Associations between serum uric acid and breast cancer incidence: A systematic review and meta-analysis.

BACKGROUND: Serum uric acid (SUA) may be involved in the development of cancer by inhibiting oxidative stress, but its relationship with breast cancer remains unclear. METHODS: The PubMed, Embase, and Web of Science databases were searched systematically for studies on SUA levels in women with breast cancer and the effect of SUA levels on the risk of breast cancer. The Newcastle‒Ottawa Quality Assessment Scale (NOS) was used to assess the quality of all relevant studies included. RESULTS: A total of 19 studies were included, including 75,827 women with breast cancer and 508,528 healthy controls. A meta-analysis found that SUA levels were negatively correlated with breast cancer risk in women (HR = 0.94, 95% CI: 0.89 - 0.99, p = 0.003). SUA levels in female breast cancer patients were not significantly different from those in healthy controls (SMD = 0.49, 95% CI = -0.09 - 1.08, p = 0.10), while SUA levels were increased in female breast cancer patients in articles published after 2010, SUA concentration detected by spectrophotometry, and non-Asian populations, regardless of menopausal state and treatment state. CONCLUSION: High levels of SUA may reduce the risk of breast cancer in women, suggesting that SUA was a protective factor in women.

Hyperuricemia is accompanied by elevated peripheral CD4+ T cells.

Hyperuricemia (HUA) makes a chronic inflammation status, which affects immune cells. The association between HUA and immune cells, such as monocytes and neutrophils, has been extensively studied. However, studies on HUA and lymphocytes are still limited. We selected 1543 healthy participants and 258 individuals with HUA to analyze the correlation between serum uric acid (SUA) levels and immune cells, and 98 healthy participants and 16 individuals with HUA were used to study the relationship between SUA levels and cytokine levels. Then, we used soluble UA to stimulate peripheral blood mononuclear cells in vitro and examined lymphocyte subset counts and activation by flow cytometry. The results revealed that the number of lymphocytes in the HUA group was significantly increased, particularly CD4+ T cell numbers, which were higher than those in the total population (P = 0.0019), females (P = 0.0142), and males (P = 0.0199) of the healthy control group. Concomitantly, interleukin (IL)-4 and IL-10 levels significantly increased in people with HUA (P = 0.0254; P = 0.0019). In vitro, soluble UA promoted the proliferation and activation of CD4+ T and CD19+ B cells. Thus, HUA is accompanied by elevated peripheral CD4+ T cells and may cause a Th2-dominant immune status.

Increased death and exhaustion of CD69high T cells and NK cells are associated with PD-1 antibody application in the in vitro co-culture system.

Background: The application of PD-1 monoclonal antibody (mAb) helps to treat non-small cell lung cancer, but acquired resistance has emerged in clinical practice. We tested the hypothesis that acquired resistance of anti-PD-1 immunotherapy is linked to death and exhaustion of activated T and NK cell. Methods: The co-culture system of HCC827 cells and peripheral mononuclear cells (PBMCs) was established to evaluate the effect of PD-1 mAb on the death rate and exhaustion of T and NK cell. The predisposing role of CD69 for death and exhaustion was validated by using PHA-activated PBMCs of CD69low NSCLC patients. The 10-colour/three laser flow cytometer was used to test related markers for cell activation, death and exhaustion. Results: We found that PD-1 mAb increase the death and exhaustion of T cells and NK cells in a dose-dependent way when PBMCs from NSCLC patients whose the percentages of CD69+ cells in peripheral blood T cells were greater than 5% (CD69high NSCLC patients). By analyzing PBMCs from healthy volunteers and CD69low NSCLC patients, we found that T cells and NK cells can be induced to die by PD-1 mAb after PHA activation, and had a tendency to raise the rate of cell exhaustion. Conclusions: Our findings imply that increased death and exhaustion of CD69high T cells and NK cells are associated with ineffective anti-PD-1 immunotherapy in lung cancer. The CD69 expression of T cells and NK cells may be developed as a potential predictor for acquired resistance of anti-PD-1 immunotherapy. These data may provide ideas to guide individualized medication of PD-1 mAb in NSCLC patients.

Low Serum Calcium Concentration in Patients With Systemic Lupus Erythematosus Accompanied by the Enhanced Peripheral Cellular Immunity.

Objective: This study aims to explore the relationship between serum calcium concentration and peripheral lymphocyte status/Th1/Th2 cytokine levels in SLE patients, and the effect of glucocorticoids (GCs) on the calcium concentration and immune cell activation. Methods: The peripheral blood TBNK lymphocyte subsets and Th1/Th2 cytokines in SLE patients with low or normal serum calcium concentration and healthy people were analyzed and compared retrospectively. Peripheral white blood cells (PWBCs) from SLE patients or healthy people were stimulated with PMA or GCs in vitro to test their extracellular calcium concentration and CD8+ T cell activation. Results: The percentages of CD8+ T in SLE patients increased, but the increase of the number of CD8+ T cells only occurred in the SLE patients with low serum calcium concentration, and the number of CD45hiCD8+ T cells also increased, suggesting that SLE patients with hypocalcemia tend to possess an enhanced cellular immunity. The results of Th1/Th2 cytokines in peripheral blood showed that the levels of serum IL-2, IL-10, IL-6 and IFN-γ in SLE patients with hypocalcemia were significantly increased. Although the serum levels of TNF-α in SLE patients were -similar to that in healthy people, it was significantly higher than that in SLE patients with normal serum calcium. When comparing the results of Th1/Th2 cytokines in two times of one patient, the serum levels of TNF-α in SLE patients increased while serum calcium levels decreased. The in vitro experiments showed that the decrease of serum calcium concentration in SLE patients was affected by the immune cell activation and the application of GCs, but GCs did not promote the immune cell activation. Conclusions: Low serum calcium may make SLE patients in an enhanced cellular immune status and GCs aggravates the decrease of serum calcium levels but has no role on the immune cell activation. It suggests that hypocalcemia possibly promotes the disease activity of SLE patient, which should be paid attention to clinically.

Exploration of the binding between ellagic acid, a potentially risky food additive, and bovine serum albumin.

Ellagic acid (EA), a natural plant polyphenol, is usually used as a functional additive in variety of health foods. However, the potential toxicity of EA to human health should be paid enough attention. To clarify its biological toxicity in vivo, this study explored the binding mechanism of EA with bovine serum albumin (BSA) by means of spectroscopic approaches and molecular docking insimulative physiological conditions. The results showed that the mixture of BSA with EA could spontaneously cause the formation of BSA-EA complex through electrostatic interaction under simulative physiological conditions (0.01 mol·L-1Tris-HCl, 0.015 mol L-1 NaCl, pH = 7.4). Molecular docking experiments revealed that EA was primarily bound to the hydrophobic pocket of the site I (subdomain IIA) of BSA. It has been reported that the binding of small functional molecules to serum albumins remarkably impacts their absorption, distribution, metabolism, and excretion features. Therefore, this study might be helpful for human to have an in-depth understanding of the biological effect of EA in vivo and guide human to take it safely and reasonably.

[Study on Application of EMA-PCR Rapid Identification of Infectious and Non-infectious Adenovirus].

OBJECTIVES: To investigate the application of cytopathic effect (EMA)-PCR to rapid identification of infectious and non-infectious adenovirus. METHODS: The different dilutions of virus were inoculated to well-grown monolayer cells and then calculated the concentration of virus through the cytopathic effect (CPE). The adenovirus and New Castle disease virus were prepared in a fixed concentration of 106 PFU/mL then diluted in ten-time gradient and the DNA of virus were extracted and PCR were applied, then the target DNA fragments were observed through gel electrophoresis. The non-infectious adenovirus were treated with different concentrations of EMA (0 µg/mL, 70 µg/mL, 120 µg/mL and 150 µg/mL) and then detected the target DNA fragment in the same way. The different concentrations of infectious adenovirus (107 PFU/mL, 106 PFU/mL, 105 PFU/mL, 104 PFU/mL and 103 PFU/mL) were treated with 120 µg/mL EMA and then detected target DNA fragment in the same way. RESULTS: The target DNA fragments were detected in adenovirus of 104 PFU/mL and above. The target DNA fragments were detected in all 3 types of adenovirus while not detected in New Castle disease virus. The DNA amplification of non-infectious adenovirus were suppressed by EMA at 120 µg/mL and 150 µg/mL concentration, while the DNA amplification of infectious adenovirus in concentration of 105 PFU/mL and above were not affected by 120 µg/mL EMA. CONCLUSIONS: EMA-PCR was proved to be feasible to identify the infectious and non-infectious adenovirus, in which false positive results of PCR were effectively avoid at the same time.

A review about the development of fucoidan in antitumor activity: Progress and challenges.

Fucoidan is composed of l-fucose, sulfate groups and one or more small proportions of d-xylose, d-mannose, d-galactose, l-rhamnose, arabinose, glucose, d-glucuronic acid and acetyl groups in different kinds of brown seaweeds. Many reports have demonstrated that fucoidan has antitumor activities on various cancers. However, until now, few reviews have discussed the antitumor activity of fucoidan and few reports have summarized detailed molecular mechanisms of its actions and antitumor challenges of fucoidan specially. In this review, the antitumor signaling pathway mechanisms related to fucoidan are elucidated as much detail as possible. Besides, the factors affecting the anticancer effects of fucoidan, the structural characteristics of fucoidan with anticancer activities and the challenges for the further development of fucoidan are also summarized and evaluated. The existing similar and different conclusions are summarized in an attempt to provide guidelines to help further research, and finally contribute to go into market as chemotherapeumtics.

Simultaneous determination of parecoxib sodium and its active metabolite valdecoxib in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after intravenous and intramuscular administration.

In this study, we developed and validated a new, rapid, specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to simultaneously determine parecoxib sodium (PX) and its active metabolite, valdecoxib (VX), in rat plasma. Plasma samples were prepared by plasma protein precipitation combined with a liquid-liquid extraction method. The separation was carried out on a Kinetex C18 column (2.1mm×50mm, 2.6µm) with a gradient elution using methanol (A) and a 2mM ammonium acetate aqueous solution (B). The analysis was performed in less than 3min with a flow rate of 0.2mL/min. Ketoprofen was used as an internal standard (IS). Mass spectrometric detection was conducted with a triple quadrupole detector equipped with electrospray ionization in the negative ion mode (ESI(-)) using multiple reaction monitoring (MRM). The calibration curves were linear over the concentration ranges of 5-4000ng/mL for PX and 5-2000ng/mL for VX with all correlation coefficients greater than 0.998. The intra- and inter-day relative standard deviations (RSD) for both analytes were within 15% and the accuracy was within 85-115% at all quality control levels. The mean extraction recoveries for all analytes obtained from three concentrations of QC plasma samples were more than 89.0% efficient. Selectivity, matrix effect, dilution integrity and stability were also validated. The method was successfully used to investigate the pharmacokinetics of PX and VX in rat plasma after intravenous and intramuscular administration of PX.