[Pristimerin enhances cisplatin-induced apoptosis in nasopharyngeal carcinoma cells via ROS-mediated deactivation of the PI3K/AKT signaling pathway].

OBJECTIVE: To explore the effect of pristimerin combined with cisplatin on proliferation and apoptosis of nasopharyngeal carcinoma cells. METHODS: CCK-8 assay was used to examine the survival rate of HNE-1 and CNE-2Z cells following treatment for 24 h with different concentrations of pristimerin, cisplatin or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/AKT signaling pathway were observed in pristimerin- and/or cisplatin-treated cells. RESULTS: Both pristimerin and cisplatin significantly lowered the survival rate of HNE-1 and CNE-2Z cells (P < 0.05). Compared with pristimerin or cisplatin alone, their combination more strongly inhibited survival and colony formation ability of the cells, increased cell apoptosis rate and intracellular ROS levels, upregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP, and downregulated the protein expressions of Bcl-2, Mcl-1, PARP and p-PI3K and p-AKT (P < 0.05). NAC pretreatment significantly attenuated proliferation inhibition and apoptosis-promoting effects of pristimerin combined with cisplatin, and partially restored the downregulated protein expressions of p-PI3K and p-AKT in HNE-1 and CNE-2Z cells with the combined treatment (P < 0.05). CONCLUSION: Pristimerin can enhance cisplatin-induced proliferation inhibition and apoptosis in nasopharyngeal carcinoma cells, the mechanism of which may involve ROS-mediated deactivation of the PI3K/AKT signaling pathway.

Claudin-10 Decrease in the Submandibular Gland Contributes to Xerostomia.

Tight junction proteins play a crucial role in paracellular transport in salivary gland epithelia. It is clear that severe xerostomia in patients with HELIX syndrome is caused by mutations in the claudin-10 gene. However, little is known about the expression pattern and role of claudin-10 in saliva secretion in physical and disease conditions. In the present study, we found that only claudin-10b transcript was expressed in human and mouse submandibular gland (SMG) tissues, and claudin-10 protein was dominantly distributed at the apicolateral membranes of acini in human, rat, and mouse SMGs. Overexpression of claudin-10 significantly reduced transepithelial electrical resistance and increased paracellular transport of dextran and Na+ in SMG-C6 cells. In C57BL/6 mice, pilocarpine stimulation promoted secretion and cation concentration in saliva in a dose-dependent increase. Assembly of claudin-10 to the most apicolateral portions in acini of SMGs was observed in the lower pilocarpine (1 mg/kg)-treated group, and this phenomenon was much obvious in the higher pilocarpine (10 mg/kg)-treated group. Furthermore, 7-, 14-, and 21-wk-old nonobese diabetic (NOD) and BALB/c mice were used to mimic the progression of hyposalivation in Sjögren syndrome. Intensity of claudin-10 protein was obviously lower in SMGs of 14- and 21-wk-old NOD mice compared with that of age-matched BALB/c mice. In the cultured mouse SMG tissues, interferon-γ (IFN-γ) downregulated claudin-10 expression. In claudin-10-overexpressed SMG-C6 cells, paracellular permeability was decreased. Furthermore, IFN-γ stimulation increased p-STAT1 level, whereas pretreatment with JAK/STAT1 antagonist significantly alleviated the IFN-γ-induced claudin-10 downregulation. These results indicate that claudin-10 functions as a pore-forming component in acinar epithelia of SMGs, assembly of claudin-10 is required for saliva secretion, and downregulation of claudin-10 induces hyposecretion. These findings may provide new clues to novel therapeutic targets on hyposalivation.

The Role of Endothelial Barrier Function in the Fibrosis of Salivary Gland.

In the salivary glands, fibrosis occurs in many pathological conditions. Endothelial tight junction (TJ)-based barrier function plays a vital role in maintaining the homeostasis of the salivary glands. However, whether endothelial barrier function is changed and involved in the pathogenesis of glandular fibrosis is unknown. Here, by using a mouse model in which the main excretory duct of the submandibular gland (SMG) was ligated to induce inflammation and fibrosis, endothelial barrier function and TJ protein expression and distribution were examined. Both 4-kDa and 70-kDa fluorescence-labeled dextrans permeated more in the 1-, 3-, and 7-d ligated SMGs. Meanwhile, the mRNA level of claudin-5 was increased with an obvious redistribution from apicolateral membranes to lateral membranes and cytoplasm in the fibrotic glands. Notably, the TJ sealer AT1001 significantly attenuated the disrupted endothelial barrier function and thereby ameliorated the glandular fibrosis. Cytokine array detection showed that monocyte chemoattractant protein-1 (MCP-1) was highly enriched in the 3-d ligated SMGs, and MCP-1 directly impaired barrier function, increased claudin-5 expression, induced the relocalization of claudin-5, and activated p-ERK1/2 in cultured human endothelial cells. Furthermore, the upregulation and disorganization of claudin-5 as well as the elevation of MCP-1 and p-ERK1/2 signaling were also confirmed in fibrotic SMGs from patients with chronic sialadenitis and immunoglobulin G4-related sialadenitis. Altogether, our findings revealed that disrupted endothelial barrier function contributed to the progression of glandular fibrosis, and targeting endothelial TJs might be a promising approach to alleviate salivary gland fibrosis-related diseases.

[Study on the incidence and influencing factors of prediabetes in Chinese adults].

Objective: To explore the incidence and influencing factors of prediabetes in adults in China. Methods: Ten provinces (cities) were selected from the surveillance survey of chronic diseases and their risk factors in China in 2010; two monitoring sites were selected from each province (city) as follow-up spots, and a follow-up survey was conducted from 2016 to 2017. An unconditional logistic regression model was used to analyze the influencing factors of prediabetes. Results: A total of 5 578 participants were included in this study. During the follow-up period, 612 patients (268 males and 344 females) developed impaired glucose tolerone (IGT), with a total follow-up of 37 364.82 person-years, and the incidence of IGT was 16.4/1 000 person-years. Impaired fasting glucose (IFG) occurred in 290 patients (128 males and 162 females) with a total follow-up of 39 731.31 person-years, and the incidence of IFG was 7.3/1 000 person-years. The multivariate unconditional logistic regression model included age, urban and rural areas, family history of diabetes, BMI, central obesity, dyslipidemia, hypertension, and physical activity, and the results showed that age (≥50 years old: OR=1.60, 95%CI: 1.32-1.95), urban residents (OR=1.41, 95%CI: 1.16-1.71), obesity (OR=1.56, 95%CI: 1.12-2.19), dyslipidemia (OR=1.52, 95%CI: 1.25-1.83), hypertension (OR=1.32, 95%CI: 1.07-1.61) and physical inactivity (OR=1.25, 95%CI: 1.04-1.50) increase the risk of IGT. Age (≥50 years old: OR=1.31, 95%CI: 1.01-1.70), family history of diabetes (OR=1.71, 95%CI: 1.13-2.60), overweight (OR=1.41, 95%CI: 1.04-1.92), obesity (OR=2.09, 95%CI: 1.38-3.17) and hypertension (OR=1.53, 95%CI: 1.18-2.00) increase the risk of IFG. Conclusions: The incidence of IGT is higher than the IFG. People aged 50 and above, overweight and obese people, hypertension patients, dyslipidemia patients, people with insufficient physical activity, and family history of diabetes are prone to prediabetic events.

[Establishment and application of new techniques for submandibular gland preservation].

The saliva secreted from submandibular gland (SMG) accounts for 60%-65%. It plays an important role in maintaining the human function of swallow, digestion, testing, speech, protection of oral mucosa, and prevention from dental carries. The SMG is frequently resected during the treatment for various kinds of oral and maxillofacial diseases, resulting in xerostomia and decreased quality of life. During the past 15 years, Research Center of Salivary Gland Diseases in Peking University School and Hospital of Stomatology conducted a series of studies on new techniques for preservation of SMG and achieved remarkable results. The clinicopathologic and imaging characteristics of IgG4-related sialadenitis (IgG4-RS) were clarified based on systematic studies. The results of studies on the pathogenesis of IgG4-RS showed that unbalance of inflammatory factors mediated the abnormality of secretion of SMG. IL-4 participates in occurring and development of glandular fibrosis of SMG. Regulation of tumor necrosis factor α (TNF-α) and cleaning of senescent cells might be taken as the targets for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents showed effective results for treating IgG4-RS, clinical remission was achieved in all the patients, serum IgG4 levels decreased, and salivary gland secretion significantly increased. Sialoendoscopy-assisted sialolithectomy was applied in the treatment of about 1 000 cases with submandibular hilar calculi with a success rate of more than 90%. Transfer of SMG was used for prevention from radiation-induced xerostomia in the patients with head and neck carcinoma. SMG was transferred to the submental region before radiotherapy and was kept away from the ra-diation field. The results of prospective clinical controlled study showed this technique could effectively preserve the function of SMG and prevent from xerostomia. Based on the micro-anatomical study on the blood vessels and ducts of SMG, partial sialoadenectomy was applied for treatment of benign tumors in the SMG. A clinical controlled study confirmed its safety for control of the tumors and its advantage of preservation of SMG function. The studies on the involvement of SMG in oral squamous cell carcinoma (OSCC) provided the anatomical and histopathological basis for preservation of SMG during neck dissection for early cases with OSCC. A innovated surgical modality "four preservations including SMG" was used during the neck dissection for the early cases with OSCC. A prospective randomized clinical controlled study confirmed its safety, feasibility, effectiveness for control of the carcinoma, and advantages of preservation of SMG function.

Advances in physiological mechanisms of selenium to improve heavy metal stress tolerance in plants.

Selenium (Se) is a metalloid mineral nutrient for human and animal health. Plants are the main foodstuff source of the Se intake of humans. For plants, the addition of an appropriate amount of Se could promotes growth and development, and improves the tolerance to environmental stress, especially stress from some of heavy metals (HM) stress, such as cadmium (Cd) and mercury (Hg). This paper mainly reviews and summarizes the physiological mechanism of Se in enhancing HM stress tolerance in plants. The antagonistic effect of Se on HM is a comprehensive effect that includes many physiological mechanisms. Se can promote the removal of excessive reactive oxygen species and reduce the oxidative damage of plant cells under HM elements stress. Se participates in the regulation of the transportation and distribution of HM ions in plants, and alleviates the damage caused by of HM stress. Moreover, Se combine with HM elements to form Se-HM complexes and promote the production of phytochelatins (PCs), thereby reducing the accumulation of HM ions in plants. Overall, Se plays an important role in plant response to HM stress, but current studies mainly focus on physiological mechanism, and further in-depth study on the molecular mechanism is essential to confirm the participation of Se in plant response to environmental stress. This review helps to comprehensively understand the physiological mechanism of Se in plant tolerance against to HM stress of plants, and provides important theoretical support for the practical application of Se in environmental remediation and agricultural development.

[Relationship between waist-to-height ratio and overall and type specific incidence of stroke in adults in China: a prospective study].

Objective: To analyze the association between waist-to-height ratio and the overall and type specific incidence of stroke in adults in China. Methods: A total of 36 632 people were selected from 60 surveillance sites (25 in urban area and 35 in rural area) in China Chronic Disease Surveillance Project in 2010. The China Chronic Disease Surveillance Project data in 2010 were used as baseline data. A total of 27 762 people were followed up from 2016 to 2017. Cox proportional risk regression model was used to analyze the risk ratio of waist-to-height ratio for the overall and type specific incidence of stroke. Subgroup analyses were performed based on baseline characteristics such as age and sex, and sensitivity analysis was performed by excluding those who died and those with diabetes at baseline survey. Results: A total of 27 112 subjects were included in the stroke analysis, and 1 333 stroke events were observed. A total of 26 907 subjects were included in the ischemic stroke analysis, and 1 128 ischemic stroke events were observed. A total of 25 984 subjects were included in the hemorrhagic stroke analysis, and 205 cases of hemorrhagic stroke were observed. After adjusting for relevant confounders and taking group with waist-to-height ratio of 0-0.45 as a reference, the stroke analysis indicated that in groups with waist-to-height ratio of 0.46-0.49, 0.50-0.54 and ≥0.55 the risk for stroke increased by 21% (HR=1.21, 95%CI:1.00-1.46), 26% (HR=1.26, 95%CI:1.04-1.53) and 60% (HR=1.60, 95%CI:1.29-1.99) respectively. Subgroup analysis revealed that age specific waist-to-height ratio had modification effect on the risk for stroke (interaction P=0.001). Ischemic stroke analysis indicated that in groups with waist-to-height ratio of 0.46-0.49, 0.50-0.54 and ≥0.55 the risk for ischemic stroke increased by 30% (HR=1.30, 95%CI: 1.05-1.60), 33% (HR=1.33, 95%CI: 1.07-1.64) and 61% (HR=1.61, 95%CI: 1.26-2.05) respectively. Subgroup analysis revealed that age specific waist-to-height ratio had modification effect on the risk for ischemic stroke (interaction P=0.024). Hemorrhagic stroke analysis indicated that in group with waist-to-height ratio of ≥0.55 the risk for hemorrhagic stroke increased by 73% (HR=1.73, 95%CI: 1.02-2.94), but the differences in the risk increase in groups with waist-to-height ratio of 0.46-0.49 and 0.50-0.54 were not significant. The sensitivity analysis showed no changes. Conclusions: In the prevention and control of stroke by body weight control, it is necessary to take waist to height ratio as one of the indicators of body weight control. Particular attention needed to be paid to the people aged <50 years with waist-to-height ratio of ≥0.55 as well as those with waist-to-height ratio of <0.5 (i.e., 0.46-0.49).

[Association between self-rated health status and risk of stroke in Chinese adults: a prospective study].

Objective: To explore the relationship between self-rated health status and risk of stroke in Chinese adults. Methods: Data was collected from the Chronic Disease Risk Factor Surveillance in China (2010) as baseline. A total of 60 follow-up monitors (25 urban and 35 rural) in 11 provinces were selected. A total of 36 195 participants without prior cardiovascular diseases were followed and investigated 27 441 people in 2016 and 2017. Cox proportional hazard regression model was used to analyze the self-assessed health status and stroke onset hazard ratio (HR), further conducted several subgroup analyses by demographic characteristics such as age and gender, and sensitivity analysis was performed by excluding death and baseline diabetes. Results: A total of 26 699 study subjects were included according to the inclusion criteria. We identified 1 332 stroke cases (32 subarachnoid hemorrhage, 197 cerebral hemorrhage, and 1 149 cerebral infarction) during an average of 6.4 years (171 431.1 person-years) of follow-up, and the incidence density was 7.77/1 000 person-years. After adjusting the related factors, the risk of stroke in participants with poor self-related health increased by 68% (HR=1.68, 95%CI:1.22-2.32) and the risk of ischemic stroke increased by 47% (HR=1.47, 95%CI:1.05-2.05), with a reference of excellent ones. In subgroup analysis, only age and BMI had an effect-modifying effect on the association between self-rated health and risk of stroke. Only age and dyslipidemia had an effect-modifying effect on the association between self-rated health and ischemic stroke risk (interaction P<0.05). The results of the sensitivity analysis were consistent with the results of the total population. Conclusion: People with poor self-assessed health, especially for those who were overweight/obesity with poor self-assessed health or age less than 60 or dyslipidemia are at increased risk of stroke and ischemic stroke and should be targeted for intervention.

[Association of body mass index and waist circumference with risk of ischemic stroke in adults in China: a prospective cohort study].

Objective: To explore the relationship between body mass index (BMI), waist circumference (WC) and the risk for ischemic stroke in adults in China. Methods: A total of 36 632 adults were selected from 60 surveillance areas (25 urban surveillance areas and 35 rural surveillance areas) in China Chronic Disease Surveillance Project in 2010 for a follow up study from 2016 to 2017 based on the baseline data in 2010. The follow up was completed for 27 762 adults. Cox proportional hazard regression model was used to analyze the association of body mass index and waist circumference with the risk for ischemic stroke in different populations. The death and hypercholesterolemia cases were excluded by sensitivity analysis. Results: A total of 26 907 adults were included in the analysis. During the follow up period, 1 128 ischemic stroke events were observed (491 in men and 637 in women). After adjusting the related confounding factors and taking normal BMI/normal WC group as the reference, the risk for ischemic stroke increased by 50% in normal BMI/abdominal obesity group (HR=1.50, 95%CI:1.07-2.08), 51% in overweight/abdominal obesity group (HR=1.51, 95%CI:1.20-1.91), 46% in obesity/abdominal obesity group (HR=1.46, 95%CI:1.09-1.96), and 63% in normal BMI/abdominal obesity group (HR=1.63, 95%CI:1.12-2.38), 56% in overweight/abdominal obesity group (HR=1.56, 95%CI: 1.20-2.03) and 45% in obesity/abdominal obesity group (HR=1.45, 95%CI: 1.05-2.01) respectively in men and in men with CVD risk factors. There was no increased risks in the overweight/normal WC group. The risk increased by 40% in overweight/abdominal obesity group (HR=1.40, 95%CI:1.15-1.72) and 46% in obesity/abdominal obesity group (HR=1.46, 95%CI:1.16-1.83), and 35% in overweight/abdominal obesity group (HR=1.35, 95%CI:1.08-1.69) and 30% in obesity/abdominal obesity group (HR=1.30, 95%CI:1.01-1.67) respectively in women and women with CVD risk factors. There were no risk increases in overweight/normal WC group and normal BMI/abdominal obesity group. Sensitivity analysis results showed no change. Conclusion: Overweight/obesity with abdominal obesity or abdominal obesity alone could increase the risk for stroke in men, and overweight/obesity with abdominal obesity could increase the risk for ischemic stroke in women; suggesting that BMI and WC should be used jointly to evaluate obesity in population for weight control to prevent ischemic stroke.

Measurement and Analysis of Human Infant Crawling for Rehabilitation: A Narrative Review.

When a child shows signs of potential motor developmental disorders, early diagnosis of central nervous system (CNS) impairment is beneficial. Known as the first CNS-controlled mobility for most of infants, mobility during crawling usually has been used in clinical assessments to identify motor development disorders. The current clinical scales of motor development during crawling stage are relatively subjective. Objective and quantitative measures of infant crawling afford the possibilities to identify those infants who might benefit from early intervention, as well as the evaluation of intervention progress. Thus, increasing researchers have explored objective measurements of infant crawling in typical and atypical developing infants. However, there is a lack of comprehensive review on infant-crawling measurement and analysis toward bridging the gap between research crawling analysis and potential clinical applications. In this narrative review, we provide a practical overview of the most relevant measurements in human infant crawling, including acquisition techniques, data processing methods, features extraction, and the potential value in objective assessment of motor function in infancy; meanwhile, the possibilities to develop crawling training as early intervention to promote the locomotor function for infants with locomotor delays are also discussed.

Behavioral and neuroanatomical outcomes following altered serotonin expression in a hypoxic-ischemic injury neonate rodent model.

BACKGROUND: Children born prematurely (<37 gestational weeks) are at risk for a variety of adverse medical events. They may experience ischemic and/or hemorrhagic events leading to negative neural sequelae. They are also exposed to repeated stressful experiences as part of life-saving care within the neonatal intensive care unit (NICU). These experiences have been associated with methylation of SLC6A4, a gene which codes for serotonin transport proteins, and is associated with anxiety, depression, and increased incidence of autism spectrum disorders.The purpose of this study was to examine the effects of altered serotonin levels on behavioral and neuroanatomical outcomes in a neonatal rodent model with or without exposure to hypoxic-ischemic (HI) injury. METHODS: Wistar rat pups were randomly assigned to either HI injury or sham groups. Pups within each group were treated with a chronic SSRI (Citalopram HBr) to simulate the effects of SLC6A4 methylation, or saline (NS). Subjects were assessed on behavioral tasks and neuropathologic indices. RESULTS: HI injured subjects performed poorly on behavioral tasks. SSRI subjects did not display significantly greater anxiety. HI + SSRI subjects learned faster than HI+NS. Histologically, SSRI subjects had predominantly larger brain volumes than NS. CONCLUSION: SSRI treated subjects without injury showed patterns of increased anxiety, consistent with theories of SLC6A4 methylation. The paradoxical trend to improved cognition in HI+SSRI subjects relative to HI alone, may reflect an unexpected SSRI neuroprotective effect in the presence of injury, and may be related to serotonin-induced neurogenesis.

[Relationship between sedentary time and incidence of type 2 diabetes in adults in China: a prospective cohort study].

Objective: To explore the relationship between sedentary time and the incidence of type 2 diabetes in adults in China. Methods: Data collected from the Chinese Chronic Disease and Risk Factor Surveillance (CCDRFS) in 2010 were used as baseline data. Eight provinces where CCDRFS were conducted in 2010 were selected, and two surveillance spots (one in urban area and another one in rural area) of each provinces were further selected for the follow-up studies. After excluding diagnosed diabetes patients according to baseline data, a total of 8 625 of subjects were recruited as participants. In the follow up carried out from 2016 to 2017, a total of 5 991 people received complete follow up. Cox proportional hazards models were used to analyze the relationship between sedentary time and the incidence of type 2 diabetes, and subgroup analysis was conducted based on variables such as gender, geographic area, and urban area or rural areas. Results: A total of 5 782 subjects were included in final analysis. During an average 6.4 years of follow up (36 927.0 person-years), 592 participants developed type 2 diabetes, the incidence rate was 16.0 per 1 000 person years. Multivariate Cox regression analysis showed that after adjustment for possible confounders, compared with the 0.0-h/d group, the risk of diabetes incidence increased by 33% (HR=1.33, 95%CI: 1.05-1.68) for those who had sedentary time for more than 6.0 h every day. The subgroup analysis showed that the significant association was only observed in those who were men, current smokers, central obese, had family history of diabetes, had rural residency, and lived in eastern and central areas of China. Conclusions: Longer sedentary time can increase the risk of type 2 diabetes. Lifestyle intervention should be strengthened to reduce sedentary time, especially for people who had sedentary time for more than 6.0 h every day.

Tricellulin Modulates Transport of Macromolecules in the Salivary Gland.

Volume and composition of saliva are crucial for oral and systemic health. How substances, particularly macromolecules, are transported across the salivary gland epithelium has not been established in detail. Tricellulin is a component of tricellular tight junctions that form a central tube to serve as an important route for macromolecule transport. Whether tricellulin is expressed in the submandibular gland (SMG) and involved in salivation has been unknown. Here, by using Western blotting and immunofluorescence, tricellulin was found to be characteristically localized at tricellular contacts of human, rat, and mouse SMGs. Knockdown of tricellulin significantly increased, whereas overexpression of tricellulin decreased, paracellular permeability for 40-kDa but not for 4-kDa fluorescein isothiocyanate-dextran, while transepithelial electrical resistance was unaffected. Conversely, claudin-4 knockdown and overexpression affected transepithelial electrical resistance but not 40-kDa fluorescein isothiocyanate-dextran transport, suggesting that tricellulin regulated transport of macromolecules but not ions, which were mainly regulated by bicellular tight junctions (bTJs). Moreover, tricellulin was dynamically redistributed from tri- to bicellular membranes in cholinergically stimulated SMG tissues and cells. Immunoglobulin-like domain-containing receptor 1 (ILDR1) recruits tricellulin to tricellular contacts. The proportion of macromolecules in the saliva was increased, whereas the amount of stimulated saliva was unchanged in Ildr1-/- mice, which displayed abnormal tricellulin distribution in SMGs. Furthermore, tricellulin interacted with bTJ proteins, such as occludin, claudin-1, claudin-3, claudin-4, and ZO-1, in rat SMG epithelial polarized cell line SMG-C6. Knockdown of tricellulin decreased occludin levels. Thus, we revealed a specific expression pattern of tricellulin in SMG epithelium. Tricellulin not only functioned as a barrier for macromolecules but also modulated the connection of bTJs to the tight junction complex. Alterations in tricellulin expression and distribution could thereby change salivary composition. Our study provided novel insights on salivary gland tight junction organization and function.

[Role and mechanism of muscarinic acetylcholine receptor in the regulation of submandibular gland secretion].

Muscarinic acetylcholine receptors (mAChRs), including M1-M5 subtypes, are classic receptors in regulating water, ion, and solute transport in salivary gland. Our work focuses on the studies on the expression pattern and function of mAChR in the submandibular gland (SMG), and the underlying mechanism involved in the mAChR-regulated secretion, together with the effect of parasympathectomy on the salivary secretion. Microvascular autotransplantation of SMG into the temporal fossa provides a continuous and endogenous source of fluids, and is currently an effective method for treating severe keratoconjunctivitis sicca. By using RT-PCR, Western blotting, and immunofluorescence, our data demonstrated that the expression of M1 and M3 subtypes were decreased in latent period in rabbit SMG autotransplantation model, whereas carbachol stimulation promoted the salivary secretion, as well as M1 and M3 expressions. By contrast, mAChRs were hypersensitive in epiphora SMGs, whereas atropine gel and botulinum toxin A application significantly inhibited the hypersecretion in both animal models and patients. Furthermore, the possible intracellular signal molecules involved in the mAChR-modulated salivary secretion were explored. Activation of mAChR upregulated the expression of aquaporin 5 (AQP5), the main transporter that mediated water secretion through transcellular pathway, and led to AQP5 trafficking from lipid rafts to non-lipid microdomain. Extracellular signal-regulated kinase 1/2 (ERK1/2) was involved in the mAChR-regulated AQP5 content. mAChR activation also modulated the expression, distribution, and function of tight junction proteins, and increased paracellular permeability. ERK1/2/ß-arrestin2/clathrin/ubiquitin signaling pathway was responsible for the mAChR-regulated downregulation of tight junction molecule claudin-4. Cytoskeleton filamentous actin (F-actin) was also involved in the distribution and barrier function of epithelial tight junctions. Besides, endothelial tight junctions were opened by mAChR agonist-evoked salivation in the mice. Furthermore, parasympathetic denervation increased resting salivary secretion in the long terminrats and minipigs. Taken together, our work demonstrated that mAChR regulated saliva secretion via transcellular and paracellular pathways in SMG epithelium as well as tight junction opening in SMG endothelium. Modulation of mAChR might be a promising strategy to ameliorate SMG dysfunction.

Indoor particle dynamics in a school office: determination of particle concentrations, deposition rates and penetration factors under naturally ventilated conditions.

Recently, the problem of indoor particulate matter pollution has received much attention. An increasing number of epidemiological studies show that the concentration of atmospheric particulate matter has a significant effect on human health, even at very low concentrations. Most of these investigations have relied upon outdoor particle concentrations as surrogates of human exposures. However, considering that the concentration distribution of the indoor particulate matter is largely dependent on the extent to which these particles penetrate the building and on the degree of suspension in the indoor air, human exposures to particles of outdoor origin may not be equal to outdoor particle concentration levels. Therefore, it is critical to understand the relationship between the particle concentrations found outdoors and those found in indoor micro-environments. In this study, experiments were conducted using a naturally ventilated office located in Qingdao, China. The indoor and outdoor particle concentrations were measured at the same time using an optical counter with four size ranges. The particle size distribution ranged from 0.3 to 2.5 µm, and the experimental period was from April to September, 2016. Based on the experimental data, the dynamic and mass balance model based on time was used to estimate the penetration rate and deposition rate at air exchange rates of 0.03-0.25 h-1. The values of the penetration rate and deposition velocity of indoor particles were determined to range from 0.45 to 0.82 h-1 and 1.71 to 2.82 m/h, respectively. In addition, the particulate pollution exposure in the indoor environment was analyzed to estimate the exposure hazard from indoor particulate matter pollution, which is important for human exposure to particles and associated health effects. The conclusions from this study can serve to provide a better understanding the dynamics and behaviors of airborne particle entering into buildings. And they will also highlight effective methods to reduce exposure to particles in office buildings.

Rapid specific and visible detection of porcine circovirus type 3 using loop-mediated isothermal amplification (LAMP).

In this study, a rapid and specific assay for the detection of porcine circovirus type 3 (PCV3) was established using loop-mediated isothermal amplification (LAMP). Four primers were specifically designed to amplify PCV3. The LAMP assay was effectively optimized to amplify PCV3 by water bath at 60°C for 60 min. The detection limit was approximately 1 × 101 copy in this LAMP assay. Compared to porcine circovirus type 2 (PCV2), both gE and gD genes of pseudorabies virus (PRV) and porcine parvovirus (PPV), the LAMP assay showed a high specific detection of PCV3. A visible detection method was developed using SYBR Green I to recognize the results rapidly. Based on the detection of 20 clinical tissue samples, the LAMP assay was more practical and convenient than classical PCR due to its simplicity, high sensitivity, rapidity, specificity, visibility and cost efficiency.

Expression of interleukin-17 in primary Sjögren's syndrome and the correlation with disease severity: A systematic review and meta-analysis.

The aberrant expression of interleukin-17 (IL-17) has been reported in primary Sjögren's syndrome (pSS). Abnormalities in IL-17 can promote the production of pro-inflammatory cytokines and aggravate autoimmune disorders. The aim of this study was to investigate alterations of IL-17 in patients with pSS and explore the correlation between IL-17 and disease severity. Eight databases were searched for original studies reporting the expression of IL-17 in patients with pSS and controls. Eligible reports were included in the pooled analysis, and subgroup evaluations were performed according to different types of controls and IL-17 measurement methods. Newcastle-Ottawa Scale criteria were used to assess the risk of bias of the included studies. In total, 45 articles are included in the meta-analysis. The expression of IL-17 is significantly increased in patients with pSS compared to controls. Furthermore, patients with pSS without immunosuppressive treatment show markedly higher IL-17 levels. In addition, patients with pSS with positive rheumatoid factors tend to express a higher level of IL-17 than patients with negative rheumatoid factors. Negative correlations between IL-17 levels and ocular parameters are also found in patients with pSS. The results are similar after adjustment by "trim and fill" methods. In conclusion, the expression of IL-17 is obviously increased in patients with pSS, especially among those without immunosuppressive treatment. In addition, IL-17 level correlates with the disease severity of pSS. These findings demonstrate the significance of IL-17 overexpression in patients with pSS and may provide insights for the development of therapeutic interventions targeting IL-17 for pSS.