High mobility group box 1/toll-like receptor 4/myeloid differentiation factor 88 signaling promotes progression of gastric cancer.

High mobility group box 1 and toll-like receptor 4/myeloid differentiation factor 88 signaling pathway have been indicated to have oncogenic effects in many cancers. However, the role of high mobility group box 1/toll-like receptor 4/myeloid differentiation factor 88 signaling pathway in the development of gastric cancer remains unclear. In this study, we demonstrated that high mobility group box 1, toll-like receptor 4, and myeloid differentiation factor 88 were overexpressed in gastric cancer tumors compared with the adjacent non-tumor tissues. The overexpression of high mobility group box 1, toll-like receptor 4, and myeloid differentiation factor 88 were correlated with tumor-node-metastasis stage (p = 0.0068, p = 0.0063, p = 0.0173) and lymph node metastasis (p = 0.0272, p = 0.0382, and p = 0.0495). Furthermore, we observed that knockdown of high mobility group box 1 by high mobility group box 1-small interfering RNA suppressed the expression of toll-like receptor 4 and myeloid differentiation factor 88. Blockage of high mobility group box 1/toll-like receptor 4/myeloid differentiation factor 88 signaling by high mobility group box 1-small interfering RNA resulted in elevation of apoptotic ratio and inhibition of cell growth, migration, and invasion by upregulating Bax expression and downregulating Bcl-2, matrix metalloproteinase-2, nuclear factor kappa B/p65 expression, and the nuclear translocation of nuclear factor kappa B/p65 in gastric cancer cells. Our findings suggest that high mobility group box 1/toll-like receptor 4/myeloid differentiation factor 88 signaling pathway may contribute to the development and progression of gastric cancer via the nuclear factor kappa B pathway and it also represents a novel potential therapeutic target for gastric cancer.

Optimal staging system for predicting the prognosis of patients with hepatocellular carcinoma in China: a retrospective study.

BACKGROUND: Several staging systems have been developed to evaluate patients with hepatocellular carcinoma (HCC), including the China Staging System (CS), the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system, and seventh edition; the Barcelona Clinic Liver Cancer (BCLC) staging system, and Cancer of the Liver Italian Program (CLIP) staging system. The optimal staging system for to evaluate patients in China with HCC has not been determined. This study was designed to determine the optimal staging system for predicting patient prognosis by comparing the performances of these four staging systems in a cohort of Chinese patients with HCC. METHODS: This study enrolled 307 consecutive Chinese patients with HCC in Shandong Province. The performances of the CS, TNM, BCLC, and CLIP staging systems were compared and ranked using a concordance index. Predictors of survival were identified using univariate and multivariate Cox model analyses. RESULTS: The mean overall survival of the patient cohort was 12.08 ± 11.87 months. Independent predictors of survival included tumor size, number of lesions, tumor thromboses, cirrhosis, serum albumin level and serum total bilirubin level. Compared with the other three staging systems, the CS staging system showed optimal performance as an independent predictor of patient survival. The BCLC staging system showed the poorest performance; its treatment algorithm was not suitable for patients in this study. CONCLUSIONS: CS was the most suitable staging system for predicting survival of patients with HCC in China.

Suppression of toll-like receptor 2 expression inhibits the bioactivity of human hepatocellular carcinoma.

Toll-like receptor (TLR) 2 signaling is regarded as one of the mechanisms of chronic inflammation, but it can also mediate tumor cell immune escape and tumor progression. However, the role of TLR2 in the progression of human hepatocellular carcinoma (HCC) remains unclear. The objective of the study was to examine the effect of TLR2 on the bioactivity of HCC cell lines, HepG2 and BEL-7402, and the relationship between high mobility group box1 (HMGB1) and TLR2. The expression of TLR2 and nuclear factor-kappaB/P65 (NF-κB/P65) in HepG2 and BEL-7402 was assayed by Western blot. Cells were transfected with specific small interfering RNAs of TLR2 (TLR2-siRNAs), then TLR2-siRNA-transfected cells were treated with recombinant HMGB1 (rHMGB1). Apoptosis was determined by flow cytometry. Results showed that TLR2 was expressed in HepG2 and BEL-7402 cells. The ability of proliferation, invasion, and migration in siRNA group was lower than that in blank group, and the apoptosis ratio was higher than that in blank group, respectively. NF-κB/P65 expression was declined in contrast with blank group. Downregulation of TLR2 by siRNA resulted in a significant inhibition of proliferation, invasion, migration, and NF-κB/P65 expression, and elevated apoptotic ratio. Conversely, rHMGB1 promoted proliferation, invasion, and migration, induced NF-κB/P65 expression, and inhibited cells apoptosis. Furthermore, downregulation of TLR2 weakened the role of rHMGB1. This study suggests TLR2 and HMGB1 are important targets for therapeutic intervention of HCC.

BpTCP19 targets BpWRKY53 to negatively regulate jasmonic acid- and dark-induced leaf senescence in Betula platyphylla.

TCP (TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1) is a plant-specific transcription factor that has garnered significant attention due to its wide-ranging involvement in the regulation of plant growth or developmental processes. However, the molecular mechanisms through which TCP genes orchestrate leaf senescence have not been extensively elucidated. BpTCP19, a member of the PCF subfamily in Betula platyphylla, and has high homology to AtTCP19. BpTCP19 displayed pronounced downregulation in response to methyl jasmonate (MeJA) and dark treatment. Overexpressing BpTCP19 in Betula platyphylla led to a delay in leaf senescence, resulting in prolonged leaf greenness under both MeJA and dark conditions. Transcriptome analysis revealed that overexpression of BpTCP19 induced alterations in the expression levels of genes linked to cell proliferation, hormone signaling transduction, and leaf senescence, including the early responsive factor BpWRKY53. Furthermore, through Yeast one-hybrid assays and GUS analysis, BpTCP19 was shown to bind to the promoter region of BpWRKY53, suppressing its expression and thereby retarding leaf senescence. This study elucidates the physiological and molecular functions of BpTCP19 as a central transcriptional regulatory module in leaf senescence and provides a potential target gene for delaying leaf senescence by mitigating sensitivity to external aging signals such as Jasmonic acid (JA) and darkness.

Siamese Network-Based All-Purpose-Tracker, a Model-Free Deep Learning Tool for Animal Behavioral Tracking.

Accurate tracking is the basis of behavioral analysis, an important research method in neuroscience and many other fields. However, the currently available tracking methods have limitations. Traditional computer vision methods have problems in complex environments, and deep learning methods are hard to be applied universally due to the requirement of laborious annotations. To address the trade-off between accuracy and universality, we developed an easy-to-use tracking tool, Siamese Network-based All-Purpose Tracker (SNAP-Tracker), a model-free tracking software built on the Siamese network. The pretrained Siamese network offers SNAP-Tracker a remarkable feature extraction ability to keep tracking accuracy, and the model-free design makes it usable directly before laborious annotations and network refinement. SNAP-Tracker provides a "tracking with detection" mode to track longer videos with an additional detection module. We demonstrate the stability of SNAP-Tracker through different experimental conditions and different tracking tasks. In short, SNAP-Tracker provides a general solution to behavioral tracking without compromising accuracy. For the user's convenience, we have integrated the tool into a tidy graphic user interface and opened the source code for downloading and using (https://github.com/slh0302/SNAP).

Effects of Moxibustion on the Levels of Insulin-Like Growth Factor 1: A Pilot Study.

Moxibustion () is a traditional Chinese medicine therapy performed using Artemisia argyii. Zusanli (, ST36) is an acupoint in the stomach meridian, long associated in ancient Chinese medical practices with the extension of life span when moxibustion is applied to it. The aim of this study was to investigate changes in insulin-like growth factor 1 (IGF-1) levels after application of moxibustion to ST36. Four healthy men and women participated in this 28-day trial and were randomly divided into 2 groups. Group A received moxibustion treatment from days 1 to 14, while group B received moxibustion treatment from days 15 to 28. Blood samples were taken 5 times during this study to measure serum IGF-1 (s-IGF-1) levels. The s-IGF-1 levels increased in both groups after 7 and 14 d of moxibustion therapy (group A: 11.02% [7 d] and 29.65% [14 d]; group B: 169.12% [7 d] and 274.85% [14 d]). After moxibustion therapy had been completed (day 14), s-IGF-1 levels continued to increase in group A (increases on day 21 and day 28 were 53.19% and 61.45%, respectively). There were no adverse events in either group. The s-IGF-1 levels were significantly raised in both groups after 7 and 14 d of moxibustion therapy. Moreover, once therapy had been completed, s-IGF-1 levels continued to increase in group A up to 14 d after the treatment.