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This study aimed to clarify the intervention effect of salidroside (SAL) on lung injury caused by PM 2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Specific pathogen-free (SPF) grade male C57BL/6 mice were randomly assigned to the following groups: control group, SAL group, PM 2.5 group, SAL+PM 2.5 group. On the first day, SAL was given by gavage, and on the second day, PM 2.5 suspension was given by intratracheal instillation. The whole experiment consist of a total of 10 cycles, lasting 20 days. At the end of treatment, blood samples and lung tissues were collected and analyzed. Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy. The expression of inflammatory, antioxidants, apoptosis, and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Exposure to PM 2.5 leads to obvious morphological and pathologica changes in the lung of mice. PM 2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1, Nrf2, SOD2, SIRT1 and PGC-1ɑ, and an increase in the protein expressions of IL-6, IL-1β, Bax, caspase-9 and cleaved caspase-3. However, SAL reversed the aforementioned changes caused by PM 2.5 by activating the SIRT1-PGC-1α pathway. SAL can activate SIRT1-PGC-1ɑ to ameliorate PM 2.5 -induced lung injury. [ABSTRACT FROM AUTHOR]

Miracle fruit (Synsepalum dulcificum) is an edible berry, and is known for its ability to turn sour to sweet. The leaf of S. dulcificum has been used as additives in food, medicine and cosmetic industries. In this study, two new pairs of enantiomeric coumarinolignans, synsepalumins A and B (1 and 2), three new pentacyclic triterpenoids, 3- O - cis - p -coumaroyl-2 α ,3 β ,29-trihydroxy-olean-12-en-28-oic acid (3), 3- O - trans - p -coumaroyl-2 α ,3 β ,29-trihydroxy-olean-12-en-28-oic acid (4), and 3- O - cis - p -coumaroyl-3 β ,19 α -hydroxy-urs-12-en-28-oic acid (6), along with twenty-five known compounds (5 , 7 − 30) were isolated from the leaves of S. dulcificum. Compounds 1 and 2 are two rare tricyclic 7-hydroxycoumarins featuring a classic bicyclic 7-hydroxycoumarin fused with a (1,4)-dioxane ring. Their structures were elucidated by the spectroscopic data analyses and quantum chemical electronic circular dichroism calculations. Meanwhile, compound 4 (SMG-1) significantly inhibited proliferation of HepG2 (IC 50 = 13.9 ± 0.3 μM) and HCCLM3 (IC 50 = 11.8 ± 0.2 μM) cells. We further explored the underlying mechanism of SMG-1 for hepatocellular carcinoma (HCC) cells death, and found that SMG-1 induced reactive oxygen to increase the level of BNIP3 through JNK/p53 pathway and decreased mitochondrial membrane potential, resulting in activating mitophagy. Moreover, SMG-1 up-regulated the Bax and cytoplasm level of Cyt-c to promote Caspase-9/Caspase-3-mediated apoptosis in HCC cells. Therefore, the leaves of S. dulcificum possess the ability to treat HCC. [Display omitted] • Synsepalum dulcificum has high medicinal and economic values. • Two pairs of undescribed enantiomeric coumarinolignans, three undescribed triterpenoids, along with twenty-five known compounds were isolated from Synsepalum dulcificum leaves. • Some compounds showed significantly antitumor activity against hepatocellular carcinoma cells. • Compound 4 induced reactive oxygen to activate mitophagy and promote Caspase-9/Caspase-3-mediated apoptosis in hepatocellular carcinoma cells. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major cause of chronic disability and death in young adults worldwide. Multiple cellular, molecular and biochemical changes impact the development and outcome of TBI. Neuronal cell apoptosis, which is an important pathological change in secondary brain damage, is crucial to determine the functional recovery after TBI. miR-21, a widely-reported oncogene, which can reduce cell apoptosis in cancer, has been confirmed to be a pronounced up-regulated miRNA after TBI in animal model. Our study is designed to investigate whether miR-21 has the function of antiapoptosis in experimental TBI model in vitro and to explore the possible regulatory mechanism of miR-21 on neuronal apoptosis. The scratch cell injury was performed to mimic TBI-induced apoptosis in neurons, and miR-21 agomir/antagomir was transfected to up-/down-regulate the miR-21 level. Our data suggests that miR-21 can reduce the number of TUNEL-positive neurons. Meanwhile, miR-21 decreased the expression level of PTEN, and increased the phosphorylation of Akt significantly. In neurons transfected with miR-21 agomir, the expression of Bcl-2 was promoted while the caspase-3, caspase-9 and Bax level were down-regulated, which are crucially the downstream apoptosis-related proteins of PTEN-Akt signaling pathway. In conclusion, miR-21 can exert the function of reducing neuronal apoptosis through activating the PTEN-Akt signaling pathway. Our research provides new insights into the molecular mechanisms of neuronal apoptosis following TBI, which reminds that miR-21may be a potential therapeutic target for TBI treatment. [ABSTRACT FROM AUTHOR]

• Silencing VCAM-1 and BMSCs synergistically improve cardiac function of MI rats. • Injection with BMSCs and sh-VCAM-1 increases CPR and survival rate of MI rats. • Injection with BMSCs and sh-VCAM-1 reduce the IS and myocardial apoptosis. • sh-VCAM-1 could inhibit the NF-κB signaling pathway. • sh-VCAM-1 enhances the therapeutic effects of BMSCs by NF-κB pathway. Bone mesenchymal stem cells (BMSCs) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). VCAM-1 can promote the migration of lymphocytes to the inflammatory zone. In the present study, we tried to explore whether VCAM-1 silenced-BMSCs have better therapeutic effects on MI. BMSCs were isolated and cultured followed by treatment of a lentivirus silencing VCAM-1 and NF-κB activator (PMA). Besides, MI rat models were also established and injected with treated BMSCs to detect the effect of VCAM-1 silenced-BMSCs in MI, as evidenced by detection of cardiac function, survival of rats within 72 h, infarct size and myocardial cell apoptosis. Moreover, the expression of NF-κB-regulated gene products was also determined. The implantation of sh-VCAM-1 BMSCs into MI rats resulted in more reductions in myocardial infarct size as well as myocardial cell apoptosis, improved cardiac function, the number of survived rats within 72 h, and survival time within 72 h compared with the individual treatments of either BMSCs or control. In addition, transplanted BMSCs down-regulated the expression of NF-κB-p65, MMP-9, TNF-α, and Bax, and up-regulated VEGF and Bcl-2 in myocardial tissue, which could be further enhanced by sh-VCAM-1 and rescued by PMA. Our study demonstrated that silencing VCAM-1 in BMSCs could inhibit inflammation and apoptosis, thus improving cardiac function in MI. [ABSTRACT FROM AUTHOR]