Recombinant Lactococcus lactis NZ3900 expressing bioactive human FGF21 reduced body weight of Db/Db mice through the activity of brown adipose tissue.

Fibroblast growth factor 21 (FGF21), a metabolism regulator, has an important effect on metabolic diseases, such as obesity and diabetes. It is also expressed in mice, and the murine source has high homology with human FGF21. Recently, it has been extensively studied and has become a potential drug target for the treatment of metabolic diseases. As it is a protein-based hormone, FGF21 cannot be easily and quickly absorbed into the blood through oral administration. Moreover, it has a 0-2 h half-life in vivo, as shown in a previous study, thus its efficacy lasts for a short period of time when used to treat metabolic diseases, limiting its clinical applications. To avoid these limitations, we used Lactococcus lactis, a food-grade bacterium, as the host to express FGF21. It could be used successfully for the expression and long-term effect of FGF21 in vivo. Instead of antibiotic resistance genes, the LacF gene was used as a selection marker in the NZ3900/PNZ8149 expression system, which is safe and could reduce the antibiotic resistance crisis. In this study, we a constructed human FGF21 expressing L. lactis strain and administered it to Db/Db mice by gavage. Compared with the control group, the body weight of mice in the experimental group was significantly reduced, and the overall homeostasis was improved in mice treated with human FGF21. Moreover, the activity of brown adipose tissue was enhanced. These results revealed that oral administration of FGF21 through heterologous expression in L. lactis appears to be an effective approach for its clinical application.

MiRNA-337 leads to podocyte injury in mice with diabetic nephropathy.

OBJECTIVE: To elucidate the function of miRNA-337 in the pathogenesis of diabetic nephropathy (DN) and its underlying mechanism. MATERIALS AND METHODS: Type 2 diabetes db/db mice were assigned into db/db group, vehicle group, and si-miR group, and age-matched db/m mice were in the db/m group. Differences in mouse serum glucose, body weight, serum creatinine, and albumin/creatinine ratio (ACR) among the four groups were compared at 6 weeks, 10 weeks, 14 weeks, 18 weeks, and 22 weeks of age. The expression level of miRNA-337 in mouse kidney tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between miRNA-337 expression with ACR was analyzed. Through Western blot analysis, protein levels of interleukin 6 (IL-6), IL-18, podocin, nephrin, and desmin in mouse kidney tissues were detected. RESULTS: With the increasing age, serum glucose, body weight, serum creatinine, and ACR in db/db mice gradually increased, which were remarkably higher than age-matched db/m mice. After treatment with miRNA-337 inhibitor in db/db mice, no remarkable changes in serum glucose and body weight were found, while serum creatinine and ACR decreased. Compared with db/m mice, miRNA-337 expression in kidney tissues of db/db mice upregulated, which was positively correlated with ACR. Expression levels of IL-6 and IL-18 in kidney tissues of db/db mice increased relative to db/m mice, but they were downregulated by miRNA-337 inhibitor treatment. Moreover, podocin and nephrin downregulated, while desmin upregulated in kidney tissues of db/db mice than db/m mice. By miRNA-337 inhibitor treatment in db/db mice, levels of podocin and nephrin increased, whereas desmin level decreased. We obtained similar results at their cellular level. CONCLUSIONS: We showed that miRNA-337 expression increases in db/db mice with diabetic nephropathy, which leads to podocyte injury by upregulating levels of IL-6 and IL-18.

Proton pump inhibitors and risk of hip fracture: a meta-analysis of observational studies.

We performed a meta-analysis of relevant studies to quantify the magnitude of the association between proton pump inhibitors (PPIs) and risk of hip fracture. Patients with PPIs had a greater risk of hip fracture than those without PPI therapy (RR 1.20, 95% CI 1.14-1.28, p < 0.0001). These results could be taken into consideration with caution, and patients should also be concerned about the inappropriate use of PPIs. INTRODUCTION: Proton pump inhibitors (PPIs) are generally considered as first-line medicine with great safety profile, commonly prescribed for gastroesophageal reflux disease (GERD) and peptic ulcer disease. However, several epidemiological studies documented that long-term use of PPIs may be associated with an increased risk of hip fracture. Although, the optimal magnitude of the hip fracture risk is still undetermined. We, therefore, performed a meta-analysis of relevant studies to quantify the magnitude of the association between PPIs and risk of hip fracture. METHODS: We collected relevant articles using MEDLINE, EMBASE, Google Scholar, and Web of Science from January 1, 1990, to March 31, 2018. We included only the large (n ≥ 500) observational studies with a follow-up duration of at least one year in which the hip fracture patients were identified by a standard procedure. Two of the authors extracted data from each included study independently according to a standardized protocol. RESULTS: A total of 24 observational studies with 2,103,800 participants (319,568 hip fracture patients) met all the eligibility criteria. Patients with PPIs had a greater risk of hip fracture than those without PPI therapy (RR 1.20, 95% CI 1.14-1.28, p < 0.0001). An increased association was also observed in both low and medium doses of PPI taken and hip fracture risk (RR 1.17, 95% CI 1.05-1.29, p = 0.002; RR 1.28, 95% CI 1.14-1.44, p < 0.0001), but it appeared to be even greater among the patients with higher dose (RR 1.30, 95% CI 1.20-1.40, p < 0.0001). Moreover, the overall pooled risk ratios were 1.20 (95% CI 1.15-1.25, p < 0.0001) and 1.24 (95% CI 1.10-1.40, p < 0.0001) for the patients with short- and long-term PPI therapy, respectively, compared with PPI non-users. CONCLUSION: Our results suggest that PPI use is significantly associated with an increased risk of hip fracture development, which is not observed in H2RA exposure. Physicians should, therefore, exercise caution when considering a long-term PPI treatment to their patients who already have an elevated risk of hip fracture. In addition, patients should be concerned about the inappropriate use of PPIs; if necessary, then, they should continue to receive it with a clear indication.

Down-regulation of microRNA-21 inhibits cell proliferation and invasion of high-invasion liver cancer stem cells.

OBJECTIVE: Cancer stem cells (CSCs) play critical roles in tumorigenesis, tumor recurrence and metastasis. This study aims to investigate the effects of small interfere microRNA-21 RNA (miR-21 RNAi) on cell proliferation, invasive ability of high-invasion liver cancer stem cells (H-ILCSCs), HCCLM3 and HL-7702 cells. MATERIALS AND METHODS: pLVX-shRNA2 lentiviral vector system was established, packaged and transfected into H-ILCSCs, HCCLM3 and HL-7702 cells. Cell counting kit-8 (CCK-8) assay was performed to observe cell viabilities of cells. Transwell assay was conducted to evaluate the invasion potential of H-ILCSCs, HCCLM3 and HL-7702 cells. Quantitative PCR (qPCR) assay was used to examine the miR-21 levels in different cell lines. RESULTS: pLVX-anti-miR21 lentiviral vector system was successfully established. miR-21 levels were down-regulated in anti-miR-21 gene steady expression cell lines compared to untreated cells (p<0.05). miR-21 levels were significantly lower in H-ILCSC2-LV-anti-miR-21 group compared to HCCLM3-anti-miR-21 and HL7702-anti-miR-21 (p<0.05). miR-21 inhibition significantly decreased cell proliferation and invasion compared to untreated cells (p<0.05). Cell proliferation and invasive ability of H-ILCSC2-LV-anti-miR-21 group were significantly higher compared to HCCLM3-anti-miR-21 and HL7702-anti-miR-21 (p<0.05). There were even not effects of miR-21 RNAi treatment on the cell proliferation and invasion of HL-7702 cells. CONCLUSIONS: The down-regulation of miR-21 significantly inhibited the cell proliferation and invasion abilities of H-ILCSCs and HCCLM3 cells, and illustrated higher effects on H-ILCSCs.

Effect of miR-21/TLR4/NF-κB pathway on myocardial apoptosis in rats with myocardial ischemia-reperfusion.

OBJECTIVE: The aim of the study was to investigate the influences of micro ribonucleic acid (miR)-21 and downstream Toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway on myocardial apoptosis induced by myocardial ischemia-reperfusion (I/R) injury in rats. MATERIALS AND METHODS: Recombinant adeno-associated virus rAAV9-ZsGreen-pre-miR-21 and blank control virus were constructed. A total of 48 Sprague-Dawley (SD) rats were randomly divided into S1 group (open chest only), S2 group (transfection with blank virus + open chest), I/R1 group (transfection with blank virus + 6 d of myocardial I/R), and I/R2 group (transfection with miR-21 + 6 d of myocardial I/R). The cardiac function and myocardial infarct size of rats were evaluated in each group. Quantitative Polymerase Chain Reaction (qPCR) was applied to measure the expression level of miR-21 in the myocardium. The level of myocardial apoptosis in each group was detected through terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining. Western blotting was performed to determine the protein expression levels of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax), Caspase-3, TLR4, and NF-κB in the myocardium. The content of interleukin-6 (IL-6) and IL-10 was measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: The cardiac function of rats in I/R1 and I/R2 groups was significantly lower than that in S1 and S2 groups (p<0.01). Rats in I/R2 group had better cardiac function than those in I/R1 group (p<0.01). In I/R1 group, the level of myocardial apoptosis of rats was overtly increased compared with that in S1, S2, and I/R2 groups (p<0.01), while the expression level of miR-21 in myocardium was evidently lower than that in S1, S2, and I/R2 groups (p<0.01). Compared with S1, S2, and I/R2 groups, I/R1 group had markedly decreased Bcl-2/Bax expression level and IL-10 content and overtly elevated expression levels of Caspase-3, p-TLR4, p-NF-κB, and IL-6 content in the myocardium (p<0.01). CONCLUSIONS: Myocardial I/R injury in rats leads to decreased expression of miR-21. The overexpression of miR-21 is able to effectively inhibit the TLR4/NF-κB pathway and reduce the level of myocardial apoptosis of rats and the release of inflammatory factors.

A combination of mRNA expression profile and miRNA expression profile identifies detection biomarkers in different tumor stages of laryngeal squamous cell carcinoma.

OBJECTIVE: This study was conducted to investigate microRNA (miRNA) target regulations during the disease progression in laryngeal squamous cell carcinoma (LSCC) and identify biomarkers in different tumor stages. MATERIALS AND METHODS: The mRNA dataset GSE59102 and miRNA dataset GSE70289 were used in this study. After pretreatment, differentially expressed genes/miRNAs (DEGs/DEMs) in different tumor stages (beginning vs. margin, advanced vs. margin, and beginning vs. advanced) were selected on the basis of their limma package. Then, the enrichment analysis for these DEGs was conducted using ClueGO. Protein-protein interaction (PPI) network analysis was performed on the basis of the BioGRID database. After prediction of target genes of DEMs according to three validated miRNA databases, an integrated miRNA target network and its pathways were drawn using the multiMiR package. RESULTS: Numerous DEGs were identified in different tumor stages of LSCC (beginning vs. margin, advanced vs. margin, and beginning vs. advanced), and a set of 18 DEMs was identified. Cell cycle was the most significantly enriched pathway of the DEGs. Four hub nodes (MCM2, EGFR, CDK2, and CDK1) were highlighted in the PPI network. In the integrated miRNA target network, 2 miRNAs were predominant: hsa-miR-331-3p (2 predicted targets, E2F1 and TNFRSF10B) and has-miR-375 (1 predicted target, TNNI3). These genes were tied up with cell cycle or apoptosis pathway. CONCLUSIONS: Several genes and miRNAs might be used as markers for LSCC in different tumor stages (e.g., MCM2, EGFR, CDK1, CDK2, hsa-miR-331-3p, hsa-miR-375). They might function through the involvement of the cell cycle pathway.

Hydrogen sulfide modulates gastric acid secretion in rats via involvement of substance P and nuclear factor-κB signaling.

Hydrogen sulfide (H2S) promotes gastric acid secretion in rats. The present study aimed to test the hypothesis that H2S regulates this response via activating TRPV1 channel and through activation of the nuclear factor-κB (NF-κB) pathway. Male Wistar rats were randomly divided into the sodium hydrosulfide (NaHS, 100 µmol/kg b.w.) group, pyrrolidine dithiocarbamate (PDTC, 100 µmol/kg b.w.) group, PDTC (100 µmol/kg b.w.) + NaHS (100 µmol /kg b.w.) group, capsazepine (0.1 mM) + NaHS (100 µmol /kg b.w.) group and L703606 (0.1 mM) + NaHS (100 µmol /kg b.w.) group. The acidity of gastric juice before injection and after injection were determined by a pH meter. The results showed that sodium hydrosulfide (NaHS), an exogenous H2S donor, significantly reduced the pH of gastric juice when injected into the enterocoelia. Further, the promotional effect of NaHS on gastric acid secretion could be attenuated by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist; L703606, a neurokinin 1 (NK1) receptor antagonist; and PDTC, a NF-κB inhibitor. The data from these experiments suggest that NaHS exerts an excitatory effect on gastric acid secretion possibly mediated by TRPV1 channel activation in sensory nerve terminals with the consequent release of substance P and in a NF-κB -dependent manner.

Expression and function of peripheral blood miRNA16a in patients with ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is a progressive spinal disease presented as rheumatoid factor negative. As an autoimmune disorder, AS is featured with an inflammatory change of tendon and ligament, accompanied by elevates serum levels of inflammatory factors. MicroRNA (miR) participates in the regulation of various diseases including tumor, inflammation, cardiovascular disease and immune response. MiR16a exerts critical roles in inflammatory disease. Its function in AS, however, has not been fully illustrated. PATIENTS AND METHODS: AS patients (at stable and active phase) and healthy controlled individuals were recruited to test peripheral expression of miR16a by Real-time PCR (RT-PCR). Enzyme-linked immunosorbent assay (ELISA) was used to test serum helper T cell 1 (Th1) cytokine levels including interferon (IFN)-γ, tumor necrosis factor-α (TNF-α) and Th2 cytokines including interleukin-4 (IL-4) and IL-10. The correlations between miR16a and cytokine levels, C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and AS activity, were analyzed. RESULTS: MiR16a expression in peripheral blood of AS patients was significantly higher compared to control people (p<0.05 compared to control group). AS patients at active phase had significantly higher miR16a levels, compared to stable phase (p<0.05). Serum IL-4 and IL-10 levels in AS patients were significantly increased, while IFN-γ and TNF-α expressions were depressed (p<0.05 compared to healthy controls). MiR16a expression was positively correlated with IL-4/IL-10 or disease active index, and was negatively correlated with IFN-γ and TNF-α levels (p<0.05), but not with CRP or ESR. CONCLUSIONS: Peripheral miR16a was up-regulated in AS patients, and reflected disease activity, probably via regulating Th1/Th2 balance.

Increased expression of long noncoding RNA AK021443 predicts worse clinical outcome in hepatocellular carcinoma.

OBJECTIVE: Dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in the process of carcinogenesis and tumor progression. LncRNA AK021443 (AK021443) has been reported to serve as a tumor promoter in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the expression of AK021443 and its prognostic value in HCC.. PATIENTS AND METHODS: Quantitative Real-Time-PCR was used to examine the expression of AK021443 in 193 HCC tissues and adjacent non-tumor tissues. The correction between AK021443 expression and clinicopathological characteristics was evaluated with Chi-square test. To determine its prognostic value, overall survival was evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to analyze the prognostic significance of AK02144 expression. RESULTS: The results revealed that AK021443 expression levels were significantly higher in HCC tissues than in the corresponding noncancerous tissues (p<0.01). Besides, high AK021443 expression was correlated with poor tumor differentiation (p = 0.002), advanced clinical stage (p=0.001) and positive lymph node metastasis (p=0.005). In addition, the Kaplan-Meier survival curves revealed that HCC patients with high AK021443 expression level had shorter overall survival than those with low AK021443 expression level (p=0.0005). Finally, the multivariable analysis suggested that increased AK021443 expression was an independent prognostic factor of overall survival in HCC patients. CONCLUSIONS: Our findings indicated that AK021443 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of HCC patients.

Knockdown of ferroportin accelerates erastin-induced ferroptosis in neuroblastoma cells.

OBJECTIVE: Ferroptosis is a new-found iron-dependent form of non-apoptotic regulated cell death (RCD), which is activated on therapy with several antitumor agents, but the potential mechanism remains unclear. Erastin, exhibiting selectivity for RAS-mutated cancer cells, induces ferroptosis by increasing iron and lipid reactive oxygen species (ROS) levels in cell. Ferroportin (Fpn), the sole iron export protein, participates in the regulation of intracellular iron concentration. In this study, we investigated the role of Fpn on ferroptosis induced by erastin in SH-SY5Y cells. MATERIALS AND METHODS: The cell viability was determined by CellTiter 96® AQueous Non-Radioactive Cell Proliferation Assay kit. The activity of caspase-3 was measured by ELISA kit. qRT-PCR was performed to examine the mRNA expression of Fpn. Western blot assay was conducted to examine the expression level of marker proteins. Specific commercial kits were used to examine the levels of MDA, ROS and iron in cells, respectively. RESULTS: Ferroptosis was evaluated by intracellular lipid ROS level and iron concentration. Hepcidin could prevent erastin-induced ferroptosis by degrading Fpn. Erastin (5 µg/mL) was observed to induce ferroptosis in neuroblastoma cells at 6 hours, which was promoted by knockdown of Fpn. The expression of Fpn gene and protein was decreased in SH-SY5Y cells treated with erastin. After treatment with erastin, Fpn siRNA transfection in SH-SY5Y cells was able to accelerate ferroptosis-associated phenotypic changes. Fpn acted as a negative regulator of ferroptosis by reducing intracellular iron concentration. Knockdown of Fpn enhanced anticancer activity of erastin. CONCLUSIONS: These results suggested that knockdown of Fpn accelerated erastin-induced ferroptosis by increasing iron-dependent lipid ROS accumulation, highlighting Fpn as a potential therapeutic target site for neuroblastoma. Thus, Fpn inhibitors may provide new access for chemosensitization of neuroblastoma.

TGF-ß1 promotes human hepatic carcinoma HepG2 cells invasion by upregulating autophagy.

OBJECTIVE: To study the role of TGF-ß1 in autophagy and invasion ability of human hepatic carcinoma HepG2 cells. MATERIALS AND METHODS: Cultured HepG2 cells were treated with different concentrations of TGF-ß1 for 24 h. The protein expression levels of autophagy relative marker LC3 and Beclin1 were detected by Western blot. The effect of TGF-ß1 on invasion ability of HepG2 cells was detected with transwell method. RESULTS: The results demonstrated that TGF-ß1 was able to activate autophagy of HepG2 cells in a dose-dependent manner. Autophagy inhibitor 3-methyladenine (3-MA) could reverse TGF-ß1 induced autophagy process. Also, TGF-ß1 significantly promotes the invasion ability of HepG2 cells; however, this process could effectively reverse by autophagy inhibitor 3-MA. CONCLUSIONS: TGF-ß1 enhances HepG2 cells invasion by upregulating autophagy.

Intracellular IL-37b interacts with Smad3 to suppress multiple signaling pathways and the metastatic phenotype of tumor cells.

Multiple signaling pathways that promote tumor cell metastasis are differentially activated in low/non-metastatic and metastatic tumor cells, resulting in the differential expression of metastasis-related genes. The underlying mechanism may involve the alterations of the intrinsic negative regulation in tumor cells. Here we report that the differential expression of interleukin-37b (IL-37b) in tumor cells alters the intrinsic negative regulation of signaling pathways, resulting in the difference of metastatic capacity. IL-37b could bind Smad3 and suppress Smad pathway by interfering with the formation and nuclear translocation of Smad2/3/4 complex. In turn, Smad3 could function as a co-regulator, enabling IL-37b to suppress multiple non-Smad pathways. IL-37b-Smad3 translocated into nucleus to upregulate the expression of non-receptor protein tyrosine phosphatases (PTPNs), thus promoting dephosphorylation to suppress the activation of tyrosine phosphorylation-dependent signaling pathways such as ERK, p38 MAPK, JNK, PI3K, NF-κB, and STAT3 pathways. Intriguingly, 13 of 17 PTPNs, most of which are metastasis suppressors, were downregulated in metastatic tumor cells because of the low expression of IL-37b. The marked decrease of intracellular IL-37b attenuated the intrinsic negative regulation in tumor cells, resulting in the enhanced activation of multiple signaling pathways and the increased capacity of invasiveness and metastatic colonization. Consistently, low expression of IL-37b in tumors was significantly associated with poor prognosis of cancer patients. Taken together, these findings reveal that intracellular IL-37b is a critical factor in the negative regulation of multiple signaling pathways that modulate the expression of metastasis-related genes, and suggest that IL-37b expression in tumor cells can potentially be a histopathological prognostic parameter for cancer patients and a therapeutic target for preventing tumor metastasis.

SATB1 promotes tumor metastasis and invasiveness in oral squamous cell carcinoma.

OBJECTIVE: Our aim is to evaluate the expression of SATB1 in human oral squamous cell carcinomas (OSCC) and its role in the invasiveness and metastasis of OSCC. SUBJECTS AND METHODS: A human OSCC tissue microarray was used to evaluate the expression pattern of SATB1. SATB1 mRNA knockdown was performed in human OSCC cell lines SCC25 and Cal27 to assess the function of SATB1 in the invasiveness and metastasis of OSCC. RESULTS: SATB1 is highly expressed in human OSCC determined by immunohistochemistry, and its nuclear/cytoplasmic ratio of histoscore is significantly correlated with patients' prognosis. Reduced cell motility, invasiveness, expression of epithelial to mesenchymal transition (EMT) markers (N-cadherin and ß-catenin), and elevated expression of epithelial markers were observed in SATB1-knockdown cells in in vitro studies. Depletion of SATB1 also restored a cobblestone-like morphology in TGF-ß1-treated cells. CONCLUSIONS: These findings suggest SATB1 may play an important role in OSCC invasiveness and metastasis.

Evaluation of the COBAS® TaqMan® system in patients with low hepatitis B virus DNA undetectable with PCR assay kit.

OBJECTIVE: We conducted a comparison of the diagnostic kit for quantification of hepatitis B virus DNA (PCR-fluorescence probing) and COBAS TaqMan automated nucleic acid extraction and real-time polymerase chain reaction (PCR) amplification systems. We tested their capacity to quantify and diagnose patients with chronic viral hepatitis B with low viral load < 1 x 103 IU/mL, in hope to provide further evidence for promoting the application of COBAS TaqMan as the diagnostic method for such patients. PATIENTS AND METHODS: Diagnostic kit and COBAS TaqMan system were tested on 100 patients diagnosed with chronic viral hepatitis B in our hospital and with a viral load lower than the detection limit of real-time extraction-quantification kit. These patients included 47 cases with chronic viral HBV, 53 cases of HBV-associated cirrhosis (11 cases were HBV-associated liver cancer with cirrhosis). COBAS TaqMan real-time quantification PCR with a sensitivity of 20 IU/ml was performed to test the reproducibility for the diagnosis result. RESULTS: The COBAS TaqMan real-time system quantified 76 cases out of 100 with a viral load higher than 20 IU/ml (detection rate, 76%). Among these patients, there were 33 cases of chronic viral HBV (without cirrhosis) (detection rate, 70.2%), 43 cases of cirrhosis (detection rate, 81.1%, including 28 cases of compensatory cirrhosis and 15 cases of decompensated cirrhosis), and 11 cases of liver cancer (detection rate, 81.2%). CONCLUSIONS: The COBAS TaqMan system has higher sensitivity than traditional real-time PCR detection kit, especially for HBV-related cirrhosis and liver cancer with low viral load. The limitation of real-time PCR should be taken into account during treatment monitoring and the alternative of COBAS TaqMan system should be promoted in patients with high risk of liver cirrhosis and cancer to avoid delayed diagnosis and improve clinical outcome.

Changing refractive outcomes with increasing astigmatism at longer-term follow-up for infant cataract surgery.

PurposeTo present longer-term refractive and ocular health outcomes for patients who had primary intraocular lens (IOL) insertion following infant cataract surgery.Patients and methodsA retrospective review of all infant cataract cases at a tertiary children's hospital between 2003 and 2006 was conducted. Surgery was performed before 12 months of age. IOL power was calculated using the SRK/T formula targeting hyperopia based on the child's age; children under 3 months were targeted at +9.0 D, between 3 and 6 months at +6.0 D, and between 6 and 12 months at +3.0 D. Locally weighted scatterplot smoothing and mixed models were used.ResultsA total of 12 eyes from 9 children were included (4 bilateral and 5 unilateral). Spherical equivalent refraction decreased dramatically in the first 2 years of life, with milder changes from age 2 to 4 years and minimal changes thereafter. Cylinder increased until age 5 years at ∼0.57 dioptres/year (95% confidence intervals 0.27-0.87 D, P<0.001). Lens reproliferation was the commonest complication (58%). All children eventually developed strabismus.ConclusionEarly and frequent refraction is critical in the first 2 years of life to try and compensate for the rapid changes encountered in the growing eye. Astigmatism may be another important consequence to manage.

Impact of lumbar instrumented circumferential fusion on the development of adjacent vertebral compression fracture.

We evaluated the impact of lumbar instrumented circumferential fusion on the development of adjacent level vertebral compression fractures (VCFs). Instrumented posterior lumbar interbody fusion (PLIF) has become a popular procedure for degenerative lumbar spine disease. The immediate rigidity produced by PLIF may cause more stress and lead to greater risk of adjacent VCFs. However, few studies have investigated the relationship between PLIF and the development of subsequent adjacent level VCFs. Between January 2005 and December 2009, a total of 1936 patients were enrolled. Of these 224 patients had a new VCF and the incidence was statistically analysed with other covariants. In total 150 (11.1%) of 1348 patients developed new VCFs with PLIF, with 108 (72%) cases at adjacent segment. Of 588 patients, 74 (12.5%) developed new subsequent VCFs with conventional posterolateral fusion (PLF), with 37 (50%) patients at an adjacent level. Short-segment fusion, female and age older than 65 years also increased the development of new adjacent VCFs in patients undergoing PLIF. In the osteoporotic patient, more rigid fusion and a higher stress gradient after PLIF will cause a higher adjacent VCF rate.

Baicalin decreases SGK1 expression in the hippocampus and reverses depressive-like behaviors induced by corticosterone.

The present study was to investigate whether baicalin can prevent repeated exogenous corticosterone injection-induced depressive-like behaviors and explore its possible mechanisms. After a 21-day treatment with baicalin (10 and 20 mg/kg), sucrose preference in the sucrose preference test (SPT) and immobility time in forced swimming test (FST) were observed, serum corticosterone levels and brain-derived neurotrophic factor (BDNF) contents in the hippocampus were examined by enzyme-linked immunosorbent assay (ELISA). In addition, quantitative real-time polymerase chain reaction (qPCR) and western blot were used to detect the mRNA and protein expression in the hippocampus. The results showed that 21-day cortiscosterone injections caused depressive-like behaviors in mice, including the reduced sucrose preference and increased duration of immobility. Baicalin reversed these behavioral changes described above and restored serum corticosterone levels. Additionally, baicalin up-regulated the mRNA and protein expression of glucocorticoid receptor (GR) and BDNF, accompanied with the down-regulation of serum- and glucocorticoid-regulated kinase 1 (SGK1) in the hippocampus. Moreover, baicalin significantly increased the protein expression of 11ß-hydroxysteroid dehydrogenase-2 (11ß-HSD2) in the hippocampus. The present results confirmed the antidepressant-like effects of baicalin in a mice model of depression induced by corticosterone and suggested that its mechanism was possibly involved in reducing serum corticosterone and thereby increasing BDNF in the hippocampus.

Traumatic brain injury causes frontotemporal dementia and TDP-43 proteolysis.

Traumatic brain injury (TBI) is a major risk factor for dementia. Recently, TBI has also been suggested as a risk factor for frontotemporal dementia (FTD), and plasma immunoreactivity to the TAR-DNA binding protein 43 (TDP-43) has been observed in both patients with acute TBI and long-term survivors of this condition. We used a population-based study to estimate and compare the risk of FTD in individuals with and without TBI. Furthermore, we used a rat model of TBI to show that increased TDP-43 proteolysis following TBI produces FTD-like impairments, including abnormal limb-clasping, and impaired performances in the Morris water maze. We recruited 24,585 patients who received ambulatory or hospital care for TBI and 122,925 patients without TBI for this study. Each individual was investigated for 4years to evaluate FTD development, and data were analyzed by Cox proportional hazard regression. In the TBI rat model, behavior and TDP-43 inclusions were assessed following intracranial administration of a caspase-3 inhibitor or vehicle. FTD was more likely to occur in the TBI group than in the group without TBI (adjusted hazard ratio, 4.43; 95% confidence interval, 3.85-5.10; P<0.001). Rats developed behavioral impairments similar to those in patients with FTD after TBI. Further, the behavioral impairments were likely associated with TDP-43 short fragment mislocalization and accumulation. Our findings suggest that in humans, TBI is associated with a greater occurrence of FTD. Moreover, clinical FTD manifestations may be associated with TDP-43 proteolysis, since impaired behaviors in TBI rats were reminiscent of those in humans with FTD.