Penetrance of <i>MYOC</i> gene mutation in primary open-angle glaucoma: A systematic review and meta-analysis

To investigate the penetrance of MYOC gene mutation in primary open-angle glaucoma (POAG) through systematic review and meta-analysis. To explore the factors affecting the penetrance of MYOC and provide evidence-based medical evidence for clinical work. We searched all studies that reported the penetrance of MYOC mutation in PubMed, Embase, Web of Science, and Chinese databases including Wanfang, CNKI (China National Knowledge Infrastructure), and CBM (China Bio-Med). Random effects meta-analysis was conducted to estimate the penetrance of MYOC mutation in POAG. Fifty-two studies were included in this analysis after screening. Meta-analysis of the penetrance of MYOC mutation showed that the penetrance of MYOC mutation in POAG was 60% (95% CI: 51.0% to 68.0%) and the penetrance of MYOC mutation in POAG and suspected POAG was 68% (95% CI: 60.0% to 75.0%). The penetrance of MYOC mutation increases with age. Among Caucasians, Asians, and Africans, the penetrance of MYOC mutation in POAG was 55%, 71%, 54%, respectively, and the penetrance of MYOC mutation in POAG and suspected POAG was 64%, 83%, and 57%, respectively. Besides, the penetrance of different MYOC mutation sites was significantly discrepant. The penetrance of MYOC mutation in POAG ranged from 10.3% to 100% depending on the mutation sites. Some MYOC mutation sites have a certain population specificity, which is only pathogenic in Caucasians or Asians. The penetrance of MYOC mutation in POAG showed significant differences due to different mutation sites. The penetrance increased with the accrescent of age. Ethnic difference was an important factor affecting the penetrance of MYOC mutation. Knowing the rules and influencing factors of the penetrance of MYOC mutations is significant for the assessment of the risk of POAG in carriers with the MYOC mutation.</p

Confocal microscopy analysis of PKH26-labeled BMSC-EVs localization in colon after injection.

<p>The localization was measured 12h after intravenous injection. (A-I) Representative micrograph of inflammatory colon with the treatment of PKH26-labeled BMSC-EVs (red) at the dose of 50, 100 and 200μg. In merge images, nuclei were stained with DAPI (blue). Original magnification×200.</p

Oxidative Recyclization of 1<i>H</i>‑Indoles for Synthesis of 2‑Indolylbenzoxazinones via Cleavage of the C2–C3 Bond with AIBN under Air

A novel and concise method for the oxidation of unprotected indole derivatives to synthesize 2-indolylbenzoxazinones in the presence of AIBN under open air has been successfully demonstrated. This metal-free reaction is both atom- and step-efficient and is applicable to a broad scope of substrates. This new methodology provides a facile pathway for oxidative C2–C3 bond cleavage and recyclization of 1<i>H</i>-indoles

Extracellular Vesicles Derived from Bone Marrow Mesenchymal Stem Cells Protect against Experimental Colitis via Attenuating Colon Inflammation, Oxidative Stress and Apoptosis

<div><p>The administration of bone mesenchymal stem cells (BMSCs) could reverse experimental colitis, and the predominant mechanism in tissue repair seems to be related to their paracrine activity. BMSCs derived extracellular vesicles (BMSC-EVs), including mcirovesicles and exosomes, containing diverse proteins, mRNAs and micro-RNAs, mediating various biological functions, might be a main paracrine mechanism for stem cell to injured cell communication. We aimed to investigate the potential alleviating effects of BMSC-EVs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Intravenous injection of BMSC-EVs attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI) and histological colonic damage. In inflammation response, the BMSC-EVs treatment significantly reduced both the mRNA and protein levels of nuclear factor kappaBp65 (NF-κBp65), tumor necrosis factor-alpha (TNF-α), induciblenitric oxidesynthase (iNOS) and cyclooxygenase-2 (COX-2) in injured colon. Additionally, the BMSC-EVs injection resulted in a markedly decrease in interleukin-1β (IL-1β) and an increase in interleukin-10 (IL-10) expression. Therapeutic effect of BMSC-EVs associated with suppression of oxidative perturbations was manifested by a decrease in the activity of myeloperoxidase (MPO) and Malondialdehyde (MDA), as well as an increase in superoxide dismutase (SOD) and glutathione (GSH). BMSC-EVs also suppressed the apoptosis via reducing the cleavage of caspase-3, caspase-8 and caspase-9 in colitis rats. Data obtained indicated that the beneficial effects of BMSC-EVs were due to the down regulation of pro-inflammatory cytokines levels, inhibition of NF-κBp65 signal transduction pathways, modulation of anti-oxidant/ oxidant balance, and moderation of the occurrence of apoptosis.</p></div

Effects of BMSC-EVs therapies on mRNA expression of inflammatory mediators in TNBS-induced colitis.

<p>The mRNA expression of NF-κBp65(A), TNF-α(B), iNOS(C) and COX-2(D) were detected by standard RT-PCR methods. β-actin was used as a control. Values mean ± SD, n = 10 for each group, differences are evaluated using the one-way ANOVA on ranks test. ^##P<0.01, vs control group. ^△p>0.05,*P<0.05, **P<0.01 vs TNBS group.</p

Effects of BMSC-EVs therapies on expression of IL-1βand IL-10 in TNBS-induced colitis.

<p>ELISA analysis was performed to detect IL-1β(A) and IL-10(B) expression. Values mean ± SD, n = 10 for each group, differences are evaluated using the one-way ANOVA on ranks test. ^##P<0.01, vs control group. ^△p>0.05, *P<0.05, **P<0.01 vs TNBS group.</p

The morphology and identification of BMSCs.

<p>(A) Representative micrographs of photics microscopy obtained on BMSCs (original magnification ×200) at passage 4. (B and C) Characterization of BMSCs at passage 4 were evaluated by flow cytometric analysis using antibodies against CD90, CD29, CD11b and CD45. 89.8% (P1) of the BMSCs expressed surface markers phenotype of CD29 and CD90, while 97.5%(P2) did not have the lineage marker expression of CD11b or CD45.</p

The characterization of BMSC-EVs.

<p>(A) Transmission electron microscopy analysis of purified EVs showed a spheroid shape. The black line refers to200 nm. (B and C) Flow cytometry was used to characterize the proper size of BMSC-EVs. Analyzed BMSC-EVs (black) were compared with Sulfate-modified polystyrene latex beads with a mean size of 1 μm (fluorescent red, λ_ex ~575 nm; λ_em ~610 nm). P1 represents the gate of the fluorescent beads. (D) FACS analysis of BMSC-EVs surface protein expression. The results indicated that BMSC-EVs were positive for CD90(76.8%), CD29(86.4%) and negative for CD11b(10.3%) and CD45(9.54%).</p

Effects of BMSC-EVs therapies on protein expression of inflammatory mediators in TNBS-induced colitis.

<p>(A) Immunohistochemical detection of NF-κBp65, TNF-α, iNOS and COX-2 protein expression. (B) Western blot detection of NF-κBp65, TNF-α, iNOS and COX-2 protein expression. (C) Grey value histogram of western blot detection. β-actin was used as a control. Values mean ± SD, n = 10 for each group, differences are evaluated using the one-way ANOVA on ranks test. ^##P<0.01, vs control group. ^△p>0.05,*P<0.05, **P<0.01 vs TNBS group.</p

Scoring of disease activity index (DAI).

<p>Scoring of disease activity index (DAI).</p