Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress

BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M phase.Recent research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood.AIM To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC development.METHODS Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down CDC25C.Subsequently,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo.Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,respectively.The expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western blotting.Additionally,apoptosis was investigated using flow cytometry,qRT-PCR,and western blotting.RESULTS CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice.CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC cells.CONCLUSION The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.

Paget’s disease of bone: Report of 11 cases

BACKGROUND Paget’s disease of bone(PDB)is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation.The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability.The disease has high missed diagnosis and misdiagnosis rates.This report summarizes the clinical manifestations,imaging and pathological features,and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB.CASE SUMMARY There were eight male and three female patients whose average age was 48.7±11.0 years with a PDB course of 1-16 years.Nine patients had bone pain and bone deformities in different parts of the body,the majority of which involved the long bones.Laboratory examinations revealed elevated serum alkaline phosphatase(ALP)in all patients with an average of 618±460 IU/L(normal range 0-130 IU/L),and serum calcium and phosphorus levels were in the normal range.Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones.^(99m)Tc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions.Six patients underwent bone tissue biopsy,and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts.Ten of the 11 patients were effectively treated with bisphosphonates.CONCLUSION Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.

物种定殖和丧失驱动近70年森林演替进程中的群落结构动态

在过去的几十年中,揭示群落谱系和功能性状结构如何随着演替变化引起了广泛关注。但长期动态数据的缺乏限制了我们对于群落格局和构建机制的理解,这一问题在森林群落中尤为突出。本研究基于南京灵谷寺森林1951、1981、2002和2019年的定点样带调查数据,分析了这一中国东南部亚热带森林68年的次生演替动态。研究发现,随着演替的深入,群落谱系和性状结构呈现相反的变化趋势。尽管近缘物种间的谱系距离在下降,物种间的平均谱系距离却在增加,群落谱系结构整体上趋于发散。相反,无论用平均还是最近距离作为度量,物种间的性状距离均随着演替逐渐下降,群落功能性状结构趋于聚集。我们进一步拆分了物种定殖和丧失对群落谱系和性状结构动态的相对贡献。结果表明:谱系结构趋于发散主要是由于定殖的物种本身亲缘关系较远,也和群落中原有的物种有着较远的亲缘距离;性状结构趋于聚集主要是因为那些与群落中原有的物种性状相似的物种具有更高的定殖机会但从群落中丧失的概率却更低。这一研究结果表明,拆分物种定殖和丧失过程是解开长期演替进程中群落动态和构建机制的关键。