Mitochondrial control of hypoxia-induced pathological retinal angiogenesis.

OBJECTIVE: Pathological retinal neovascularization is vision-threatening. In mouse oxygen-induced retinopathy (OIR) we sought to define mitochondrial respiration changes longitudinally during hyperoxia-induced vessel loss and hypoxia-induced neovascularization, and to test interventions addressing those changes to prevent neovascularization. METHODS: OIR was induced in C57BL/6J mice and retinal vasculature was examined at maximum neovessel formation. We assessed total proteome changes and the ratio of mitochondrial to nuclear DNA copy numbers (mtDNA/nDNA) of OIR vs. control retinas, and mitochondrial oxygen consumption rates (OCR) in ex vivo OIR vs. control retinas (BaroFuse). Pyruvate vs. vehicle control was supplemented to OIR mice either prior to or during neovessel formation. RESULTS: In OIR vs. control retinas, global proteomics showed decreased retinal mitochondrial respiration at peak neovascularization. OCR and mtDNA/nDNA were also decreased at peak neovascularization suggesting impaired mitochondrial respiration. In vivo pyruvate administration during but not prior to neovessel formation (in line with mitochondrial activity time course) suppressed NV. CONCLUSIONS: Mitochondrial energetics were suppressed during retinal NV in OIR. Appropriately timed supplementation of pyruvate may be a novel approach in neovascular retinal diseases.

Long non-coding RNA MIR22HG inhibits the proliferation and migration, and promotes apoptosis by targeting microRNA-9-3p/ SOCS1 axis in small cell lung cancer cells.

BACKGROUND: This study aims to determine the role of long non-coding RNA (LncRNA) MIR22HG in small cell lung cancer (SCLC), and to explore its relevant mechanism. METHODS AND RESULTS: The expressions of genes and proteins in SCLC cells were examined applying qRT-PCR and western blot. Cell proliferation estimation was implemented utilizing cell counting kit-8 (CCK-8) and colony formation assays; the assessment of cell migration and invasion was operated employing Wound healing and Transwell; apoptosis evaluation was conducted adopting flow cytometric assay. Binding relationships was confirmed by luciferase reporter assay. Moreover, SCLC animal model was established to explore the role of MIR22HG in vivo. It was found that MIR22HG was declined and miR-9-3p was elevated in five SCLC cell lines (NCI-H446, NCI-H69, SHP-77, DMS79 and NCI-H345) in comparison with normal human bronchial epithelial cell line (NHBE). More interestingly, overexpression of MIR22HG resulted in decreased cell viability, declined colony formation, diminished capacities of cell migration and invasion in NCI-H446 and NCI-H345 cells but induced more apoptotic cells. However, these impacts were reversed by miR-9-3p upregulation. Meanwhile, MIR22HG could bind to miR-9-3p and negatively regulate its expression in SCLC. What's more, LncRNA MIR22HG overexpression was also testified to elevate SOCS1 via downregulating miR-9-3p expression. Furthermore, in vivo study further confirmed the role of MIR22HG/miR-9-3p in tumor regulation of SCLC. CONCLUSIONS: In conclusion, MIR22HG in SCLC was found to modulate miR-9-3p level and might act as a possible biomarker for SCLC treatment.

ß-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes.

Fibroblast growth factor 21 (FGF21) is secreted by hepatocytes as a peptide hormone to regulate glucose and lipid metabolism. FGF21 promotes hepatic ketogenesis and increases ketone body utilization in starvation. Histones are the target molecules of nutrients in regulating hepatic metabolic homeostasis. However, the effect of ketone bodies on FGF21 expression and the involvement of histones in it is not clear yet. The present study observed the effects of ß-hydroxybutyrate (ß-OHB), the main physiological ketone body, on FGF21 expression in human hepatoma HepG2 cells in vitro and in mice in vivo, and the role of histone deacetylases (HDACs) in ß-OHB-regulated FGF21 expression was investigated. The results showed that ß-OHB significantly upregulated FGF21 gene expression and increased FGF21 protein levels while it inhibited HDACs' activity in HepG2 cells. HDACs' inhibition by entinostat upregulated FGF21 expression and eliminated ß-OHB-stimulated FGF21 expression in HepG2 cells. Intraperitoneal injections of ß-OHB in mice resulted in the elevation of serum ß-OHB and the inhibition of hepatic HDACs' activity. Meanwhile, hepatic FGF21 expression and serum FGF21 levels were significantly increased in ß-OHB-treated mice compared with the control. It is suggested that ß-OHB upregulates FGF21 expression through inhibition of HDACs' activity in hepatocytes.

The inhibitory effects of Dulaglutide on cellular senescence against high glucose in human retinal endothelial cells.

Diabetic nephropathy is one of the most important chronic microvascular complications of diabetes, and its main feature is diabetic glomerulosclerosis. Endothelial sirtuin 1 (SIRT1) expression is related to aging, and reducing SIRT1 expression promotes endothelial cell aging. Plasminogen activator inhibitor-1 (PAI-1) can be synthesized in a variety of cells, such as endothelial cells. Dulaglutide is a glucagon-like peptide-1 (GLP-1) drug, and it can activate the GLP-1 receptor and promote the conversion of intracellular adenosine triphosphate to adenylate cyclase, thereby activating phosphokinase A, and regulating blood glucose levels effectively in the body. We analyzed the effects of Dulaglutide on inhibiting cell senescence by studying the effects of its different concentrations on telomerase activity and senescence-related gene expression. Our results suggest that Dulaglutide can alleviate high-glucose-induced oxidative stress in human retinal endothelial cells by restoring the expressions of SIRT1 and endothelial nitric oxide synthase (eNOS), thereby inhibiting the expression of PAI-1, and restoring telomerase activity. This suggests that the activity of retinal endothelial cells can be controlled by regulating the expression of SIRT1, so as to achieve the effect of treating diabetic retinopathy.

Far upstream element -binding protein 1 (FUBP1) participates in the malignant process and glycolysis of colon cancer cells by combining with c-Myc.

Human distal upstream element (Fuse) binding protein 1 (FUBP1) is a transcriptional regulator of c-Myc and represents an important prognostic marker in many cancers. Therefore, the present study aimed to investigate whether FUBP1 could combine with c-Myc to participate in the progression of colon cancer. Detection of FUBP1 expression was done through reverse transcription-quantitative PCR (RT-qPCR), and the combination of FUBP1 and c-Myc was detected by immunoprecipitation assay. Cell counting kit (CCK)-8, colony formation, transwell and wound healing were applied for assessing the ability of cells to proliferate, migrate, and invade; glycolysis and lactic acid detection kits were used to detect glucose uptake and lactic acid content, while western blotting was adopted to detect the protein expression of glycolysis-related genes. FUBP1 expression was elevated in HCT116 cells relative to other colon cancer cell lines, and silencing FUBP1 could inhibit the ability of HCT116 cells to proliferate, migrate, invade and glycolysis, and enhance its apoptosis. In addition, the results of immunoprecipitation experiments showed that FUBP1 could bind to c-Myc. c-Myc overexpression reversed the inhibitory effects of FUBP1 knockdown on the ability of HCT116 cells to proliferate, migrate, invade and glycolysis. The results indicated that FUBP1 could participate in the deterioration process of colon cancer cells by combining with c-Myc, and it has clinical significance for understanding the key role of FUBP1 in tumor genesis.

Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets.

Diabetic retinopathy (DR), one of the common complications of diabetes, is the leading cause of visual loss in working-age individuals in many industrialized countries. It has been traditionally regarded as a purely microvascular disease in the retina. However, an increasing number of studies have shown that DR is a complex neurovascular disorder that affects not only vascular structure but also neural tissue of the retina. Deterioration of neural retina could precede microvascular abnormalities in the DR, leading to microvascular changes. Furthermore, disruption of interactions among neurons, vascular cells, glia and local immune cells, which collectively form the neurovascular unit, is considered to be associated with the progression of DR early on in the disease. Therefore, it makes sense to develop new therapeutic strategies to prevent or reverse retinal neurodegeneration, neuroinflammation and impaired cell-cell interactions of the neurovascular unit in early stage DR. Here, we present current perspectives on the pathophysiology of DR as a neurovascular disease, especially at the early stage. Potential novel treatments for preventing or reversing neurovascular injuries in DR are discussed as well.

Risk of Substance Use Disorder and Its Associations With Comorbidities and Psychotropic Agents in Patients With Autism.

Importance: The risk of substance use disorder (SUD) in patients with autism spectrum disorder (ASD) remains unclear. Objective: To investigate the risk of SUD in patients with ASD and its associations with comorbidities, psychotropic agents (PAs), and mortality. Design, Setting, and Participants: This retrospective, population-based, cohort study of 1 936 512 participants used data from the Taiwan National Health Insurance Research Database and was conducted from January 1, 2000, to December 31, 2015. Included participants attended at least 3 outpatient visits within the 1-year study period for symptomatic ASD as determined by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes. Individuals diagnosed with ASD before 2000, those diagnosed with SUD before the first visit for ASD, and those with missing data were excluded from the analysis. Patients with ASD and non-ASD controls were matched 1:4 by age, sex, and index date. Exposures: Symptomatic ASD evaluated for at least 3 outpatient visits within the 1-year study period. Main Outcomes and Measures: Adjusted hazard ratios (aHRs) with 95% CIs for SUD, including alcohol use disorder (AUD) and drug use disorder (DUD), and the risk of mortality were calculated. Data were analyzed from March 1 to July 13, 2020. Results: A total of 6599 individuals with ASD (mean [SD] age, 11.9 [5.1] years; 5094 boys [77.2%]; mean [SD] follow-up period, 8.1 [8.3] years; median follow-up period, 4.3 [interquartile range [IQR], 2.3-5.3] years) and 26 396 controls (mean [SD] age, 12.1 [5.8] years; 20 376 boys [77.2%]; mean [SD] follow-up period, 8.6 [8.9] years; median follow-up period, 4.4 [IQR, 2.4-5.4] years) were enrolled in the study. According to multivariable-adjusted analysis, the aHRs for SUD (2.33; 95% CI, 1.89-2.87), AUD (2.07; 95% CI, 1.60-2.63), and DUD (3.00; 95% CI, 2.15-4.58) were significantly higher in the ASD group than in the non-ASD controls. The aHRs for SUD in the ASD subgroups with 1 PA (0.60; 95% CI, 0.43-0.66) and with multiple PAs (0.37; 95% CI, 0.28-0.49) were significantly lower than those in the ASD subgroup with no PAs. Comparisons between patients with ASD and non-ASD controls with the same comorbidities showed higher aHRs for SUD among patients with ASD (range, 1.17-2.55); moreover, the ASD subgroup not receiving any PAs had an aHR of 6.39 (95% CI, 5.11-7.87) for SUD when they had comorbid tic disorder and aHRs of 5.48 (95% CI, 5.12-5.70) for AUD and 5.42 (95% CI, 5.12-5.80) for DUD when they had comorbid impulse control disorder. The mortality risk was significantly higher in patients with ASD and concomitant SUD than in non-ASD controls without SUD (aHR, 3.17; 95% CI, 2.69-3.89). Conclusions and Relevance: These findings suggest that patients with ASD are vulnerable to the development of SUD. Comorbid ASD and SUD were associated with an increase in mortality risk.

Plasma polymer surface modified expanded polytetrafluoroethylene promotes epithelial monolayer formation in vitro and can be transplanted into the dystrophic rat subretinal space.

The aim of this study was to evaluate whether the surface modification of expanded polytetrafluoroethylene (ePTFE) using an n-heptylamine (HA) plasma polymer would allow for functional epithelial monolayer formation suitable for subretinal transplant into a non-dystrophic rat model. Freshly isolated iris pigment epithelial (IPE) cells from two rat strains (Long Evans [LE] and Dark Agouti [DA]) were seeded onto HA, fibronectin-coated n-heptylamine modified (F-HA) and unmodified ePFTE and fibronectin-coated tissue culture (F-TCPS) substrates. Both F-HA ePTFE and F-TCPS substrates enabled functional monolayer formation with both strains of rat. Without fibronectin coating, only LE IPE formed a monolayer on HA-treated ePTFE. Functional assessment of both IPE strains on F-HA ePTFE demonstrated uptake of POS that increased significantly with time that was greater than control F-TCPS. Surgical optimization using Healon GV and mixtures of Healon GV: phosphate buffered saline (PBS) to induce retinal detachment demonstrated that only Healon GV:PBS allowed F-HA ePTFE substrates to be successfully transplanted into the subretinal space of Royal College of Surgeons rats, where they remained flat beneath the neural retina for up to 4 weeks. No apparent substrate-induced inflammatory response was observed by fundus microscopy or immunohistochemical analysis, indicating the potential of this substrate for future clinical applications.

Dry eye induced by exposure to cigarette smoke pollution: An in vivo and in vitro study.

Exposure to cigarette smoke (CS) pollution has previously associated with dry eye symptoms but without detailed experimental data and elucidation of the mechanism. We aimed to evaluate the effects of CS on the ocular surfaces of mice and the extraction of DMSO lipid-soluble cigarette smoke particles (DCSP) on cultured human corneal epithelial cells (HCECs), and explore to elucidate the probable mechanism. C57BL mice were exposed to CS challenging. In vivo clinical evaluations, including corneal fluorescein staining, tear film break-up time, and confocal microscopic observations, were performed before exposure and post-exposure. At the end of the in vivo study, changes in corneal and conjunctival histology, corneal ultrastructure, and conjunctival goblet cell intensity were examined, expression of TUNLE and Ki67 in tissue were also detected. In vitro, cell confluence and caspase3/7 were assessed in DCSP treated HCECs. Production of TNF-α, IL-1ß and IL-6, activation of NF-κB and Ki67 were evaluated by means of ELISA and Western blot respectively in HCECs cultured with 0.6 µL/mL DCSP. We found that longer-term CS exposure induced dry eye symptoms in mice. Additionally, corneal and conjunctival epithelial damage occurred, the corneal ultrastructure changed, and the density of goblet cells decreased. Apoptosis and Ki67 increased in both the conjunctiva and the cornea of CS-exposed animals. Furthermore, although DCSP inhibited the proliferation of HCECs, expression of Ki67 increased and apoptosis was only induced significantly by 2.0 µL/mL DCSP. The release of IL-1ß and IL-6, activation of NF-κB were prompted by DCSP. The results indicated that CS is toxic to the ocular surface of mice and HCECs. Longer-term CS exposure in mice stimulates ocular surface changes that resemble those observed with dry eye. The mechanism may relate to inflammation and activation of NF-κB. In this study, we established a novel animal model to study dry eye, with the experimental data and elucidation of mechanism facilitating further research.

Stimulants associated with reduced risk of hospitalization for motor vehicle accident injury in patients with obstructive sleep apnea-a nationwide cohort study.

BACKGROUND: The risk of injury directly related to hospitalization for motor vehicle accidents (MVAs) in the obstructive sleep apnea (OSA) patients has not been thoroughly understood. Our study aimed to examine the association between the OSA and the hospitalization for an MVA injury. METHODS: This retrospective cohort study used Taiwan's National Health Insurance Research Database (NHIRD) between 2000 and 2015. The OSA patients aged ≥20 years by age, sex, and index-year matched by non-OSA controls were enrolled (1:3). We used the Cox proportional regression model to evaluate the association between the OSA and the hospitalization for an MVA injury. RESULTS: The incidence rate of hospitalization for an MVA injury was higher in the OSA cohort (N = 3025) when compared with the non-OSA controls (N = 9075), as 575.3 and 372.0 per 100,000 person-years, respectively (p < 0.001). The Kaplan-Meier analysis showed that the OSA cohort had a significantly higher incidence of hospitalization for the MVA injury (log-rank test, p < 0.001). After adjusting for the covariates, the risk of hospitalization for the MVA injury among the OSA was significantly higher (hazard ratio [HR] =2.18; 95% confidence interval [CI] = 1.79-2.64; p < 0.001). Stimulants usage was associated with a nearly 20% decrease in the risk of an overall hospitalization for an MVA injury in the OSA patients. CONCLUSIONS: This study provides evidence that patients with OSA are at a two-fold higher risk of developing hospitalization for an MVA injury, and the usage of modafinil and methylphenidate was associated with a lower risk of an overall hospitalization for the MVA injury.

Deficiency of aldose reductase attenuates inner retinal neuronal changes in a mouse model of retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness where vascular abnormality and retinal dysfunction are reported. We showed earlier that genetic deletion of aldose reductase (AR), the rate-limiting enzyme in the polyol pathway, reduced the neovascularization through attenuating oxidative stress induction in the mouse oxygen-induced retinopathy (OIR) modeling ROP. In this study, we further investigated the effects of AR deficiency on retinal neurons in the mouse OIR. Seven-day-old wild-type and AR-deficient mice were exposed to 75 % oxygen for 5 days and then returned to room air. Electroretinography was used to assess the neuronal function at postnatal day (P) 30. On P17 and P30, retinal cytoarchitecture was examined by morphometric analysis and immunohistochemistry for calbindin, protein kinase C alpha, calretinin, Tuj1, and glial fibrillary acidic protein. In OIR, attenuated amplitudes and delayed implicit time of a-wave, b-wave, and oscillatory potentials were observed in wild-type mice, but they were not significantly changed in AR-deficient mice. The morphological changes of horizontal, rod bipolar, and amacrine cells were shown in wild-type mice and these changes were partly preserved with AR deficiency. AR deficiency attenuated the Müller cell gliosis induced in OIR. Our observations demonstrated AR deficiency preserved retinal functions in OIR and AR deficiency could partly reduce the extent of retinal neuronal histopathology. These findings suggested a therapeutic potential of AR inhibition in ROP treatment with beneficial effects on the retinal neurons.

Mechanism of tanshinone II A in inhibiting transformation of aortic valvular myofibroblast to osteoblast-like phenotype / 中国中药杂志

Aortic valve calcification (AVC) is a pathological process correlated with multiple disease causes and actively regulated by cardiac valve cells. In this study, porcine aortic valve myofibroblasts cultured in vitro were treated with 50 μg z L(-1) of pathological factor tumor necrosis factor α (TNF-α). Tanshinone II A (TSN) with the concentration of 50 mg x L(-1) and TNF-α were combined in incubating cells for 72 h (3 d) and 120 h (5 d). The Western blotting and Real-time PCR were adopted to detect the changes in smooth muscle α actin (α-SMA), bone morphogenetic protein 2 ( BMP2), alkaline phosphatase (ALP) in cells, and expressions of key effect proteins GSK-3β and β-catenin on Wnt/β-catenin signal pathway. According to the findings, TNF-α can significantly increase the expression of myofibroblasts α-SMA and add the transformation activity to them, with nearly no expression of BMP2, ALP and mRNA in the control group and the TSN group but significant increase in their expressions in the TNF-α group (P < 0.01), which showed osteoblast-like phenotype. Moreover, TNF-α down-regulated the expression of up-streaming regulator GSK-3β and mRNA expression (P < 0. 01) , notably increased the expression of key effect protein β-catenin, but with no significant difference in mRNA with the control group and the TSN group. The result demonstrated that TSN showed a certain inhibitory effect on TNF-α's pathological impact (P < 0.05) in a time-dependent manner. Inflammatory factor TNF-α may promote the transformation of aortic valvular myofibroblasts to osteoblast-like phenotype by activating Wnt/β-catenin signal pathway in aortic valvular myofibroblasts, so as to cause AVC. Tanshinone II A can have a preventive effect in AVC by activating GSK-3β proteins and regulating signal transduction of Wnt/β-catenin signal pathway.

Ecological surveys of the Cryptococcus species complex in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Despite recent reports on the molecular epidemiology of cryptococcal infections in China, clinical isolates have been mostly reported from human immunodeficiency virus (HIV)-negative patients, and environmental isolates from China have rarely been included. The aim of this study was to investigate the ecological profile of Cryptococcus (C.) neoformans and C. gattii in China.</p><p><b>METHODS</b>A survey was performed in 10 cities from 20°N (North latitude) to 50°N and in a Eucalyptus (E.) camaldulensis forestry farm at the Guixi forestry center, China.</p><p><b>RESULTS</b>Six hundred and twenty samples of pigeon droppings from 10 cities and 819 E. camaldulensis tree samples were collected and inoculated on caffeic acid cornmeal agar (CACA). The brown-colored colonies were recultured to observe their morphology, growth on canavanine-glycine-bromothymol-blue (CGB) medium, phenol oxidase and urease activities, serotype and mating type. There were obvious differences in the positive sample rates of C. neoformans in pigeon droppings collected from the different cities, ranging from 50% in the cities located at latitudes from 30°N - 40°N, 29% at 20°N - 30°N and 13% at 40°N - 50°N.</p><p><b>CONCLUSIONS</b>There were no differences in positive bevy rates (approximately 80%) among the three grouped cities. Mycological tests of 101 isolates purified from pigeon droppings revealed that they were C. neoformans var. grubii. We also observed variable capsular size around the C. neoformans cells in colonies with variable melanin production and the bio-adhesion of the natural C. neoformans cells with other microorganisms. One urease-negative C. neoformans isolate was isolated from pigeon droppings in Jinan city. No C. gattii was isolated in this study.</p>

Effect of phospholipomannan of Candida albicans on the production of interleukin 6 and interleukin 8 in monocytes / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate whether Candida albicans-native phospholipomannan (PLM) induce an inflammation response through Toll-like receptor(TLRé2 in human acute monocytic leukemia cell line (THP-1) cells.</p><p><b>METHODS</b>Human THP-1 monocytes were challenged with PLM in vitro. The mRNA expressions of TLR2, TLR4, proinflammatory cytokine [interleukin(IL)-6], and chemokine (IL-8) were assayed by real time reverse transcription polymerase chain reaction. The secretions of IL-6 and IL-8 were measured by enzyme-linked immunosorbent assay. The expression of TLR2 was analyzed with Western blot.</p><p><b>RESULTS</b>PLM increased the mRNA expressions and secretions of proinflammatory cytokines (IL-6) and chemokines (IL-8) in THP-1 cells (all P=0.0000). PLM up-regulated the mRNA and protein levels of TLR2 (P=0.0000), whereas the mRNA level of TLR4 was not altered. PLM hydrolyzed with β-D-mannoside manno hydrolase failed to induce gene and protein expressions of TLR2, IL-6, and IL-8. Anti-TLRS-neutralizing antibody blocked the PLM-induced secretions of IL-6 and IL-8 in THP-1 cells (P = 0.0003, P = 0.0010).</p><p><b>CONCLUSION</b>Canidada albicans-native PLM may contribute to the inflammatory responses during Candida infection in a TLR2-dependent manner.</p>

Insoluble beta-glucan from the cell wall of Candida albicans induces immune responses of human THP-1 monocytes through Dectin-1 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>beta-glucan is the major structure component of Candida albicans (C. albicans) cell wall. It has been demonstrated that Dectin-1 as the principal C-type lectin pattern-recognition receptor (PRR) can recognize fungal beta-glucan and induce immune responses. In this study, we sought to clarify whether insoluble beta-glucan from the cell wall of C. albicans (CaIG) could induce immune responses in human THP-1 monocytes (a human acute monocytic leukemia cell line) and to determine the underlying mechanisms.</p><p><b>METHODS</b>Human THP-1 monocytes were challenged with CaIG in vitro. The mRNA expression of Dectin-1, Toll-like receptors (TLR2), proinflammatory cytokine (TNF-alpha) and chemokine (IL-8) was assayed by real-time reverse transcription polymerase chain reaction (RT-PCR). The secretion of TNF-a and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA). H(2)O(2) release was determined by microplate fluorescent assay. Western blotting was used to analyze IkappaB-a phosphorylation and degradation.</p><p><b>RESULTS</b>Exposure of THP-1 monocytes to CaIG led to increased gene expression and secretion of TNF-alpha and IL-8. CaIG induced H(2)O(2) release in a time-dependent manner. CaIG hydrolyzed with zymolyase failed to induce gene expression and secretion of TNF-alpha, IL-8 and H(2)O(2) release. CaIG up-regulated the mRNA of Dectin-1, whereas the mRNA level of TLR2 was not altered. THP-1 monocytes challenged with CaIG resulted in the activation of NF-kappaB in a time-dependent manner. Dectin-1 inhibitor laminarin blocked the CaIG-induced production of TNF-alpha and H(2)O(2) in THP-1 monocytes, but no such effect was observed in pretreatment with anti-TLR2 neutralizing antibody and the LPS inhibitor (polymyxin B).</p><p><b>CONCLUSION</b>CaIG may play a role in activation of immune responses in human THP-1 cells through Dectin-1, not TLR2.</p>

Genotype comparisons of strains of Candida albicans from patients with cutaneous candidiasis and vaginal candidiasis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is uncertain whether genotypes of Candida albicans (C. albicans) are associated with colonizing body locations or variant conditions of infection. The aim of this study was to investigate whether there are significant associations between strain genotypes and body sites of infection and to determine the potential pathogenesis of cutaneous candidiasis at multiple locations.</p><p><b>METHODS</b>A total of 151 strains of C. albicans were isolated from 74 infant patients with cutaneous candidiasis and 61 female patients with vaginal candidiasis. Patients were grouped according to the body sites and underlying conditions of infection. Genotypes were identified by polymerase chain reaction (PCR) of the 25S rDNA and PCR-restriction fragment length polymorphism (RFLP) of ALT repeats digested with EcoRI and Clal.</p><p><b>RESULTS</b>Ten genotypes were detected. There were significant differences in genotype frequencies between the two groups. However, we found no clear association between genotypes and the sites of cutaneous infection or the underlying conditions of vaginal candidiasis (VVC). In addition, strains of C. albicans from multiple cutaneous locations of the same patient had identical genotypes.</p><p><b>CONCLUSIONS</b>Populations of C. albicans from patients with cutaneous and vaginal candidiasis were genetically different. However, the lack of genetic difference between strains from different body sites with cutaneous infections or from different underlying conditions for VVC suggests no evidence of genotype selection for different skin surfaces or patients with different underlying conditions for VVC.</p>

Establishing an experimental guinea pig model of dermatophytosis Using Trichophyton rubrum / 中国医学科学院学报

<p><b>OBJECTIVE</b>To construct an animal model infected by Trichophyton rubrum.</p><p><b>METHODS</b>Three different strains of Trichophyton rubrum were separated from clinical specimen for the infection of guinea pigs. Corticosteroids were given before and after the construction of animal model to facilitate the infection. Direct microscopy, culture, and histopathologic methods were adopted to verify the construction.</p><p><b>RESULTS</b>Ten days after the inoculation of Trichophyton rubrum, with the intervention of corticosteroid, the guinea pigs were examined. Prominent scales and inflammation could be seen on the inoculation site of the Trichophyton rubrum infected guinea pig. Scales and hairs of Trichophyton rubrum infected guinea pig dealt with 10% potassium hydroxide, hypha out of the hair and microconidia or hypha in the hair shaft could be seen. Seven days after the inoculation of scales and hair on SDA plate, cultures of Trichophyton rubrum showed that the colonial morphology were identical to the original dermatophytes. PAS staining of infected guinea pig skin tissue showed that hypha and microconidia could be seen in the infundibula and hair root.</p><p><b>CONCLUSION</b>With the intervention of corticosteroid, a stable guinea pig model infected by Trichophyton rubrum were successfully constructed.</p>

Effects of Malassezia isolates on cytokines production associated with melanogenesis by keratinocytes / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the co-culture of keratinocytes with Malassezia isolates which cause the pityriasis versicolor with different color and to analyze the changes of cytokines associated with melanogenesis.</p><p><b>METHODS</b>The effects of Malassezia species with different proportions on the growth rate of keratinocytes was assessed with 5 g/L methyl thiazolyl tetrazolium (MTT). Co-culture of keratinocytes and Malassezia species were performed with isolates from hyer- and hypo-pigmentation areas of pityriasis versicolor. The supernatants were collected at different time points, and the changes of basic fibroblast growth factor (b-FGF), endothelin-1 (ET-1), nerve growth factor-beta (NGF-beta), interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), stem cell factor (SCF) were recorded. Three control groups were established accordingly.</p><p><b>RESULTS</b>When the ratio between keratinocytes and Malassezia species was lower than 1: 10, the growth rate of keratinocytes was not affected by Malassezia (P > 0.05). When the ratio was increased above 1:20, the growth rate of keratinocytes was significantly inhibited by Malassezia (P < 0.01). The secretions of IL-1alpha, IL-6, TNF-alpha, and ET-1 was significantly increased after the co-culture of keratinocytes and Malassezia (P < 0.01), while those of b-FGF, NGF-beta, and SCF had no significant changes (P > 0.05). Compared with the isolates from the hypo-pigmentation area, ET-1 induced by isolate from hyperpigmentation area significantly increased (P < 0.01).</p><p><b>CONCLUSION</b>When Malassezia isolates are co-cultured with keratinocytes, the secretions of cytokines associated with melanogenesis may differ from each other. ET-1 may play certain role in the hyper-pigmentation of pityriasis versicolor.</p>

Effect of Metformin Therapy on Obese Nondiabetic Children with Hyperinsulinemia / 实用儿科临床杂志

Objective To explore the efficacy and safety of metformin therapy on obese nondiabetic children with hyperinsulinemia.Methods Twenty-two obese nondiabetic children with hyperinsulinemia were divided into two groups:control group(dietary counseling and exercise) and treatment group(dietary counseling and exercise combined with metformin).The changes of body mass index(BMI),fasting glucose(FPG),fasting insulin(FINS),insulin resistance(HOMA-IR),2 h PG,2 h INS,total cholesterol(TC) and triglyceride(TG),before and after treatment were determined,and the findings were compared and analyzed.Results After treatment,there were significant differences in BMI,TC,FINS,HOMA-IR levels(P0.05),except the BMI(P

COMPARISON OF GUIZOTIA ABYSSINICA SEED AGAR WITH CAFFEIC ACID CORNMEAL AGAR TO SELECTIVELY ISOLATE CRYPTOCOCCUS NEOFORMANS / 微生物学通报

The two verities of Crgptococcus neoforinans were first observed as well growing with brown color changes on Guizotia abyssinica seed agar(GASA)and caffeic acid commeal agar(CACA.Then,C.neoformans var.neoformans was found in 18/26 pigeon droppings by both two media.C.neoformans var.gattii was not isolated by the two media in 76 Eucalyptus camaldulensis samples.However,an,overgrowth of filamentous fungus was more frequently seen on GASA.Our results suggest that CACA be capable of selevtively isolating C.neoformans with the advantages of less interference fron the overgrowth of filamentous fungi.