Probiotic Lactobacillus johnsonii BS15 Promotes Growth Performance,Intestinal Immunity,and Gut Microbiota in Piglets

Probiotics and Antimicrobial Proteins - Numerous studies have investigated the beneficial effects of Lactobacillus johnsonii strain BS15 on mice and broilers. This study aimed to understand the...     

Conserved regulation of MAP kinase expression by PUF RNA-binding proteins

Mitogen-activated protein kinase (MAPK) and PUF (for Pumilio and FBF [fem-3 binding factor]) RNA-binding proteins control many cellular processes critical for animal development and tissue homeostasis. In the present work, we report that PUF proteins act directly on MAPK/ERK-encoding mRNAs to downregulate their expression in both the Caenorhabditis elegans germline and human embryonic stem cells. In C. elegans, FBF/PUF binds regulatory elements in the mpk-1 3′ untranslated region (3′ UTR) and coprecipitates with mpk-1 mRNA; moreover, mpk-1 expression increases dramatically in FBF mutants. In human embryonic stem cells, PUM2/PUF binds 3′UTR elements in both Erk2 and p38α mRNAs, and PUM2 represses reporter constructs carrying either Erk2 or p38α 3′ UTRs. Therefore, the PUF control of MAPK expression is conserved. Its biological function was explored in nematodes, where FBF promotes the self-renewal of germline stem cells, and MPK-1 promotes oocyte maturation and germ cell apoptosis. We found that FBF acts redundantly with LIP-1, the C. elegans homolog of MAPK phosphatase (MKP), to restrict MAPK activity and prevent apoptosis. In mammals, activated MAPK can promote apoptosis of cancer cells and restrict stem cell self-renewal, and MKP is upregulated in cancer cells. We propose that the dual negative regulation of MAPK by both PUF repression and MKP inhibition may be a conserved mechanism that influences both stem cell maintenance and tumor progression.     

Fibroblast Activation Protein Overexpression and Clinical Implications in Solid Tumors: A Meta-Analysis

Objective

Fibroblast activation protein (FAP) plays a vital role in tumor invasion and metastasis. Previous studies have reported its prognostic value in different tumors. However, the results of these reports remain controversial. In this study, a meta-analysis was performed to clarify this issue.

Methods

A search of the PubMed, Embase and CNKI databases was conducted to analyze relevant articles. The outcomes included the relations between FAP expression and histological differentiation, tumor invasion, lymph node metastasis, distant metastasis and overall survival (OS). Sensitivity analysis by FAP expression in different cells and tumor types were further subjected to sensitivity analyses as subgroups. Pooled odds ratios (ORs) and hazard ratios (HRs) were evaluated using the random-effects model.

Results

The global analysis included 15 studies concerning various solid tumors. For global analysis, FAP overexpression in tumor tissue displayed significant associations with poor OS and tumor progression (OS: HR = 2.18, P = 0.004; tumor invasion: OR = 4.48, P = 0.007; and lymph node metastasis: OR = 3.80, P = 0.004). The subgroup analyses yielded two notable results. First, the relation between FAP overexpression and poor OS and tumor lymph node metastasis was closer in the patients with FAP expression in tumor cells. Second, the pooled analyses of colorectal cancers or pancreatic cancers all indicated that FAP overexpression was associated with a detrimental OS (HR: 1.72, P = 0.009; HR: 3.18, P = 0.005, respectively). The magnitude of this effect was not statistically significant compared with that in patients with non-colorectal cancers or non-pancreatic cancers. These analyses did not display a statistically significant correlation between FAP expression and histological differentiation and distant metastasis in all of the groups.

Conclusions

FAP expression is associated with worse prognosis in solid tumors, and this association is particularly pronounced if FAP overexpression is found in the tumor cells rather than the stroma.     

Effect of red mold rice on antifatigue and exercise-related changes in lipid peroxidation in endurance exercise

This study evaluated the effect of red mold rice supplementation on antifatigue and exercise-related changes in lipid peroxidation of male adult Wistar rats through swimming exercise. Thirty 16-week-old rats were studied by dividing them into three groups (ten for each group). Other than the control group (CD), the other two groups were divided into a high-dose (HD) treatment group (5 g red mold rice/kg body weight for the HD group), and a low-dose (LD) group (1 g red mold rice/kg body weight for the LD group). Swimming endurance tests were conducted after 28 days of red mold rice supplementation, and the result showed that the treatment group showed a higher exercise time (CD, 78.0±6.4; LD, 104.2±9.6; and HD, 129.4±10.9 min; p<0.05) and a higher blood glucose concentration (CD, 76.67±8.08; LD, 111.34±8.50; and HD, 117.67±11.06 mg/dl; p<0.05) than the CD. Moreover, the blood lactate (CD, 45.00±0.90; LD, 31.41±1.80; and HD, 28.89±1.62 mg/dl; p<0.05), blood urea nitrogen (CD, 21.87±0.75; LD, 20.33±0.83; and HD, 20.53±1.09 mg/dl; p<0.05), and hemoglobin (CD, 14.20±0.21; LD, 13.70±0.55; and HD, 13.28±0.35 g/dl; p<0.05) were also significantly lower than those of the CD. Besides, the result suggested that the red mold rice supplementation may decrease the contribution of exercise-induced oxidative stress and improve the physiological condition of the rats.     

Titanium Elastic Nail (TEN) versus Reconstruction Plate Repair of Midshaft Clavicular Fractures: A Finite Element Study

BackgroundThe biomechanical characteristics of midshaft clavicular fractures treated with titanium elastic nail (TEN) is unclear. This study aimed to present a biomechanical finite element analysis of biomechanical characteristics involved in TEN fixation and reconstruction plate fixation for midshaft clavicular fractures.MethodsFinite element models of the intact clavicle and of midshaft clavicular fractures fixed with TEN and with a reconstruction plate were built. The distal clavicle displacement, peak stress, and stress distribution on the 3 finite element models were calculated under the axial compression and cantilever bending.ResultsIn both loading configurations, TEN generated the highest displacement of the distal clavicle, followed by the intact clavicle and the reconstruction plate. TEN showed higher peak bone and implant stresses, and is more likely to fail in both loading configurations compared with the reconstruction plate. TEN led to a stress distribution similar to that of the intact clavicle in both loading configurations, whereas the stress distribution with the reconstruction plate was nonphysiological in cantilever bending.ConclusionsTEN is generally preferable for treating simple displaced fractures of the midshaft clavicle, because it showed a stress distribution similar to the intact clavicle. However, TEN provides less stability, and excessive exercise of and weight bearing on the ipsilateral shoulder should be avoided in the early postoperative period. Fixation with a reconstruction plate was more stable but showed obvious stress shielding. Therefore, for patients with a demand for early return to activity, reconstruction plate fixation may be preferred.     

Auto‐phosphorylation of a voltage‐gated K+ channel controls non‐associative learning

Here, we characterize a new K⁺ channel–kinase complex that operates in the metazoan Caenorhabditis elegans to control learning behaviour. This channel is composed of a pore‐forming subunit, dubbed KHT‐1 (73% homology to human Kv3.1), and the accessory subunit MPS‐1, which shows kinase activity. Genetic, biochemical and electrophysiological evidence show that KHT‐1 and MPS‐1 form a complex in vitro and in native mechanosensory PLM neurons, and that KHT‐1 is a substrate for the kinase activity of MPS‐1. Behavioural analysis further shows that the kinase activity of MPS‐1 is specifically required for habituation to repetitive mechanical stimulation. Thus, worms bearing an inactive MPS‐1 variant (D178N) respond normally to touch on the body but do not habituate to repetitive mechanical stimulation such as tapping on the side of the Petri dish. Hence, the phosphorylation status of KHT‐1–MPS‐1 seems to be linked to distinct behavioural responses. In the non‐phosphorylated state the channel is necessary for the normal function of the touch neurons. In the auto‐phosphorylated state the channel acts to induce neuronal adaptation to mechanical stimulation. Taken together, these data establish a new mechanism of dynamic regulation of electrical signalling in the nervous system.     

Secretion of annexin A3 from ovarian cancer cells and its association with platinum resistance in ovarian cancer patients

Early detection of resistance to platinum-based therapy is critical for improving the treatment of ovarian cancers. We have previously found that increased expression of annexin A3 is a mechanism for platinum resistance in ovarian cancer cells. Here we demonstrate that annexin A3 can be detected in the culture medium of ovarian cancer cells, particularly these cells that express high levels of annexin A3. Levels of annexin A3 were then determined in sera from ovarian cancer patients using an enzyme-linked immunosorbent assay. Compared with those from normal donors, sera from ovarian cancer patients contain significantly higher levels of annexin A3. Furthermore, serum levels of annexin A3 were significantly higher in platinum-resistant patients than in platinum-sensitive patients. To gain insight into the mechanism of secretion, the ovarian cancer cell lines were examined using both transmission electron microscopy and immunoelectron microscopy. Compared with parent cells, there are significantly more vesicles in the cytoplasm of ovarian cancer cells that express high levels of annexin A3, and at least some vesicles are annexin A3-positive. Moreover, some vesicles appear to be fused with the cell membrane, suggesting that annexin A3 secretion may be associated with exocytosis and the release of exosomes. This is supported by our observation that ovarian cancer cells expressing higher levels of annexin A3 released increased numbers of exosomes. Furthermore, annexin A3 can be detected in exosomes released from cisplatin-resistant cells (SKOV3/Cis) by immunoblotting and immunoelectron microscopy.