High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-ß1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

Secondhand smoke exposure can increase the risk of first ischemic stroke: A 10.7-year prospective cohort study in China.

INTRODUCTION: Passive smoking is considered a major public health issue in China. Prospective evidence regarding the link between secondhand smoke (SHS) and ischemic stroke in China is scarce. METHODS: The China Kadoorie Biobank (CKB) study in Liuzhou City recruited 50,174 participants during 2004-2008. Of these 30,456 never-smokers were included in our study. The median follow-up period was 10.7 years. The incidence of ischemic stroke was obtained through the China Disease Surveillance Points (DSP) system and the Health Insurance (HI) database. Cox proportional risk models were used to evaluate the association between SHS exposure and ischemic stroke. RESULTS: During 320,678 person-years of follow-up, there were 2059 patients with ischemic stroke observed and the incidence of ischemic stroke was 6.42 per thousand person-years. Participants exposed to SHS daily faced a 21 % higher risk of ischemic stroke (HR = 1.21, 95 %CI: 1.09-1.34) compared to those exposed to SHS less than once a week. Subgroup analyses revealed that daily SHS exposure was linked to heightened risk of ischemic stroke among women, non-employed, and non-weekly tea drinkers. CONCLUSIONS: Daily SHS exposure was associated with higher risks of ischemic stroke. Proactive tobacco control strategies are necessary to decrease the risk of ischemic stroke in never smokers.

pH-Activatable Charge-Reversal Polymer-Based Nanocarriers for Targeted Delivery of Antihepatoma Compound.

Chemotherapy is one of the available cancer treatments which has been successfully employed to prolong the survival of cancer patients. However, it remains a major challenge to develop effective chemotherapeutic agents by reducing off-target toxicity, improving bioavailability, and effectively prolonging blood circulation. The pH profile of tumor cells is abnormal to that of normal cells, making it a potential breakthrough for designing effective chemotherapeutic drug agents. Here, the pH-activatable charge-reversal supramolecular nanocarriers, named MI7-ß-CD/SA NPs, were prepared through a simple and "green" constructive process. MI7-ß-CD/SA NPs possess both pH-induced charge-reversal and disassembly properties that were exploited to investigate the loading, delivery, and pH-responsive controlled release of the antitumor compound celastrol (CSL). CSL@MI7-ß-CD/SA NPs displayed low hemolysis, good biocompatibility, and targeted uptake. Furthermore, CSL@MI7-ß-CD/SA NPs exhibited superior apoptosis rates against SMMC-7721 cell lines compared with CSL, when CSL@MI7-ß-CD/SA NPs and CSL were administered at a mass concentration of 5.0 µg/mL, i.e., the CSL content in CSL@MI7-ß-CD/SA NPs was relatively lower than that of intact CSL. We expected that MI7-ß-CD/SA NPs featuring pH-triggered charge reversal could offer a promising controlled release strategy that would then facilitate the clinical conversion of antitumor drugs.

Ureido Hyperbranched Polymer Modified Urea-Formaldehyde Resin as High-Performance Particleboard Adhesive.

The performance of urea-formaldehyde (UF) resin and its formaldehyde emission is a natural contradiction. High molar ratio UF resin performance is very good, but its formaldehyde release is high; low molar ratio UF resin formaldehyde release is reduced, but the resin itself performance becomes very bad. In order to solve this traditional problem, an excellent strategy of UF resin modified by hyperbranched polyurea is proposed. In this work, hyperbranched polyurea (UPA6N) is first synthesized by a simple method without any solvent. UPA6N is then added into industrial UF resin in different proportions as additives to manufacture particleboard and test its related properties. UF resin with a low molar ratio has a crystalline lamellar structure, and UF-UPA6N resin has an amorphous structure and rough surface. The results show that internal bonding strength increased by 58.5%, modulus of rupture increased by 24.4%, 24 h thickness swelling rate (%) decreased by 54.4%, and formaldehyde emission decreased by 34.6% compared with the unmodified UF particleboard. This may be ascribed to the polycondensation between UF and UPA6N, while UF-UPA6N resin forms more dense three-dimensional network structures. Finally, the application of UF-UPA6N resin adhesives to bond particleboard significantly improves the adhesive strength and water resistance and reduces formaldehyde emission, suggesting that the adhesive can be used as a green and eco-friendly adhesive resource for the wood industry.

Computed tomography enteroclysis combined with double-balloon endoscopy is beneficial to the diagnosis of small bowel submucosal tumors.

AIM: To compare the effectiveness and diagnostic accuracy of computed tomography enteroclysis (CTE), double-balloon endoscopy (DBE), and CTE with DBE (CTE/DBE) for detecting submucosal tumors (SMTs) in the small intestine. METHODS: The clinical data of 42 patients with pathologically confirmed small bowel SMTs seen at Renmin Hospital of Wuhan University between March 2012 and October 2020 were retrospectively analyzed. The value of CTE and DBE for detecting small bowel SMTs was then compared. RESULTS: No remarkable difference was found with regard to the sensitivity, positive and negative predictive values, as well as diagnostic accuracy rate between DBE and CTE, but the specificity of CTE was significantly higher than that of DBE (50.0% versus 25.0%, P = 0.001). Additionally, CTE/DBE also presented a higher sensitivity than CTE (97.4% versus 84.2%, P = 0.031). However, CTE/DBE and CTE were not greatly different in the positive predictive values and diagnostic accuracy rates. CONCLUSION: These findings suggest that CTE was better at detecting small bowel SMTs than DBE. Additionally, the combination of CTE and DBE is more beneficial for detecting SMTs in the small intestine.

CTHRC1, a novel gene with multiple functions in physiology, disease and solid tumors (Review).

Collagen triple helix repeat containing 1 (CTHRC1) is a gene discovered in 2005; it is highly conserved, and no homologous proteins have been disclosed thus far. A number of studies have shown that CTHRC1 is present in normal tissues and organs, and it has vital functions in physiological processes, including participating in the regulation of metabolism, arterial remodeling, bone formation and myelination of the peripheral nervous system. It has been reported that abnormal expression of CTHRC1 is involved in the carcinogenesis of various human organs, such as the breast, colon, pancreas, lung, stomach and liver. Therefore, the present review aims to collate all known findings and results on the regulation of CTHRC1 expression and related signaling pathways. To conclude, this review also provides a hypothesis of the functional mechanism of this gene.

Influence of AFP on surgical outcomes in non-B non-C patients with curative resection for hepatocellular carcinoma.

To study the clinical and prognostic features of non-B non-C alpha-fetoprotein (AFP)(-)-hepatocellular carcinoma (HCC) (NBNC-AFP(-)-HCC) and the relationship between the prognostic features of HCC and hepatitis B virus surface antigen (HBsAg) status and AFP. We enrolled 227 patients who underwent hepatic resection for HCC between January 1998 and December 2007 at Sun Yat-sen University Cancer Center, all of whom were diagnosed with HCC by pathology. All patients were stratified into one of four groups (B-AFP(+)-HCC, B-AFP(-)-HCC, NBNC-AFP(+)-HCC, and NBNC-AFP(-)-HCC) according to AFP levels and HBsAg status. The clinicopathologic and survival characteristics of NBNC-AFP(-)-HCC patients were compared with those of all other three groups. Out of the 105 NBNC-HCC patients, 43 patients (40.9%) had AFP-negative HCC. There were some differences in factors between the B-AFP(+) and NBNC-AFP(-) patients, such as age, body mass index (BMI), diabetes, and ALT (P < 0.05). On univariate analysis, tumour size, secondary tumour, and portal invasion were prognostic factors for overall survival (OS) and disease-free survival (DFS) (P < 0.05). Cox multivariate regression analysis suggested that tumour size and tumour number (P < 0.05) were independent predictors. In addition, compared with the B-AFP(+)-HCC, B-AFP(-)-HCC, and NBNC-AFP(+)-HCC groups, the NBNC-AFP(-)-HCC patients had the best DFS (P < 0.05). Compared with the B-AFP(+)-HCC and NBNC-AFP(+)-HCC groups, the NBNC-AFP(-)-HCC patients had better OS (P < 0.05), and survival rates were similar to those of B-AFP(-)-HCC patients. NBNC-AFP(-)-HCC patients had a relatively favourable prognosis. It can serve as a useful marker in predicting the risk of tumour recurrence in the early stages.

Non-Coding RNAs of Extracellular Vesicles: Key Players in Organ-Specific Metastasis and Clinical Implications.

Extracellular vesicles (EVs) are heterogeneous membrane-encapsulated vesicles released by most cells. They act as multifunctional regulators of intercellular communication by delivering bioactive molecules, including non-coding RNAs (ncRNAs). Metastasis is a major cause of cancer-related death. Most cancer cells disseminate and colonize a specific target organ via EVs, a process known as "organ-specific metastasis". Mounting evidence has shown that EVs are enriched with ncRNAs, and various EV-ncRNAs derived from tumor cells influence organ-specific metastasis via different mechanisms. Due to the tissue-specific expression of EV-ncRNAs, they could be used as potential biomarkers and therapeutic targets for the treatment of tumor metastasis in various types of cancer. In this review, we have discussed the underlying mechanisms of EV-delivered ncRNAs in the most common organ-specific metastases of liver, bone, lung, brain, and lymph nodes. Moreover, we summarize the potential clinical applications of EV-ncRNAs in organ-specific metastasis to fill the gap between benches and bedsides.

Guillain-Barré-like syndrome: an uncommon feature of CASPR2 and LGI1 autoimmunity.

Contactin-associated protein-like 2 (CASPR2) and leucine-rich glioma-inactivated 1 (LGI1) are essential components of the voltage-gated Kv1 potassium channel complex and are extensively expressed in both central and peripheral nervous system. Autoimmune CASPR2 and LGI1 disorders commonly present with Morvan syndrome (Mos) and/or limbic encephalitis, but whether Guillain-Barré syndrome (GBS) is a specific clinical phenotype is unknown. Here, we first reported an adult patient with dual CASPR2 and LGI1 antibodies in both serum and cerebrospinal fluid, who initially presented with a GBS-like syndrome and developed a typical MoS and respiratory paralysis, with a rapid resolution of his neurological symptoms and disappearance of autoantibodies after treatment with plasma exchange. Additionally, we also provided an overview of the previously reported GBS cases associated with CASPR2 or LGI1 antibodies. These cases expand the phenotypic spectrum of CASPR2 and LGI1 autoimmune syndromes, implying that these two antigens, especially CASPR2, are likely to participate in the etiology of GBS as a potential new target antigen, which deserves further exploration.

Exosomal transfer of circ_0006174 contributes to the chemoresistance of doxorubicin in colorectal cancer by depending on the miR-1205/CCND2 axis.

Exosomes are the mediators of intercellular signal transduction, and they have been involved in the carcinogenesis and chemoresistance of tumor cells. Herein, we intended to investigate whether circular RNA (circRNA) circ_0006174 can regulate chemoresistance of doxorubicin (DOX) in colorectal cancer via exosomes. Forty-one pairs of normal and CRC (DOX sensitive, n = 16; DOX resistant, n = 25) samples were collected. The resistant cell lines (LoVo/DOX and HCT116/DOX) were constructed by exposure of parental cell lines (LoVo and HCT116) to DOX. The detection of circ_0006174, microRNA-1205 (miR-1205), and cyclin D2 (CCND2) was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8(CCK-8) was applied for determining the half of inhibitory concentration (IC50) of DOX and cell proliferation. The migration and invasion capacities were analyzed via transwell assay. Exosomes were extracted using ultracentrifugation. Protein levels were determined using western blot. Dual-luciferase reporter assay was used for affirming target interaction. In vivo experiment was performed by establishing xenograft models in mice. Circ_0006174 level was upregulated in DOX-resistant CRC tissues and cells. The downregulation of circ_0006174 inhibited DOX resistance, cell proliferation, migration, and invasion in DOX-resistant CRC cells. Interestingly, the abundant circ_0006174 was enriched in exosomes derived from DOX-resistant CRC cells. Furthermore, circ_0006174 could enhance DOX resistance via the exosomal intercellular transfer. Moreover, we validated the target relation of circ_0006174/miR-1205 or miR-1205/CCND2. The effect of exosomal circ_0006174 on DOX resistance was achieved by upregulating the miR-1205-mediated CCND2. In vivo, knockdown of circ_0006174 also enhanced tumor sensitivity to DOX by targeting miR-1205/CCND2 axis. Altogether, these findings unraveled that circ_0006174-enriched exosomes elevated DOX chemoresistance in CRC by the miR-1205/CCND2 axis. The exosomal circ_0006174 can be used as an available biomarker for the diagnosis of chemoresistance in CRC.

TRIM11 Promotes Proliferation, Migration, Invasion and EMT of Gastric Cancer by Activating ß-Catenin Signaling.

INTRODUCTION: Gastric cancer (GC) is the sixth most common malignant tumor and the third leading cause of cancer-related death in the world. Studies have shown that TRIM protein can regulate transcription factor activity and is associated with many cancers. However, the role of TRIM11 in gastric cancer remains unclear. METHODS: TRIM11 protein levels were examined in 36 cases of GC tissues and 4 gastric cancer cell lines. TRIM11 overexpression and knockdown cells were constructed in MGC-803, HGC-27 and SGC-7901, respectively. The biological roles and mechanisms of TRIM11 were examined using CCK8, colony formation, transwell migration assay, invasion assay, Western blotting, Immunohistochemistry and in vivo nude mice experiments. RESULTS: We found that TRIM11 was upregulated in gastric cancer tissues and gastric cancer cell lines. Functionally, TRIM11 overexpression increased growth rate, colony formation, invasion and migration ability, EMT and ß-catenin protein level and its downstream proteins such as CyclinD1 and C-myc, while TRIM11 knockdown shows the opposite effects. CONCLUSION: In summary, our data show that TRIM11 is overexpressed in GC. TRIM11 promotes proliferation, migration, invasion and EMT of gastric cancer by activating ß-catenin signaling.

Integrated analysis of differentially expressed genes and construction of a competing endogenous RNA network in human Huntington neural progenitor cells.

BACKGROUND: Huntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are also dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking. METHODS: In this study, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using a CRISPR-Cas9 approach at the HTT locus) to screen out DE mRNAs and DE lncRNAs and create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein-protein interaction (PPI) network for mRNAs interacting with these lncRNAs. RESULTS: We identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. The results showed that the function of DE lncRNAs mainly correlated with transcriptional regulation as demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors. CONCLUSIONS: Our research provides new clues for uncovering the mechanisms of lncRNAs in HD and can be used as the focus for further investigation.

A case report of appendix mucinous adenocarcinoma that recurred after additional surgery and a brief literature review.

BACKGROUND: The clinical incidence of appendiceal mucinous adenocarcinoma is low. Moreover, the case reports of postoperative relapse after surgery are rarely based on literature search results. Here, we report such a case spanning nearly 7 years and and review the relevant literature. CASE PRESENTATION: A 50-year-old female underwent additional surgery after appendectomy, and pathological examination confirmed mucinous adenocarcinoma. The patients underwent HIPEC (hyperthermic intraoperative chemotherapy) and adjuvant chemotherapy. Twenty-six months after the previous surgeries, another surgery, HIPEC, and adjuvant chemotherapy were performed again due to tumour recurrence. To date, the follow-up time is 43 months, and no recurrence or metastasis has been found. CONCLUSIONS: Appendix mucinous adenocarcinoma has a poor prognosis and the diagnosis depends on pathological and immunohistochemical examinations. Its clinical manifestations are non-specific, and CRS + HIPEC should be used for treatment, which is safe and effective.

Proteome interrogation using gold nanoprobes to identify targets of arctigenin in fish parasites.

Gold nanoparticles (GNPs) are one of the most widely used nanomaterials in various fields. Especially, the unique chemical and physical properties make them as the promising candidates in drug target identification, unfortunately, little is known about their application in parasites. In this paper, GNPs were employed as new solid support to identify drug targets of natural bioactive compound arctigenin (ARG) against fish monogenean parasite Gyrodactylus kobayashi. Before target identification, GNPs with ARG on the surface showed the ability to enter the live parasites even the nucleus or mitochondria, which made the bound compounds capable of contacting directly with target proteins located anywhere of the parasites. At the same time, chemically modified compound remained the anthelminthic efficacy against G. kobayashii. The above results both provide assurance on the reliability of using GNPs for drug target-binding specificity. Subsequently, by interrogating the cellular proteome in parasite lysate, myosin-2 and UNC-89 were identified as the potential direct target proteins of ARG in G. kobayashii. Moreover, results of RNA-seq transcriptomics and iTRAQ proteomics indicated that myosin-2 expressions were down-regulated after ARG bath treatment both in transcript and protein levels, but for UNC-89, only in mRNA level. Myosin-2 is an important structural muscle protein expressed in helminth tegument and its identification as our target will enable further inhibitor optimization towards future drug discovery. Furthermore, our findings demonstrate the power of GNPs to be readily applied to other parasite drugs of unknown targets, facilitating more broadly therapeutic drug design in any pathogen or disease model.

Ratiometric SERS biosensor for sensitive and reproducible detection of microRNA based on mismatched catalytic hairpin assembly.

MicroRNAs (miRNAs) serve as significant regulators in a variety of diseases and have been emerging as a class of promising biomarkers for early cancer diagnosis. Herein, an enzyme-free surface-enhanced Raman scattering (SERS) platform was proposed for sensitive and reliable detection of target miRNA-21 using a corrective internal standard (IS)-based ratiometric SERS probe coupled with mismatched catalytic hairpin assembly (CHA) amplification. The 4-aminothiophenol (4-ATP) was used as IS molecule and modified on the surface of silver nanoparticles decorated silicon wafer. In principle, the presence of miRNA-21 could cyclically trigger the allosteric effects of mismatched CHA amplification and the 3'-R6G labeled hairpin probe 1 (H1) was opened. Then, the hairpin probe 2 (H2) hybridized with H1 to form H1-H2 complex and the released miRNA-21 was free to participate in the next cycle of CHA reaction. Meanwhile, the H1-H2 complex could hybridize with the capture DNA on the SERS chip, making the Raman tag of R6G close to the surface of SERS substrate, and the intensity of SERS signal from R6G labels increase while that from 4-ATP remain relatively unchanged. Benefiting from outstanding performances of the ratiometric SERS strategy and enzyme-free CHA amplification system, this platform exhibits sensitivity toward miRNA-21 with a limit of detection of 3.5 fM and a broad dynamic range from 10 fM to 100 nM. More importantly, this proposed method presents an excellent reliable SERS analysis with the correction of IS. The developed strategy holds a potential alternative tool for miRNA detection in biomedical research and early clinical diagnosis.

MiR-23b-3p induces the proliferation and metastasis of esophageal squamous cell carcinomas cells through the inhibition of EBF3.

MicroRNAs (miRNAs), some small non-coding RNAs that regulate gene expression at the posttranscriptional level, are always aberrantly expressed in carcinomas. In this study, we found that miR-23b-3p was remarkably up-regulated in human esophageal squamous cell carcinoma cells and tissues. Moreover, miR-23b-3p could induce the proliferation, invasion, and metastasis in vitro. EBF3 was identified as the direct downstream target gene of miR-23b-3p and ectogenic EBF3 could strongly inhibit the proliferation, invasion, and metastasis in vitro. Furthermore, it was found that miR-23b-3p could regulate epithelial-to-mesenchymal transition progress by blocking EBF3. Therefore, it was concluded that miR-23b-3p targeted EBF3 to accelerate the proliferation, invasion, and metastasis in ESCC.

A robust electrochemical immunosensor based on hydroxyl pillar[5]arene@AuNPs@g-C3N4 hybrid nanomaterial for ultrasensitive detection of prostate specific antigen.

Prostate specific antigen (PSA) is the most significant biomarker for the screening of prostate cancer in human serum. However, most methods for the detection of PSA often require major laboratories, precisely analytical instruments and complicated operations. Currently, the design and development of satisfying electrochemical biosensors based on biomimetic materials (e.g. synthetic receptors) and nanotechnology is highly desired. Thus, we focused on the combination of molecular recognition and versatile nanomaterials in electrochemical devices for advancing their analytical performance and robustness. Herein, by using the present prepared multifunctional hydroxyl pillar[5]arene@gold nanoparticles@graphitic carbon nitride (HP5@AuNPs@g-C3N4) hybrid nanomaterial as robust biomimetic element, a high-performance electrochemical immunosensor for detection of PSA was constructed. The as-prepared immunosensor, with typically competitive advantages of low cost, simple preparation and fast detection, exhibited remarkable robustness, ultra-sensitivity, excellent selectivity and reproducibility. The limit of detection (LOD) and linear range were 0.12 pg mL-1 (S/N = 3) and 0.0005-10.00 ng mL-1, respectively. The satisfying results provide a promising approach for clinical detection of PSA in human serum.