Lung cancer (LC) is one of the most serious malignant tumors, which has the fastest growing morbidity and mortality worldwide. A role of the lung microbiota in LC pathogenesis has been analyzed, but a comparable role of the gut microbiota has not yet been investigated. In this study, the gut microbiota of 30 LC patients and 30 healthy controls were examined via next-generation sequencing of 16S rRNA and analyzed for diversity and biomarkers. We found that there was no decrease in significant microbial diversity (alpha diversity) in LC patients compared to controls ( P observed = 0.1422), while the composition (beta diversity) differed significantly between patients and controls (phylum [stress = 0.153], class [stress = 0.16], order [stress = 0.146], family [stress = 0.153]). Controls had a higher abundance of the bacterial phylum Actinobacteria and genus Bifidobacterium , while patients with LC showed elevated levels of Enterococcus . These bacteria were found as possible biomarkers for LC. A decline of normal function of the gut microbiome in LC patients was also observed. These results provide the basic guidance for a systematic, multilayered assessment of the role of the gut microbiome in LC, which has a promising potential for early prevention and targeted intervention.

Osteoarthritis is a common cause of functional deterioration in older adults and is an immense burden on the aging population. Altered chondrogenesis is the most important pathophysiological process involved in the development of osteoarthritis. However, the molecular mechanism underlying the regulation of chondrogenesis in patients with osteoarthritis requires further elucidation, particularly with respect to the role of microRNAs. MiR-21 expression in cartilage specimens was examined in 10 patients with knee osteoarthritis and 10 traumatic amputees. The effect of miR-21 on chondrogenesis was also investigated in a chondrocyte cell line. The effect of miR-21 on the expression of growth differentiation factor 5 (GDF-5) was further assessed by luciferase reporter assay and western blot. We found that endogenous miR-21 is upregulated in osteoarthritis patients, and overexpression of miR-21 could attenuate the process of chondrogenesis. Furthermore, we identified GDF-5 as the direct target of miR-21 during the regulation of chondrogenesis. Our data suggest that miR-21 has an important role in the pathogenesis of osteoarthritis and is a potential therapeutic target.

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Statins are widely used hypocholesterolemic drugs that block the mevalonate pathway. Some studies have shown that statins may have the potential to inhibit intervertebral disk (IVD) degeneration (IDD). Interleukin (IL)-1β, a catabolic cytokine, is a key regulator of IDD. This study aimed to investigate the mechanism underlying the effect of simvastatin on IDD. The viability of nucleus pulposus (NP) cells was determined by the methyl-thiazolyl-tetrazolium (MTT) assay. The apoptosis of NP cells was measured by flow cytometric analysis, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blotting of relevant apoptotic proteins. The protein levels of catabolic factors and anabolic factors were determined by western blotting. The cells were stimulated with IL-1β in the absence or presence of simvastatin to investigate the effects on matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, type II collagen, and aggrecan expression. Our findings indicate that simvastatin considerably inhibited IL-1β-induced apoptosis in NP cells. We also found that simvastatin attenuated IL-1β-induced expression and MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 activities and also reduced the decrease in type II collagen and aggrecan expression. In addition, simvastatin considerably suppressed the nuclear translocation and activation of nuclear factor-kappa B (NF-KB) by inhibiting p65 phosphorylation and translocation and blocking inhibitor kB-α degradation. It also inhibited MAPK pathway activation by blocking c-Jun N-terminal kinase (JNK), p38, and ERK phosphorylation. The results of our study revealed that simvastatin is a potential agent for IDD prevention and treatment.

Bone is one of the most common sites for metastasis in breast cancer (BC). Micro-metastasis in bone marrow was detected in 30% of patients with stage I, II, or III BC at primary surgery and is a strong indicator of poor prognosis. The role dietary soy isoflavones play in BC with bone micro-metastasis is unclear. In this study, we examined the effects of genistein, daidzein, (−)-equol or a mixture of soy isoflavones on BC with bone micro-metastasis using an experimental model of murine mammary cancer 4T1 cells engineered with luciferase. A small number (1,000) of 4T1 cells were injected into the tibia of female Balb/c mice to establish micro-tumors in bone. Soy isoflavones were supplemented in the AIN-93G diet at 750 mg/kg and were provided to mice from 3 weeks before to 3 weeks after cell injection. Bioluminescent imaging was conducted on day 2 (D2), D6, D8, D16 and D20 post cell injection and the results indicated dietary soy isoflavones enhanced the growth of bone micro-tumors on D8. Furthermore, dietary soy isoflavones stimulated metastatic tumor formation in lungs and increased Ki-67 protein expression in these metastasized tumors. In vitro, soy isoflavones (< 10 µM) had limited effects on the growth, motility or invasion of 4T1 cells. Thus, the in vivo stimulatory effect could be likely due to systemic effects between the host, 4T1 tumors and soy isoflavones. In conclusion, soy isoflavones stimulate BC with bone micro-metastasis in mice and further investigations are needed regarding their consumption by BC survivors.

Environmental stressors caused by inadequate aquaculture management strategies suppress the immune response of fish and make them more susceptible to diseases. Therefore, efforts have been made to relieve stress in fish by using various functional feed additives in the diet, including probiotics. The present work evaluates the effects of Lactobacillus rhamnosus (LR) on physiological stress response, blood chemistry and mucus secretion of red sea bream (Pagrus major) under low salinity stress. Fish were fed four diets supplemented with LR at [0 (LR0), 1 × 10 (LR1), 1 × 10 (LR2) and 1 × 10 (LR3) cells g] for 56 days. Before stress, blood cortisol, urea nitrogen (BUN) and total bilirubin (T-BIL) showed no significant difference (P > 0.05), whereas plasma glucose and triglyceride (TG) of fish-fed LR2 and LR3 diets were significantly lower (P < 0.05) than those of the other groups. Plasma total cholesterol (T-CHO) of fish-fed LR3 diet was significantly (P < 0.05) lower than that of the other groups. Furthermore, total plasma protein, mucus myeloperoxidase activity and the amount of mucus secretion were significantly enhanced in LR-supplemented groups when compared with the control group (P < 0.05). After the application of the low salinity stress test, plasma cortisol, glucose, T-CHO and TG contents in all groups showed an increased trend significantly (P < 0.01) compared to the fish before the stress challenge. However, plasma total protein and the amount of secreted mucus showed a decreased trend in all groups. On the other hand, BUN, T-BIL and mucus myeloperoxidase activity showed no significant difference after exposure to the low salinity stress (P > 0.05). In addition, the fish that received LR-supplemented diets showed significantly higher tolerance against low salinity stress than the fish-fed LR-free diet (P < 0.05). The physiological status and the detected immune responses, including total plasma protein and mucus myeloperoxidase activity in red sea bream, will provide a more comprehensive outlook of the effects of probiotics to relieve stress in fish.

BackgroundRecent studies haveshown that ginsenoside Rg1, extracted from the dry roots of Panax notoginseng as a traditional Asian medicine, plays an anti-fibrosis role in myocardial remodeling. However, the mechanism still remains unclear. In the present study, we investigate the effect of ginsenoside Rg1on the collagenic remodeling of myocardium in chronic thromboembolic pulmonary hypertension (CTEPH), and its potential mechanism.MethodsA rat model of CTEPH was established by injecting thrombi through the jugular vein wice in2 weeks. Four weeks later, four groups (Group A: normal rats + normal saline; Group B: normal rats + Rg1; Group C: CTEPH model + normal saline; Group D: CTEPH model + Rg1) were established. Normal saline and Rg1 were administrated by intraperitoneal injection. Ineach group, we measured the hemodynamic parameters, as well as the right ventricle to left ventricle (RV/LV) thickness ratio. Myocardial tissue sections of the RV were stained by hematoxylin-eosin +gentian violet and the morphological characteristics were observed by light microscopy. The matrix metalloproteinases (MMP) -2 and −9 were detected by the western blot.ResultsCompared with Group A and Group B, the right ventricular systolic pressure was significantly increased in Group C and significantly decreased in Group D. Compared with Group A and Group B, the RV/LV thickness ratio of the rats was significantly higher in Group C and Group D. There was significant fibrosis with collagen in Group C compared with Group A and Group B, and less significant changes in Group D were observed compared with those in Group C. The expression of MMP-2 and MMP-9 exhibited a significant decrease in Group C and was also significantly decreased in Group D compared withGroup A and Group B. Also, a negative linear relationship was shown between collagen-I and the expression of MMP-2 and MMP-9.ConclusionsOur animal study showed that ginsenoside Rg1 positively affects myocardial remodeling and pulmonary hemodynamics in CTEPH. Upregulation of the expression of MMP-2 and MMP-9 could explain the beneficial effects of ginsenoside Rg1 in CTEPH.

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