Longan seed and mangosteen skin based activated carbons for the removal of Pb(II) ions and rhodamine-B dye from aqueous solutions

Agricultural biomass wastes of longan seed and mangosteen skin were collected as precursors to prepare activated carbons (LS-AC-5 and MS-AC-5, respectively) through carbonization at medium temperature and KOH activation at high temperature. Their pore structures, structural properties and surface morphologies were characterized by X-ray diffractometer, Brunauer–Emmett–Teller surface measurement system, and scanning electron microscopy, respectively. Effects of contact time and pH on adsorption performances of samples were investigated by removal of Pb(II) ions and Rhodamine-b from aqueous solutions. Experimental adsorption isotherms of Rhodamine-b and Pb(II) ions on LS-AC-5 and MS-AC-5 fitted well with the Langmuir model. Results further showed that MS-AC-5 exhibited a larger surface area of 2960.56 m2/g and larger portions of micropores and mesopores (pore volume of 1.77 cm3/g) than LS-AC-5 (surface area: 2728.98 m2/g; pore volume: 1.39 cm3/g). Maximum monolayer adsorption capabilities of 1265.82 and 117.65 mg/g for Rhodamine-b and Pb(II) ions on MS-AC-5 were higher than those on LS-AC-5 (1000.20 and 107.53 mg/g), respectively

Overexpression of PLK1 relieved the myocardial ischemia-reperfusion injury of rats through inducing the mitophagy and regulating the p-AMPK/FUNDC1 axis

Myocardial cell injury caused by myocardial ischemia and reperfusion is one of the main causes of the occurrence and development of heart disease. Recent study has shown that inducing mitophagy of cardiomyocytes is a crucial method to alleviate ischemia-reperfusion injury. While, Polo-like kinase 1 (PLK1) can induce the mitophagy of breast cancer cells. Moreover, PLK1 was able to promote the expression of p-AMPK and FUNDC1, which are the protective factors for myocardium. Therefore, the mouse model of ischemia/reperfusion was established and the effect of PLK1 on ischemia reperfusion induced myocardial damage was investigated. The PLK1 was overexpressed in H9c2 cells and rat model of ischemia/reperfusion. Ischemia reperfusion inhibited the expression of PLK1. While overexpression of PLK1 relieved the myocardial infarction and myocardium apoptosis through inducing mitophagy in rats model of ischemia reperfusion. In vitro, the H9c2 cells overexpressing the PLK1 were treated with the hypoxia and reoxygenation and the apoptosis, survival rate and expression of mitophagy-related proteins of H9c2 cells were detected using the flow cytometry, CCK-8 assay and western blotting. The results reveled that overexpression of PLK1 alleviated the hypoxia and reoxygenation induced apoptosis of H9c2 cells and promoted the expression of mitophagy-related proteins. In addition, enhanced PLK1 expression promoted the expression of p-AMPK and FUNDC1 in H9c2 cells. However, the inhibition of FUNDC1 abolished the positive effect of PLK1 on H9c2 cells mentioned above. In conclusion, PLK1 alleviated the ischemia reperfusion induced myocardial damage by inducing the mitophagy in a p-AMPK/FUNDC1 signaling dependent pathway

Efficacy of Postnatal In Vivo Nonsense Suppression Therapy in a Pax6 Mouse Model of Aniridia

Nonsense mutations leading to premature stop codons are common occurring in approximately 12% of all human genetic diseases. Thus, pharmacological nonsense mutation suppression strategies would be beneficial to a large number of patients if the drugs could be targeted to the affected tissues at the appropriate time. Here, we used nonsense suppression to manipulate Pax6 dosage at different developmental times in the eye of the small eye (Pax6Sey/+; G194X) mouse model of aniridia. Efficacy was assessed by functional assays for visual capacity, including electroretinography and optokinetic tracking (OKT), in addition to histological and biochemical studies. Malformation defects in the Pax6Sey/+ postnatal eye responded to topically delivered nonsense suppression in a dose- and time-dependent manner. Elevated levels of Mmp9, a direct downstream target of Pax6 in the cornea, were observed with the different treatment regimens. The lens capsule was particularly sensitive to Pax6 dosage, revealing a potential new role for Pax6 in lens capsule maintenance and development. The remarkable capacity of malformed ocular tissue to respond postnatally to Pax6 dosage in vivo demonstrates that the use of nonsense suppression could be a valuable therapeutic approach for blinding diseases caused by nonsense mutations

Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis

The 2p15p16.1 microdeletion syndrome has a core phenotype consisting of intellectual disability, microcephaly, hypotonia, delayed growth, common craniofacial features, and digital anomalies. So far, more than 20 cases of 2p15p16.1 microdeletion syndrome have been reported in the literature; however, the size of the deletions and their breakpoints vary, making it difficult to identify the candidate genes. Recent reports pointed to 4 genes (XPO1, USP34, BCL11A, and REL) that were included, alone or in combination, in the smallest deletions causing the syndrome. Here, we describe 8 new patients with the 2p15p16.1 deletion and review all published cases to date. We demonstrate functional deficits for the above 4 candidate genes using patients’ lymphoblast cell lines (LCLs) and knockdown of their orthologs in zebrafish. All genes were dosage sensitive on the basis of reduced protein expression in LCLs. In addition, deletion of XPO1, a nuclear exporter, cosegregated with nuclear accumulation of one of its cargo molecules (rpS5) in patients’ LCLs. Other pathways associated with these genes (e.g., NF-κB and Wnt signaling as well as the DNA damage response) were not impaired in patients’ LCLs. Knockdown of xpo1a, rel, bcl11aa, and bcl11ab resulted in abnormal zebrafish embryonic development including microcephaly, dysmorphic body, hindered growth, and small fins as well as structural brain abnormalities. Our multifaceted analysis strongly implicates XPO1, REL, and BCL11A as candidate genes for 2p15p16.1 microdeletion syndrome

Loss of function mutations in KIF14 cause severe microcephaly and kidney development defects in humans and zebrafish

International audienceMutations in KIF14 have previously been associated with either severe, isolated or syndromic microcephaly with renal hypodysplasia (RHD). Syndromic microcephaly-RHD was strongly reminiscent of clinical ciliopathies, relating to defects of the primary cilium, a signalling organelle present on the surface of many quiescent cells. KIF14 encodes a mitotic kinesin, which plays a key role at the midbody during cytokinesis and has not previously been shown to be involved in cilia-related functions. Here, we analysed four families with fetuses presenting with the syndromic form and harbouring biallelic variants in KIF14. Our functional analyses showed that the identified variants severely impact the activity of KIF14 and likely correspond to loss-of-function mutations. Analysis in human fetal tissues further revealed the accumulation of KIF14-positive midbody remnants in the lumen of ureteric bud tips indicating a shared function of KIF14 during brain and kidney development. Subsequently, analysis of a kif14 mutant zebrafish line showed a conserved role for this mitotic kinesin. Interestingly, ciliopathy-associated phenotypes were also present in mutant embryos, supporting a potential direct or indirect role for KIF14 at cilia. However, our in vitro and in vivo analyses did not provide evidence of a direct role for KIF14 in ciliogenesis and suggested that loss of kif14 causes ciliopathy-like phenotypes through an accumulation of mitotic cells in ciliated tissues. Altogether, our results demonstrate that KIF14 mutations result in a severe syndrome associating microcephaly and RHD through its conserved function in cytokinesis during kidney and brain development