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The mismatch in the conserved structure but different expression levels of C-reactive protein (CRP) in distinct species is reconciled by functional selection on hidden activities of unfolded CRPs.

Background and aims: C-reactive protein (CRP) is a hepatocyte-produced marker of inflammation yet with undefined function in liver injury. We aimed to examine the role of CRP in acetaminophen-induced liver injury (AILI). Methods: The effects of CRP in AILI were investigated using CRP knockout mice and rats combined with human CRP rescue. The mechanisms of CRP action were investigated in vitro and in mice with Fcγ receptor 2B knockout, C3 knockout, or hepatic expression of CRP mutants defective in complement interaction. The therapeutic potential of CRP was investigated by intraperitoneal administration at 2 or 6 hours post–AILI induction in wild-type mice. Results: CRP knockout exacerbated AILI in mice and rats, which could be rescued by genetic knock-in, adeno-associated virus–mediated hepatic expression or direct administration of human CRP. Mechanistically, CRP does not act via its cellular receptor Fcγ receptor 2B to inhibit the early phase injury to hepatocytes induced by acetaminophen; instead, CRP acts via factor H to inhibit complement overactivation on already injured hepatocytes, thereby suppressing the late phase amplification of inflammation likely mediated by C3a-dependent actions of neutrophils. Importantly, CRP treatment effectively alleviated AILI with a significantly extended therapeutic time window than that of N-acetyl cysteine. Conclusion: Our results thus identify CRP as a crucial checkpoint that limits destructive activation of complement in acute liver injury, and we argue that long-term suppression of CRP expression or function might increase the susceptibility to AILI.

Abstract Functioning as miRNA sponges, long non-coding RNA (lncRNA) exert its pharmacological action via regulating expression of protein-coding genes. However, the lncRNA-mediated ceRNA in cerebral Infarction (CI) remains unclear. In this study, the expression recordsets of mRNA, lncRNA and miRNA of CI samples were obtained from the NCBI GEO datasets separately. The differentially expressed lncRNAs (DELs), miRNAs (DEMis) and mRNAs (DEMs) were identified by limma package in R platform. A total of 267 DELs, 26 DEMis, and 760 DEMs were identified as differentially expressed profiles, with which we constructed the ceRNA network composed of DELs-DEMis-DEMs. Further, clusterProfiler package in R platform is employed for performing Gene Ontology (GO) and KEGG pathway analysis. An aberrant ceRNA network was constructed according to node degrees in CI, including 28 DELs, 19 DEMs and 12 DEMis, from which we extracted the core network, in which 9 nodes were recognized as kernel genes including Tspan3, Eif4a2, rno-miR-208a-3p, rno-miR-194-5p, Pdpn, H3f3b, Stat3, Cd63 and Sdc4. Finally, with the DELs-DEMis-DEMs ceRNA network provided above, we can improve our understanding of the pathogenesis of CI mediated by lncRNA.

Abstract Background The Solanum species have been used for the treatment of warts, tumor and cancer in folk medicine. The S. incanum extract is an important traditional Chinese medicine in Taiwan since 1973. The purpose of the present study was to evaluate the efficacy and safety of Solanum incanum (synonym: Solanum undatum) extract (SR-T100), a water-soluble product primarily composed of alkaloid solamargine, for the treatment of human condyloma and to study the possible underlying anti-condyloma mechanisms. Methods We conducted a pilot study to test the effectiveness and side effects of SR-T100 gel (2.3% solamargine in Solanum incanum plant extract) for the treatment of external genital warts. We produced different types of human papillomavirus (HPV) E6/E7-infected cells by lentiviral technology and studied the differences in apoptosis and autophagy between these cells under the treatment of SR-T100. Results Nineteen (73%) of 26 patients using the SR-T100 gel exhibited a response, and 16 (61.5%) patients achieved total clearance. Only one patient showed severe (grade 3-4) skin-related side effects. SR-T100 induced mitochondria-dependent apoptosis in HPV-infected cells. Cells expressing the high-risk HPV E6/E7 type were resistant to SR-T100-induced apoptosis. SR-T100 induced a greater autophagic response in HPV 16, 18-E6/E7 cells than in HPV 6b, 11-E6/E7 cells. Autophagy inhibition enhanced SR-T100-induced apoptosis in HPV 16, 18-E6/E7 cells, whereas apoptosis inhibition enhanced SR-T100-induced autophagy in HPV 6b, 11-E6/E7 cells. Conclusions SR-T100 is effective for the treatment of human vulva condyloma, with few side effects. Compared with those with high-risk HPVs, cells with low-risk HPVs were more sensitive to SR-T100 treatment. Autophagy played a protective role in SR-T100-induced apoptosis in HPV-infected cells. Trial registration NCT01676792 ; Registered: August 29, 2012 (retrospectively registered).

AIM: To study the relativity between reject reaction from donation after cardiac death(DCD)and corneal endothelial cell source of corneal graft after penetrating keratoplasty.METHODS:Totally 28 cases of corneal graft rejection after penetrating keratoplasty with cardiac death donor cornea were analyzed using corneal endothelial microscope at less than 1mo, 2-3mo, 4-6mo, 7-12mo after operation.RESULTS:Coefficient variation of corneal endothelial cell of the 28 cases at less than 1mo,2-3mo, 4-6mo and 7-12mo were 38.23%, 49.56%, 57.18%, 65.04%. Corneal endothelial cell density were 2071.15±311.47, 1771.33±348.18, 1626.59±353.92, 1553.14±307.31. The coefficient variation of corneal endothelial cells was positively correlated with rejection(r=0.95, Pr=-0.93, PCONCLUSION: The corneal endothelial cell coefficient variation increased gradually and the corneal endothelial cell density decreased gradually after DCD corneal allograft rejection. Corneal endothelial cell coefficient variation and corneal endothelial cell density can be used as indicators of early detection of postoperative rejection.

Background: Percutaneous coronary intervention (PCI) is widely used in treatment of acute coronary syndrome (ACS) clinically. It is believed that Danhong injection (DHI) extracted from salviae miltiorrhizae and flos carthami combined with PCI could increase the therapeutic efficacy on ACS. We provide an updated meta-analysis with detailed information on combination of DHI and PCI therapy.Materials and Methods: Electronic databases were searched for appropriate articles without language limitations on key words before October 22, 2017. All trails were screened according to certain criteria. Quality of eligible studies was also assessed. We made a detailed record of outcome measurements. RevMan 5.3 software was used to perform the meta-analysis.Results: 14 articles involving 1533 patients with ACS were selected. Compared to PCI treatment alone, total efficacy rate (TER) was enhanced and major adverse cardiovascular events (MACE) were reduced significantly for the combination of DHI and PCI (P < 0.00001). Vascular endothelial function was improved by significantly decreasing the contents of ET-1, vWF and increasing the levels of NO and FMD (P < 0.00001). The serum levels of IL-1, IL-6, IL-18, TNF-α, LpPLA2, MMP-9, and pentraxin-3 were significantly decreased (P < 0.00001), whereas IL-10 in serum was increased (P < 0.00001), indicating a stronger anti-inflammatory effect of the combination. The combination therapy decreased the serum levels of CD62P, PAGT, PADT, FIB-C significantly (P < 0.05), which was beneficial for preventing coagulation of platelets. Blood lipid was also affected by regulating TC, TG, LDL, and HDL, but the results were not statistically significant (P > 0.05). Cardiac function was improved by increasing LEVF (P = 0.006) but not LVED (P = 0.08). The combination treatment was associated with an improvement in antioxidant effect by decreasing MDA and increasing SOD significantly (P < 0.00001).Conclusion: Combination of DHI and PCI in treatment of ACS could improve TER and reduce incidence of MACE after PCI therapy. These effects may be mediated by combined actions of several mechanisms. However, these results of this study should be handled cautiously due to the limitations of this research. Several rigorous RCTs are in need to confirm these findings.

C-reactive protein (CRP) is an established marker of rheumatoid arthritis (RA) but with ill-defined actions in the pathogenesis. Here, we show that CRP regulates the differentiation of osteoclasts, a central mediator of joint inflammation and bone erosion in RA, in a conformation- and receptor activator of NF-κB ligand (RANKL)-dependent manner. CRP in the native conformation is ineffective, whereas the monomeric conformation (mCRP) actively modulates osteoclast differentiation through NF-κB and phospholipase C signaling. Moreover, mCRP can bind RANKL, the major driver of osteoclast differentiation, and abrogate its activities. The binding and inhibition of RANKL are mediated by the cholesterol binding sequence (CBS) of mCRP. Corroborating the in vitro results, CRP knockout exacerbates LPS-induced bone resorption in mice. These results suggest that mCRP may be protective in joint inflammation by inhibiting pathological osteoclast differentiation and that the CBS peptide could be exploited as a potential RANKL inhibitor.

AIM: To observe the clinical effect subconjunctival bevacizumab and triamcinolone acetonide(TA)on corneal neovascularization(CNV)induced by penetrating keratoplasty.METHODS: Nineteen patients(20 eyes)with CNV induced by penetrating keratoplasty after 3mo were selected and were divided into 4 groups randomly: Group A was control group, group B was treated by subconjunctival of bevacizumab(2.5mg, 0.1mL), group C was treated by subconjunctival of bevacizumab(2.5mg, 0.1mL)and TA(4mg, 0.1mL), group D was treated by subconjunctival of TA(4mg, 0.1mL), one time each month, twice.RESULTS: The average follow-up period was 3a. Visual acuity of groups B and C kept stable or increase slightly. CNV and immunologic rejection were lighten(PCONCLUSION: Treatment of subconjunctival bevacizumab and TA can effectively inhibite CNV and immunologic rejection, also has the therapeutical effect to maintain implant transparence after penetrating keratoplasty.

AIM:To observe the application efficiency of 5g/L indocyanine green(ICG)staining technique for continuous circular capsulorhexis(CCC)during phacoemulsification in white cataract.METHODS:Ninety-eight patients(98 eyes)with white cataract were randomly divided into staining group(50 cases, 50 eyes)and control group(48 cases, 48 eyes). The control group didn't do anterior capsule staining. The staining group was injected to fill the anterior chamber, 5g/L ICG 0.1mL was applied on the central surface of the anterior capsule, using a 27G blunt needle through the side-port after 30s, and the redundant ICG was replaced by BSS, and continuous curvilinear capsulorhexis was accomplished using capsulorhexis forceps.RESULTS: In staining group: after ICG staining, the capsule, which presented uniform light green and visualization of the anterior capsule was significantly improved. There are 48 eyes capsulorhexis success. The rate of success was 96%. Meanwhile, in control group, there was 29 eyes capsulorhexis success. The rate of success was 60%. The difference was statistically significant(PCONCLUSION:Indocyanine green staining increases the visibility of anterior capsule in over mature cataract, and it should be an effective and helpful method which can increase the success rate of capsulorehxis. At the same time, it can reduce the incidence of intraoperative complications. This will help beginners quickly grasp continuous curvilinear capsulorhexis, and shorten the learning curve.