Pyrrolizidine alkaloids (PAs) are widely distributed in many plants including medicinal herbs. The hepatotoxicity of PAs has been known academically for a long time, however, their reproductive toxicity, mutagenesis and carcinogenicity have been less researched. This article is an overview of the clinical and experimental reports of the reproductive toxicity, mutagenesis and carcinogenicity of PAs, the effective factors and generating mechanism of the toxicity.
Animals ; Biomedical Research ; Humans ; Plant Extracts ; analysis ; toxicity ; Plants, Medicinal ; chemistry ; toxicity ; Pyrrolizidine Alkaloids ; analysis ; toxicity

Whole embryo culture (WEC) is an experimental tool, which is made use of embryos in vitro to replace whole animals to investigate the growth and development of early organs, the embryo toxicity of chemical materials and the mechanism of the occurrence of embryo toxicity. Compared with experiment with whole animals, WEC could reduce the number of experimental animals, shorten experimental time, decrease experimental expenses, eliminate disturbing factors and control dosage more exactly. So it is generally received that WEC tool is a good experimental method to match the principles of replacement, reduction, refinement and responsibility. This article is a review of the WEC tool of rat and mouse, including the development of this tool, announcements, and the application in the development of organs, the embryo toxicity of environmental pollution and heavy metal, safety evaluation of medicine and the embryo toxicity of traditional Chinese medicine and its mechanism. There is also a discussion of the application of this tool in the investigation of the embryo toxicity of traditional Chinese medicine.
Animals ; Culture Media ; Embryo Culture Techniques ; methods ; Embryonic Development ; drug effects ; Environmental Pollutants ; toxicity ; Metals, Heavy ; toxicity ; Mice ; Rats

OBJECTIVETo investigate the fetotoxicity of retrorsine.

METHODMouse whole embryo culture (WEC) was applied. Post-implantation (8.5 d) mouse embryos were isolated from their mothers and put into the medium of immediately centrifuged serum (ICS) prepared from rats. Different concentrations of retrorsine (12.5, 25, 50, 100 mg x L(-1)) were added into the WEC culture. Development (yolk sac diameter, crown-rump length, head length, somite number) and organic morphodifferentiation (yolk sac circulation, allantois, embryonic flexion, heart, brain, optic-otic-olfactory organ, branchial arch, maxillary, mandible, bud) of embryos were observed at 48 h after treatment.

RESULTObvious fetotoxicity could be observed in various retrorsine treatment groups in a dose-dependent manner. Development of embryos was delayed significantly at dose 12.5-100 mg x L(-1). Malformations were shown in all organic morphodifferentiation indexes, especially in otic-olfactory organ, branchial arch, maxillary, mandible, bud.

CONCLUSIONRetrorsine had obvious fetotoxicity in vitro WEC culture, indicating that exposure of pregnant mice to retrorsine may have potential risk on fetals.

Animals ; Dose-Response Relationship, Drug ; Embryo, Mammalian ; drug effects ; Female ; Male ; Mice ; Pregnancy ; Pyrrolizidine Alkaloids ; toxicity ; Rats ; Toxicity Tests ; methods

Objective To analyze the epidemiology and clinical characteristics of acquired immunodeficiency syndrome (AIDS) and pulmonary tuberculosis (TB) co-infection.Methods A retrospective study was conducted with the clinical data of patients diagnosed with AIDS and TB in Shanghai Public Health Clinical Center during the period from 2011 to 2015.The outcome of the patients were evaluated by outpatient and telephone follow-up.The data were analyzed by descriptive analysis using SPSS 22.0 software package.Results A total of 359 patients with AIDS/TB co-infection were included in this analysis,including 325 males and 34 females,the highest proportion in 30-44 age group.The diagnosis was delayed in about 42.6％ of the patients.The clinical symptoms were mainly fever,cough and weight loss,but hemoptysis uncommon.Both lungs were affected in most cases,with lesions in at least 3 lung fields,but rare pulmonary cavity.T-SPOT.TB test showed lower positive rate.CD4+T lymphocyte count was 50 cells/μL or less in 50.7％ of the patients at their first test.About 43.5％ of the 69 patients with antimicrobial susceptibility data showed resistance to therapy.Majority (93.2％) of the patients with known viral status received antiretroviral treatment.Extra-pulmonary tuberculosis was identified in 282 cases.The complication and opportunistic infection included central nervous system infection,syphilis,hepatitis B virus infection,hepatitis C virus infection,pulmonary infection,and drug-induced liver injury.Of the 333 patients with known outcome,53 died,most (79.2％,42/53) within 6 months.Conclusions The patients with AIDS/TB co-infection showed higher proportion of young people.The CT finding was atypical.The patients showed lower positive rate for T-SPOT TB test and lower CD4+T lymphocyte count at their first test.Most patients had extra-pulmonary tuberculosis and other complications or opportunistic infections.

The purpose of this study is to evaluate the embryotoxicity of alkaloids in Senecionis Scandentis Hebra on in vitro cultured mouse embryos. Mouse whole embryo culture (WEC) was applied in this study. Post-implantation (8.5 d) mouse embryos were isolated from their mothers, and cultured in medium of immediately centrifuged serum (ICS) with different concentrations of seneciphylline (target concentrations were 100, 50, 25 and 12.5 μg x mL(-1)) or senkirkine (target concentrations were 50, 25 and 12.5 μg x mL(-1)) for 48 h. After culturing completed, the development and organic morphodifferentiation of the cultured embryos were evaluated microscopically. Treatment with seneciphylline and senkirkine had adverse effects on the development and organic morphodifferentiation of embryos. The effect also had clear dose-response. Alkaloidals in Senecionis Scandentis Hebra had embryotoxicity on cultured embryos, which indicated that pregnant people exposed to Senecionis Scandentis Hebra may get potential risk on fetus.

Reproductive toxicity research takes an important place in traditional Chinese medicine pre-clinical safety evaluation. Modern reproductive toxicity experiment includes drug-related miscarriage, fetal death, teratism, and adverse effects on fertility, genital system, embryonic development and fetus, which is different from contraindicated in pregnancy in traditional Chinese medicine theory. Now the three-phases reproductive toxicity study is the method mainly applied in traditional Chinese medicine reproductive toxicity evaluation. Besides that, alternative methods of whole embryos culture and embryonic stem cell test are also used in traditional Chinese medicine embryo toxicity evaluation. This article reviews research progress and pre-clinical evaluation on reproductive toxicity of traditional Chinese medicine.

OBJECTIVETo investigate the fetotoxicity of monocrotaline.

METHODMouse whole embryo culture (WEC) was applied. Post-implantation (8.5 d) mouse embryos were isolated from their mothers and put into the medium of immediately centrifuged serum (ICS) prepared from rats. Different concentrations of monocrotaline (100, 50, 25, 12.5 mg x L(-1)) were added into the WEC. Development (yolk sac diameter, crown-rump length, head length, somite number) and organic morphodifferentiation (yolk sac circulation, allantois, embryonic flexion, heart, brain, optic-otic-olfactory organ, branchial arch, maxillary, mandible, bud) of embryos were observed at 48 h after treatment.

RESULTObvious fetotoxicity could be observed in various monocrotaline treatment groups in a dose-dependent manner. Development of embryos was delayed significantly at dose 12.5-100 mg x L(-1). Malformations were shown in all organic morphodifferentiation indice, especially in opti-otic organ, mandible and bud.

CONCLUSIONMonocrotaline had obvious fetotoxicity in vitro WEC, indicating that exposure of pregnant mice to monocrotaline may have potential risk on fetus.

Animals ; Cell Differentiation ; drug effects ; Culture Media ; Embryo, Mammalian ; drug effects ; physiology ; Female ; Male ; Mice ; Monocrotaline ; toxicity

Magnesium-doped calcium silicate(CS)bioceramic scaffolds have unique advantages in mandibular defect repair;however,they lack antibacterial properties to cope with the complex oral microbiome.Herein,for the first time,the CS scaffold was functionally modified with a novel copper-containing polydopamine(PDA(Cu2+))rapid deposition method,to construct internally modified(*P),externally modified(@PDA),and dually modified(*P@PDA)scaffolds.The morphology,degradation behavior,and mechanical properties of the obtained scaffolds were evaluated in vitro.The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance.During the prolonged immersion stage,the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release.The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA,while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects.Finally,the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model.Overall,it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+)modification,and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

Psoraleae Fructus （PF） is a non-toxic Chinese herbal medicine， while the liver injury caused by PF has aroused wide concern in recent years. At present， animal experiments and in vitro studies have been carried out to explore the mechanism， targets， and toxic components of PF in inducing liver injury， which， however， have differences compared with the actual conditions in clinical practice， and there are still some potential hepatotoxic components and targets of PF that have not been discovered. With the continuous progress in systems biology， establishing the drug-induced liver injury model and the liver injury prediction model based on network toxicology can reduce the cost of animal experiments， improve the toxicity prediction efficiency， and provide new tools for predicting toxic components and targets. To systematically explain the characteristics of liver injury in the application of PF and explore the potential hepatotoxic components and targets of PF， we reviewed the related articles published by China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， and PubMed from 1962 to 2021 and analyzed the characteristics and influencing factors of liver injury caused by PF in the patients. Furthermore， we summarized the chemical components of PF and the components entering blood. By reviewing the mechanism， targets， and components of PF in inducing liver injury that were discovered by in vivo and in vitro experiments， we summarized the known compounds in PF that may cause liver injury. Finally， the current methods for building the prediction model of PF-induced liver injury were summarized， and the predicted toxic components and targets were introduced. The possible factors of PF in causing liver injury were explained from three aspects： clinical characteristics， preclinical studies， and computer-assisted network prediction， which provide a reference for predicting the risk of PF-induced liver injury.

Objective To analyze the modeling elements and subjects of the animal model of skin photoaging, and to provide a reference for the preparation and improvement of the model and a basis for the scientific evaluation of the subject.Methods By searching and collecting relevant literature on the preparation of animal models of skin photoaging from 2010 to 2022 in the China National Knowledge Infrastructure, Wanfang Database, and PubMed database, the model animal species, gender, modeling method, modeling cycle, radiation source and its distance from the modeling site, cumulative radiation volume, detection indicators, and subjects (drugs or treatments) recorded in the literature were collated and summarized, and a database was established for statistical analysis.Results 257 articles that met the inclusion criteria were selected. Among them, the most common animal model was SKH-1 hairless mice, followed by SD rats and KM mice; the gender of animals was mainly female, medium-wave ultraviolet B (UVB) was often used as the radiation source, the distance between the radiation source and the modelling site was mostly 30 cm, and the modelling period was usually 40-60 days. The cumulative dose of long-wave ultraviolet A (UVA) was between 100-150 J/cm², and the cumulative dose of UVB was between 5-10 J/cm². The tests used after model establishment were skin histopathological examination, skin tissue homogenization, fibre staining, immunoblotting, etc. Subjects included Chinese herbal medicines, Chinese herbal extracts, Chinese patent medicines, Chinese herbal compound medicines, chemical drugs, biological agents and other treatments, while the animal model of skin photoaging was also used for clinical efficacy studies of external Chinese medicine, physiotherapy and positive control drugs.Conclusion In skin photoaging animal experiments, female SKH-1 hairless mice are often used, and UVB is used as the radiation source. The modeling period is usually 40-60 days, and the minimum erythema dose (MED) is incremented week by week. The cumulative UVB irradiation dose ranges from 0 to 10 J/cm², which has the advantages of high success rate, good reproducibility and high similarity with clinical disease.