Ellagic acid protects ovariectomy-induced bone loss in mice by inhibiting osteoclast differentiation and bone resorption

Osteoporosis is a devastating disease that features reduced bone quantity and microstructure, which causes fragility fracture and increases mortality, especially in the aged population. Due to the long-term side-effects of current drugs for osteoporosis, it is of importance to find other safe and effective medications. Ellagic acid (EA) is a phenolic compound found in nut galls, plant extracts, and fruits, and exhibits antioxidant and antineoplastic effects. Here, we showed that EA attenuated the formation and function of osteoclast dose-dependently. The underlying mechanism was further discovered by western blot, immunofluorescence assay, and luciferase assay, which elucidated that EA suppressed osteoclastogenesis and bone resorption mainly through attenuating receptor activator of nuclear factor-κB (NF-κB) ligand-induced NF-κB activation and extracellular signal-regulated kinase signaling pathways, accompanied by decreased protein expression of nuclear factor of activated T-cells calcineurin-dependent 1 and c-Fos. Moreover, EA inhibits osteoclast marker genes expression including Dc-stamp, Ctsk, Atp6v0d2, and Acp5. Intriguingly, we also found that EA treatment could significantly protect ovariectomy-induced bone loss in vivo. Conclusively, this study suggested that EA might have the therapeutic potentiality for preventing or treating osteoporosis.     

A Novel Synthesized Sulfonamido-Based Gallate—JEZ-C as Potential Therapeutic Agents for Osteoarthritis

Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on osteoarthritis (OA). However, GA has much weaker anti-oxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel compound named JEZ-C and analyzed its anti-arthritis and chondro-protective effects. Comparison of JEZ-C with its sources i.e. GA and Sulfamethoxazole (SMZ) was also performed. Results showed that JEZ-C could effectively inhibit the IL-1-mediated induction of MMP-1 and MMP-13 and could induce the expression of TIMP-1, which demonstrated its ability to reduce the progression of OA. JEZ-C can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Meanwhile, expression of the collagen I gene was effectively downregulated, revealing the inhibition of chondrocytes dedifferentiation by JEZ-C. Hypertrophy that may lead to chondrocyte ossification was also undetectable in JEZ-C groups. The recommended dose of JEZ-C ranges from 6.25×10^-7 μg/ml to 6.25×10^-5 μg/ml, among which the most profound response was observed with 6.25×10^-6 μg/ml. In contrast, its source products of GA and SMZ have a weak effect not only in the inhibition of OA but also in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed JEZ-C as a promising novel agent in the treatment of chondral and osteochondral lesions.     

中国两栖、爬行动物更新名录

本文在2015年发表的爬行动物名录及同年《中国两栖类信息系统》发布的两栖动物名录的基础上, 通过整理新发表的分类学研究及先前名录遗漏的部分早期文献, 更新了截至2019年底中国现生本土两栖、爬行动物物种名录。2015-2019年间, 中国两栖动物新记录1科, 新描述2属, 恢复1属有效性, 新记录1属, 新描述或恢复有效种74种, 新增国家纪录18种; 另6属、8种的有效性未得到近年研究证据支持(在此视为次定同物异名而未做收录, 后同)。同期, 中国爬行动物新恢复5科, 新描述1亚科, 新描述1属, 恢复3属有效性, 新记录3属, 新描述、恢复或提升有效种43个, 新增国家纪录10种; 另有5属、4种的有效性未得到近年研究证据支持, 并移除1属、4种在我国的分布纪录。此外, 通过整理2015年前文献, 爬行动物增补3属, 提升3亚种至种级地位, 增补国家新纪录3种, 另有3属、2种的有效性未得到近年研究证据支持, 同时移除1种在我国的分布纪录。综上, 截至2019年底, 我国共记录现生本土两栖动物3目13科62属515种(蚓螈目1科1属1种, 有尾目3科14属82种, 无尾目9科47属431种), 爬行动物3目35科135属511种(鳄形目1科1属1种, 龟鳖目6科18属34种, 有鳞目蛇亚目18科73属265种、蜥蜴亚目10科43属211种)。此外, 本文还对先前名录中部分爬行动物的中文名提出了修改建议, 建议恢复部分物种的惯用中文名。2015-2019年, 新物种及新纪录已知物种数量占现两栖、爬行动物物种总数的17.1%和10.2%。近年来, 我国发表的两栖、爬行动物新物种和已知物种的新纪录数量持续增加, 分类体系也在研究中不断完善, 建议今后及时地进行阶段性总结, 同时对存在的问题提出讨论, 以推动中国两栖、爬行动物分类学研究工作的进一步开展。     

Daphnetin attenuates LPS-induced osteolysis and RANKL mediated osteoclastogenesis through suppression of ERK and NFATc1 pathways

Aseptic prosthetic loosening and periprosthetic infection resulting in inflammatory osteolysis is a leading complication of total joint arthroplasty (TJA). Excessive bone destruction around the bone and prosthesis interface plays a key role in the loosening prostheses leading to revision surgery. The bacterial endotoxins or implant-derived wear particles-induced inflammatory response is the major cause of the elevated osteoclast formation and activity. Thus, agents or compounds that can attenuate the inflammatory response and/or inhibit the elevated osteoclastogenesis and excessive bone resorption would provide a promising therapeutic avenue to prevent aseptic prosthetic loosening in TJA. Daphnetin (DAP), a natural coumarin derivative, is clinically used in Traditional Chinese Medicine for the treatment of rheumatoid arthritis due to its anti-inflammatory properties. In this study, we report for the first time that DAP could protect against lipopolysaccharide-induced inflammatory bone destruction in a murine calvarial osteolysis model in vivo. This protective effect of DAP can in part be attributed to its direct inhibitory effect on RANKL-induced osteoclast differentiation, fusion, and bone resorption in vitro. Biochemical analysis found that DAP inhibited the activation of the ERK and NFATc1 signaling cascades. Collectively, our findings suggest that DAP as a natural compound has potential for the treatment of inflammatory osteolysis.     

Homologous chromosome pairing: The linchpin of accurate segregation in meiosis

Meiosis is a specialized cell division that occurs in sexually reproducing organisms, generating haploid gametes containing half the chromosome number through two rounds of cell division. Homologous chromosomes pair and prepare for their proper segregation in subsequent divisions. How homologous chromosomes recognize each other and achieve pairing is an important question. Early studies showed that in most organisms, homologous pairing relies on homologous recombination. However, pairing mechanisms differ across species. Evidence indicates that chromosomes are dynamic and move during early meiotic stages, facilitating pairing. Recent studies in various model organisms suggest conserved mechanisms and key regulators of homologous chromosome pairing. This review summarizes these findings and compare similarities and differences in homologous chromosome pairing mechanisms across species.     

High correlation between thermotolerance and photosystem II activity in tall fescue

Heat stress affects a broad spectrum of cellular components and metabolism. The objectives of this study were to investigate the behavior of Photosystem II (PSII) in tall fescue (Festuca arundinacea Schreb) with various thermotolerance capacities and to broaden our comprehension about the relationship between thermotolerance and PSII function. Heat-tolerant and heat-sensitive accessions were incubated at 24 °C (control) and 46 °C (heat stress) for 5 h. The fluorescence transient curves (OJIP curves), slow Chl fluorescence kinetic, and light response curve were employed to study the behavior of PSII subjected to heat stress. After heat stress, performance index for energy conservation from photons absorbed by PSII antenna until the reduction of PSI acceptors (PI_Total), the value of electrons produced per photon (a), and the maximal rate of electron transport (ETR_max) of heat-tolerant accessions were lower than those of heat-sensitive accessions. Relatively lower reactive oxygen species (ROS) contents were detected in heat-tolerant accessions. Simultaneously, there was a significant decline in the quantum yield of photochemical energy conversion in PS II (Y(II)), probability that a PSII Chl molecule functions as reaction center (γ_RC), and the increase of quantum yield for non-regulated non-photochemical energy loss (Y(NO)) in heat-tolerant accessions. Moreover, a significant inverse correlation between heat tolerance indexes (HTI) and Y(II) was observed. Therefore, maintaining a lower photochemical activity in heat-tolerant accessions could be a crucial strategy to improve their thermotolerance. This finding could be attributed to the structural difference in the reaction center, and for heat-tolerant accessions, it could simultaneously limit energy input into linear electron transport, and dissipate more energy through non-regulated non-photochemical energy loss processes.     

Protective effects of R-alpha-lipoic acid and acetyl-L-carnitine in MIN6 and isolated rat islet cells chronically exposed to oleic acid

Mitochondrial dysfunction due to oxidative stress and concomitant impaired beta-cell function may play a key role in type 2 diabetes. Preventing and/or ameliorating oxidative mitochondrial dysfunction with mitochondria-specific nutrients may have preventive or therapeutic potential. In the present study, the oxidative mechanism of mitochondrial dysfunction in pancreatic beta-cells exposed to sublethal levels of oleic acid (OA) and the protective effects of mitochondrial nutrients [R-alpha-lipoic acid (LA) and acetyl-L-carnitine (ALC)] were investigated. Chronic exposure (72 h) of insulinoma MIN6 cells to OA (0.2-0.8 mM) increased intracellular oxidant formation, decreased mitochondrial membrane potential (MMP), enhanced uncoupling protein-2 (UCP-2) mRNA and protein expression, and consequently, decreased glucose-induced ATP production and suppressed glucose-stimulated insulin secretion. Pretreatment with LA and/or ALC reduced oxidant formation, increased MMP, regulated UCP-2 mRNA and protein expression, increased glucose-induced ATP production, and restored glucose-stimulated insulin secretion. The key findings on ATP production and insulin secretion were verified with isolated rat islets. These results suggest that mitochondrial dysfunction is involved in OA-induced pancreatic beta-cell dysfunction and that pretreatment with mitochondrial protective nutrients could be an effective strategy to prevent beta-cell dysfunction.