Study of fatigue damage behavior in off-axis CFRP composites using digital image correlation technology.

This study investigates the fatigue behavior of off-axis carbon fiber reinforced polymer (CFRP) composites under varying stress levels, with a focus on both tensile-tensile and compressive-compressive loading modes. We conduct a comprehensive analysis of energy dissipation and stiffness across various loading conditions, highlighting the critical role of fiber deflection effects in the recovery of tensile-tensile fatigue properties. Utilizing digital image correlation (DIC) technology, we identify both commonalities and distinctions in crack propagation pathways and failure mechanisms between these two fatigue scenarios. In the case of tensile-tensile fatigue, the predominant damage mechanism involves the development of multiple interlaminar shear cracks. These cracks initiate debonding at the fiber/resin interface, propagating from macrocracks at the edges to microcracks at the center, ultimately culminating in fiber pull-out failure. Conversely, in compressive fatigue, damage occurs centrally in the form of intralaminar shear cracks. As damage accumulates, these cracks progressively propagate along the fibers towards the edges, accompanied by localized fiber buckling, ultimately resulting in compressive failure. Furthermore, we determine a critical compressive strain threshold, which serves as a pivotal indicator of failure in compressive-compressive fatigue testing for off-axis CFRP composites.

Erythropoietin improves pulmonary hypertension by promoting the homing and differentiation of bone marrow mesenchymal stem cells in lung tissue.

Pulmonary arterial hypertension (PAH) is a chronic disease thatultimately progresses to right-sided heart failure and death. Erythropoietin (EPO) has been shown to have therapeutic potential in cardiovascular diseases, including PAH. In this study, we aimed to investigate the improvement effect of EPO pretreated bone marrow mesenchymal stem cells (BMSCs) on PAH. BMSCs were obtained from the bone marrow of male SD rats. Female rats were randomly divided into six groups, including control group, monocrotaline (MCT)-induced group, and four groups with different doses of EPO pretreated BMSCs. Lung tissue was taken for testing at 2 weeks of treatment. Our results showed EPO promoted homing and endothelial cell differentiation of BMSCs in the lung tissues of PAH rats. EPO and BMSCs treatment attenuated pulmonary arterial pressure, polycythemia, and pulmonary artery structural remodeling. Furthermore, BMSCs inhibited pulmonary vascular endothelial-to-mesenchymal transition (EndoMT) in PAH rats, which was further suppressed by EPO in a concentration-dependent manner. Meanwhile, EPO and BMSC treatment elevated pulmonary angiogenesis in PAH rats. BMSCs inhibited TNF-α, IL-1ß, IL-6, and MCP-1 in lung tissues of PAH rats, which was further decreased by EPO in a concentration-dependent manner. Thus, EPO improved pulmonary hypertension (PH) by promoting the homing and differentiation of BMSCs in lung tissue.

Systematic comparison of tools used for m6A mapping from nanopore direct RNA sequencing.

N6-methyladenosine (m6A) has been increasingly recognized as a new and important regulator of gene expression. To date, transcriptome-wide m6A detection primarily relies on well-established methods using next-generation sequencing (NGS) platform. However, direct RNA sequencing (DRS) using the Oxford Nanopore Technologies (ONT) platform has recently emerged as a promising alternative method to study m6A. While multiple computational tools are being developed to facilitate the direct detection of nucleotide modifications, little is known about the capabilities and limitations of these tools. Here, we systematically compare ten tools used for mapping m6A from ONT DRS data. We find that most tools present a trade-off between precision and recall, and integrating results from multiple tools greatly improve performance. Using a negative control could improve precision by subtracting certain intrinsic bias. We also observed variation in detection capabilities and quantitative information among motifs, and identified sequencing depth and m6A stoichiometry as potential factors affecting performance. Our study provides insight into the computational tools currently used for mapping m6A based on ONT DRS data and highlights the potential for further improving these tools, which may serve as the basis for future research.

Sleep loss impairs intestinal stem cell function and gut homeostasis through the modulation of the GABA signalling pathway in Drosophila.

Sleep is essential for maintaining health. Indeed, sleep loss is closely associated with multiple health problems, including gastrointestinal disorders. However, it is not yet clear whether sleep loss affects the function of intestinal stem cells (ISCs). Mechanical sleep deprivation and sss mutant flies were used to generate the sleep loss model. qRT-PCR was used to measure the relative mRNA expression. Gene knock-in flies were used to observe protein localization and expression patterns. Immunofluorescence staining was used to determine the intestinal phenotype. The shift in gut microbiota was observed using 16S rRNA sequencing and analysis. Sleep loss caused by mechanical sleep deprivation and sss mutants disturbs ISC proliferation and intestinal epithelial repair through the brain-gut axis. In addition, disruption of SSS causes gut microbiota dysbiosis in Drosophila. As regards the mechanism, gut microbiota and the GABA signalling pathway both partially played a role in the sss regulation of ISC proliferation and gut function. The research shows that sleep loss disturbed ISC proliferation, gut microbiota, and gut function. Therefore, our results offer a stem cell perspective on brain-gut communication, with details on the effect of the environment on ISCs.

Successful therapeutic intervention in new mouse models of frizzled 2-associated congenital malformations.

Frizzled 2 (FZD2) is a transmembrane Wnt receptor. We previously identified a pathogenic human FZD2 variant in individuals with FZD2-associated autosomal dominant Robinow syndrome. The variant encoded a protein with a premature stop and loss of 17 amino acids, including a region of the consensus dishevelled-binding sequence. To model this variant, we used zygote microinjection and i-GONAD-based CRISPR/Cas9-mediated genome editing to generate a mouse allelic series. Embryos mosaic for humanized Fzd2W553* knock-in exhibited cleft palate and shortened limbs, consistent with patient phenotypes. We also generated two germline mouse alleles with small deletions: Fzd2D3 and Fzd2D4. Homozygotes for each allele exhibit a highly penetrant cleft palate phenotype, shortened limbs compared with wild type and perinatal lethality. Fzd2D4 craniofacial tissues indicated decreased canonical Wnt signaling. In utero treatment with IIIC3a (a DKK inhibitor) normalized the limb lengths in Fzd2D4 homozygotes. The in vivo replication represents an approach for further investigating the mechanism of FZD2 phenotypes and demonstrates the utility of CRISPR knock-in mice as a tool for investigating the pathogenicity of human genetic variants. We also present evidence for a potential therapeutic intervention.

Juglans regia L. extract promotes osteogenesis of human bone marrow mesenchymal stem cells through BMP2/Smad/Runx2 and Wnt/ß-catenin pathways.

BACKGROUND: The present study investigates the effects of Juglans regia L. (walnut, JRL) leaves extract on osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs). METHODS: hBMSCs were incubated with different concentrations of JRL extract (10, 20, 40, or 80 µM). Cell proliferation was evaluated by Cell Counting Kit-8 assay (CCK-8) assay. ALP activity and Alizarin Red staining were used to assess the osteogenesis of BMSCs. Western blot was performed to measure the levels of proteins. RESULTS: Our results showed all concentrations of JRL extract had no significant effect on cell proliferation. JRL extract concentration-dependently promoted osteoblastic differentiation and cell autophagy of hBMSCs, characterized by the increased expression of pro-osteogenic markers alkaline phosphatase (ALP), osteocalcin (BGLAP), osterin, and osteoprotegerin (OPG) and autophagy marker proteins (LC3II, Beclin-1, and p62). Furthermore, JRL extract stimulated the activation BMP2/Smad/Runx2 and Wnt/ß-catenin signaling pathways in hBMSCs, which play key roles in osteogenesis differentiation. Meanwhile, BMP inhibitor (Noggin) and Wnt antagonist Dickkopf-1 (DKK1) both reversed the increases of BGLAP, osterin, and OPG expression induced by JRL extract. CONCLUSIONS: Our findings indicate that JRL extract regulated osteogenic differentiation and cell autophagy of hBMSCs through the BMP2/Smad/Runx2 and Wnt/ß-catenin pathways.

Rhizoma drynariae total flavonoids combined with calcium carbonate ameliorates bone loss in experimentally induced Osteoporosis in rats via the regulation of Wnt3a/ß-catenin pathway.

BACKGROUND: Rhizoma drynariae, a traditional Chinese herb, is commonly used in treatment of bone healing in osteoporotic fractures. However, whether the Rhizoma drynariae total flavonoids (RDTF) can promote the absorption of calcium and enhance the bone formation is unclear. The aim of the present study was to investigate the preventive effects of RDTF combined with calcium carbonate (CaCO3) on estrogen deficiency-induced bone loss. METHODS: Three-month-old Sprague-Dawley rats were ovariectomized (OVX) and then treated with CaCO3, RDTF, and their admixtures for ten weeks, respectively. The bone trabecular microstructure, bone histopathological examination, and serum biomarkers of bone formation and resorption were determined in the rat femur tissue. The contents of osteoprotegerin (OPG), receptor activator of the NF-κB (RANK), and its ligand (RANKL) in marrow were analyzed by ELISA, and the protein expressions of Wnt3a, ß-catenin, and phosphorylated ß-catenin (p-ß-catenin) were analyzed by Western blot. Statistical analysis was conducted by using one-way analysis of variance (ANOVA) followed by LSD post hoc analysis or independent samples t test using the scientific statistic software SPSS version 20.0 RESULTS: RDTF combined with CaCO3 could promote osteosis and ameliorate bone loss to improve the repair of cracked bone trabeculae of OVX rats. Furthermore, RDTF combined with CaCO3 also could prevent OVX-induced decrease in collagen fibers in the femoral tissue of ovariectomized rats and promote the regeneration of new bone or cartilage tissue, while CaCO3 supplementation promoted the increase in bone mineral content. Nevertheless, there was no difference in the expression of Wnt3a, ß-catenin and p-ß-catenin between osteopenic rats and RDTF treated rats, but RDTF combined with CaCO3 could activate the Wnt3a/ß-catenin pathway. CONCLUSIONS: RDTF combined with CaCO3 could ameliorate estrogen deficiency-induced bone loss via the regulation of Wnt3a/ß-catenin pathway.

Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy Combined with Radical Surgery and Capecitabine on Stage III Gallbladder Cancer.

Purpose: The aim of the study was to investigate the effect of hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) combined with radical surgery and capecitabine on stage III gallbladder cancer. Method: Seventy-eight patients with stage III gallbladder cancer treated in our hospital between December 2015 and April 2019 were retrospectively enrolled. Depending on the treatment approach, the patients were divided into the control group (radical surgery and capecitabine) and the HIPEC group (hyperthermic intraperitoneal perfusion chemotherapy combined with radical surgery and capecitabine). The patients were followed up by outpatient or through telephone until April 1, 2020. SPSS 19.0 software was applied for data analysis. Survival analysis was performed using the Kaplan-Meier method and parallel log-rank test. Results: There were 43 cases in the control group and 35 cases in the HIPEC group. There were no significant differences in operation time, lymph node metastasis, microvascular infiltration, and nerve invasion; there was no significant difference in postoperative complications between the two groups (P > 0.05). The average hospitalization time of the HIPEC group was 23.0 ± 6.9 days, which was longer than the 20.0 ± 5.8 days of the control group (P < 0.05). The body temperatures of HIPEC group patients at 0 h and 6 h after operation were higher than those of patients in the control group (P < 0.05); however, the body temperature of the two groups gradually became the same at 12-24 h after operation. There was no liver and kidney damage in the two groups after surgery. The platelets in the HIPEC group were less than those in the control group (P < 0.05). The median survival time of HIPEC was 19.2 months, which was longer than 15.3 months in the control group. The 1-year survival rates of the two groups were 91.43% vs. 76.71%, and the 2-year survival rates were 26.29% vs. 17.53%, respectively (P < 0.05). Conclusion: HIPEC combined with radical surgery and capecitabine for stage III gallbladder cancer can effectively prolong survival time without increasing surgery-related complications.

Osthole induces apoptosis of the HT-29 cells via endoplasmic reticulum stress and autophagy.

Endoplasmic reticulum stress (ERS) and autophagy are important pathways, which induce apoptosis of tumor cells. Osthole has been demonstrated to exert anticancer effects via the induction of apoptosis in several human colon cancer lines, but the mechanism underlying its involvement in the induction of ERS and autophagy in the human HT-29 colorectal cancer cell line remains unknown. The present study aimed to identify the possible signaling pathways involved in osthole-induced apoptosis of HT29 cells. Methodologically, colony formation and Cell Counting Kit-8 assays were used to assess cell proliferation and viability, respectively, while flow cytometry was performed to investigate apoptosis. Signaling pathways, including apoptosis, autophagy and ERS, were also investigated in the HT-29 cell line using western blot analysis. The results demonstrated that osthole inhibited cellular proliferation and viability in a dose-dependent manner. In addition, osthole induced the expression level of proteins associated with mitochondria-mediated cell apoptosis, autophagy and ERS. The association between autophagy and ERS in osthole-induced apoptosis in the HT-29 cell line was further clarified. Inhibiting cell autophagy with the inhibitor, 3-methyladenine, suppressed osthole-induced cell apoptosis and enhanced osthole-induced ERS. By contrast, alleviating ERS with the inhibitor, 4-phenylbutyric acid attenuated osthole-induced cell apoptosis and autophagy. In conclusion, osthole could significantly suppress the proliferation and viability of the HT-29 colorectal cancer cell line and induce cell apoptosis via autophagy and ERS. Furthermore, ERS may play a more important role in osthole-induced cell apoptosis.

Total flavonoids of Rhizoma Drynariae combined with calcium attenuate osteoporosis by reducing reactive oxygen species generation.

In the present study, the effects of total flavonoids of Rhizoma Drynariae (TFRD) and calcium carbonate (CaCO3) on osteoporosis (OP) were assessed in a rat model of OP. For this purpose, 36 Sprague-Dawley rats, aged 3 months, were randomly divided into a group undergoing sham surgery (sham-operated group), model group (OP group), CaCO3 group (OP + CaCO3 group), TFRD group (OP + TFRD group), TFRD combined with CaCO3 group (OP + TFRD + CaCO3 group) and TFRD and CaCO3 combined with N-acetyl cysteine group (OP + TFRD + CaCO3 + NAC group). The rat model of OP was established by bilateral ovariectomy. The changes in bone mineral density (BMD), bone volume parameters and bone histopathology in the rats from each group were observed. The levels of serum reactive oxygen species, superoxide dismutase (SOD), malondialdehyde, glutathione peroxidase (GSH-Px), interleukin (IL)-6, IL-1ß, TNF-α, and the levels of bone tissue runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), osteocalcin (BGP), PI3K, p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR) and p-mTOR were measured in the rats of each group. The induction of OP was associated with a marked decrease in BMD, bone mineral content, bone volume fraction and trabecular thickness, and decreased serum levels of SOD and GSH-Px. Moreover, the expressions of RUNX2, OPG, BGP were downregulated and an upregulation of p-PI3K, p-AKT and p-mTOR were observed in osteoporotic rats. However, treatment with TFRD and CaCO3 restored all the aforementioned parameters to almost normal values. Furthermore, the findings on histopathological evaluation were consistent with the biochemical observations. Taken together, the findings of the present study demonstrated that TFRD and CaCO3 significantly increased the antioxidant capacity in rats with OP, increased BMD and reduced bone mineral loss, and may be useful for the prevention and treatment of OP.

Regulation of Wnt receptor activity: Implications for therapeutic development in colon cancer.

Hyperactivation of Wnt/ß-catenin (canonical) signaling in colorectal cancers (CRCs) was identified in the 1990s. Most CRC patients have mutations in genes that encode components of the Wnt pathway. Inactivating mutations in the adenomatous polyposis coli (APC) gene, which encodes a protein necessary for ß-catenin degradation, are by far the most prevalent. Other Wnt signaling components are mutated in a smaller proportion of CRCs; these include a FZD-specific ubiquitin E3 ligase known as ring finger protein 43 that removes FZDs from the cell membrane. Our understanding of the genetic and epigenetic landscape of CRC has grown exponentially because of contributions from high-throughput sequencing projects such as The Cancer Genome Atlas. Despite this, no Wnt modulators have been successfully developed for CRC-targeted therapies. In this review, we will focus on the Wnt receptor complex, and speculate on recent discoveries about ring finger protein 43regulating Wnt receptors in CRCs. We then review the current debate on a new APC-Wnt receptor interaction model with therapeutic implications.

Curcuma's extraction attenuates propranolol-induced psoriasis like in mice by inhibition of keratin, proliferating cell nuclear antigen and toll-like receptor expression.

Curcuma was the dried rhizomes of Curcuma kwangsiensis S.G. Lee et C.F. Liang (Chinese name: e zhu), have been used in China for thousands of years. There are some reports have shown that curcumin, the major component of curcuma, has a good curative effect on psoriasis, but the mechanism is still unknown, so the present study was designed to investigate the effect of curcuma's extraction on psoriasis-like mouse, and to explore the mechanisms of therapy. First, we observed that curcuma's extractions effect on mitosis of mouse vaginal epithelial cells; then making psoriasis like model and measuring the score of skin damage on days 7 and 14; finally, we observed the expression of immune factors (CK14, CK16, CK17, PCNA, TLR-2, TLR-4, TLR-9) in propranolol induced psoriasis like rats. Curcuma's extraction prohibited the mitosis of mouse vaginal epithelial cells; curcuma's extractions have a significantly efficacy and dose dependent inhibition on imiquimod induced psoriasis like rats; and the expression of immune factors (CK14, CK16, CK17, PCNA, TLR-2, TLR-4, TLR-9) was decreasing in the curcuma's extraction treated groups compared with normal groups. Our research proved that curcuma's extractions have a significantly efficacy on psoriasis like rats, thus, curcuma's extractions can be a potential novel treatment for psoriasis. Furthermore, the expression of immune factors was decreasing after treatment with curcuma's extraction suggest us cytokines has strong relation with the mechanism of therapy for psoriasis. Our results contribute towards validation of curcuma in the treatment of psoriasis and other joint disorders.

Mixed adenoneuroendocrine carcinoma of the hepatic bile duct: a case report and review of the literature.

BACKGROUND: The World Health Organization's updated classification of digestive system neuroendocrine tumors in 2010 first proposed the classification of mixed adenoneuroendocrine carcinoma (MANEC). The incidence of biliary malignant tumors with neuroendocrine tumors accounts for less than 1% of all neuroendocrine tumors. Moreover, the incidence of hilar bile duct with MANEC is very rare. CASE PRESENTATION: A 65-year-old female patient came to our hospital for repeated abdominal pain for more than 4 months and skin sclera yellow staining for 1 week. Contrast-enhanced computed tomography imaging and magnetic resonance results suggested a hilar tumor for Bismuth-Corlette Type II. The patient underwent radical surgery for hilar cholangiocarcinoma. Finally, the patient was diagnosed with hilar bile duct MANEC, staged 1 (pT1N0M0) based on the eighth edition of the AJCC. Histopathology showed that the tumor was a biliary tumor with both adenocarcinoma and neuroendocrine carcinoma. No evidence of recurrence and metastasis after 20 months of follow-up. CONCLUSIONS: We first reported a MANEC that originated in the hilar bile duct. As far as we known, there were few reports of biliary MANEC, and the overall prognosis was poor. We also found that the higher the Ki-67 index, the worse the prognosis of this type of patient. Radical surgery is the most effective treatment.

Clinicopathological findings and imaging features of intraductal papillary neoplasms in bile ducts.

BACKGROUND: Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is considered an uncommon tumor, and there is limited understanding of IPMN-B. This study aimed to investigate the prognosis and influential factors of the IPMN-B from 58 cases. METHODS: The clinical data of 58 patients with pathologically confirmed IPMN-B admitted to our hospital from January 1, 2012 to August 2017 were collected and analyzed. The patients were followed up by outpatient or telephone until January 1, 2019. SPSS 19.0 software was applied for data analysis. Survival analysis was performed using Kaplan-Meier method and parallel Log-rank test. Prognostic factors were analyzed by univariate analysis and multiple Cox regression model. RESULTS: Among of all the patients, 26 cases were benign tumors and 32 cases were malignant tumors. The preoperative tumor markers CA242 and CEA of malignant IPNM-B patients were significantly higher than those in benign tumors (P < 0.05). Survival analysis showed that patients with malignant tumors had a worse prognosis. The median survival time of malignant IPMN-B patients was 40.6 ±  3.0 months, yet median survival time of benign IPMN-B patients was not reached (P = 0.19). The one-year survival rate and three-year survival rate of benign IPMN-B were 84% and 74% respectively. The one-year survival rate and three-year survival rate of malignant IPMN-B were 88% and 64% respectively. Univariate analysis showed that combined lymph node metastasis, surgical method, and differentiation degree could affect patients' prognosis (P < 0.05). Multivariate analysis showed differentiation degree was an independent risk factor affecting prognosis (OR = 0.06, 95% confidence interval: 0.007∼0.486, P < 0.05). CONCLUSION: The levels of CEA and CA242 were helpful to identify benign and malignant of IPNM-B. Moreover, radical surgical resection could prolong patients' survival. Finally, differentiation degree was an independent risk factor affecting malignant IPNM-B prognosis.

LDL receptor-related protein LRP6 senses nutrient levels and regulates Hippo signaling.

Controlled cell growth and proliferation are essential for tissue homeostasis and development. Wnt and Hippo signaling are well known as positive and negative regulators of cell proliferation, respectively. The regulation of Hippo signaling by the Wnt pathway has been shown, but how and which components of Wnt signaling are involved in the activation of Hippo signaling during nutrient starvation are unknown. Here, we report that a reduction in the level of low-density lipoprotein receptor-related protein 6 (LRP6) during nutrient starvation induces phosphorylation and cytoplasmic localization of YAP, inhibiting YAP-dependent transcription. Phosphorylation of YAP via loss of LRP6 is mediated by large tumor suppressor kinases 1/2 (LATS1/2) and Merlin. We found that O-GlcNAcylation of LRP6 was reduced, and the overall amount of LRP6 was decreased via endocytosis-mediated lysosomal degradation during nutrient starvation. Merlin binds to LRP6; when LRP6 is less O-GlcNAcylated, Merlin dissociates from it and becomes capable of interacting with LATS1 to induce phosphorylation of YAP. Our data suggest that LRP6 has unexpected roles as a nutrient sensor and Hippo signaling regulator.

Electroacupuncture Prevents Osteoarthritis of High-Fat Diet-Induced Obese Rats.

The effects of acupuncture on osteoarthritis (OA) pathogenesis have been demonstrated in vitro and in animal models. However, the potential for acupuncture to mediate protective effects on obese-induced OA has not been examined. Here, we investigated the effects of different acupuncture patterns on OA pathogenesis in high-fat diet- (HFD-) induced obese rats. After 12-week diet-induced obesity, obese rats were treated with three acupuncture protocols for 2 weeks, including ST36, GB34, and ST36+GB34. The results showed that the three acupuncture protocols both prevented obesity-induced cartilage matrix degradation and MMP expression and mitigated obesity-induced systemic and local inflammation but had different regulatory effects on lipid metabolism and gut microbiota disorder of obese-induced OA rats. Furthermore, the three acupuncture protocols increased the microbial diversity and altered the structure of community of feces in obese rats. We found that ST36 and GB34 could inhibit proinflammatory shift in the gut microbiome with an increase in the ratio of Bacteroidetes/Firmicutes and promote the recovery of relative abundance of Clostridium, Akkermansia, Butyricimonas, and Lactococcus. Although both ST36 and GB34 had an anti-inflammatory effect on serum inflammatory mediators, only the acupuncture protocol with both ST36 and GB34 could effectively inhibit LPS-mediated joint inflammation in obesity rats. Therefore, relieving obesity-related chronic inflammation, lipid metabolism disorder, and gut microbiota disorder may be an important mechanism for acupuncture with ST36 and GB34 to promote OA recovery.

Downregulation of CLDN6 inhibits cell proliferation, migration, and invasion via regulating EGFR/AKT/mTOR signalling pathway in hepatocellular carcinoma.

Accumulating evidence showed that the claudin-6 (CLDN6) expression was abnormal in many cancers, while its expression and biological functions in hepatocellular carcinoma (HCC) is still unclear. The present study demonstrated that CLDN6 was upregulated in HCC tissues compared with tumour-adjacent tissues. CLDN6 silencing was significantly inhibited proliferation, migration, and invasion of HepG2 cells. Meanwhile, downregulation of CLDN6 remarkably inhibited the activation of EGFR/AKT/mTOR signalling pathway. Interestingly, the effect of CLDN6 overexpression on HepG2 cell proliferation and invasion could be inhibited by EGFR/AKT/mTOR signalling pathway inhibitor (AG1478). SIGNIFICANCE OF THE STUDY: These findings suggested that CLDN6 may act as an oncogene in HCC and improve HepG2 cell proliferation, migration, and invasion may via EGFR/AKT/mTOR signalling pathway.

Clinical Research on Prognostic Evaluation of Subjects With IPF by Peripheral Blood Biomarkers, Quantitative Imaging Characteristics and Pulmonary Function Parameters.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an irreversible and progressive fatal interstitial lung disease with a poor prognosis. The aim of this study is to investigate the predictive value of combined blood biomarkers, pulmonary function and quantitative monitoring by computer-aided diagnosis (CAD) system in IPF patients. METHODS: Pulmonary baseline function and pathological features of 126 patients with IPF were analyzed using spirometry and chest X-ray. Patients were divided into survival group and non-survival group after 5 years follow-up. The relationships the levels of peripheral blood biomarkers, quantitative imaging characteristics and pulmonary function were analyzed between the two groups. RESULTS: The baseline level of serum Krebs von den Lungen-6 (KL-6) and C-X-C motif chemokine 13 (CXCL13) were moderately or highly correlated with annual changes in forced vital capacity (FVC), carbon monoxide diffusing capacity (DLCO), total lung capacity (TLC), total interstitial lung disease (ILD) lesions, and the volume changes of reticular. The baseline level of serum KL-6 was higher than the cut-off value of 800.0U/ml and baseline level of serum CXCL13 was higher than the cut-off value of 62.0pg/ml. IPF patients with baseline levels of serum KL-6 and CXCL13 lower than the cut-off value had longer median survival time. CONCLUSIONS: Serum KL-6 and CXCL13 may be predictive biomarkers for the outcomes of patients with IPF patients and their baseline levels were related to the progression of pulmonary function and quantitative monitoring by CAD system.

Effects of swimming on pain and inflammatory factors in rats with lumbar disc herniation.

The aim of the present study was to identify the effect of swimming on nerve root pain in rats with lumbar disc herniation (LDH). A total of 72 male Sprague Dawley rats (215±15 g) were randomly divided into three groups (n=24/group): The sham operation, model and exercise intervention groups, with the latter undergoing 4 weeks of swimming training. On days 0, 7, 14 and 28 following surgery, the changes in the post-limb mechanical claw threshold, the phospholipase A2 (PLA2), interleukin (IL)-6 and tumor necrosis factor (TNF)-α mRNA expression levels, the secretory PLA2 (sPLA2) expression, the IL-6 and TNF-α content, the nuclear factor (NF)-κBp65 protein expression level in the nucleus pulposus, and the apoptotic rate of the nucleus pulposus cells were detected. The results demonstrated that, in the model group, the threshold of hind paw withdrawal was decreased, and that the sPLA2 expression, IL-6 and TNF-α content, PLA2, IL-6 and TNF-α mRNA and NF-κBp65 protein expression levels in the nucleus pulposus were increased. The apoptotic rate of the nucleus pulposus cells was increased from day 7 following surgery, as compared with the sham operation group. In the exercise intervention group, the hind paw withdrawal threshold increased and the TNF-α and IL-6 content, sPLA2 expression and PLA2, IL-6 and TNF-α mRNA and NF-κBp65 protein expression levels were decreased from day 14 following surgery, and the apoptotic nucleus pulposus cells were decreased from day 7 following surgery, as compared with the model group. Collectively, the present data suggest that swimming can significantly reduce nerve root pain and inhibit inflammatory reaction in LDH, which can have positive effects on the treatment of LDH.

Loss of Myeloid-Specific TGF-ß Signaling Decreases CTHRC1 to Downregulate bFGF and the Development of H1993-Induced Osteolytic Bone Lesions.

The role of myeloid cell-specific TGF-ß signaling in non-small-cell lung cancer (NSCLC)-induced osteolytic bone lesion development is unknown. We used a genetically engineered mouse model, Tgfbr2LysMCre knockout (KO), which has a loss of TGF-ß signaling specifically in myeloid lineage cells, and we found that the area of H1993 cell-induced osteolytic bone lesions was decreased in Tgfbr2LysMCre KO mice, relative to the area in control littermates. The bone lesion areas were correlated with tumor cell proliferation, angiogenesis, and osteoclastogenesis in the microenvironment. The smaller bone lesion area was partially rescued by bFGF, which was expressed by osteoblasts. Interestingly, bFGF was able to rescue the osteoclastogenesis, but not the tumor cell proliferation or angiogenesis. We then focused on identifying osteoclast factors that regulate bFGF expression in osteoblasts. We found that the expression and secretion of CTHRC1 was downregulated in osteoclasts from Tgfbr2LysMCre KO mice; CTHRC1 was able to promote bFGF expression in osteoblasts, possibly through the Wnt/ß-catenin pathway. Functionally, bFGF stimulated osteoclastogenesis and inhibited osteoblastogenesis, but had no effect on H1993 cell proliferation. On the other hand, CTHRC1 promoted osteoblastogenesis and H1993 cell proliferation. Together, our data show that myeloid-specific TGF-ß signaling promoted osteolytic bone lesion development and bFGF expression in osteoblasts; that osteoclast-secreted CTHRC1 stimulated bFGF expression in osteoblasts in a paracrine manner; and that CTHRC1 and bFGF had different cell-specific functions that contributed to bone lesion development.