Abstract Schistosomiasis is a prevalent but neglected tropical disease caused by parasitic trematodes of the genus Schistosoma, with the primary disease-causing species being S. haematobium , S. mansoni, and S. japonicum. Male-female pairing of schistosomes is necessary for sexual maturity and the production of a large number of eggs, which are primarily responsible for schistosomiasis dissemination and pathology. Here, we used microarray hybridization, bioinformatics, quantitative PCR, in situ hybridization, and gene silencing assays to identify genes that play critical roles in S. japonicum reproduction biology, particularly in vitellarium development, a process that affects male-female pairing, sexual maturation, and subsequent egg production. Microarray hybridization analyses generated a comprehensive set of genes differentially transcribed before and after male-female pairing. Although the transcript profiles of females were similar 16 and 18 days after host infection, marked gene expression changes were observed at 24 days. The 30 most abundantly transcribed genes on day 24 included those associated with vitellarium development. Among these, genes for female-specific 800 (fs800 ), eggshell precursor protein , and superoxide dismutase (cu-zn-SOD) were substantially upregulated. Our in situ hybridization results in female S. japonicum indicated that cu-zn-SOD mRNA was highest in the ovary and vitellarium, eggshell precursor protein mRNA was expressed in the ovary, ootype, and vitellarium, and Sjfs800 mRNA was observed only in the vitellarium, localized in mature vitelline cells. Knocking down the Sjfs800 gene in female S. japonicum by approximately 60% reduced the number of mature vitelline cells, decreased rates of pairing and oviposition, and decreased the number of eggs produced in each male-female pairing by about 50%. These results indicate that Sjfs800 is essential for vitellarium development and egg production in S. japonicum and suggest that Sjfs800 regulation may provide a novel approach for the prevention or treatment of schistosomiasis. Author Summary Schistosomiasis is a common but largely unstudied tropical disease caused by parasitic trematodes of the genus Schistosoma. The eggs of schistosomes are responsible for schistosomiasis transmission and pathology, and the production of these eggs is dependent on the pairing of females and males. In this study, we determined which genes in Schistosoma japonicum females were differentially expressed before and after pairing with males, identifying the 30 most abundantly expressed of these genes. Among these 30 genes, we further characterized those in female S. japonicum that were upregulated after pairing and that were related to reproduction and vitellarium development, a process that affects male-female pairing, sexual maturation, and subsequent egg production. We identified three such genes, S. japonicum female-specific 800 (Sjfs800), eggshell precursor protein, and superoxide dismutase, and confirmed that the mRNAs for these genes were primarily localized in reproductive structures. By using gene silencing techniques to reduce the amount of Sjfs800 mRNA in females by about 60%, we determined that Sjfs800 plays a key role in development of the vitellarium and egg production. This finding suggests that regulation of Sjfs800 may provide a novel approach to reduce egg counts and thus aid in the prevention or treatment of schistosomiasis.
Abstract Most nonalcoholic steatohepatitis (NASH) patients develop severe fibrosis through extracellular matrix (ECM) accumulation, which can lead to hepatocellular carcinoma (HCC). Fibroblast growth factor 9 (FGF9) is involved in serial types of cancer; however, the specific role of FGF9 in NASH‐driven HCC is not fully understood. This study finds that FGF9 is increased in patients with NASH‐associated HCC. Furthermore, NASH‐driven HCC mice models by feeding wildtype mice with high‐fat/high‐cholesterol (HFHC) diet and low dose carbon tetrachloride (CCl 4 ) treatment is established; and identified that hepatic FGF9 is increased; with severe fibrosis. Additionally, AAV‐mediated knockdown of FGF9 reduced the hepatic tumor burden of NASH‐driven HCC mice models. Hepatocyte‐specific FGF9 transgenic mice (FGF9 Alb ) fed with a HFHC diet without CCl 4 treatment exhibited an increased hepatic ECM and tumor burden. However, XAV‐939 treatment blocked ECM accumulation and NASH‐driven HCC in FGF9 Alb mice fed with HFHC diet. Molecular mechanism studies show that FGF9 stimulated the expression of ECM related genes in a β‐catenin dependent manner; and FGF9 exerts its effect on β‐catenin stability via the ERK1/2‐GSK‐3β signaling pathway. In summary, the data provides evidence for the critical role of FGF9 in NASH‐driven HCC pathogenesis; wherein it promotes the tumors formation through the ECM pathway.
Objective
To explore whether the proprioceptive sensory cueing delivered by electrical stimulator to common peroneal nerve can improve the freezing of gait of parkinsonian patients.
Methods
Thirty patients with Parkinson′s disease experiencing freezing of gait (FOG) admitted to the First Affiliated Hospital of Anhui Medical University from January to December 2018 were included in the trial. Proprioceptive sensory cueing was provided by alternating electrical stimuli to bilateral common peroneal nerves delivered through the wearable electrical stimulator automatically triggered by walking. The modified 12 meters Timed Walking Test, six items of the modified Parkinson Activity Scale (PSA-6), and FOG score were used to test the gait function respectively when the stimulator was turned on and off.
Results
Compared to the off status, time duration for two 360° turns (T360), initiating (T1) and the turning (T2) was reduced with statistical significance when the stimulator was turned on in the three trial situations which were walking with no extra task (17.49 (13.55, 23.48) s vs 14.73 (10.31, 21.71) s, 2.16 (1.78, 2.68) s vs 1.70 (1.38, 2.29) s, 6.37 (4.10, 7.45) s vs 4.77 (3.40, 6.85) s; Z=-3.219, -4.206, -2.910, P<0.05), walking with cognitive task (21.35 (16.30, 30.72) s vs 18.36 (13.83, 27.98) s, 2.80 (2.05, 3.75) s vs 2.04 (1.64, 3.00) s, 6.58 (5.23, 8.96) s vs 5.75 (4.59, 7.76) s; Z=-3.486, -4.206, -3.363, P<0.05) and walking with motor task (25.34 (17.79, 30.30) s vs 22.24 (14.11, 29.33) s, 2.46 (2.19, 3.18) s vs 2.35 (1.66, 2.59) s, 7.77 (4.75, 9.93) s vs 6.45 (3.81, 7.66) s; Z=-3.468, -3.983, -3.570, P<0.05). In all the three exercise modes, the maintaining time (T3) was not significantly different. With the stimulator turned on, the total walking time (Tt) was not significantly different when the patients walked without extra task and with cognitive task but obviously improved with motor task (29.26 (20.11, 33.21) s vs 27.66 (17.70, 32.73) s, Z=-2.644, P=0.008). Compared to the off status, patients showed higher PAS-6 scores (18.99±2.55 vs 16.82±2.92, t=-6.617, P=0.000) and lower FOG scores (14.10±5.02 vs 10.61±5.05, t=6.151, P=0.000) with statistical significance when the stimulator was turned on.
Conclusion
The wearable electrical stimulator can alleviate FOG in patients with Parkinson′s disease by improving rotation, gait initiation and turning and may be used as a new rehabilitative therapy for patients with FOG.
Key words:
Parkinson disease; Freezing of gait; Peroneal nerve; Electrical stimulation; Proprioception
The urose of this study was to observe the dynamic changes of liver damage in mice infected with Schistosoma jaonicum(S.jaonicum) and investigate the correlation among granulomatous lesions,liver fibrosis and serological indexes.Mice were infected subcutaneously with cercariae of S.jaonicum,and then sacrificed to observe the athological changes of livers and record the liver index regularly.Liver samles were embedded in araffin for routine histological examination.The sizes of egg granuloma and degrees of liver fibrosis were observed dynamically by HE stain and Masson's trichrome stain,resectively.The liver-associated AST and ALT levels in individual serum samles were measured in enzymatic assay using a commercial kit.The content of hyaluronic acid(HA),laminin(LN) and Ⅳ collagen(Ⅳ-C) in serum were detected by radioimmunoassay.It was found that bleeding oints began to emerge on 24d.i.and yellowish-white dots began to emerge on 29d.i.on the surface of livers.HE stain showed that numerous small and mixed inflammatory cell foci aeared on 21d,and eggs without granulomatous reaction could be seen on 28d.Egg granuloma resented on 29d and the size of the granuloma reached maximum on 42d.i.The ALT/AST level in serum elevated obviously on 28d,eaked on 39d,began to decrease on 42d and was closed to normal level on 70d.i..There were ositive correlation between aminotransferase concentration and the size of liver granuloma of infected mice(0.01).Masson's stain demonstrated that liver fibrosis could be seen from 42d.i.and increased gradually.Meanwhile,the levels of serum HA and LN increased with the emergence of fibrosis.Ⅳ-C,however,showed no obvious change along with fibrosis aggravation.But there were no correlation between fibrosis arameters and Masson's stain.It is evident that liver granuloma and fibrosis are the rimary causes for liver damage.The serological aminotransferase changes are consistent with the rogress in liver athology.But serum fibrosis indexes could not reresent early liver fibrosis aroriately.
Male and female Schistosoma japonicum worms have dissimilar appearances in their final host. In this study, a morphometric and morphological assessment of whole worms derived from unisexual and mixed infections in mice was conducted using confocal laser scanning microscopy. Worms from mixed infections showed significant morphological changes between 15 and 25 days post-infection (PI). On the fifteenth day PI, 33% of males had formed the conspicuous gynecophoric canal, but only 8% of them had testicular lobes containing a few germinative cells; 13% of females had incipient ovaries with a few immature ovarian cells inside. On the twentieth day PI, the testicular lobes contained more germinative cells in all male worms, while female worms presented vitelline glands. On the twenty-fifth day PI, more germinative cells were observed in the male testicular lobes, and differentiated cells were present in the female ovaries. All worms had fully developed reproductive organs from 30 days PI onwards. Morphometric analysis showed significant differences between mixed and unisexual infections at 35 days PI. Ovaries of worms from unisexual infections contained cells in one stage of maturation and vitelline glands had undifferentiated cells. Our study of S. japonicum provides a detailed comparison of different morphological traits from worms of mixed and unisexual infections throughout development.
To explore the relationship between IL-1β expression and two common autoimmune thyroid diseases: Hashimoto thyroiditis (HT) and Graves' disease (GD).qRT-PCR, Quantiglo ELISA, and flow cytometry were used to evaluate the expression levels of IL-1β in serum, peripheral blood mononuclear cells (PBMCs), and thyroid tissue samples from patients with HT or GD. Local infiltration of monocytes was assessed by immunohistochemical study of patients' thyroid tissue samples.Although no significant differences in IL-1β levels were found between samples of serum from patients with HT or GD and normal controls, we found that IL-1β mRNA and protein levels in PBMCs of HT patients were significantly higher than those of patients with GD, which were in turn higher than the level in normal controls. In addition, IL-1β mRNA was also increased in thyroid gland tissue from patients with HT compared to those with GD, and this was accompanied by increased local infiltration of monocytes into thyroid tissues. Correlation analysis of the clinical samples validated the association of high IL-1β levels with the pathogenesis of HT.Our study suggests that IL-1β may be an active etiologic factor in the pathogenesis of HT and thus present a new target for novel diagnostics and treatment.
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