Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer.

BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. METHODS: A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. RESULTS: In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. CONCLUSIONS: Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.

Genotype-Controlled Vertical Transmission Exerts Selective Pressure on Community Assembly of Salvia miltiorrhiza.

The plant's endophytic fungi play an important role in promoting host development and metabolism. Studies have shown that the factors affecting the assembly of the endophyte community mainly include host genotype, vertical transmission, and soil origin. However, we do not know the role of vertically transmitted endohytic fungi influences on the host-plant's endophytic community assembly. Salvia miltiorrhiza from three production areas were used as research objects; we constructed three production area genotypes of S. miltiorrhiza regenerated seedlings simultaneously. Based on high-throughput sequencing, we analyzed the effects of genotype, soil origin, and vertical transmission on endophytic fungal communities. The results show that the community of soil origins significantly affected the endophytic fungal community in the regenerated seedlings of S. miltiorrhiza. The influence of genotype on community composition occurs through a specific mechanism. Genotype may selectively screen certain communities into the seed, thereby exerting selection pressure on the community composition process of offspring. As the number of offspring increases gradually, the microbiota, controlled by genotype and transmitted vertically, stabilizes, ultimately resulting in a significant effect of genotype on community composition.Furthermore, we observed that the taxa influencing the active ingredients are also selected as the vertically transmitted community. Moreover, the absence of an initial vertically transmitted community in S. miltiorrhiza makes it more vulnerable to infection by pathogenic fungi. Therefore, it is crucial to investigate and comprehend the selection model of the vertically transmitted community under varying genotypes and soil conditions. This research holds significant implications for enhancing the quality and yield of medicinal plants and economic crops.

Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with Preeclampsia.

Preeclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality. However, the exact pathophysiology of PE is still unclear. The recent widely accepted notion that successful pregnancy relies on maternal immunological adaptation is of utmost importance. Moreover, salt-inducible kinase 3 (SIK3) is an AMP-activated protein kinase-related kinase, and it has reported a novel regulator of energy and inflammation, and its expression related with some diseases. To explore whether SIK3 expression correlated with PE, we analyzed SIK3 gene expression and its association with PE through GEO datasets. We identified that SIK3 was significantly downregulated in PE across four datasets (p < 0.05), suggesting that SIK3 participated in the pathogenesis of PE. We initially demonstrated the significant downregulation of SIK3 in trophoblast cells of PE. SIK3 downregulation was positively correlated with the increased number of CD204(+) cells in in vivo and in vitro experiments. The increased number of CD204(+) cells could inhibit the migration and invasion of trophoblast cells. We then clarified the potential mechanism of PE with SIK3 downregulation: M2 skewing was triggered by trophoblast cells derived via the CCL24/CCR3 axis, leading to an increase in CD204(+) cells, a decrease in phagocytosis, and the production of IL-10 at the maternal-fetal interface of the placenta with PE. IL-10 further contributed to a reduction in the migration and invasion of trophoblast cells. It also established a feedback loop wherein trophoblast cells increased CCL24 production to maintain M2 dominance in the placental environments of PE.

Blockade of epidermal growth factor and its receptor and axial elongation in experimental myopia.

To examine the influence of epidermal growth factor (EGF) and its receptor (EGFR) on axial ocular elongation, we intraocularly injected an EGF antibody and an EGFR antibody into young guinea pigs with lens-induced axial elongation (myopization). Mean axial elongation was reduced in the eyes injected with the EGF/EGFR-antibody compared with the contralateral control eyes injected with PBS (phosphate-buffered solution) (0.43 ± 0.13 mm vs 0.53 ± 0.13 mm; P < .001). The intereye difference in axial length increased (P = .005) as the doses of the EGF antibody and EGFR antibody increased. As a corollary, the thickness of the retina at the posterior pole was dose-dependently increased in the injected eyes compared to the contralateral control eyes. Immunohistochemical staining for EGF and the relative mRNA expression of EGF and EGFR were the highest in eyes not injected with the EGF antibody or EGFR antibody and decreased (P < .05) as the dose of EGF antibody or EGFR antibody increased. In an in vitro study, EGF had a stimulating effect and the EGF antibody had an inhibitory effect on the proliferation and migration of RPE cells. The findings showed that the intravitreal application of an EGF antibody and EGFR antibody is associated with a dose-dependent reduction in lens-induced axial elongation in young guinea pigs. The EGFR family may play a role in axial elongation of the eye and in the development of myopia.

Interleukin-38 alleviates cardiac remodelling after myocardial infarction.

Excessive immune-mediated inflammatory reaction plays a deleterious role in ventricular remodelling after myocardial infarction (MI). Interleukin (IL)-38 is a newly characterized cytokine of the IL-1 family and has been reported to exert a protective effect in some autoimmune diseases. However, its role in cardiac remodelling post-MI remains unknown. In this study, we found that the expression of IL-38 was increased in infarcted heart after MI induced in C57BL/6 mice by permanent ligation of the left anterior descending artery. In addition, our data showed that ventricular remodelling after MI was significantly ameliorated after recombinant IL-38 injection in mice. This amelioration was demonstrated by better cardiac function, restricted inflammatory response, attenuated myocardial injury and decreased myocardial fibrosis. Our results in vitro revealed that IL-38 affects the phenotype of dendritic cells (DCs) and IL-38 plus troponin I (TNI)-treated tolerogenic DCs dampened adaptive immune response when co-cultured with CD4+ T cells. In conclusion, IL-38 plays a protective effect in ventricular remodelling post-MI, one possibility by influencing DCs to attenuate inflammatory response. Therefore, targeting IL-38 may hold a new therapeutic potential in treating MI.

Lens-induced myopization and intraocular pressure in young guinea pigs.

BACKGROUND: Intraocular pressure (IOP) is an important physiological measure of the eye and is associated with some ocular disorders. We aimed to assess the influence of topical beta blocker-induced IOP reduction on lens-induced axial elongation in young guinea pigs. METHODS: The experimental study included 20 pigmented guinea pigs (age: 2-3 weeks). Myopia was induced in the right eyes for 5 weeks with - 10 diopter lenses. The right eyes additionally received either one drop of carteolol 2% (study group, n = 10) or one drop of artificial tears daily (control group, n = 10), while the contralateral eyes of all animals remained untouched. The outcome parameter was axial elongation during the follow-up period. The mean of all IOP measurements taken during the study was referred to as mean IOP. RESULTS: Greater axial elongation was associated with a shorter axial length at baseline (P < 0.001; standardized regression coefficient beta: - 0.54) and lens-induced myopization (P < 0.001; beta: 0.55). In the multivariable model, axial elongation was not significantly correlated with the IOP at study end (P = 0.59), the mean IOP during the study period (P = 0.12), the mean of all IOP measurements (P = 0.17), the difference between the IOP at study end and baseline IOP (P = 0.38), the difference between the mean IOP during the study period and the baseline IOP (P = 0.11), or the application of carteolol eye drops versus artificial tears eye drops (P = 0.07). The univariate analysis of the relationships between axial elongation and the IOP parameters yielded similar results. The inter-eye difference between the right eye and the left eye in axial elongation was significantly associated with the inter-eye difference in baseline axial length (P = 0.001; beta:-0.67) but not significantly correlated with the inter-eye difference in any of the IOP-related parameters (all P > 0.25). CONCLUSIONS: In young guinea pigs with or without lens-induced axial elongation, neither the physiological IOP nor the IOP reduced by carteolol, a topical beta-blocker, was associated with the magnitude of axial elongation. These results suggest that IOP, regardless of whether it is influenced by carteolol, does not play a major role in axial elongation in young guinea pigs.

[Lower Extremity Exercise Improves Functional Fitness, Physiological Indexes, Exercise Self-Efficacy, Sleep Quality, and Mental Health in Middle-Aged and Older Individuals].

BACKGROUND: Middle-aged and older individuals suffer from skeletal muscle loss due to aging, increasing the risk of sarcopenia. Muscular dystrophy reduces lower-extremity muscle endurance. The annual incidence of falls in the community is about 30-40%. Falls contribute to disability and fractures, affect quality of life, reduce mental health, and, in severe cases, result in death. Therefore, preventing lower limb muscle weakness in middle-aged and older individuals should be taken seriously. PURPOSE: The purpose of this study was to promote community health with a focus on older, community-dwelling individuals. The effects of a lower-extremity exercise intervention on middle-aged and older individuals in terms of improving functional fitness, physiological indexes, exercise self-efficacy, sleep quality, and mental health were explored. METHODS: This study used convenience sampling to recruit community residents over 55 years old as participants, with 50 participants assigned to the control group and to the experimental group, respectively. The experimental group participated in a 50-min lower extremity exercise intervention three times a week for 12 weeks. Differences in functional fitness, basic physiological index, exercise self-efficacy, sleep quality, and mental health variables between the two groups were assessed at the conclusion of the intervention. RESULTS: The lower-extremity muscle exercise program significantly improved functional fitness, physiological indexes, exercise self-efficacy, sleep quality, and overall mental health status in the experimental group, as compared to the control group (p < .05). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: It is recommended that the concept and application of lower extremity movement intervention should be popularized among middle-aged and older individuals to promote physical and mental health, prevent the decline and loss of lower extremity muscle strength, and help realize healthy aging goals.

[Identification of Pathogens Causing Root Rot Disease on Ligusticum chuanxiong in Sichuan].

OBJECTIVE: To identify the pathogens causing root rot disease on Ligusticum chuanxiong from the main producing areas in Sichuan, and to provide gist of management of this disease in the future. METHODS: The diseased rhizomes of Ligusticurn chuanxiong with root rot symptom were sampled in two main producing areas in Sichuan. According to Koch's postulate, the pathogenicity on Ligusticum chuanxiong rhizomes of the isolates was confirmed. The representative isolates were identified based on their morphological characteristics and ribosomal DNA internal transcribed spacer(rDNA-ITS) sequences. RESULTS: The isolates(f2-16, 3-2, f4-19 and f5-7)which caused root rot disease held high homology reached 99%, 99%, 100% and 100% respectively, when compared with GenBank sequences GQ229075, JQ796755, JN232136 and FJ481024. CONCLUSION: The causing agents of root rot disease on Ligusticum chuanxiong belong to Fusarium solani, Fusarium oxysporum, Plectosphaerella cucumerina and Phoma glomerata. Pathogens from different regions are varied.

[Applications of mathematical statistics methods on compatibility researches of traditional Chinese medicines formulae].

The compatibility of traditional Chinese medicines (TCMs) formulae containing enormous information, is a complex component system. Applications of mathematical statistics methods on the compatibility researches of traditional Chinese medicines formulae have great significance for promoting the modernization of traditional Chinese medicines and improving clinical efficacies and optimizations of formulae. As a tool for quantitative analysis, data inference and exploring inherent rules of substances, the mathematical statistics method can be used to reveal the working mechanisms of the compatibility of traditional Chinese medicines formulae in qualitatively and quantitatively. By reviewing studies based on the applications of mathematical statistics methods, this paper were summarized from perspective of dosages optimization, efficacies and changes of chemical components as well as the rules of incompatibility and contraindication of formulae, will provide the references for further studying and revealing the working mechanisms and the connotations of traditional Chinese medicines.

Current Progress in Cancer Treatment Using Nanomaterials.

The pathological processes of cancer are complex. Current methods used for chemotherapy have various limitations, such as cytotoxicity, multi-drug resistance, stem-like cells growth, and lack of specificity. Several types of nanomaterials are used for cancer treatment. Nanomaterials 1-100 nm in size have special optical, magnetic, and electrical characteristics. Nanomaterials have been fabricated for cancer treatments to overcome cytotoxicity and low specificity, and improve drug capacity and bioavailability. Despite the increasing number of related studies, few nanodrugs have been approved for clinical use. To improve translation of these materials, studies of targeted drug delivery using nanocarriers are needed. Cytotoxicity, enhanced permeability and retention effects, and the protective role of the protein corona remain to be addressed. This mini-review summarizes new nanomaterials manufactured in studies and in clinical use, analyses current barriers preventing their translation to clinical use, and describes the effective application of nanomaterials in cancer treatment.

Perceptions towards charcoal-burning suicide and the surge of this lethal method in Taiwan.

OBJECTIVE: Whether sociocultural perceptions of charcoal-burning suicide have influenced its rapid increase in prevalence is unclear. We aimed to explore perceptions of Taiwan's general population regarding charcoal-burning suicide, their personal belief in life after death, and related feelings of thoughts associated with those who attempt charcoal-burning suicide. METHODS: An online web-based survey, focussing on sociocultural attitudes towards death, as well as perceptions towards charcoal-burning suicide, and those who attempt charcoal-burning suicide, was conducted from 14 January to 14 June 2016. RESULTS: In total, 1343 adults completed the online survey (mean age of 33.46; 66.6% women). Notably, 90.3% of participants considered charcoal burning to be an easily accessible suicide method. Multivariable analyses revealed that among the examined factors, the perceived 'painlessness' of charcoal-burning suicide was associated with an over seven-fold increased risk of choosing charcoal-burning suicide (OR = 7.394; p < 0.001; 95% CI: 2.614-20.912). CONCLUSION: As reflected in this study, charcoal-burning suicide is perceived as easily accessible and painless. The perceived 'painlessness' may be the factor that distinguishes the choice of charcoal-burning suicide from that of other suicide methods. Future efforts to target these perceptions regarding charcoal-burning suicide may be warranted in both media reporting and suicide prevention programmes.

In vivo Imaging of Retina and Choroid in Guinea Pigs.

Purpose: To evaluate the feasibility of in-vivo imaging of the retina and choroid using spectral domain optical coherence tomography (OCT) in guinea pigs. Methods: The study included 19 pigmented guinea pigs (age: 3-4 weeks) which underwent sonographic axial length measurements and OCT imaging. At study end, the animals were sacrificed and histomorphometric examinations of the retina and choroid were performed. We assessed the reproducibility of the OCT measurements and compared in-vivo measurements to histomorphometric data. Results: The mean thickness of the retina and choroid near the optic nerve head was 175.6 ± 25.8 and 63.4 ± 16.5 µm, respectively, and mean Bruch's membrane opening (BMO) diameter was 831 ± 121 µm. The intra-observer comparison of measurements of retinal thickness (intraclass correlation coefficient (ICC) = 0.92, 95% CI: 0.86-0.96; P < 0.001), choroidal thickness (ICC = 0.92, 95% CI: 0.86-0.96; P < 0.001), and BMO diameter (ICC = 0.92, 95% CI: 0.86-0.96; P < 0.001) showed a high correlation. A high agreement was present also for the inter-observer reproducibility of the measurements of retinal thickness (Pearson correlation coefficient (R) = 0.98; P < 0.001), choroidal thickness (R = 0.96; P < 0.001), and BMO diameter (R = 0.98; P < 0.001). The Bland-Altman plots showed that 2.6% (1/38), 5.3% (2/38), and 7.9% (3/38) of the measurement points of retinal thickness, choroidal thickness and BMO diameter, respectively, were located outside of the 95% limits of agreement. The OCT-based thickness measurements of retina and choroid were significantly higher than those measured by histomorphometry (both P-values <0.01). Conclusion: OCT-based in-vivo morphometric imaging of the retina and choroid in guinea pigs is feasible with an acceptable intra-observer repeatability and inter-observer reproducibility.

Endometriosis-related spontaneous hemoperitoneum in the early second trimester: A case report.

OBJECTIVE: To present a rare case of endometriosis-related spontaneous hemoperitoneum in pregnancy (SHiP) with atypical subacute symptoms, which is likely to be mistaken as an infectious disease initially. CASE REPORT: A 35-year-old primigravid woman presented with diffuse lower abdominal pain and signs of peritoneal irritation for five days at 18 weeks' gestation, and the initial diagnosis was acute peritonitis. An abrupt deterioration with maternal shock and stillbirth of fetus was found in spite of close observation in emergent department. Emergent laparotomy was performed for delay-appeared hemoperitoneum. Bleeding from decidualized endometriotic tissue over posterior uterine surface was found, and hemostasis was achieved with uterine preservation. The patient recovered smoothly. CONCLUSION: SHiP is a serious obstetric complication of endometriosis with diagnostic difficulty. Its initial presentation may mimic infectious disease, so close monitoring for possible abrupt deterioration is crucial. Early detection and timely management are the key to avoid adverse pregnancy outcomes.

Deep Learning-Based Estimation of Axial Length and Subfoveal Choroidal Thickness From Color Fundus Photographs.

This study aimed to develop an automated computer-based algorithm to estimate axial length and subfoveal choroidal thickness (SFCT) based on color fundus photographs. In the population-based Beijing Eye Study 2011, we took fundus photographs and measured SFCT by optical coherence tomography (OCT) and axial length by optical low-coherence reflectometry. Using 6394 color fundus images taken from 3468 participants, we trained and evaluated a deep-learning-based algorithm for estimation of axial length and SFCT. The algorithm had a mean absolute error (MAE) for estimating axial length and SFCT of 0.56 mm [95% confidence interval (CI): 0.53,0.61] and 49.20 µm (95% CI: 45.83,52.54), respectively. Estimated values and measured data showed coefficients of determination of r 2 = 0.59 (95% CI: 0.50,0.65) for axial length and r 2 = 0.62 (95% CI: 0.57,0.67) for SFCT. Bland-Altman plots revealed a mean difference in axial length and SFCT of -0.16 mm (95% CI: -1.60,1.27 mm) and of -4.40 µm (95% CI, -131.8,122.9 µm), respectively. For the estimation of axial length, heat map analysis showed that signals predominantly from overall of the macular region, the foveal region, and the extrafoveal region were used in the eyes with an axial length of < 22 mm, 22-26 mm, and > 26 mm, respectively. For the estimation of SFCT, the convolutional neural network (CNN) used mostly the central part of the macular region, the fovea or perifovea, independently of the SFCT. Our study shows that deep-learning-based algorithms may be helpful in estimating axial length and SFCT based on conventional color fundus images. They may be a further step in the semiautomatic assessment of the eye.

Heat Shock Protein 22 Attenuates Doxorubicin-Induced Cardiotoxicity via Regulating Inflammation and Apoptosis.

BACKGROUND: The antitumor effect of doxorubicin (DOX) is limited by its acute and chronic toxicity to the heart, which causes heart injury. Heat shock protein 22 (Hsp22) is a protein proved to exert anti-apoptosis and anti-inflammatory effects in other diseases and physical conditions. In this study, we aim to explore whether Hsp22 could exert a protective role during cardiac injury in response to DOX. METHODS: The overexpression of Hsp22 was mediated via adenovirus vector to clarify the role of Hsp22 in the cardiac injury caused by DOX. DOX-induced acute heart injury mouse model was established by single intraperitoneal injection of DOX (15 mg/kg). Subsequently, cardiac staining and molecular biological analysis were performed to analyze the morphological and biochemical effects of Hsp22 on cardiac injury. H9c2 cells were used for validation in vitro. RESULTS: An increase in the expression level of Hsp22 was observed in DOX-treated heart tissue. Furthermore, cardiac-specific overexpression of Hsp22 showed reduced cardiac dysfunction, decrease in inflammatory response, and reduction in cell apoptosis in injury heart and cardiomyocytes induced by DOX in vivo and in vitro. Moreover, the suppression of Toll-like receptor (TLR)4/NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) was associated with the protective effect of Hsp22. Finally, the protective effect of Hsp22 cardiac function was almost abolished by overexpression of NLRP3 in DOX-treated mice. CONCLUSION: In summary, Hsp22 overexpression in the heart could suppress cardiac injury in response to DOX treatment through blocking TLR4/NLRP3 activation. Hsp22 may become a new therapeutic method for treating cardiac injury induced by DOX in cancer patients.

Effect of Electroacupuncture at Different Acupoints on the Expression of NMDA Receptors in ACC and Colon in IBS Rats.

OBJECTIVE: To observe the effects of electroacupuncture (EA) at different acupoints on the expression of N-methyl-D-aspartate receptor (NMDA receptor ) and behaviors in irritable bowel syndrome (IBS) rats. METHODS: Wistar rats were randomly divided into blank control group (blank group, n=10) and model preparation group (n=50); experimental rat model of IBS was established by the "neonatal maternal separation and acetic acid enema" combined with "colorectal distension stimulation" method. A total of 50 IBS rats were randomly assigned to five groups of 10 each: model group, Yintang (GV29) group, Neiguan (PC6) group, Tianshu (ST25) group, and Zusanli (ST36) group. Rats in four treatment groups, aged 9 weeks old, were treated with EA by HANS with a sparse-dense wave with a frequency of 2/100 Hz, current of 0.1-0.3mA, and 20 min/stimulation, every other day for a total of 5 sessions. After treatment, the abdominal visceral sensitivity was evaluated by abdominal withdrawal reflex (AWR), and the psychological and emotional behavior of rats were evaluated by the open-field test (OFT). The expression of NMDA receptors in anterior cingulate cortex (ACC) was detected by Quantitative Real-time PCR, and the positive expression of NMDA receptors in colon was detected by immunohistochemistry. RESULTS: The IBS rat's abdomen is more sensitive and irritable; NR1, NR2A, and NR2B in ACC and NR1 and NR2B in colon of rats significantly increased in the model group versus the normal group (P<0.01) and were inhibited in all treatment groups (P<0.01, P<0.05). Additionally, NR2A and NR2B in ACC reduced more in GV29 group (P<0.01) than in other treatment groups (P all<0.05) compared with the model group. The expression of NR2B in colon was significantly inhibited in ST36 group (P<0.01) and inhibited in GV29 group and ST25 group (P all <0.05) compared with the model group. And the expression of NR2B in colon was more inhibited in ST36 group than in PC6 group (P<0.01). CONCLUSIONS: EA at different acupoints could obviously relieve abdominal pain and abnormal behaviors in IBS rats in different degrees of effects. The effect of abdominal pain-relief, from greatest to least, is ST25, ST36, GV29, and PC6, while the effect of relieving abnormal behaviors caused by IBS, from greatest to least, is GV29, PC6, ST36, and ST25. There are significant differences in the expressions of NMDA receptors in ACC and colon among different acupoints. This difference should be related to the location distribution and indications of acupoints.

Antagonistic potential against pathogenic microorganisms and hydrogen peroxide production of indigenous lactobacilli isolated from vagina of Chinese pregnant women.

OBJECTIVE: To investigate the indigenous lactobacilli from the vagina of pregnant women and to screen the isolates with antagonistic potential against pathogenic microorganisms. METHODS: The strains were isolated from pregnant women's vagina and identified using the API50CH system. The ability of the isolates to produce hydrogen peroxide was analyzed semi-quantitatively using the TMB-HRP-MRS agar. The antagonistic effects of the isolates on pathogenic microorganisms were determined with a double layer agar plate. RESULTS: One hundred and three lactobacilli strains were isolated from 60 samples of vaginal secretion from healthy pregnant women. Among them, 78 strains could produce hydrogen peroxide, in which 68%, 80%, 80%, and 88% had antagonistic effects against Candida albicans CMCC98001, Staphylococcus aureus CMCC26003, Escherichia coli CMCC44113, and Pseudomonas aeruginosa CMCC10110, respectively. CONCLUSION: The recovery of hydrogen peroxide-producing lactobacilli decreases with the increasing pregnant age and time. The most commonly isolated species from vagina of Chinese pregnant women are Lactobacillus acidophilus and Lactobacillus crispatus. Most of L. acidophilus and L. crispatus produce a high H2O2 level.

Toll-Like Receptor 3 Is Involved in Detection of Enterovirus A71 Infection and Targeted by Viral 2A Protease.

Enterovirus A71 (EV-A71) has emerged as a major pathogen causing hand, foot, and mouth disease, as well as neurological disorders. The host immune response affects the outcomes of EV-A71 infection, leading to either resolution or disease progression. However, the mechanisms of how the mammalian innate immune system detects EV-A71 infection to elicit antiviral immunity remain elusive. Here, we report that the Toll-like receptor 3 (TLR3) is a key viral RNA sensor for sensing EV-A71 infection to trigger antiviral immunity. Expression of TLR3 in HEK293 cells enabled the cells to sense EV-A71 infection, leading to type I, IFN-mediated antiviral immunity. Viral double-stranded RNA derived from EV-A71 infection was a key ligand for TLR3 detection. Silencing of TLR3 in mouse and human primary immune cells impaired the activation of IFN-ß upon EV-A71 infection, thus reinforcing the importance of the TLR3 pathway in defending against EV-A71 infection. Our results further demonstrated that TLR3 was a target of EV-A71 infection. EV-A71 protease 2A was implicated in the downregulation of TLR3. Together, our results not only demonstrate the importance of the TLR3 pathway in response to EV-A71 infection, but also reveal the involvement of EV-A71 protease 2A in subverting TLR3-mediated antiviral defenses.

Thymic stromal lymphopoietin-induced HOTAIR activation promotes endothelial cell proliferation and migration in atherosclerosis.

Endothelial cells' (EC) injury is a major step for the pathological progression of atherosclerosis. Recent study demonstrated that thymic stromal lymphopoietin (TSLP) exerts a protective role in atherosclerosis. However, the effect of TSLP and the exact molecular mechanism involved in EC remains unknown. In the present study, we found that long noncoding RNA (lncRNA) HOTAIR was much lower in EC from atherosclerotic plaque. Functional assays showed that HOTAIR facilitated cell proliferation and migration, and suppressed apoptosis in EC. Moreover, we demonstrated that TSLP functions upstream of HOTAIR. We found that serum level of TSLP was decreased in atherosclerosis patients and serum TSLP level positively correlated with HOTAIR expression in EC. Further investigation demonstrated that TSLP activated HOTAIR transcription through PI3K/AKT-IRF1 pathway and then regulates the EC proliferation and migration. TSLP-HOTAIR axis also plays a protective role in low-density lipoprotein (ox-LDL)-induced EC injury. Taken together, TSLP-HOTAIR may be a potential therapy for EC dysfunction in atherosclerosis.