Retinitis pigmentosa with iris coloboma due to miR-204 gene variant in a Chinese family.

PURPOSE: To characterize the phenotype and genotype of a Chinese family with autosomal-dominant retinitis pigmentosa (RP) accompanied by iris coloboma. METHODS: The proband, a 34-year-old male, was examined with his family by using fundus photography, optical coherence tomography (OCT), autofluorescence, and full-field electroretinography (ffERG). Genetic analyses were conducted through whole-exome sequencing (WES) to screen for variations. RESULTS: Three members of this Chinese family were shown to be bilateral iris coloboma. The male proband and his mother exhibited typical RP feature. The proband's late grandfather had been documented manifestation of iris coloboma. The mode of inheritance was confirmed to be autosomal dominance. Through linkage analysis and WES, a heterozygous variation in the miR-204 gene (n.37C>T), a noncoding RNA gene, was identified in these three members. CONCLUSIONS: In this third independent and the first Asian family, the existence of a miR-204 variant associated with RP accompanied by iris coloboma was confirmed. Our findings reinforce the significance of miR-204 as an important factor influencing visual function in the retina. When phenotypes like RP accompanied by iris coloboma in an autosomal-dominant pattern, including in Chinese patients, miR-204 aberrations should be considered.

CCL7 playing a dominant role in recruiting early OCPs to facilitate osteolysis at metastatic site of colorectal cancer.

BACKGROUND: Chemoattractant is critical to recruitment of osteoclast precursors and stimulates tumor bone metastasis. However, the role of chemoattractant in bone metastasis of colorectal cancer (CRC) is still unclear. METHODS: Histochemistry analysis and TRAP staining were utilized to detect the bone resorption and activation of osteoclasts (OCs) after administration of CCL7 neutralizing antibody or CCR1 siRNA. qRT-PCR analysis and ELISA assay were performed to detect the mRNA level and protein level of chemoattractant. BrdU assay and Tunel assay were used to detect the proliferation and apoptosis of osteoclast precursors (OCPs). The migration of OCPs was detected by Transwell assay. Western blots assay was performed to examine the protein levels of pathways regulating the expression of CCL7 or CCR1. RESULTS: OCPs-derived CCL7 was significantly upregulated in bone marrow after bone metastasis of CRC. Blockage of CCL7 efficiently prevented bone resorption. Administration of CCL7 promoted the migration of OCPs. Lactate promoted the expression of CCL7 through JNK pathway. In addition, CCR1 was the most important receptor of CCL7. CONCLUSION: Our study indicates the essential role of CCL7-CCR1 signaling for recruitment of OCPs in early bone metastasis of CRC. Targeting CCL7 or CCR1 could restore the bone volume, which could be a potential therapeutical target. Video Abstract.

[Determination of content of iridoids and flavonoids in Tibetan medicine "Lanhua Longdan" by quantitative analysis of multi-components by single marker (QAMS)].

In this study, the content of iridoids and flavonoids in Tibetan medicine "Lanhua Longdan" was determined simul-taneously by quantitative analysis of multi-components by single marker(QAMS), which was used to verify the feasibility and applicability of the method in the application of Lanhua Longdan quality evaluation. Using HPLC with two typical elements gentiopicroside and isoorientin as the internal reference, the relative correction factor(RCF) between the mand loganin acid, swertiamarin, sweroside, isoscoparin-2″-ß-D-glucopyranoside and isoscoparin was determined and then used, to calculate the content of several other components to achieve QAMS. At the same time, the external standard method(ESM) was used to determine the contents of these 7 components in the medicinal materials, and the differences were compared to verify the accuracy and feasibility of QAMS. The results showed that the RCF repeatability is good. There were no significant differences in the determination results of the contents of 12 batches of 4 varieties of Tibetan medicine Lanhua Longdan obtained by QAMS and ESM. Therefore, the QAMS can be used for the quality evaluation of Lanhua Longdan, and provides a reference for the quality evaluation of multi-index components of Lanhua Longdan. The results showed that the content of iridoid and flavonoid in the dried product should not be less than 0.6% and 0.8% respectively.

Protective effect of betaine against lead-induced testicular toxicity in male mice.

Lead (Pb) is an environmental toxicant reported to impair male reproductive system. Betaine is a natural product which has promising beneficial effects against oxidative stress. In this experimental study, we evaluated the ameliorative effect of betaine on sperm quality and oxidative stress induced by lead (Pb) in the testis of adult male mice. Sixty male Kunming mice were divided equally into four groups: control group, betaine group (1% in drinking water), lead group (100 mg kg-1  bw-1  day-1 ) and betaine + lead group. In the last group, mice were supplemented with betaine for two weeks prior to the initiation of lead treatment and concurrently during lead treatment for 3 weeks until sacrificed. Our results indicated that in the lead-administrated group, body weights together with sperm count were significantly decreased (p < .05). The numbers of abnormal sperms were found to be higher in lead-treated mice. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (Cat) were significantly reduced, while the level of malondialdehyde (MDA) content was increased in the testis tissue following lead treatment. The mRNA levels of antioxidant-related genes (SOD1, GPX1 and CAT) were significantly decreased in the lead group. Betaine enhanced these parameters in betaine + lead group. In testis histology span, Johnson score was decreased (p < .05) in lead group and co-treatment with betaine increased Johnson score significantly in betaine + lead group. These results indicate that betaine improves sperm quality and ameliorate oxidative damage in testis of mice exposed to lead.

The effect and biological mechanism of granular sludge size on performance of autotrophic nitrogen removal system.

The autotrophic process for nitrogen removal has attracted worldwide attention in the field of wastewater treatment, and the performance of this process is greatly influenced by the size of granular sludge particles present in the system. In this work, the granular sludge was divided into three groups, i.e. large size (> 1.2 mm), medium size (0.6-1.2 mm) and small size (< 0.6 mm). The medium granular sludge was observed to dominate at high volumetric nitrogen loading rates, while offering strong support for good performance. Its indispensable contribution was found to originate from improved settling velocity (0.84 ± 0.10 cm/s), high SOUR-A (specific oxygen uptake rate for ammonia oxidizing bacteria, 25.93 mg O2/g MLVSS/h), low SOUR-N (specific oxygen uptake rate for nitrite oxidizing bacteria, 3.39 mg O2/g MLVSS/h), and a reasonable microbial spatial distribution.

Modulation of NKT cells and Th1/Th2 imbalance after alpha-GalCer treatment in progressive load-trained rats.

PURPOSE: The purpose of this study was to determine whether alpha-galactosylceramide (alpha-GalCer), a synthetic glycolipid agonist of natural killer T (NKT) cells, can ameliorate exercise-induced immune imbalance. METHODS: Eight-week-old female Sprague-Dawley rats were trained with a progressively increasing load for 9 weeks. At 36 h and at 7 d after training, groups of rats were euthanized. The whole blood was used to detect hemoglobin(Hb), plasma was analyzed for hormones testosterone(T) and corticosterone(C), and spleen was harvested for detecting NKT cells and interferon-gamma (IFN-gamma) and interleukin (IL)-4 producing cells. RESULTS: Two-way analysis of variance (ANOVA) showed significant differences between training and time in Series 1. The results showed, at 36h after training, that the decrease in Hb, T and C concentration reflected overtraining or excessive exercise. At 7 d after training, NKT cell populations decreased, and a T helper 1/T helper 2 (Th1/Th2) lymphocyte imbalance occurred. In Series 2, alpha-galactosylceramide (alpha-GalCer), an NKT cell activator was found to enhance NKT cell numbers by 69% and shift the Th1/Th2 lymphocyte imbalance by observably decreasing the frequency of IL-4 secreting cells. CONCLUSION: These data showed that, in addition to Th1/Th2 self-regulation, alpha-GalCer played an important modulatory role in the exercise-induced Th1/Th2 lymphocyte imbalance, which may be correlative with NKT immunoregulatory cells.