Search

Background: Reactive oxygen species (ROS), predominantly generated by mitochondria, play a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Reduction of ROS levels may be an effective strategy to delay IVDD. In this study, we assessed whether umbilical cord mesenchymal stem cell-exosomes (UCMSC-exos) can be used to treat IVDD by suppressing ROS production caused by mitochondrial dysfunction. Materials and methods: Human UCMSC-exos were isolated and identified. Nucleus pulposus cells (NPCs) were stimulated with H2O2 in the presence or absence of exosomes. Then, 4D label free quantitative (4D-LFQ) proteomics were used to analyze the differentially expressed (DE) proteins. Mitochondrial membrane potential (MMP), mitochondrial ROS and protein levels were determined via immunofluorescence staining, flow cytometry and western blotting respectively. Additionally, high-throughput sequencing was performed to identify the DE miRNAs in NPCs. Finally, therapeutic effects of UCMSC-exos were investigated in a puncture-induced IVDD rat model. Degenerative grades of rat IVDs were assessed using magnetic resonance imaging and histochemical staining. Results: UCMSC-exos effectively improved the viability of NPCs and restored the expression of the extracellular matrix (ECM) proteins, collagen type II alpha-1 (COL2A1) and matrix metalloproteinase-13 induced by H2O2. Additionally, UCMSC-exos not only reduced the total intracellular ROS and mitochondrial superoxide levels, but also increased MMP in pathological NPCs. 4D-LFQ proteomics and western blotting further revealed that UCMSC-exos up-regulated the levels of the mitochondrial protein, mitochondrial transcription factor A (TFAM), in H2O2-induced NPCs. High-throughput sequencing and qRT-PCR uncovered that UCMSC-exos down-regulated the levels of miR-194-5p, a potential negative regulator of TFAM, induced by H2O2. Finally, in vivo results showed that UCMSC-exos injection improved the histopathological structure and enhanced the expression levels of COL2A1 and TFAM in the rat IVDD model. Conclusions: Our findings suggest that UCMSC-exos promote ECM synthesis, relieve mitochondrial oxidative stress, and attenuate mitochondrial dysfunction in vitro and in vivo, thereby effectively treating IVDD. The translational potential of this article: This study provides solid experimental data support for the therapeutic effects of UCMSC-exos on IVDD, suggesting that UCMSC-exos will be a promising nanotherapy for IVDD.

Benzotriazoles (BTRs) are a class of benzoheterocyclic chemicals that are frequently used as metal-corrosive inhibitors, both in industry and daily use. However, the exposure effect information on BTRs remains relatively limited. In this study, an integrated metabolomic and transcriptomic approach was utilized to evaluate the effect of three BTRs, benzotriazole, 6-chloro-1-hydroxi-benzotriazole, and 1-hydroxy-benzotriazole, in the mouse liver with results showing disrupted basal metabolic processes and vitamin and cofactor metabolism after 28 days. The expression of several genes that are related to the inflammatory response and aryl hydrocarbon receptor pathways, such as Gstt2 and Arntl, was altered by the exposure to BTRs. Exposure to BTRs also affected metabolites and genes that are involved in the immune system and xenobiotic responses. The altered expression of several cytochrome P450 family genes reveal a potential detoxification mechanism in the mouse liver. Taken together, our findings provide new insights into the multilayer response of the mouse liver to BTRs exposure as well as a resource for further exploration of the molecular mechanisms by which the response occurs.

Abstract The incorporation of isolated Sn (IV) and Zr (IV) ions into silica frameworks is attracting widespread attention, which exhibits remarkable catalytic performance (conversion, selectivity, and stability) in a broad range of reactions, especially in the field of biomass catalytic conversion. As a representative example, the conversion route of carbohydrates into valuable platform and commodity chemicals such as lactic acid and alkyl lactates, has already been established. The zeotype materials also possess water‐tolerant ability and are capable to be served as promising heterogeneous catalysts for aqueous reactions. Therefore, dozens of Sn‐ and Zr‐containing silica materials with various channel systems have been prepared successfully in the past decades, containing 8 membered rings (MR) small pore CHA zeolite, 10‐MR medium pore zeolites (FER, MCM‐56, MEL, MFI, MWW), 12‐MR large pore zeolites (Beta, BEC, FAU, MOR, MSE, MTW), and 14‐MR extra‐large pore UTL zeolite. This review about Sn‐ and Zr‐containing metallosilicate materials focuses on their synthesis strategy, catalytic applications for diverse reactions, and the effect of zeolite characteristics on their catalytic performances.

The Si/Al molar ratio of MAZ aluminosilicate zeolite prepared by the direct hydrothermal method is generally less than five, thus giving rise to poor thermal and hydrothermal stability for this low-silica zeolite. With the purpose of enhancing the Si/Al molar ratio of MAZ zeolite, post-synthesized methods including acetic acid treatment and steaming treatment, as well as interzeolite transformation from FAU zeolite, were employed to prepare MAZ zeolite with high silica. It was found that steaming treatment was more effective in increasing the Si/Al molar ratio in comparison with acetic acid treatment, affording a maximum Si/Al molar ratio of 16.9 along with a preserved crystallinity of approximately 75%. Additionally, high-silica MAZ zeolite with a Si/Al molar ratio of up to 7.3 was also capable of being directly hydrothermally synthesized using interzeolite transformation from FAU zeolite.

Key Clinical Message The patient was found to have multiple uterine myomas at the age of 19, underwent laparoscopic myomectomy at the age of 20, and underwent laparotomic myomectomy again at the age of 23 due to the recurrence of uterine myoma. At the age of 25, the patient reappeared with symptoms and recurrence, and was diagnosed with uterine leiomyomas (ULMs) of FH mutation and high‐grade squamous intraepithelial lesion (HSIL/CIN III) with gland involvement, after complete examination. Fumarate hydratase (FH) mutation screening is important when gynecologists encounter patients with early onset and multiple ULMs, it can give early diagnosis and treatment and fertility guidance. The patient had their uterus removed at the age of 26. FH mutation screening is important when gynecologists encounter patients with early onset and multiple ULMs, it can give early diagnosis and treatment and fertility guidance. It is also helpful for early diagnosis of renal cell carcinoma.