids, and terpenoids. These active ingredients reduce blood sugar via various mechanism of actions that include boosting endogenous insulin secretion, enhancing insulin sensitivity and adjusting key enzyme activity and scavenging free radicals. These actions regulate glycolipid metabolism in the body, eventually achieving the goal of normalizing blood glucose. Using different animal models, a number of molecular markers are available for the detection of diabetes induction and the molecular pathology of the disease is becoming clearer. Nonetheless, there is a dearth of scientific data about the pharmacology, dose-effect relationship, and structure-activity relationship of TCM and its constituents. Further research into the efficacy, toxicity and mode of action of TCM, using different metabolic and molecular markers, is key to developing novel TCM antidiabetic formulations. The endocrine disorder diabetes mellitus (DM) is a global phenomenon significantly influencing human health. Traditional Chinese medicine (TCM), with its long history, has been treating diabetes for over two millennia. The main types of animal used to model diabetes are rodents, zebrafish and primates. Using different animal models, the number of molecular markers available for the detection of diabetes induction, such as f

关键词： animal model Chinese herbal medicine diabetes mellitus evaluation index mechanism of action HYPOGLYCEMIC ACTIVITY GLUCOSE-METABOLISM POLYGONATUM-ODORATUM LIPID-METABOLISM RHESUS-MONKEYS CELL APOPTOSIS STREPTOZOTOCIN POLYSACCHARIDE EXTRACT FRACTION

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Uncovering the impact of alcohol on internal organs and reproductive health: Exploring TLR4/NF-kB and CYP2E1/ROS/Nrf2 pathways

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ANIMAL MODELS AND EXPERIMENTAL medICINE 2024年第4期7卷 444-459页

作者： Kong, Eason Qi Zheng Subramaniyan, Vetriselvan Lubau, Natasha Sura Anak Monash univ Malaysia Jeffrey Cheah Sch Med & Hlth Sci Pharmacol Unit Jalan Lagoon Selatan Subang Jaya 47500 Selangor Malaysia Saveetha Inst med & Tech sci Saveetha Med Coll Ctr Global Hlth Res Chennai Tamil Nadu India

This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health, elucidating the underlying mechanisms involving the Toll-like receptor 4 (TLR4)/Nuclear factor kappa light chain enhancer of activated B cells (NF-kB) pathway and the Cytochrome P450 2E1 (CYP2E1)/reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. The TLR4/NF-kB pathway, crucial for inflammatory and immune responses, triggers the production of pro-inflammatory agents and type-1 interferon, disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to alcohol. Alcohol-induced dysbiosis in gut microbes heightens gut wall permeability to pathogen-associated molecular patterns (PAMPs), leading to liver cell infection and subsequent inflammation. Concurrently, CYP2E1-mediated alcohol metabolism generates ROS, causing oxidative stress and damaging cells, lipids, proteins, and deoxyribonucleic acid (DNA). To counteract this inflammatory imbalance, Nrf2 regulates gene expression, inhibiting inflammatory progression and promoting antioxidant responses. Excessive alcohol intake results in elevated liver enzymes (ADH, CYP2E1, and catalase), ROS, NADH, acetaldehyde, and acetate, leading to damage in vital organs such as the heart, brain, and lungs. Moreover, alcohol negatively affects reproductive health by inhibiting the hypothalamic-pituitary-gonadal axis, causing infertility in both men and women. These findings underscore the profound health concerns associated with alcohol-induced damage, emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi-organ impacts of alcohol consumption.

关键词： alcohol health impact inflammation metabolism molecular pathways FACTOR-KAPPA-B OXIDATIVE STRESS SIGNAL-TRANSDUCTION CANCER-CELLS NF-KB INFLAMMATION INHIBITION ACID NRF2 ANTIOXIDANT

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Comparative studies between humans and golden Syrian hamsters via thromboelastography

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ANIMAL MODELS AND EXPERIMENTAL medICINE 2024年第4期7卷 570-577页

作者： Yang, Ze Xie, Lili Ba, Jingjing Zan, Simin Zhang, Letong Zhang, Xinyi Yu, Yang Shandong First med univ Sch Lab Anim Jinan Peoples R China Shandong First med univ Shandong Lab Anim Ctr Jinan Peoples R China Shandong Acad med sci Jinan Peoples R China Shandong First med univ Affiliated Hosp 2 Tai An Peoples R China

Background: Thromboelastography (TEG) is a widely utilized clinical testing method for real-time monitoring of platelet function and the thrombosis process. Lipid metabolism disorders are crucial risk factors for thrombosis. The lipid metabolism characteristics of hamsters resemble those of humans more closely than mice and rats, and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms. Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical procedures. TEG was employed to evaluate coagulation factor function, fibrinogen (Fib) function, platelet function, and the fibrinolytic system. Methods: The whole blood from hamster or healthy human was isolated following the clinical procedure, and TEG was employed to evaluate the coagulation factor function, Fib function, platelet function, and fibrinolytic system. Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline. Blood routine testing used XN-2000 automatic blood analyzer. Results: TEG parameters revealed that hamsters exhibited stronger coagulation factor function than humans (reaction time [R], p = 0.0117), with stronger Fib function (alpha angle, p < 0.0001; K-time [K], p < 0.0001). Platelet function did not differ significantly (maximum amplitude [MA], p = 0.077). Hamsters displayed higher coagulation status than humans (coagulation index [CI], p = 0.0023), and the rate of blood clot dissolution in hamsters differed from that in humans (percentage lysis 30 min after MA, p = 0.02). Coagulation analysis parameters indicated that prothrombin time (PT) and activated partial thromboplastin time (APTT) were faster in hamsters than in humans (PT, p = 0.0014; APTT, p = 0.03), whereas the Fib content was significantly lower in hamsters than in humans (p < 0.0001). No significant difference was observed in thrombin time (p = 0.1949). Conclusions: In summary, TEG could be us

关键词： platelet function Syrian hamster thromboelastography (TEG) thrombosis MODEL

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Against all odds: The road to success in the development of human immune reconstitution mice

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ANIMAL MODELS AND EXPERIMENTAL medICINE 2024年第4期7卷 460-470页

作者： Bin, Yixiao Ren, Jing Zhang, Haowei Zhang, Tianjiao Liu, Peijuan Xin, Zhiqian Yang, Haijiao Feng, Zhuan Chen, Zhinan Zhang, Hai Shaanxi univ Chinese med Sch Basic Med Sci Xianyang Peoples R China Fourth Mil med univ Natl Translat Sci Ctr Mol Med Dept Cell Biol Xian Peoples R China Fourth Mil med univ State Key Lab New Targets Discovery & Drug Dev Maj Xian Peoples R China Fourth Mil med univ Sch Publ Hlth Dept Occupat & Environm Hlth Xian Peoples R China Fourth Mil med univ Sch Publ Hlth Minist Educ Key Lab Hazard Assessment & Control Special Operat Xian Peoples R China

The mouse genome has a high degree of homology with the human genome, and its physiological, biochemical, and developmental regulation mechanisms are similar to those of humans; therefore, mice are widely used as experimental animals. However, it is undeniable that interspecies differences between humans and mice can lead to experimental errors. The differences in the immune system have become an important factor limiting current immunological research. The application of immunodeficient mice provides a possible solution to these problems. By transplanting human immune cells or tissues, such as peripheral blood mononuclear cells or hematopoietic stem cells, into immunodeficient mice, a human immune system can be reconstituted in the mouse body, and the engrafted immune cells can elicit human-specific immune responses. Researchers have been actively exploring the development and differentiation conditions of host recipient animals and grafts in order to achieve better immune reconstitution. Through genetic engineering methods, immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts. From initially only being able to reconstruct single T lymphocyte lineages, it is now possible to reconstruct lymphoid and myeloid cells, providing important research tools for immunology-related studies. In this review, we compare the differences in immune systems of humans and mice, describe the development history of human immune reconstitution from the perspectives of immunodeficient mice and grafts, and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution, aiming to provide important references for immunological related researches. Over recent decades, researchers have been actively exploring the development and differentiation conditions of host recipient animals and grafts in order to achieve better immune reconstitution. The human immune system can be reconstituted

关键词： hematopoietic stem cell human immune reconstitution immune response immunodeficient mice peripheral blood mononuclear cell transplantation HEMATOPOIETIC STEM-CELLS SEVERE COMBINED IMMUNODEFICIENCY MOUSE MODEL NITRIC-OXIDE BONE-MARROW sciD MOUSE CLASS-I ENGRAFTMENT SYSTEM DEFICIENT

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Efficient and multiplex gene upregulation in plants through CRISPR-Cas-mediated knockin of enhancers

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MOLECULAR PLANT 2024年第9期17卷 1472-1483页

作者： Yao, Qi Shen, Rundong Shao, Yang Tian, Yifu Han, Peijin Zhang, Xuening Zhu, Jian-Kang Lu, Yuming Shanghai Jiao Tong univ Shanghai Collaborat Innovat Ctr Agriseeds Joint Ctr Single Cell Biol Sch Agr & Biol Shanghai 200240 Peoples R China Chinese Acad sci Shanghai Ctr Plant Stress Biol Ctr Excellence Mol Plant Sci Shanghai 201602 Peoples R China univ Chinese Acad sci Beijing Peoples R China Huazhong Agr univ Coll Plant Sci & Technol Wuhan 430070 Peoples R China Southern univ sci & Technol Inst Adv Biotechnol Shenzhen 518055 Peoples R China Southern univ sci & Technol Sch Med Shenzhen 518055 Peoples R China

Gene upregulation through genome editing is important for plant research and breeding. Targeted insertion of short transcriptional enhancers (STEs) into gene promoters may offer a universal solution akin to transgene-mediated overexpression while avoiding the drawbacks associated with transgenesis. Here, we introduce an "in locus activation"technique in rice that leverages well-characterized STEs for refined, heritable, and multiplexed gene upregulation. To address the scarcity of potent enhancers, we developed a large-scale mining approach and discovered a suite of STEs that are capable of enhancing gene expression in rice protoplasts. The in locus integration of these STEs into eight rice genes resulted in substantial transcriptional upregulation in the edited plants, with up to 869.1-fold increases in their transcript levels. Employing a variety of STEs, we achieved delicate control of gene expression, enabling the fine-tuning of key phenotypic traits such as plant height. Our approach also enabled efficient multiplexed gene upregulation, with up to four genes activated simultaneously, significantly enhancing the nicotinamide mononucleotide metabolic pathway. Importantly, heritability studies from the T0 to T3 generations confirmed the stable and heritable nature of STE-driven gene activation. Collectively, our work demonstrates that coupled with STE mining, leveraging genome editing for in locus activation and gene upregulation holds great promise to be widely adopted in fundamental plant research and crop breeding.

关键词： genome editing short transcriptional enhancers gene upregulation crop breeding QUANTITATIVE TRAIT VARIATION CROP IMPROVEMENT GENOME

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Establishment of abdominal aortocaval fistula in adenine-induced renal failure rats

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China medical Abstracts(Internal medicine) 2024年第2期41卷 115-116页

作者：张艺斐 Shandong med sci Acad Shandong 1st Med UnivJinan 250000

Objective To explore the construction of abdominal aortocaval fistula(ACF)model in adenine-induced renal failure rats,and to provide a suitable animal model for subsequent mechanism and intervention *** Adult female Sprague-Dawley rats(250-300 g)were fed with 0.75%adenine diet(renal failure group,n=60)and the same diet without adenine(control group,n=10)for 4 weeks,and the rats were randomly grouped by block randomization method with a ratio of 6:*** rats in the renal failure group were randomly selected by block randomization method at a ratio of 1:1 to undergo laparotomies to establish ACF models(renal failure+ACF group).The serum creatinine,blood urea nitrogen detection and Masson staining were used to evaluate the establishment of renal failure *** animal ultrasound imaging system was applied to verify the successful construction of the ACF *** 6 weeks of ACF observation,blood samples were collected from the heart of rats,and ACF-vascular tissues were collected for pathological study(HE staining).Results At 4 weeks of feeding.

关键词： rats fistula renal

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Gravesoil fungi are more sensitive than bacteria in response to precipitation

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SOIL ECOLOGY LETTERS 2024年第3期6卷 230225-230225页

作者： Han, Binghua Gan, Xueying Shi, Shunqin Hu, Xueqian Mu, Xianxian Yu, Qiaoling Zhang, Shiheng Li, Huan Lanzhou univ Inst Microbiome Frontiers & One Hlth Sch Publ Hlth Lanzhou 730000 Peoples R China Lanzhou univ Ctr Grassland Microbiome State Key Lab Grassland Agroecosyst Lanzhou 730000 Peoples R China Chongqing Three Gorges med Coll Fac Basic Med Sci Chongqing Key Lab Dev & Utilizat Genuine Med Mat T Wanzhou 404120 Peoples R China Chongqing Three Gorges med Coll Affiliated Peoples Hosp Wanzhou 404120 Peoples R China

Fungi are more sensitive to precipitation than *** susceptibility of abundant and rare bacteria to precipitation has no *** taxa of fungi are more vulnerable to precipitation than rare *** scenario alteration leads to grievous ecological consequences in ecosystems, especially on the Qinghai-Tibet Plateau. Bacterial and fungal community and their abundant and rare taxa in soil ecosystems may respond differently to the changed precipitation. Therefore, more attention needs to be paid to the sensitivity of bacteria and fungi and their abundant and rare taxa to precipitation shifts. The responses of bacterial and fungal populations and their abundant and rare taxa concerning diversity, assembly, and interactions to manipulative changes of precipitation were explored via imitating no precipitation, little precipitation, and medium precipitation using 16S rRNA gene and ITS amplicon sequencing. The results indicated that the change rate of fungal Simpson diversity with precipitation was higher than that of bacteria. The slope of the modified stochasticity ratio (MST) value of fungi to precipitation was steeper than that of bacteria. The Simpson diversity and the MST value of abundant and rare taxa within bacteria had no difference with precipitation. In contrast, those of abundant taxa within fungi varied more than rare ones with precipitation. By unveiling the differential responses of microbial populations with discrepant characteristics, this study allowed us to understand the different microbial communities responding to rainfall on the Qinghai-Tibet Plateau.

关键词： Qinghai-Tibet Plateau sensitivity precipitation assembly co-occurrence networks MICROBIAL COMMUNITY STRUCTURE ASSEMBLY PROCESSES INDICATORS DISPERSAL DIVERSITY NETWORK CLIMATE

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Efficacy of digital multi-dimensional parent-child training for children with attention deficit hyperactivity disorder:a controlled clinical study

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China medical Abstracts(Internal medicine) 2024年第1期41卷 63-64页

作者：郑荣君 Sch Mental Health&Psychol sci Anhui Med UnivHefei 230032

Objective To explore whether digital multidimensional parent-child training combined with medication is more effective than medication alone in treating symptoms and social function in children with attention deficit ... 详细信息

关键词： medication clinical alone

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