Periostin (POSTN) expression in cancer cells and circulation has been related to poor prognosis of colorectal carcinoma (CRC). However, the role of POSTN expressed in intra-tumoral stroma on CRC progression remains largely unknown. This study enrolled 1098 CRC patients who received surgical treatment in Shanghai and Guangzhou, Mainland China. In Shanghai cohort, immunohistochemistry score of stromal POSTN expression increased consecutively from adjacent mucosa, primary CRC tissues, to metastatic CRC tissues (P < 0.001), while medium- and high-stromal POSTN expression, rather than epithelial POSTN expression, independently predicted unfavorable prognoses of CRC, adjusted for covariates including TNM stage and postoperative chemotherapy in multivariate Cox models. The results in Shanghai cohort were faithfully replicated in Guangzhou cohort. Stromal POSTN expression dose-dependently predicted an unfavorable prognosis of stage III CRC patients with postoperative chemotherapy in both cohorts. POSTN derived from colonic fibroblasts or recombinant POSTN significantly promoted proliferation, anchorage independent growth, invasion, and chemo-resistance of CRC cells; whereas these effects were counteracted via targeting to PI3K/Akt or Wnt/β-catenin signaling pathway. CRC cell RKO-derived factor(s) significantly induced POSTN production in colonic fibroblasts and autocrine POSTN promoted proliferation, migration, and anchorage independent growth of fibroblasts. Conclusively, stromal POSTN is prognostic and predictive for CRC via creating a niche to facilitate cancer progression. Targeting POSTN-induced signaling pathways may be therapeutic options for metastatic or chemoresistant CRC.

Baicalin has been reported to have anti-fibrosis effect; however, its mechanism still remains to be elucidated. Adenosine A2a receptor (A2aR) is a novel inflammation regulator, and transforming growth factor-β1 (TGF-β1)-induced extracellular signal regulated kinase1/2 (ERK1/2) signaling pathway plays an important role in idiopathic pulmonary fibrosis (IPF). This study was to explore the relationship of A2aR and TGF-β1-induced ERK1/2 in bleomycin (BLM)-induced pulmonary fibrosis in mice, and to investigate whether A2aR mediate the anti-fibrosis effect of Baicalin on BLM-induced pulmonary fibrosis.

After three decades of intensive research efforts, an effective vaccine against HIV-1 remains to be developed. Several broadly neutralizing antibodies to HIV-1, such as 10E8, recognize the membrane proximal external region (MPER) of the HIV-1 gp41 protein. Thus, the MPER is considered to be a very important target for vaccine design. However, the MPER segment has very weak immunogenicity and tends to insert its epitope residues into the cell membrane, thereby avoiding antibody binding. To address this complication in vaccine development, we herein designed a peptide, designated 10E8-4P, containing four copies of the 10E8 epitope as an immunogen. As predicted by structural simulation, 10E8-4P exhibits a well-arranged tandem helical conformation, with the key residues in the 10E8 epitope oriented at different angles, thus suggesting that some of these key residues may be exposed outside of the lipid membrane. Compared with a peptide containing a single 10E8 epitope (10E8-1P), 10E8-4P not only exhibited better antigenicity but also elicited neutralizing antibody response against HIV-1 pseudoviruses, whereas 10E8-1P could not induce detectable neutralizing antibody response. Importantly, antibodies elicited by 10E8-4P also possessed a strong ability to activate an antibody-dependent cell-mediated cytotoxicity (ADCC) reporter gene, thus suggesting that they may have ADCC activity. Therefore, this strategy shows promise for further optimization and application in future HIV-1 vaccine design.

Chronic kidney disease (CKD) has been regarded as a risk for bone health. The aim of this study was to evaluate the effect of CKD on bone defect repair in rats. Uremia was induced by subtotal renal ablation, and serum levels of BUN and PTH were significantly elevated four weeks after the second renal surgery. Calvarial defects of 5-mm diameter were created and implanted with or without deproteinized bovine bone mineral (DBBM). Micro-CT and histological analyses consistently revealed a decreased newly regenerated bone volume for CKD rats after 4 and 8 weeks. In addition, 1.4-mm-diameter cortical bone defects were established in the distal end of femora and filled with gelatin sponge. CKD rats exhibited significantly lower values of regenerated bone and bone mineral density (BMD) within the cortical gap after 2 and 4 weeks. Moreover, histomorphometric analysis showed an increase in both osteoblast number (N.Ob/B.Pm) and osteoclast number (N.Oc/B.Pm) in CKD groups due to hyperparathyroidism. Notably, collagen maturation was delayed in CKD rats as verified by Masson's Trichrome staining. These data indicate that declined renal function negatively affects bone regeneration in both calvarial and femoral defects.

The presence of diabetes mellitus (DM) is associated with increased liver morbidity and mortality risk in patients with chronic hepatitis B (CHB). Aim of this study was to identify factors associated with type 2 diabetes mellitus (T2DM) in CHB patients.

Diabetes is one of the major chronic diseases diagnosed worldwide with a common complication of diabetic nephropathy (DN). There are multiple possible mechanisms associated with DN. Aldose reductase (AR) and Toll-like receptor 4 (TLR4) may be involved in the occurrence and development of DN. Here, we describe the distribution of AR and TLR4 in cells and renal tissues of diabetic rats through a quantum dot (QD)-based immunofluorescence technique and conventional immunohistochemistry. As a new type of nanosized fluorophore, QDs have been recognized in imaging applications and have broad prospects in biomedical research. The results of the reported study demonstrate that both the AR and the TLR4 proteins were upregulated in the renal tissues of diabetic rats. Further, to explore the relationship between AR and TLR4 in the pathogenesis of DN, a dual-color immunofluorescent labeling technique based on QDs was applied, where the expressions of AR and TLR4 in the renal tissues of diabetic rats were simultaneously observed - for the first time, as far as we are aware. The optimized QD-based immunofluorescence technique has not only shown a satisfying sensitivity and specificity for the detection of biomarkers in cells and tissues, but also is a valuable supplement of immunohistochemistry. The QD-based multiplexed imaging technology provides a new insight into the mechanistic study of the correlation among biological factors as well as having potential applications in the diagnosis and treatment of diseases.

To evaluate whether the genetic susceptibility of T2D was associated with overall survival (OS) and disease-free survival (DFS) outcomes for breast cancer (BC).

Colorectal carcinoma is one of the common cancers in human. It has been intensely debated whether the in vitro cancer cell lines are closely enough for recapitulating the original tumor in understanding the molecular characteristic of CRC. Organoid as a new in vitro 3D culture system has sprang out in CRC study for the capability in reviving the original tissue. The aim of this study is to profile the gene expression of CRC organoid. The gene expression GSE64392 was from GEO database contained 20-patients-derived 37 organoid samples, including 22 colorectal tumor organoid samples and 15 paired healthy samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied for classifying differentially expressed genes (DEGs). Protein interaction among DEGs was analyzed by Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. In total, 853 gene sequences were identified. GO analysis revealed that DEGs were extensively involved in various biological process (BP), like proliferation, cell cycle, and biosynthesis. KEEG pathway analysis showed that WNT, MAPK, TGF-β, SHH, ECM-receptor interaction, and FGF pathways were altered. DEGs which were identified with protein interactions were major response for extracellular matrix organization and the GPCR pathway. In conclusion, our study profiled the DEGs in CRC organoids and promotes our understanding of the CRC organoids as a new model for colorectal cancer research.

Proliferating cell nuclear antigen (PCNA), a ring-shaped homotrimer complex, promotes DNA replication via binding to DNA polymerase. Trimerized PCNA is critical for DNA replication. Enhancer of zeste homologue 2 (EZH2), which primarily acts as a histone methyltransferase, is essential for proliferation. However, how EZH2 promotes proliferation by controlling DNA replication through PCNA remains elusive.

The broad ecological distribution of L. casei makes it an insightful subject for research on genome evolution and lifestyle adaptation. To explore evolutionary mechanisms that determine genomic diversity of L. casei, we performed comparative analysis of 17 L. casei genomes representing strains collected from dairy, plant, and human sources.

MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate gene expression at the post-transcriptional levels. Recent studies show that miRNAs may function as oncogenes or tumor suppressor genes. In this study, we demonstrated that miR-518b was down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and correlated with metastasis and survival. miR-518b suppressed the proliferation by inducing apoptosis and repressed the invasion in ESCC cells, but had no effect on the cell cycle. Furthermore, Rap1b was revealed to be directly regulated by miR-518b. These findings indicate that miR-518b may function as a tumor suppressor by targeting Rap1b in the development of ESCC and has important clinical and prognostic value.

Although chondrogenesis and osteogenesis are considered as two separate processes during endochondral bone formation after birth, recent studies have demonstrated the direct cell transformation from chondrocytes into bone cells in postnatal bone growth. Here we use cell lineage tracing and multiple in vivo approaches to study the role of Bmpr1a in endochondrogenesis. Our data showed profound changes in skeletal shape, size and structure when Bmpr1a was deleted using Aggrecan-Cre ERT2 in early cartilage cells with a one-time tamoxifen injection. We observed the absence of lineage progression of chondrocyte-derived bone cells to form osteoblasts and osteocytes in metaphyses. Furthermore, we demonstrated the key contribution of growth plate chondrocytes and articular chondrocytes, not only for long bone growth, but also for bone remodeling. In contrast, deleting Bmpr1a in early osteoblasts with 3.6 Col 1-Cre had little impact on skeletal shape and size except for a sharp increase in osteoblasts and osteocytes, leading to a profound increase in bone volume. We conclude that chondrogenesis and osteogenesis are one continuous developmental and lineage-defined biological process, in which Bmpr1a signaling in chondrocytes is necessary for the formation of a pool or niche of osteoprogenitors that then contributes in a major way to overall bone formation and growth.

Solasodine is a main active component isolated from Solanum incanum L. that performs a wide range of functions containing anti-oxidant, anti-infection, and neurogenesis promotion. In this study, we explored the influence of solasodine on three types of human colorectal cancer (CRC) cell lines. The results show that solasodine prohibited CRC cell proliferation dose- and time-dependently and impeded CRC cell motility by downregulating MMPs. Solasodine was also found to fuel caspase-cascade reaction and increase the ratio between Bax and Bcl-2 so as to induce CRC cell apoptosis. When cells were pretreated with AKT activator (insulin-like growth factor-1) followed by solasodine, the solasodine-induced apoptosis was partially abrogated by insulin-like growth factor-1. Moreover, solasodine hindered tumor development and stimulated similar mechanisms in vivo. In general, our study provides the first evidence that solasodine has a suppressive effect on CRC cells and that this agent may be a novel therapeutic drug for CRC treatment.

In vitro studies have demonstrated the role of the BCL-2 family of genes in endometrial carcinogenesis. The role of genetic variants in BCL-2 genes and their interactions with non-genetic factors in the development of endometrial cancer has not been investigated in epidemiological studies.

The Hippo-YAP signaling pathway is altered and implicated as oncogenic in many human cancers. However, extracellular signals that regulate the mammalian Hippo pathway have remained elusive until very recently when it was shown that the Hippo pathway is regulated by G-protein-coupled receptor (GPCR) ligands including lysophosphatidic acid (LPA) and sphingosine 1-phosphophate (S1P). LPA inhibits Lats kinase activity in HEK293 cells, but the potential involvement of a protein phosphatase was not investigated. The extracellular regulators of YAP dephosphorylation (dpYAP) and nuclear translocation in epithelial ovarian cancer (EOC) are essentially unknown.

Wnt5a plays an essential role in tissue development by regulating cell migration, though the molecular mechanisms are still not fully understood. Our study investigated the pathways involved in Wnt5a-dependent cell motility during the formation of dentin and pulp. Over-expression of Wnt5a promoted cell adhesion and formation of focal adhesion complexes (FACs) in human dental papilla cells (hDPCs), while inhibiting cell migration. Instead of activating the canonical Wnt signal pathway in hDPCs, Wnt5a stimulation induced activation of the JNK signal in a RhoA-dependent or independent manner. Inhibiting JNK abrogated Wnt5a-induced FACs formation but not cytoskeletal rearrangement. Both dominant negative RhoA (RhoA T19N) and constitutively active RhoA mutants (RhoA Q63L) blocked the Wnt5a-dependent changes in hDPCs adhesion, migration and cytoskeletal rearrangement here too, with the exception of the formation of FACs. Taken together, our study suggested that RhoA and JNK signaling have roles in mediating Wnt5a-dependent adhesion and migration in hDPCs, and the Wnt5a/JNK pathway acts both dependently and independently of the RhoA pathway.

Dent's disease, an X-linked renal tubular disorder, is characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure. Dent's disease results from mutations of the voltage-gated chloride channel CLC-5.

Colorectal cancer (CRC) is one of the most common malignant tumors and one of the leading causes of cancer-related death in both men and women. The prognosis of CRC remains poor due to the advanced stage and cancer metastasis at the time of diagnosis. However, the exact mechanism of tumorigenesis in CRC remains unclear. Long non-coding RNAs (lncRNAs), which refer to transcripts longer than 200 nucleotides that are not translated into protein, are known to play important roles in multiple human cancers. Lnc-DILC is reported to be an important tumor suppressor gene and its inactivation is closely associated with liver cancer stem cells. However, the role of lnc-DILC in CRC remains to be elucidated. In the present study, we observed that lnc-DILC overexpression inhibited the growth and metastasis of CRC cells. Consistently, lnc-DILC knockdown facilitated the proliferation and metastasis of CRC cells. Mechanically, lnc-DILC suppressed CRC cell progression via IL-6/STAT3 signaling inactivation. More importantly, the specific STAT3 inhibitor S3I-201 and IL-6R inhibitor tocilizumab abolished the discrepancy of growth and metastasis capacity between lnc-DILC-interference CRC cells and control cells, which further confirmed that IL-6/STAT3 signaling was required in lnc-DILC-disrupted CRC cell growth and metastasis. Taken together, our results suggest that lnc-DILC is a novel CRC suppressor and may prove to be an inhibitor of CRC progression by inactivating IL-6/STAT3 signaling.

Depression is one of the most prevalent mental disorders worldwide. Little information is available regarding association of depressive symptoms (DS) with cancer and chronic diseases among middle-aged and elderly Chinese in a population-based setting. In this study we evaluated the prevalence and examined correlates of DS in two population-based cohort studies. Included in the analyses were 103,595 people with a mean age of 61.8 years at the DS assessment. The prevalence of DS was 2.4% in men and 5.6% in women. We found elderly participants, those with lower BMI, or chronic diseases were more likely to experience DS. Having a history of stroke (odds ratio (OR) = 2.2 in men and 1.8 in women), cancer (OR = 3.3 in men and 1.9 in women), or Parkinson's disease (OR = 3.1 in men and 2.7 in women) was associated with high DS. In women, high income and high education levels were inversely related to DS. Being a single woman, long-term or heavy female smoker was associated with high prevalence of DS. High BMI was correlated with low prevalence of depression in men. Our data suggests a low prevalence of DS among middle-aged and elderly people in Shanghai, China. Age, education, income, marital status, smoking, BMI, and certain health conditions were associated with DS.

Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized by inflammatory synovitis, and the subsequent destruction of articular cartilage and bone. Sinomenine is a traditional Chinese medicine, which has been employed as a clinical treatment for RA for several years in China. The present study investigated the anti‑arthritic effects of sinomenine on Sprague‑Dawley rats with collagen‑induced arthritis (CIA). The differentially expressed proteins in serum were measured by proteomic analysis in order to generate a differentially expressed protein network. A total of 320 differentially expressed proteins were detected in the drug‑treated group compared with in the control group. In the sinomenine‑treated group, 79 differentially expressed proteins were detected compared with in the model group, and among these, 46 proteins were upregulated. Gene ontology analysis revealed that five functions were affected by sinomenine treatment of CIA rats compared with in the model group. In addition, Ingenuity® Pathway Analysis was used to measure enriched signaling pathways, which revealed nuclear factor‑κB, histones, heat shock proteins and protein kinase B as core proteins, generating ~60 pair associations in the network. To the best of our knowledge, the present study is the first to perform proteomic analysis in sinomenine‑treated CIA rats, and the results revealed that numerous targets were involved in the process. In addition, the present study provided a novel approach and evidence for exploring the biological effects of sinomenine. Therefore, the findings of the present study may provide a novel insight into the anti‑RA mechanisms of sinomenine, and may justify further exploration into its function in other relevant diseases.