I-FABP protein/mRNA and IL-6 as biomarkers of intestinal barrier dysfunction in neonates with necrotizing enterocolitis and SPF BALB/c mouse models.

OBJECTIVE: Neonatal necrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease. We investigated intestinal fatty acid binding protein (I-FABP), I-FABP mRNA, and interleukin-6 (IL-6) as potential diagnostic biomarkers in NEC. METHODS: Forty mice were subjected to hypoxic-ischemic intestinal injury, and then serum I-FABP protein and mRNA levels were quantified. Ileal tissue pathological scores were determined by hematoxylin and eosin staining. I-FABP expression levels and translocation in these tissues were detected using western blotting and immunofluorescence, respectively. Samples from 30 human neonates with NEC and 30 healthy neonates had serum I-FABP protein/mRNA and IL-6 levels measured. RESULTS: The mouse ileal tissue pathological score and I-FABP levels, as well as serum I-FABP and I-FABP mRNA levels, were significantly higher in the model group than in the control group. Serum I-FABP, I-FABP mRNA, and IL-6 levels were significantly higher in human neonates with NEC than in the healthy group. Logistic regression and receiver operating curve analyses revealed that I-FABP protein/mRNA and IL-6 levels could be diagnostic biomarkers for NEC. CONCLUSIONS: I-FABP protein/mRNA and IL-6 levels are useful biomarkers of intestinal ischemic injury in neonates with NEC. The combined detection of I-FABP protein/mRNA and IL-6 is recommended rather than using a single biomarker.

Let-7c-3p suppresses lens epithelial-mesenchymal transition by inhibiting cadherin-11 expression in fibrotic cataract.

Fibrotic cataract, including anterior subcapsular cataract (ASC) and posterior capsule opacification, always lead to visual impairment. Epithelial-mesenchymal transition (EMT) is a well-known event that causes phenotypic alterations in lens epithelial cells (LECs) during lens fibrosis. Accumulating studies have demonstrated that microRNAs are important regulators of EMT and fibrosis. However, the evidence explaining how microRNAs modulate the behavior and alter the cellular phenotypes of the lens epithelium in fibrotic cataract is insufficient. In this study, we found that hsa-let-7c-3p is downregulated in LECs in human ASC in vivo as well as in TGFß2-induced EMT in vitro, indicating that hsa-let-7c-3p may participate in modulating the profibrotic processes in the lens. We then demonstrated that overexpression of hsa-let-7c-3p markedly suppressed human LEC proliferation and migration and attenuated TGFß2-induced EMT and injury-induced ASC in a mouse model. In addition, hsa-let-7c-3p mediated lens fibrosis by directly targeting the CDH11 gene, which encodes cadherin-11 protein, an important mediator in the EMT signaling pathway. It decreased cadherin-11 protein expression at the posttranscriptional level but not at the transcriptional level by binding to a specific site in the 3-untranslated region (3'-UTR) of CDH11 mRNA. Moreover, blockade of cadherin-11 expression with a specific short hairpin RNA reversed TGFß2-induced EMT in LECs in vitro. Collectively, these data demonstrated that hsa-let-7c-3p plays a clear role in attenuating ASC development and may be a novel candidate therapeutic for halting fibrosis and maintaining vision.

Boosting Antibacterial Photodynamic Therapy in a Nanosized Zr MOF by the Combination of Ag NP Encapsulation and Porphyrin Doping.

Antibacterial photodynamic therapy (aPDT) is regarded as one of the most promising antibacterial therapies due to its nonresistance, noninvasion, and rapid sterilization. However, the development of antibacterial materials with high aPDT efficacy is still a long-standing challenge. Herein, we develop an effective antibacterial photodynamic composite UiO-66-(SH)2@TCPP@AgNPs by Ag encapsulation and 4,4',4″,4‴-(porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid) (TCPP) dopant. Through a mix-and-match strategy in the self-assembly process, 2,5-dimercaptoterephthalic acid containing -SH groups and TCPP were uniformly decorated into the UiO-66-type framework to form UiO-66-(SH)2@TCPP. After Ag(I) impregnation and in situ UV light reduction, Ag NPs were formed and encapsulated into UiO-66-(SH)2@TCPP to get UiO-66-(SH)2@TCPP@AgNPs. In the resulting composite, both Ag NPs and TCPP can effectively enhance the visible light absorption, largely boosting the generation efficiency of reactive oxygen species. Notably, the nanoscale size enables it to effectively contact and be endocytosed into bacteria. Consequently, UiO-66-(SH)2@TCPP@AgNPs show a very high aPDT efficacy against Gram-negative and Gram-positive bacteria as well as drug-resistant bacteria (MRSA). Furthermore, the Ag NPs were firmly anchored at the framework by the high density of -SH moieties, avoiding the cytotoxicity caused by the leakage of Ag NPs. By in vitro experiments, UiO-66-(SH)2@TCPP@AgNPs show a very high antibacterial activity and good biocompatibility as well as the potentiality to promote cell proliferation.

Cervical and endometrial cancers of intestinal origin diagnosed 18 years after vaginal replacement with a sigmoid colon segment: a case report and review of the literature.

Background: Sigmoid colpoplasty is a surgical method for the treatment of vagina agenesis. Malignant tumors of neovaginas derived from sigmoid colons are rare. Case presentation: We report a 33-year-old woman who underwent sigmoid colpoplasty for vaginal agenesis and presented 18 years later with vaginal bleeding. Examination revealed cancer of the neovagina with involvement of the cervix and endometrium. The patient was administered four cycles of chemotherapy because she refused surgery. Conclusions: Patients with a history of colpoplasty should undergo long-term comprehensive testing after reconstruction, including regular gynecological, colposcopic, and gastrointestinal examinations. In patients with cancer of the neovagina, a comprehensive treatment plan should be developed in consultation with gynecologists and surgeons. There is no standard treatment, although surgery plus chemotherapy or radiotherapy appears to be effective.

Retinitis pigmentosa-associated anterior subcapsular cataract: morphological features and visual performance.

PURPOSE: To investigate the morphological features and surgical outcomes of retinitis pigmentosa (RP)-associated anterior subcapsular cataract (ASC). METHODS: Consecutive RP-associated ASC cases were reviewed, and one hundred patients (171 eyes) were included. Anterior segment photographed images by slit-lamp microscope were reviewed. Best-corrected visual acuity (BCVA) was recorded. The cases were classified according to preoperative best BCVA, the area (central, midperipheral and peripheral) and the density (Grade 1, vacuolar/bubble-like; Grade 2, plaque-like/translucent; and Grade 3, fibrotic/opaque) of ASC; subgroup analysis of surgical outcomes was then performed. RESULTS: The mean age was 52.1 ± 13.7 years, and the 41-50-year group had the best BCVA. 13.5% of eyes had BCVA better than 20/63, 30.4% were between 20/400 and 20/63, and 56.1% were worse than 20/400. The percentage of ASCs in the central, midperipheral and peripheral areas was 55.0%, 37.4% and 7.6%, respectively. Postoperative BCVA was improved in the central and midperipheral groups (P < 0.001) but was not in the peripheral group (P = 0.07). The percentage of ASCs in density of Grade 1, 2 and 3 was 11.1%, 38.6% and 50.3%, respectively. Grade 2 and 3 achieved improved postoperative BCVA (P < 0.001), but Grade 1 did not (P = 0.693). CONCLUSIONS: Mostly, ASC is located at the center of the pupillary area and affected the residual vision of RP patients. The patients benefited from cataract removal except for those with ASC extended to peripheral area. Surgery was also recommended for RP with ASC developed to be plaque-like and even fibrotic.

Identification and Validation of Angiogenesis-Related Gene Expression for Predicting Prognosis in Patients With Ovarian Cancer.

Ovarian cancer (OC) is a highly heterogeneous disease with different cellular origins reported; thus, precise prognostic strategies and effective new therapies are urgently needed for patients with OC. A growing number of studies have shown that most malignancies have intensive angiogenesis and rapid growth. Therefore, angiogenesis plays an important role in the development of tumor metastasis. However, the prognostic value of angiogenesis-related genes (ARGs) in OC remains to be further elucidated. In this study, the expression data and corresponding clinical data from patients with OC and normal control samples were downloaded with UCSC XENA. A total of 1,960 differentially expressed ARGs were screened and functionally annotated through Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Univariate Cox regression analysis was performed to identify ARGs associated with prognosis. New ARGs signatures (including ESM1, CXCL13, TPCN2, PTPRD, FOXO1, and ELK3) were constructed for the prediction of overall survival (OS) in OC based on the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. Patients were divided based on their median risk score. In the The Cancer Genome Atlas (TCGA) training dataset, the survival analysis showed that overall survival was lower in the high-risk group than that in the low-risk group (p < 0.0001). The International Cancer Genome Consortium (ICGC) database was used for validation, and the receiver operating characteristic (ROC) curves showed good performance. Univariate and multivariate Cox analyses were conducted to identify independent predictors of OS. The nomogram, including the risk score, age, stage, grade, and position, can not only show good predictive ability but also can explore the correlation analysis based on ARGs for immunogenicity, immune components, and immune phenotypes with risk score. Risk scores were correlated strongly with the type of immune infiltration. Furthermore, homologous recombination defect (HRD), NtAIscore, LOH score, LSTm score, stemness index (mRNAsi), and stromal cells were significantly correlated with risk score. The present study suggests that the novel signature constructed from six ARGs may serve as effective prognostic biomarkers for OC and contribute to clinical decision making and personalized prognostic monitoring of OC.

Bone-strengthening effects and safety of compound peptides from skin of Chiloscyllium plagiosum and Mustelus griseus.

Fish processing produces a lot of by-products highly containing large amount of proteins which mainly consist of collagen, implying great potential value for application as nutraceutical ingredients. In present study, two kinds of sharks, Chiloscyllium plagiosum and Mustelus griseus, were used as raw material to gain three kinds of "compound peptides" (CPs) by enzymolysis, FCP (CPs from the flesh of C. plagiosum), SCP (CPs from the skin of C. plagiosum), and SMG (CPs from the skin of M. griseus). According to a series of constituent analysis, the molecule weights of FCP, SCP, and SMG were under 800 Da; amino acids composition analysis of FCP, SCP, and SMG showed that there were high glycine, proline, and hydroxyproline and low cysteine contents in SCP and SMG, which is the characteristic of collagen peptides; their total protein contents were 87.500%, 91.875%, and 95.625%, respectively; and heavy metal contents of CPs were all beneath national standards. After three kinds of CPs were administrated intragastrically to C57BL/6 mice at a total dosage of 15 g/kg, bone-strengthening effects of SCP and SMG were manifested by osteoblasts activity promotion, bone mineral density (BMD) increase, and marrow adipocyte number decrease, yet nonsignificant effects were shown in FCP group. No index showed toxicity of SCP and SMG in subacute toxicology trial, indicating their safety as functional foods. Herein, industrial application foundation of the skins from these two sharks was explored but more efforts should subsequently be implemented for further exploitation.

Subjective Visual Performance and Objective Optical Quality With Intraocular Lens Glistening and Surface Light Scattering.

PURPOSE: To evaluate the long-term effect of glistenings and surface light scattering of intraocular lenses (IOLs) on visual and optical performance after cataract surgery. METHODS: Pseudophakic eyes that underwent standard phacoemulsification and two types of hydrophobic acrylic spherical IOL implantation without complications for at least 5 years were included in this retrospective study. Participants were divided into the glistenings, surface light scattering, and control groups according to the current condition of the IOLs. Then participants received a follow-up examination including uncorrected and corrected distance visual acuity (UDVA and CDVA), contrast sensitivity, straylight, and intraocular higher order aberrations, as well as point spread function (PSF) and modulation transfer function (MTF). RESULTS: A total of 140 eyes were included in the study. UDVA, CDVA, and glare sensitivity were not significantly different among the three groups (P > .05). However, compared with the control group, the IOLs of the glistenings and surface light scattering groups were associated with significantly lower contrast sensitivity under no glare conditions. Furthermore, eye with glistenings exhibited the highest straylight value (P < .05), whereas no difference was found between the surface light scattering and control groups. In contrast to the control group, the spherical aberration increased and the mean values of PSF and MTF decreased in the glistenings and surface light scattering groups. CONCLUSIONS: Both glistenings and surface light scattering tend to impair subjective visual performance, such as contrast sensitivity, and potentially affect objective optical quality, including straylight, spherical aberration, PSF, and MTF. [J Refract Surg. 2018;34(6):372-378.].

[The effect of gemcitabine on proliferation and telomerase activity of Tca8113 cell lines].

PURPOSE: To investigate the effect of gemcitabine on the proliferation and telomerase activity of Tca8113 cell line cells. METHODS: MTT assay, flow cytometry were used to examine the effect of gemcitabine on cell proliferation and cell cycle respectively, telomerase activity was detected with telomeric repeat amplification protocol (TRAP) and polyacrylamide gel electrophoresis (PAGE). The data were analyzed by independent samples t test and one-way ANOVA of SPSS10.0 for windows. RESULTS: Cell proliferations were significantly inhibited in these cells after exposure to gemcitabine as well as cell cycles were arrested. Furthermore, the effect was closely associated with the concentration and time of gemcitabine. The average rate of cell proliferating inhibition in group 5.0 microg/ml at 72 h was 72.2%.The number of cells in S phase was decreased,the average rate of S phase in group 5.0 microg/ml at 72 h was 18.1%,which was lower than that in group 0 microg/ml(38.5%) (t=5.801,P<0.05).Longer exposure time and higher concentration to gemcitabine, much telomerase activity was inhibited. After 72h, the A values of group 0 and 5.0 microg/ml were 1.32+/-0.12, 0.28+/-0.02, respectively (F=811.208, P<0.05). CONCLUSIONS: Gemcitabine could significantly inhibit Tca8113 proliferation and decrease its telomerase activity. Gemcitabine may be applied in clinical therapy of oral cancer.