The treatment of osteochondral defects (OCD) remains a great challenge in orthopaedics. Tissue engineering holds a good promise for regeneration of OCD. In the light of tissue engineering, it is critical to establish an appropriate animal model to evaluate the degradability, biocompatibility, and interaction of implanted biomaterials with host bone/cartilage tissues for OCD repair in vivo. Currently, model animals that are commonly deployed to create osteochondral lesions range from rats, rabbits, dogs, pigs, goats, and sheep horses to nonhuman primates. It is essential to understand the advantages and disadvantages of each animal model in terms of the accuracy and effectiveness of the experiment. Therefore, this review aims to introduce the common animal models of OCD for testing biomaterials and to discuss their applications in translational research. In addition, we have reviewed surgical protocols for establishing OCD models and biomaterials that promote osteochondral regeneration. For small animals, the non-load-bearing region such as the groove of femoral condyle is commonly chosen for testing degradation, biocompatibility, and interaction of implanted biomaterials with host tissues. For large animals, closer to clinical application, the load-bearing region (medial femoral condyle) is chosen for testing the durability and healing outcome of biomaterials. This review provides an important reference for selecting a suitable animal model for the development of new strategies for osteochondral regeneration.

The purpose of the current study was to evaluate the optimal compatibility proportion of 18α-Glycyrrhizic acid (18α-GA) and 18β-Glycyrrhizic acid (18β-GA) against carbon tetrachloride (CCl4)-induced hepatic damage in rats, and further explored the underlying mechanism. Rats were injected with CCl4 (0.1%, 0.3 ml/kg) once a week and were orally administrated with different proportions of 18α-, and 18β-GA daily for 4 weeks. Rats were then sacrificed and blood samples were collected for biochemical assay. Liver tissues were assessed histologically for severity of liver injury. Enzyme activities in liver homogenate were determined using commercial kits. The mRNA levels of associated proteins were evaluated by RT-PCR. The data showed that the combination of 18α-, and 18β-GA, especially at proportion of 4:6, obviously alleviated CCl4-induced liver injury as evidenced by the improvement of liver histopathological changes, and decreased levels of ALT and AST in serum. Moreover, 18α- and 18β-GA at all proportions substantially improved glucose tolerance, and markedly reversed the decrease of SOD, MDA, and GSH, and increase of lipid markers (TG, TC, HDL, LDL) induced by CCl4 via regulating the mRNA levels of SREBP-1c, ACC, PPAR-α, and CPT-1a. Collectively, these results suggested that 18α-GA in combination with 18β-GA, especially at proportion of 4:6, effectively reduced liver injury induced by CCl4, comparable to the positive control silibinin, and the mechanism may be associated with reduced marker of liver oxidative stress and improvement of lipid metabolism via regulation of ACC, CTP-1A, PPARα, and SREBP1.

Glycyrrhhizic acid (GA), including 18α-glycyrrhizic acid (18α-GA) and 18β-glycyrrhizic acid (18β-GA), is the main active ingredient of licorice. GA is generally considered an effective pharmacological strategy protecting against hepatic disease; however, the optimal compatibility proportion of 18α-GA and 18β-GA against alcoholic liver disease (ALD) and the underlying mechanism are not well established. Hence, this study was designed to explore the optimal compatibility proportion of 18α-GA and 18β-GA against ALD, followed by investigating the underlying mechanisms. SD rats were administered 40% ethanol once a day, accompanied by treatment with different proportions of 18α-GA and 18β-GA for four weeks. Then all rats were anesthetized with chloral hydrate and blood samples were taken from the abdominal aorta for biochemical assay. Livers were also collected and the liver function, lipid profile, ROS production, and mRNA and protein levels of related genes involved in lipid metabolism were assessed. The results showed that 18α-GA and 18β-GA, particularly at a proportion of 4:6, significantly reduced liver damage, lipid accumulation, and oxidative stress in ethanol-induced rats, as indicated by the decreased levels of alanine aminotransferase (ALT) and aminotransferase (AST) in serum, improvement of liver histopathological changes, regulation of total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), and modulation of superoxide dismutase (SOD), glutathione (GSH), and malonaldehyde (MDA). Moreover, the combination treatment with 18α-GA and 18β-GA substantially reduced the mRNA and protein levels of sterol regulatory element-binding protein-1c (SREBP-1c) and acetyl-coal carboxylase (ACC); meanwhile, increased levels of peroxisome proliferators activated receptor-α (PPAR-α) and carnitine palmitoy transferase-1 (CTP-1) in the liver tissues of ethanol-induced rats. In conclusion, our results indicated that the optimal compatibility proportion of 18α-GA and 18β-GA protecting against ALD was 4:6, and the mechanism was associated with the regulation of oxidative stress and lipid metabolism.

The glycyrrhizic acid (GA) epimers 18α‑ and 18β‑GA exert anti‑inflammatory and hepatoprotective activities, which may help to protect against alcoholic liver disease, particularly alcoholic hepatitis (AH). The aim of the present study was to investigate the optimal ratio of 18α‑ and 18β‑GA for preventing AH in rats. Different groups of rats were administered seven different ratios of 18α‑ and 18β‑GA (10:0, 8:2, 6:4, 5:5, 4:6, 2:8 and 0:10; 10.83 mg/kg), vehicle control, or silymarin (22.75 mg/kg) as a positive control, followed by administration of 40% alcohol (10 ml/kg) once a day for four weeks. Subsequently, livers were isolated and routinely processed for histological examination. The serum levels of 23 cytokines and chemokines associated with AH were examined with a Bio‑Plex 200 Luminex assay. It was revealed that all ratios of 18α‑ and 18β‑GA prevented alcohol‑induced liver injury, as evidenced by a lesser degree of histopathological changes in the liver as compared with those in the model group. Furthermore, the levels of 15 cytokines/chemokines were significantly altered after alcohol administration, which was significantly inhibited by, pre‑treatment with different proportions of 18α‑ and 18β‑GA, particularly at a ratio of 4:6, for most cytokines/chemokines associated with AH, including tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑2, IL‑4, IL‑5, IL‑7, IL‑6, monocyte chemotactic protein 1 (MCP‑1), macrophage inflammatory protein (MIP)‑1α, MIP‑3α, macrophage‑ and granulocyte macrophage colony‑stimulating factor, chemokine (C‑X‑C motif) ligand 1(GRO/KC), vascular endothelial growth factor and C‑C motif chemokine ligand 5 (RANTES). Taken together, based on these results the optimal ratio of 18α‑ and 18β‑GA to prevent AH in model rats was considered to be 4:6.

Objectives: It has been provided that if incubation time of prepared sperm can affect sperm motility and DNA fragment, but little is known about the influence of sperm preincubation time (SI) on the sperm’s fertilizing ability, subsequent embryonic development and pregnancy outcomes in in vitro fertilization (IVF). The aim of this study was to explore the association of SI with fertilization rate, embryo development and clinical outcomes in IVF, further, to find an optimal preincubation time for prepared sperm before insemination in IVF. Material and methods: This retrospective cohort study included a total of 1453 infertile couples undergoing IVF in our center performed from January 2016 to January 2019. Sperm were preincubated at 37℃ 6% CO₂ for different times before insemination. Preincubation time associated with fertilization rate (FR), 2PN rate, D3 good quality embryo rate, fresh embryo implantation rate (IR), blastocyst formation rate, cumulative pregnancy rate (CPR), cumulative ongoing pregnancy rate (COPR), cumulative live birth rate (CLBR), newborn health and gender ratio were analyzed by chi-square analysis. Results: FR and 2PN rate of SI more than four hours SI groups (> 4 h SI group) decreased significantly compared with other SI groups (p < 0.01). There were no significant differences of the D3 high quality embryo rate among five SI groups. The blastocyst formation rate of > 4 h SI group was significantly lower than that of 2–3 h SI group (45.5% vs 56.1%, p < 0.05); and 1–2 h SI group also had significant difference with 2–3 h and 3–4 h SI group (48.9% vs 56.1% and 54.6%, p < 0.05). There were a significant decrease of fresh IR and CPR in ≤1 h SI group compared with 1–2 h SI group (19.6% vs. 38.0%, p < 0.05; 62.7% vs 73.7%, p < 0.05); ≤ 1 h SI group also have the lowest CLBR (45.6%), it had statistic differences with 1–2 SI group and 3–4 SI group (45.6% vs 63.2%, p < 0.01; 45.6% vs 61.2%, p < 0.05). Conclusions: The sperm preincubated time at 37℃ 6% CO₂ before insemination could influence sperm fertilizing ability, blastocyst formation, embryo implantation and CLBR in IVF cycles. The best time for prepared sperm preincubation at 37℃ is one to four hours before insemination in IVF. Objectives: It has been provided that if incubation time of prepared sperm can affect sperm motility and DNA fragment, but little is known about the influence of sperm preincubation time (SI) on the sperm’s fertilizing ability, subsequent embryonic development and pregnancy outcomes in in vitro fertilization (IVF). The aim of this study was to explore the association of SI with fertilization rate, embryo development and clinical outcomes in IVF, further, to find an optimal preincubation time for prepared sperm before insemination in IVF. Material and methods: This retrospective cohort study included a total of 1453 infertile couples undergoing IVF in our center performed from January 2016 to January 2019. Sperm were preincubated at 37℃ 6% CO₂ for different times before insemination. Preincubation time associated with fertilization rate (FR), 2PN rate, D3 good quality embryo rate, fresh embryo implantation rate (IR), blastocyst formation rate, cumulative pregnancy rate (CPR), cumulative ongoing pregnancy rate (COPR), cumulative live birth rate (CLBR), newborn health and gender ratio were analyzed by chi-square analysis. Results: FR and 2PN rate of SI more than four hours SI groups (> 4 h SI group) decreased significantly compared with other SI groups (p < 0.01). There were no significant differences of the D3 high quality embryo rate among five SI groups. The blastocyst formation rate of > 4 h SI group was significantly lower than that of 2–3 h SI group (45.5% vs 56.1%, p < 0.05); and 1–2 h SI group also had significant difference with 2–3 h and 3–4 h SI group (48.9% vs 56.1% and 54.6%, p < 0.05). There were a significant decrease of fresh IR and CPR in ≤1 h SI group compared with 1–2 h SI group (19.6% vs. 38.0%, p < 0.05; 62.7% vs 73.7%, p < 0.05); ≤ 1 h SI group also have the lowest CLBR (45.6%), it had statistic differences with 1–2 SI group and 3–4 SI group (45.6% vs 63.2%, p < 0.01; 45.6% vs 61.2%, p < 0.05). Conclusions: The sperm preincubated time at 37℃ 6% CO₂ before insemination could influence sperm fertilizing ability, blastocyst formation, embryo implantation and CLBR in IVF cycles. The best time for prepared sperm preincubation at 37℃ is one to four hours before insemination in IVF.

As the authors of the title paper