Increasing lines of evidence identified that dexmedetomidine (DEX) exerted protective effects against sepsis-stimulated acute lung injury via anti-inflammation, anti-oxidation and anti-apoptosis. However, the mechanisms remain unclear. Herein, we investigated whether DEX afforded lung protection by regulating the process of mitochondrial dynamics through the HIF-1a/HO-1 pathway in vivo and in vitro. Using C57BL/6J mice exposed to lipopolysaccharide, it was initially observed that preemptive administration of DEX (50μg/kg) alleviated lung pathologic injury, reduced oxidative stress indices (OSI), improved mitochondrial dysfunction, upregulated the expression of HIF-1α and HO-1, accompanied by shifting the dynamic course of mitochondria into fusion. Moreover, HO-1-knockout mice or HO-1 siRNA transfected NR8383 cells were pretreated with HIF-1α stabilizer DMOG and DEX to validate the effect of HIF-1a/HO-1 pathway on DEX-mediated mitochondrial dynamics in a model of endotoxin-induced lung injury. We found that pretreatment with DEX and DMOG distinctly relieved lung injury, decreased the levels of mitochondrial ROS and mtDNA, reduced OSI, increased nuclear accumulation of HIF-1a and HO-1 protein in wild type mice but not HO-1 KO mice. Similar observations were recapitulated in NC siRNA transfected NR8383 cells after LPS stimulation but not HO-1 siRNA transfected cells. Concertedly, DEX reversed the impaired mitochondrial morphology in LPS stimulated-wild type mice or NC siRNA transfected NR8383 cells, upregulated the expression of mitochondrial fusion protein, while downregulated the expression of fission protein in HIF-1a/HO-1 dependent pathway. Altogether, our data both in vivo and in vitro certified that DEX treatment ameliorated endotoxin-induced acute lung injury by preserving the dynamic equilibrium of mitochondrial fusion/fission through the regulation of HIF-1a/HO-1 signaling pathway.

Neuropathic pain associated with cancers was caused by tumor itself or tumor therapy, which was aggravated by sensitizing nociceptor sensory neurons. The tumor microenvironment contributed to tumorigenesis, tumor progress, tumor metastasis, tumor immune resistance, tumor chemotherapy, and tumor immunotherapy. In the current study, we explored the contributions of the infiltrated dendritic cells insulted by Wnt1 in tumor microenvironment to neuropathic pain associated with cancers. The different transcriptome of infiltrated dendritic cells from lung adenocarcinoma and from juxtatumor indicated that thousands of genes were up-regulated by the tumor microenvironment, some of which were enriched in pain pathway. The paracrine factors such as TNF, WNT10A, PDGFA, and NRG1 were also elevated in tumor-infiltrating dendritic cells. The receptors of paracrine factors were highly expressed on dorsal root ganglia (DRG), and not altered in pain conditions. Single-cell RNA-seq data unveiled that TNFSF1 was expressed in neurons, microglial cells, and endothelial cells. PDGFRA was only expressed in microglial cells. ERBB3 was only expressed in neurons. FZD1 and 3 were extensively expressed in various cells. The components composed of signaling pathways associated with the above paracrine factors participated in pain networks. The transcription factors activated by paracrine factor signaling regulated the expression of genes associated with pain. TNF, WNT10A, and PDGFA were extensively expressed in multiple cancers, but their expression in patients did not distribute normally. These data indicated that infiltrated dendritic cells in tumor microenvironment promoted neuropathic pain by sensitizing nociceptor sensory neurons via paracrine factors. Blockage of paracrine factor signaling might alleviate cancer pain.

Abstract:A new ionone glycoside, frehmaglutoside I (1), and three new rhemaneolignans A-C (2-4) were isolated from the 95% EtOH extract of the roots of Rehmannia glutinosa. Their structures were determined by extensive spectroscopic (UV, IR, HR-ESI-MS, 1D and 2D NMR) analyses. In addition, these compounds were evaluated for their protective effects on cardiocytes impaired by doxorubicin in H9c2 cells. Among them, compounds 1-3 exhibited protective effects against DOX-induced cardiotoxicity.

Two new ionone glycosides, named frehmaglutoside G (1) and frehmaglutoside H (2), together with six known compounds, rehmapicroside (3), sec-hydroxyaeginetic acid (4), dihydroxy-β-ionone (5), trihydroxy-β-ionone (6), rehmaionoside A (7) and rehmaionoside C (8), were isolated from the 95% EtOH extract of the dried roots of Rehmannia glutinosa Libosch. Their structures were determined on the basis of extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D and 2D NMR ((1)H-(1)H COSY, HSQC, HMBC and NOESY) methods. The absolute configurations were confirmed via the circular dichroism spectra.

Four new monoterpenoid glycosides 1-4, named magnoliaterpenoid A-D, were isolated from a 50% aqueous acetone extract of flower buds of Magnolia biondii, along with one known compound, (1'R,3'S,5'R,8'S,2Z,4E)-dihydrophaseic acid 3-O-β-d-glucopyranoside (5). Their structures and relative configuration were identified by extensive spectroscopic analysis (IR, UV, MS, 1D and 2D NMR). The aglycones of these four new compounds possess seven-membered rings systems, which are very rare. A plausible biosynthetic route for the four new compounds was proposed via the biogenetic isoprene rule. Compounds 1, 2, 3, and 4 showed no antimicrobial activity at the concentration range of 1.95-250 µg/mL.

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Alpha lipoic acid (ALA), a natural lipophilic compound, plays an important role in regulating several metabolic pathways due to its antioxidant properties. This study aims to investigate whether ALA could be used as a feed additive to enhance the antioxidant capacity of the ovary tissue in hens exposed to heat stress (HS). One hundred and sixty 128-days-old female chickens were randomly assigned into four groups: the control group (Con), ALA treatment group (ALA), ALA and HS treatment group (ALA + HS), and HS treatment group (HS). The ALA and ALA + HS groups were fed a basal diet with 0.25% ALA, whereas the Con and HS groups were fed a basal diet only. Serum oestradiol, progesterone levels, biomarkers of antioxidant capacity, and endoplasmic reticulum (ER) stress markers were detected in the ovaries of heat-stressed chickens. HS decreased serum oestradiol and progesterone concentrations compared with the control group, whereas dietary ALA (0.25%) increased oestradiol and progesterone levels in the serum of heat-stressed hens. Malondialdehyde concentration in the ovary was higher in the HS group than that of the ALA + HS group. Compared with the HS group, ALA increased the enzymatic activities of superoxide dismutase, glutathione peroxidase, and catalase in the ovaries of ALA + HS group. Simultaneously, ALA enhanced the total antioxidative capacity of the ovaries of heat-stressed hens. Moreover, ALA also significantly inhibited the increased expression of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein, which are two markers of ER stress, and heat shock protein 70, a key biomarker of heat stress, in the ovaries of the ALA + HS group as compared to those of the HS group. This work implied that dietary ALA supplementation improved the antioxidant capacity and attenuated the HS-induced reduction of serum oestradiol and progesterone levels and modulated the oxidative and ER stress, which are involved in the protective effect of ALA in hens exposed to hyperthermia.

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