This meta-analysis aimed to investigate the association between type 2 diabetes (T2D) and the risk of cataract.

The Notch signaling pathway has been shown to be involved in the development of the nervous system. Recent studies showed that Notch receptors and ligands are also expressed in the nervous system of adult animals. However, whether the Notch signaling pathway has a function in adults is not fully understood. The present study is designed to investigate the function of the Notch signaling pathway in nociceptive transmission, especially during neuropathic pain in adult rats.

Enhanced matrix metalloproteinases (MMPs) activity is implicated in the process of atherosclerotic plaque instability. We hypothesized that doxycycline, a broad MMPs inhibitor, was as effective as simvastatin in reducing the incidence of plaque disruption. Thirty rabbits underwent aortic balloon injury and were fed a high-fat diet for 20 weeks. At the end of week 8, the rabbits were divided into three groups for 12-week treatment: a doxycycline-treated group that received oral doxycycline at a dose of 10 mg/kg/d, a simvastatin-treated group that received oral simvastatin at a dose of 5 mg/kg/d, and a control group that received no treatment. At the end of week 20, pharmacological triggering was performed to induce plaque rupture. Biochemical, ultrasonographic, pathologic, immunohistochemical and mRNA expression studies were performed. The results showed that oral administration of doxycycline resulted in a significant increase in the thickness of the fibrous cap of the aortic plaque whereas there was a substantial reduction of MMPs expression, local and systemic inflammation, and aortic plaque vulnerability. The incidence of plaque rupture with either treatment (0% for both) was significantly lower than that for controls (56.0%, P<0.05). There was no significant difference between doxycycline-treated group and simvastatin-treated group in any serological, ultrasonographic, pathologic, immunohistochemical and mRNA expression measurement except for the serum lipid levels that were higher with doxycycline than with simvastatin treatment. In conclusion, doxycycline at a common antimicrobial dose stabilizes atherosclerotic lesions via inhibiting matrix metalloproteinases and attenuating inflammation in a rabbit model of vulnerable plaque. These effects were similar to a large dose of simvastatin and independent of serum lipid levels.

Widely used restriction-dependent cloning methods are labour-intensive and time-consuming, while several types of ligase-independent cloning approaches have inherent limitations. A rapid and reliable method of cloning native DNA sequences into desired plasmids are highly desired.

Acid-sensing ion channels (ASICs) are present in neurons and may contribute to chemoreception. Among six subunits of ASICs, ASIC1 is mainly expressed in the central nervous system. Recently, multiple sites in the brain including the lateral hypothalamus (LH) have been found to be sensitive to extracellular acidification. Since LH contains orexin neurons and innervates the medulla respiratory center, we hypothesize that ASIC1 is expressed on the orexin neuron and contributes to acid-induced increase in respiratory drive. To test this hypothesis, we used double immunofluorescence to determine whether ASIC1 is expressed on orexin neurons in the LH, and assessed integrated phrenic nerve discharge (iPND) in intact rats in response to acidification of the LH. We found that ASIC1 was co-localized with orexinA in the LH. Microinjection of acidified artificial cerebrospinal fluid increased the amplitude of iPND by 70% (pH 7.4 v.s. pH 6.5:1.05±0.12 v.s. 1.70±0.10, n = 6, P<0.001) and increased the respiratory drive (peak amplitude of iPND/inspiratory time, PA/Ti) by 40% (1.10±0.23 v.s. 1.50±0.38, P<0.05). This stimulatory effect was abolished by blocking ASIC1 with a nonselective inhibitor (amiloride 10 mM), a selective inhibitor (PcTX1, 10 nM) or by damaging orexin neurons in the LH. Current results support our hypothesis that the orexin neuron in the LH can exert an excitation on respiration via ASIC1 during local acidosis. Since central acidification is involved in breathing dysfunction in a variety of pulmonary diseases, understanding its underlying mechanism may improve patient management.

The present study examined nociceptive behaviors and the expression of phosphorylated cAMP response element-binding protein (pCREB) in the dorsal horn of the lumbar spinal cord and the dorsal root ganglion (DRG) evoked by bee venom (BV). The effect of intraplantar preapplication of the somatostatin analog octreotide on nociceptive behaviors and pCREB expression was also examined. Subcutaneous injection of BV into the rat unilateral hindpaw pad induced significant spontaneous nociceptive behaviors, primary mechanical allodynia, primary thermal hyperalgesia, and mirror-thermal hyperalgesia, as well as an increase in pCREB expression in the lumbar spinal dorsal horn and DRG. Octreotide pretreatment significantly attenuated the BV-induced lifting/licking response and mechanical allodynia. Local injection of octreotide also significantly reduced pCREB expression in the lumbar spinal dorsal horn and DRG. Furthermore, pretreatment with cyclosomatostatin, a somatostatin receptor antagonist, reversed the octreotide-induced inhibition of the lifting/licking response, mechanical allodynia, and the expression of pCREB. These results suggest that BV can induce nociceptive responses and somatostatin receptors are involved in mediating the antinociception, which provides new evidence for peripheral analgesic action of somatostatin in an inflammatory pain state.

No specific antiviral agent against hand foot and mouth disease (HFMD) is available for clinical practice today.

The aim of the present study was to evaluate the effect that a dietary intake of resveratrol (RSV) had on the expression of glutamate cysteine ligase (GCL) in the kidneys of aged rats. Young, middle-aged and aged rats were each randomly divided into two groups. The control groups were fed a controlled diet and the experimental groups received a controlled diet supplemented with RSV. GCL activity levels in the kidneys were determined. Protein content and relative gene expression levels of the two subunits of GCL were evaluated by western blot analysis and quantitative polymerase chain reaction, respectively. GCL activity levels significantly increased in the kidneys of aged rats fed the RSV-supplemented diet. In addition, RSV markedly increased the protein content and relative mRNA expression levels of the GCL subunits in the kidneys of aged rats. These observations have important implications for the development of therapeutic agents for the kidneys that may enable the elderly population to combat oxidative stress.

Ginseng has become one of the most commonly used alternative herbal medicines, and its active component, ginsenoside Rg1 has known pharmacological effects, including anticancer properties. However, the effects of ginsenoside Rg1 on metastasis have yet to be investigated. In this study, we demonstrated the ability of ginsenoside Rg1 to suppress phorbol myristate acetate (PMA)-induced invasion and migration in MCF-7 breast cancer cells. MCF-7 cells were treated with ginsenoside Rg1 and incubated with or without PMA. The protein and mRNA expression of MMP-9 and MMP-2 was analyzed using Transwell and wound‑healing assays and western blotting. The results showed that suppression was associated with the reduced secretion of MMP-9, a key metastatic enzyme. MMP-9 levels were regulated transcriptionally and correlated with the suppression of NF-κB phosphorylation and DNA binding activity. Conversely, ginsenoside Rg1 did not affect MMP-2 mRNA and TIMP-1 mRNA levels, or the activation of AP-1, suggesting a specificity of pathway inhibition. Inhibition of NF‑κB activation by p65 small‑interfering RNA (siRNA) was shown to suppress PMA-induced cell invasion and migration. The siRNA studies also showed that PMA-induced MMP-9 expression is NF-κB-dependent. The results suggested that the anticancer properties of ginsenoside Rg1 may derive from its ability to inhibit invasion and migration, and that these processes are regulated in breast cancer cells through the NF-κB‑mediated regulation of MMP-9 expression.

CD8(+) T cells are essential for host defense to Mycobacterium tuberculosis (Mtb) infection and identification of CD8(+) T cell epitopes from Mtb is of importance for the development of effective peptide-based diagnostics and vaccines. We previously demonstrated that the secreted 10-KDa culture filtrate protein (CFP10) from Mtb is a potent CD8(+) T cell antigen but the repertoire and dominance pattern of human CD8 epitopes for CFP10 remained poorly characterized. In the present study, we undertook to define immunodominant CD8 epitopes involved in CFP10 using a panel of CFP10-derived 13-15 amino acid (aa) peptides overlapping by 11 aa. Four peptides in CFP10 were observed to induce significant CD8(+) T cell responses and we further determined the size of the epitopes involved in each individual peptide tested. Four 9 aa CD8 epitopes were finally identified and deleting a single amino acid from the N or C terminus of either peptide markedly reduced IFN-γ production, suggesting that they are minimum of CD8 epitopes. In the individuals tested, each epitope represented a single immunodominant response in CD8(+) T cells. The epitope-specific CD8(+) T cells displayed effector or effector memory phenotypes and could upregulate the expression of CD107a/b upon antigen stimulation. In addition, we found that epitope-specific CD8(+) T cells shared biased usage of T cell receptor (TCR) variable region of β chain (Vβ) 12, 9, 7.2 or Vβ4 chains. As judged from HLA-typing results and using bioinformatics technology for prediction of MHC binding affinity, we found that the epitope-specific CD8(+) T cells are all restricted by HLA-B alleles. Our findings suggest that the four epitopes in CFP10 recognized by CD8(+) T cells might be of importance for the development of Mtb peptide-based vaccines and for improved diagnosis of TB in humans.

Accelerated senescence (ACS) leading to proliferative arrest is a physiological mechanism of the DNA damage response that occurs during tumor therapy. Our experiment was designed to detect unknown genes that may play important roles in cisplatin-induced senescence and to illustrate the related senescence mechanism. Using 2-dimension electrophoresis (2-DE), we identified 5 protein spots with different expression levels in the normal and senescent NG108-15 cells. According to MALDI-TOF MS analysis, the 5 proteins were determined to be peptidylprolyl isomerase A (PPIA), peroxiredoxin 1 (PRX1), glutathione S-transferase mu 1 (GSTM1), vimentin (VIM) and glucose-regulated protein 78 (GRP78). Then, we investigated how cisplatin-induced senescence was mediated by GRP78 in the NG108-15 cells. Knockdown of GRP78 significantly increased P53 expression in NG108-15 cells. Additionally, 2-deoxy-D-glucose (2DG)-induced GRP78 overexpression protected the NG108-15 cells from cisplatin-induced senescence, which was accompanied by the obvious suppression of P53 and p-CDC2 expression. Inhibition of Ca2+ release from endoplasmic reticulum (ER) stores was also found to be associated with the anti-senescence effect of 2DG-induced GRP78 overexpression. In conclusion, we found 5 proteins that were differentially expressed in normal NG108-15 cells and senescent NG108-15 cells. GRP78 plays an important role in cisplatin-induced senescence in NG108-15 cells, mainly through its regulation of P53 expression and ER calcium efflux.

Male germline stem cells (mGSCs) offer great promise in regenerative medicine and animal breeding due to their capacity to maintain self-renewal and to transmit genetic information to the next generation following spermatogenesis. Human testis-derived embryonic stem cell-like cells have been shown to possess potential of mesenchymal progenitors, but there remains confusion about the characteristics and origin of porcine testis-derived stem cells.

Dopamine (DA) profoundly stimulates motor function as demonstrated by the hypokinetic motor symptoms in Parkinson's disease (PD) and by the hyperkinetic motor side effects during dopaminergic treatment of PD. Dopamine (DA) receptor-bypassing, optogenetics- and chemogenetics-induced spike firing of striatal DA D1 receptor (D1R)-expressing, direct pathway medium spiny neurons (dSPNs or dMSNs) promotes movements. However, the endogenous D1R-mediated effects, let alone those of DA replacement, on dSPN spike activity in freely-moving animals is not established. Here we show that using transcription factor Pitx3 null mutant (Pitx3Null) mice as a model for severe and consistent DA denervation in the dorsal striatum in Parkinson's disease, antidromically identified striatonigral neurons (D1R-expressing dSPNs) had a lower baseline spike firing rate than that in DA-intact normal mice, and these neurons increased their spike firing more strongly in Pitx3Null mice than in WT mice in response to injection of L-dopa or the D1R agonist, SKF81297; the increase in spike firing temporally coincided with the motor-stimulating effects of L-dopa and SKF81297. Taken together, these results provide the first evidence from freely moving animals that in parkinsonian striatum, identified behavior-promoting dSPNs become hyperactive upon the administration of L-dopa or a D1 agonist, likely contributing to the profound dopaminergic motor stimulation in parkinsonian animals and PD patients.

Sunitinib resistance is a major clinical problem hampering the treatment of renal cell carcinoma (RCC). Studies on the comprehensive characterisation of morphological, functional and molecular changes in sunitinib-resistant RCC cells are lacking. The aim of the current study was to develop sunitinib resistance in four human RCC cell lines (786-0, Caki-1, Caki-2 and SN12K1), and to characterise the changed cell biology with sunitinib resistance. RCC cells were made resistant by continuous, chronic exposure to 10 μM of sunitinib over a period of 12 months. Cell proliferation, morphology, transmigration, and gene expression for interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), Bcl-2 and Bax were studied. There was no significant difference in growth rate or transmigration between the parental and resistant cells. Sunitinib-resistant cells were significantly hypertrophic compared with parental cells as evidenced by increases in the surface areas of the whole cells and the nuclei. IL-6 was significantly increased in all resistant cells. IL-8 was increased in sunitinib-resistant Caki-2 and SN12K1 cells and decreased in 786-0 without any significant changes in Caki-1. VEGF was increased in resistant Caki-2 and SN12K1 cells but not in 786-0 and Caki-1. The Bcl2/Bax ratio was increased in Caki-1, Caki-2 and SN12K1 cells but decreased in 786-0 cells. The increased IL-6 may contribute to sunitinib resistance either via VEGF-mediated angiogenesis or through shifting of the Bcl2/Bax balance in favour of anti-apoptosis.

The study aims to systematically evaluate the clinical effect of gabapentin in the treatment of postherpetic neuralgia (PHN).

Long stress-induced noncoding transcript 5 (LSINCT5) is a member of the LSINCT family, members of which are expressed during stress-induced cell formation and have also been reported to promote cancer progression. In the present study, the association between LSINCT5 expression and clinical significance was investigated and the biological function of LSINCT5 in epithelial ovarian cancer (EOC) was explored. LSINCT5 expression was examined in EOC tissues by reverse transcription-quantitative polymerase chain reaction and its association with clinicopathological factors was analysed. Cell proliferation, migration and invasion tests were performed to observe the role of LSINCT5 in human ovarian cancer cell lines in vitro. The negative control (NC) and siLSINCT5 SKOV3 cells were treated with chemokine ligand 12 (CXCL12) and their proliferation, migration and invasion activities were examined. LSINCT5 was overexpressed in EOC compared with normal ovarian tissue. LSINCT5 expression was significantly associated with the International Federation of Gynecologists and Obstetricians cancer stage and the presence of lymphatic metastases. Silencing LSINCT5 significantly reduced the expression of chemokine receptor 4 (CXCR4) and inhibited SKOV3 cell proliferation, migration and invasion, however the CXCL12 expression level had no significant change. When NC and siLSINCT5-SKOV3 cells were treated with CXCL12, the proliferation and invasion ability were significantly enhanced. The migration ability of the siLSINCT5-SKOV3 cells was also significantly enhanced. The present study indicated that LSINCT5 serves an important role in ovarian cancer metastasis by regulating the CXCL12/CXCR4 signalling axis, suggesting that this pathway may be a potential target for the treatment of patients with EOC.

Columnar mass concentrations of aerosol components over the Arctic are estimated using microphysical parameters derived from direct sun extinction and sky radiance measurements of Aerosol Robotic Network. Aerosol optical, microphysical, chemical and radiative properties show that Arctic aerosols are dominated by fine mode particles, especially for high aerosol load cases. The average aerosol optical depth (AOD) of the selected Arctic sites in the sampling period is approximately 0.08, with 75% composed of fine mode particles. The fine mode fraction mostly exceeds 0.9 when AOD greater than 0.4. The ammonium sulfate-like component (AS) contributes about 68% of total dry aerosol mass for high-AOD events. The estimated compositions and back trajectories show that the transported aerosol particles from biomass burning events have large amounts of black carbon (BC) and brown carbon, while those from pollution events are characterised by large AS fractions. The instantaneous radiative forcing at the top-of-atmosphere is higher for the more absorbing components, and varies greatly with surface albedo and solar zenith angle. A regression model of columnar composition and radiative forcing within the atmosphere (RFATM) for Arctic aerosol is established, showing that BC dominates a positive RFATM with a high warming efficiency.

Increased expression of integrin β1 has been reported to correlate with progression and therapy resistance in many types of cancers. The aim of this study was to investigate the effects of integrin β1 on the invasion and radioresistance of laryngeal cancer cells.

The aim of the present study was to investigate the biological role of glypican 3 (GPC3), and to identify its mechanism and clinical significance in the carcinogenesis of liver cancer. A total of 114 patients with liver cancer were involved. Their clinical data, hematoxylin and eosin-stained and Antigen Ki-67 protein (Ki-67) and GPC3 immunohistochemically-stained liver cancer tissue sections were analyzed to evaluate the correlation between the liver cancer proliferation, differentiation and GPC3 expression. Fluorescence microscopy, western blotting, MTT and reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays were performed in HepG2 and HLE cell lines to investigate the potential mechanisms of action. Among the 114 patients with liver cancer enrolled in the present study, 12 exhibited well-differentiated liver cancer, of which 6 (50%) were positive for GPC3. A total of 30 cases exhibited poorly differentiated liver cancer; 26 (87%) of these expressed GPC3 and 11 cases (37%) demonstrated strong positive expression levels. The other 72 liver cancer cases were moderately differentiated; 75% (54/72) of these expressed GPC3 and 12.5% (9/72) exhibited strong positive expression levels. There was a significant association between the levels of GPC3 expression and liver cancer differentiation (χ2=16.306, P=0.008). Ki-67 staining as the criteria of the liver cancer cell proliferation index also indicated a cross correlation between liver cancer proliferation and GPC3 levels. Among the 39 liver cancer samples with a cell proliferation index <5%, only 2.6% (1/39) exhibited strong positive GPC3 staining, but of the 16 cases with a high cell proliferation index >50%, 6 exhibited strong GPC3 staining (37.5%). The difference of cell proliferation indexes between cancer cells were well, moderate and poorly differentiated, and was markedly significant (χ2=26.334, P=0.002), and suggested that liver cancer cell proliferation was positively correlated with GPC3 expression (r=0.316, P=0.001). Consistently, in vitro analysis indicated that GPC3 promoted HepG2 and HLE cell growth, which was more apparent in HepG2 cells. The RT-qPCR results indicated that GPC3 promoted proliferation through the Hedgehog (Hh) pathway in HepG2 cells, but not in HLE cells. In the present study, it was demonstrated that patients with liver cancer with higher GPC3 levels exhibited poorer differentiation and higher proliferation levels. In vitro GPC3 may promote liver cancer cell lines proliferation through the Hh pathway.

Ruan, M, Li, L, Chen, C, and Wu, X. Stretch could reduce hamstring injury risk during sprinting by right shifting the length-torque curve. J Strength Cond Res 32(8): 2190-2198, 2018-It was hypothesized that static stretch would shift the length-torque curve to the right, which may reduce the risk of muscle strain injuries. The purpose of this study was to evaluate the acute effects of static stretching of hamstring (SSH) on the risk of hamstring injury during sprinting indicated by the shift of the length-torque relationship. Twelve female college athletes (age: 20.8 ± 0.7 years; height: 1.61 ± 0.05 m; body mass: 54.25 ± 4.22 kg) participated in this study. Subjects performed overground sprinting under 2 conditions: after warm-up with 4 × 30 seconds SSH or after warm-up without SSH. Three-dimensional kinematic and kinetic data and electromyography of biceps femoris long head (BFlh), rectus femoris, and vastus medialis were collected during testing. The maximum length of BFlh during late swing phase increased after SSH with large effect size and close to statistically significant (p = 0.05, d = 1.22), but the knee flexion torque at the peak length did not change significantly. Static stretching of hamstring significantly reduced peak values of both horizontal (d = 1.46) and vertical (d = 1.79) ground reaction forces, and BFlh's activation level during the preactivation (late swing) phase (p = 0.05, d = 2.16). The results indicated that the length of BFlh-knee torque relationship and the length of BFlh-hip torque relationships during the late swing phase and initial stance phase were shifted to the right after SSH, which may reduce risk of hamstring strain injuries. We suggest that preactivity static stretching should not be simply removed and participators should give priority to stretch muscles that are vulnerable to strain injuries.