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Radiation pneumonitis (RP) is a prevalent and fatal complication of thoracic radiotherapy due to the lack of effective treatment options. RP primarily arises from mitochondrial injury in lung epithelial cells. The mitochondrial-derived peptide MOTS-c has demonstrated protective effects against various diseases by mitigating mitochondrial injury. C57BL/6 mice were exposed to 20 Gy of lung irradiation (IR) and received daily intraperitoneal injections of MOTS-c for 2 weeks. MOTS-c significantly ameliorated lung tissue damage, inflammation, and oxidative stress caused by radiation. Meanwhile, MOTS-c reversed the apoptosis and mitochondrial damage of alveolar epithelial cells in RP mice. Furthermore, MOTS-c significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells and primary mouse lung epithelial cells. Mechanistically, MOTS-c increased the nuclear factor erythroid 2-related factor (Nrf2) level and promoted its nuclear translocation. Notably, Nrf2 deficiency abolished the protective function of MOTS-c in mice with RP. In conclusion, MOTS-c alleviates RP by protecting mitochondrial function through an Nrf2-dependent mechanism, indicating that MOTS-c may be a novel potential protective agent against RP. [ABSTRACT FROM AUTHOR]

The oriental river prawn, Macrobrachium nipponense, is an economically and nutritionally important freshwater crustacean in China. However, in recent years, some diseases have emerged in M. nipponense. In the present study, a pathogenic bacterium from M. nipponense with a red hepatopancreas was isolated. Then, through phenotypic analysis, biochemical analysis and genotypic identification, the MN strain was identified as a member of the Bacillus cereus group. The pathogenic mechanism analysis showed that the MN strain had virulence genes, including nheA, cytK and bceT gene, and could secrete urease and haemolysin. Furthermore, the drug sensitivity test suggested Cefazolin, amikacin, gentamicin and chloramphenicol could significantly inhibit the growth of the MN strain. All these results provide a theoretical basis for clinical medication to prevent or treat disease caused by MN strain in M. nipponense. [ABSTRACT FROM AUTHOR]

Backgrounds: Myeloma‐related bone disease (MBD) is a common complication of multiple myeloma (MM), which can both decrease life quality and influence the prognosis of the patients. We have found that CCN1 stimulated proliferation and differentiation of osteoblasts in MM in vitro and in vivo, while its mechanism still remains unknown. Method: Bone marrow mononuclear cells were collected from MM patients and differentiated into the osteoblasts. After co‐culture with CCN1 in vitro, the intracellular signaling antibody array and western blot were performed to explore the signaling pathway. Furthermore, GSK3β inhibitor TWS119 was used to check the pathway of CCN1 might have on osteoblasts in vitro. Results: For the protein array kit, the expressions of GSK3β, 4E‐BP1, and PTEN are decreased in CCN1 group. For western blots, the CCN1 group also has lower expression comparing to the control group in PTEN (P =.031). Meanwhile p‐AKT and cyclinD1 levels have increased in the CCN1 group (P =.002, P =.039). After adding TWS119 as another group, western blot was performed again to verify the pathway. For upstream proteins PTEN and p‐AKT, TWS119 group has higher expression level compared to that in CCN1 group (P =.003, P =.001). And for downstream protein cyclinD1, TWS119 group also presented higher level than the control group (P =.02). CCN1 could have almost the same effect on GSK3β as the specific inhibitor TWS119 had. Conclusions: CCN1 can stimulate osteoblasts through PTEN/AKT/GSK3β/cyclinD1 pathway in MBD, which has the potential to be a novel therapy of MBD. [ABSTRACT FROM AUTHOR]

Cysteine-rich 61 (CYR61/CCN1), a secreted protein in bone marrow (BM) microenvironment, has diverse effects on many cellular activities such as growth and differentiation. However, the effect of CCN1 on osteoblasts (OBs) in myeloma bone disease remains unclear. In our study, the level of CCN1 in multiple myeloma (MM) patients was detected by ELISA and RT-PCR. The proliferation and differentiation of OBs from MM patients were observed after stimulated by CCN1 in vitro. The myeloma cells transduced with CYR61 gene (RPMI‑8226/CYR61) were injected in a mouse model to evaluate the efficacy of CCN1 in vivo and compare with zoledronic acid. The results showed that CYR61/CCN1 levels in BM supernatant and OBs both elevated significantly in all newly diagnosed MM patients, especially in patients without bone disease (P=0.001 and P<0.001). After 30 ng/l CCN1 stimulation for 24 h, the quantity and mineralization of OBs increased significantly in vitro (P=0.046 and 0.048). The transcription factors of Wnt pathway, runt-related transcription factor 2 (Runx2) and β-catenin were upregulated in OBs after CCN1 stimulation (P=0.012 and 0.011). After injection of RPMI‑8226 cells, bone lesions were observed obviously by microCT and histochemistry at 7 weeks. Radiographic analysis of the bones showed decreased resorption in CCN1 overexpression group and zoledronic acid group, while severe resorption in negative control. Furthermore, trabecular bone volume in CCN1 overexpression group (1.7539±0.16949) was significantly higher than zoledronic acid group (1.2839±0.077) (P=0.012). In conclusion, CCN1 can stimulate the proliferation and differentiation of OBs in vitro and contribute to bone remodeling in vivo in MBD.