Objective To investigate the epidemiological characteristics, influencing factors, and community dietary network drivers of clonorchiasis in Longjiang Village, Congjiang County, Guizhou Province using social network analysis from a One Health perspective, so as to provide insights into implementation of precision control measures. Methods Longjiang Village, Congjiang County, Guizhou Province was selected as a survey point. A total of 128 permanent residents at ages of over 6 years were sampled using a random sampling method, and subjects’ stool samples were collected. In addition, at least 10 fecal samples were collected from domestic cats and dogs, reservoir hosts of Clonorchis sinensis, and at least 80 freshwater snails and at least 200 freshwater fish, intermediate hosts of C. sinensis, were sampled in Longjiang Village. C. sinensis eggs were detected in human, domestic cat and domestic dog fecal samples using a modified Kato-Katz thick smear method (two slides for one stool sample) . The C. sinensis metacercariae were detected in freshwater fish with a compression method and the C. sinensis cercariae were detected in freshwater snails with a cercarial shedding method, respectively. Participants’ demographic characteristics, dietary and drinking hygiene behaviors and food-sharing relationships were collected with structured questionnaires and semi-structured in-depth interviews, and factors affecting C. sinensis infection were identified using regression analysis. Based on the north-south orientation delineated by the village river, participants were divided into groups a and b. Subjects’ food-sharing network was analyzed using social network analysis, and the Louvain algorithm was employed to investigate the community structure and key nodes of the network. Results The overall prevalence of C. sinensis infection was 33.59% (43/128) among participants in Longjiang Village, Congjiang County, Guizhou Province. The detection of C. sinensis metacercariae was 7.63% (22/288) in freshwater fish, and no C. sinensis cercariae were detected in freshwater snails. The prevalence of C. sinensis infection was 7.69% (1/13) in domestic cats, and no infection was detected in domestic dogs. Regression analysis identified age groups of 25 to 45 years [adjusted odds ratio (AOR) = 23.17, 95% confidence interval (CI): (1.85, 490.29)], Dong ethnicity [AOR = 26.80, 95% CI: (1.54, 1 105.09)], frequent consumption of raw water [AOR = 9.39, 95% CI: (1.58, 99.79)], and consumption of raw fish [AOR = 3.49, 95% CI: (1.52, 34.69)] as independent risk factors for C. sinensis infection among villagers in Longjiang Village (all P values < 0.05). Social network analysis showed a significantly higher global clustering coefficient (0.52 vs. 0.16; t = 2.41, P = 0.02) and average local clustering coefficient (0.52 vs. 0.16; t = 2.41, P = 0.02) in Group b than in Group a, and a significantly higher degree centrality was found among C. sinensis-infected individuals than among uninfected individuals in Group b (17.54 vs. 4.26; t = 2.33, P = 0.02). There was a high-risk community S11 with a 45.83% prevalence rate of C. sinensis infection in Group b, and C. sinensis-infected individuals with high betweenness centrality in Group b might serve as critical “bridges” in the food-sharing network, which facilitated the aggregation and diffusion of the risk of C. sinensis infection in the community. Conclusions Individual dietary behaviors, such as drinking raw water and consuming raw or undercooked fish, and sociocultural factors of household-neighborhood food-sharing networks, may contribute to the clustering transmission of clonorchiasis in Longjiang Village. The clonorchiasis control strategy is recommended to shift from individual-centered health education towards integrated interventions under a One Health framework in this region, which focus on key individuals within social networks, strengthen coordinated water and environmental management, and enhance community participation to improve the acceptability and sustainability of interventions.

Fast progresses in stem cell-based tooth tissue engineering have been achieved in recent years in several animal models including the mouse, rat, dog, and pig. Moreover, various postnatal mesenchymal stem cells of dental origin have been isolated and shown capable of differentiating into odontoblasts and generating dentin. Meanwhile, human keratinocyte stem/progenitor cells, gingival epithelial cells, and even iPSC-derived epithelium have been demonstrated to be able to differentiate into functional ameloblasts. Translational medicine studies in the nonhuman primate are irreplaceable steps towards clinical application of stem cell-based tissue engineering therapy. In the present study, we first examined the epithelial stem cell markers in the rhesus skin using immunostaining. Keratinocyte stem cells were then isolated from rhesus epidermis, cultured in vitro, and characterized by epithelial stem cell markers. Epithelial sheets of these cultured keratinocytes, which were recombined with E13.5 mouse dental mesenchyme that possesses odontogenic potential in the presence of exogenous FGF8, were induced to differentiate into enamel-secreting ameloblasts. Our results demonstrate that in the presence of appropriate odontogenic signals, rhesus keratinocytes can be induced to gain odontogenic competence and are capable of participating in odontogenesis, indicating that rhesus keratinocytes are an ideal epithelial cell source for further translational medicine study of tooth tissue engineering in nonhuman primates.
Ameloblasts* ; Animals ; Dentin ; Dogs ; Epidermis ; Epithelial Cells ; Epithelium ; Humans ; In Vitro Techniques ; Keratinocytes* ; Macaca mulatta ; Mental Competency ; Mesenchymal Stromal Cells ; Mesoderm* ; Mice* ; Models, Animal ; Odontoblasts ; Odontogenesis ; Primates ; Rats ; Skin ; Stem Cells ; Tissue Engineering ; Tooth ; Translational Medical Research

Hyperuricemia contributes to renal inflammation. We aimed to investigate the role of Na⁺–K⁺–ATPase (NKA) in hyperuricemia-induced renal tubular injury. Human primary proximal tubular epithelial cells (PTECs) were incubated with uric acid (UA) at increasing doses or for increasing lengths of time. PTECs were then stimulated by pre-incubation with an NKA α1 expression vector or small interfering RNA before UA (100 μg ml⁻¹, 48 h) stimulation. Hyperuricemic rats were induced by gastric oxonic acid and treated with febuxostat (Feb). ATP levels, the activity of NKA and expression of its α1 subunit, Src, NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and interleukin 1β (IL-1β) were measured both in vitro and in vivo. Beginning at concentrations of 100 μg ml−1, UA started to dose-dependently reduce NKA activity. UA at a concentration of 100 μg ml⁻¹ time-dependently affected the NKA activity, with the maximal increased NKA activity at 24 h, but the activity started to decrease after 48 h. This inhibitory effect of UA on NKA activity at 48 h was in addition to a decrease in NKA α1 expression in the cell membrane, but an increase in lysosomes. This process also involved the subsequent activation of Src kinase and NLRP3, promoting IL-1β processing. In hyperuricemic rats, renal cortex NKA activity and its α1 expression were upregulated at the 7th week and both decreased at the 10th week, accompanied with increased renal cortex expression of Src, NLRP3 and IL-1β. The UA levels were reduced and renal tubular injuries in hyperuricemic rats were alleviated in the Feb group. Our data suggested that the impairment of NKA and its consequent regulation of Src, NLRP3 and IL-1β in the renal proximal tubule contributed to hyperuricemia-induced renal tubular injury.

Generation of bio-engineered teeth by using stem cells will be a major approach for bioengineered implantation. Previous studies have demonstrated that dissociated tooth germ cells are capable of generating a tooth after reaggregation in vitro. However, the cellular and molecular mechanisms underlying this tooth regeneration are not clear. In this study, we dispersed E13.5 molar germ into single cells, immediately reaggregated them into cell pellet, then grafted the reaggregates under mouse kidney capsule for various times of culture. We investigated the morphogenesis and the expression of several developmental genes in dental epithelial cells in reaggregates of tooth germ cells. We found that dissociated tooth germ cells, after reaggregation, recapitulated normal tooth developmental process. In addition, dissociated dental epithelial cells retained the expression of Fgf8, Noggin, and Shh during reaggregation and tooth regeneration processes. Our results demonstrated that, despite of under dissociated status, dental epithelial cells maintained their odontogenic fate after re-aggregation with dental mesenchymal cells. These results provided important information for future in vitro generation of bio-engineered teeth from stem cells.
Animals ; Cell Culture Techniques ; methods ; Cell Differentiation ; Embryo, Mammalian ; Epithelial Cells ; cytology ; metabolism ; Female ; Gene Expression Regulation, Developmental ; genetics ; Male ; Mice ; Odontogenesis ; genetics ; Tooth Germ ; cytology ; physiology

Objective To clarify the relationship between clinical manifestation and pathological features of IgA nephropathy (IgAN) patients with mild proteinuria and/or hematuria.Methods Clinicopathological data from 316 biopsy-proven IgAN cases (proteinuria＜1 g/24 h and/or hematuria, and Scr＜133 μmol/L) from our hospital between January 1993 and October 2009 were studied retrospectively. The renal histopathology was quantified according to Lee's grading and Katafuchi's semi-quantitative standard, and the risk factors for renal pathological lesions were evaluated using multifactor logistic regression analysis. Results Among these 316 patients, 123 were male and 193 patients were female. The mean age at the time of renal biopsy was (33.10±10.69) years old. Clinical features were found as follows: hematuria with proteinuria was found in 267 patients (84.5%), isolated hematuria in 24 patients (7.6%), and isolated proteinuria in 25 patients (7.9%). 16.5% of patients had hypertension. The percentages of CKD stage Ⅰ, Ⅱ, Ⅲ were 76.9%, 20.9% and 2.2%, respectively. 31.3% of patients presented Lee's grade Ⅲ or more severe.52.8% of patients had various degrees of glomerulosclerosis. Crescent formation was observed in 20.3% of patients. 22.5% of patients showed tubular atrophy;16.8% showed interstitial fibrosis and 24.7% also had renal vascular lesions. The extent of glomerulosclerosis was negatively correlated with eGFR levels, but positively correlated with the amount of proteinuria and mean arterial pressure (MAP) level (P＜0.05). The score of tubulointerstitial lesion was positively correlated with the amount of proteinuria and negatively correlated with eGFR and hemoglobin (Hb)level (P＜0.05). The degree of renal vascular lesion was also correlated to MAP level positively and eGFR level negatively (P＜0.05). Multifactor logistic regression analysis revealed that proteinuria, Scr and Hb at the time of renal biopsy were independent risk factors for severe renal pathological lesions (Lee's grade Ⅲ or more severe) with odds ratio of 8.564, 1.031 and 0.975 respectively (all P＜0.01). Conclusions Severe renal histological lesions and decrease of renal function may be seen in some IgAN patients with mild proteinuria and/or hematuria. The levels of proteinuria,Scr and Hb are the independent risk factors for severe renal pathological lesions. Renal biopsy is important in these patients in order to make diagnosis and individual treatment.