Journal of Zhejiang University SCIENCE B最新文献

Aging and age-related ailments have emerged as critical challenges and great burdens within the global contemporary society. Addressing these concerns is an imperative task, with the aims of postponing the aging process and finding effective treatments for age-related degenerative diseases. Recent investigations have highlighted the significant roles of nicotinamide adenine dinucleotide (NAD⁺) in the realm of anti-aging. It has been empirically evidenced that supplementation with nicotinamide mononucleotide (NMN) can elevate NAD⁺ levels in the body, thereby ameliorating certain age-related degenerative diseases. The principal anti-aging mechanisms of NMN essentially lie in its impact on cellular energy metabolism, inhibition of cell apoptosis, modulation of immune function, and preservation of genomic stability, which collectively contribute to the deferral of the aging process. This paper critically reviews and evaluates existing research on the anti-aging mechanisms of NMN, elucidates the inherent limitations of current research, and proposes novel avenues for anti-aging investigations.

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide. According to the distribution of tumor tissue, breast cancer can be divided into invasive and non-invasive forms. The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body, forming metastatic breast cancer. Drug resistance and distant metastasis are the main causes of death from breast cancer. Research on breast cancer has attracted extensive attention from researchers. In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening. The tumor microenvironment consists of cancer cells and various types of stromal cells, including fibroblasts, endothelial cells, mesenchymal cells, and immune cells embedded in the extracellular matrix. The extracellular matrix contains fibrin proteins (such as types I, II, III, IV, VI, and X collagen and elastin) and glycoproteins (such as proteoglycan, laminin, and fibronectin), which are involved in cell signaling and binding of growth factors. The current traditional two-dimensional (2D) tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo. Therefore, in recent years, research on three-dimensional (3D) tumor models has gradually increased, especially 3D bioprinting models with high precision and repeatability. Compared with a 2D model, the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment. Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments. Acellular matrix, gelatin, sodium alginate, and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection. Here, we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models, as a reference for research in the field of breast cancer.

The original version of this article (Zhao et al., 2021) unfortunately contained two mistakes.

The online version of the original article can be found at https://doi.org/10.1631/jzus.B2300401.

The use of nitrification inhibitors has been suggested as a strategy to decrease cadmium (Cd) accumulation in crops. However, the most efficient nitrification inhibitor for mitigating crop Cd accumulation remains to be elucidated, and whether and how changes in soil microbial structure are involved in this process also remains unclear. To address these questions, this study applied three commercial nitrification inhibitors, namely, dicyandiamide (DCD), 3,4-dimethylpyrazole phosphate (DMPP), and nitrapyrin (NP), to pakchoi. The results showed that both DCD and DMPP (but not NP) could efficiently decrease Cd concentrations in pakchoi in urea- and ammonium-fertilized soils. In addition, among the three tested nitrification inhibitors, DMPP was the most efficient in decreasing the Cd concentration in pakchoi. The nitrification inhibitors decreased pakchoi Cd concentrations by suppressing acidification-induced Cd availability and reshaping the soil microbial structure; the most effective nitrification inhibitor was DMPP. Ammonia oxidation generates the most protons during nitrification and is inhibited by nitrification inhibitors. Changes in environmental factors and predatory bacterial abundance caused by the nitrification inhibitors changed the soil microbial structure and increased the potential participants in plant Cd accumulation. In summary, our study identified DMPP as the most efficient nitrification inhibitor for mitigating crop Cd contamination and observed that the soil microbial structural changes caused by the nitrification inhibitors contributed to decreasing Cd concentration in pakchoi.

Doxorubicin (DOX) is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors; however, its clinical application is limited by significant cardiotoxicity. Cynaroside (Cyn) is a flavonoid glycoside distributed in honeysuckle, with confirmed potential biological functions in regulating inflammation, pyroptosis, and oxidative stress. Herein, the effects of Cyn were evaluated in a DOX-induced cardiotoxicity (DIC) mouse model, which was established by intraperitoneal injections of DOX (5 mg/kg) once a week for three weeks. The mice in the treatment group received dexrazoxane, MCC950, and Cyn every two days. Blood biochemistry, histopathology, immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment. The results demonstrated the significant benefits of Cyn treatment in mitigating DIC; it could effectively alleviate oxidative stress to a certain extent, maintain the equilibrium of cell apoptosis, and enhance the cardiac function of mice. These effects were realized via regulating the transcription levels of pyroptosis-related genes, such as nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1, and gasdermin D (GSDMD). Mechanistically, for DOX-induced myocardial injury, Cyn could significantly modulate the expression of pivotal genes, including adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), sirtuin 3 (SIRT3), and nuclear factor erythroid 2-related factor 2 (Nrf2). We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway, which plays a central role in preventing DOX-induced cardiomyocyte injury. In conclusion, the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.

Selenium nanoparticles (SeNPs) have garnered extensive research interest and shown promising applications across diverse fields owing to their distinctive properties, including antioxidant, anticancer, and antibacterial activity (Ojeda et al., 2020; Qu et al., 2023; Zambonino et al., 2021, 2023). Among the various approaches employed for SeNP synthesis, green synthesis has emerged as a noteworthy and eco-friendly methodology. Keshtmand et al. (2023) underscored the significance of green-synthesized SeNPs, presenting a compelling avenue in this domain. This innovative strategy harnesses the potential of natural resources, such as plant extracts or microorganisms, to facilitate the production of SeNPs.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia (AML) in recent years, chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients. Here, we demonstrated the antileukemia activity of a novel small molecular compound NL101, which is formed through the modification on bendamustine with a suberanilohydroxamic acid (SAHA) radical. NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells. It induces DNA damage and caspase 3-mediated apoptosis. A genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) library screen revealed that phosphatase and tensin homologous (PTEN) gene is critical for the regulation of cell survival upon NL101 treatment. The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome (MDS) cells, accompanied by the activation of protein kinase B (AKT) signaling pathway. The inhibition of mammalian target of rapamycin (mTOR) by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death. These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

BACKGROUND: Hepatitis B virus (HBV) is one of the most widespread viruses worldwide and a major cause of hepatitis, cirrhosis, and hepatocellular carcinoma. Previous studies have revealed the impacts of HBV infection on fertility. An increasing number of infertile couples with chronic hepatitis B (CHB) virus infection choose assisted reproductive technology (ART) to meet their fertility needs. Despite the high prevalence of HBV, the effects of HBV infection on assisted reproduction treatment remain limited and contradictory. OBJECTIVE: The aim of this study was to provide a comprehensive overview of the effect of HBV infection on fertility and discuss its effects on pregnancy outcomes, vertical transmission, pregnancy complications, and viral activity during ART treatment. METHODS: We conducted a literature search in PubMed for studies on HBV infection and ART published from 1996 to 2022. RESULTS: HBV infection negatively affected fertility in both males and females. Existing research shows that HBV infection may increase the risk of pregnancy complications in couples undergoing assisted reproduction treatment. The impact of HBV infection on the pregnancy outcomes of ART is still controversial. Current evidence does not support that ART increases the risk of vertical transmission of HBV, while relevant studies are limited. With the development of ART, the risk of HBV reactivation (HBVr) is increasing, especially due to the wide application of immunosuppressive therapy. CONCLUSIONS: Regular HBV infection screening and HBVr risk stratification and management are essential to prevent HBVr during ART. The determination of optimal strategy and timing of prophylactic anti-HBV therapy during ART still needs further investigation.

Waldenström macroglobulinemia (WM) is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M (IgM) protein (Owen et al., 2003). Common signs and symptoms include fatigue due to anemia, lymph node enlargement, hepatosplenomegaly, thrombocytopenia, symptoms related to high viscosity, and peripheral neuropathy, among others. Despite significant advances in WM treatment, this type of indolent lymphoma remains incurable, with a wide array of patient outcomes (Ruan et al., 2020). In recent years, chimeric antigen receptor T (CAR-T) cell therapy targeting cluster of differentiation 19 (CD19) has shown unprecedented response rates and durability in the treatment of B-cell malignancies. In this report, we describe a challenging case of WM that involved multiple extramedullary sites, relapsed, and was refractory to chemotherapy, immunotherapy, and targeted therapy. After anti-CD19 CAR-T cell therapy, the tumor burden significantly decreased and the patient's condition remained stable at the writing of this report.