Immunoreactive Substance Research Articles

Research Progress on Regulation of Immune Response by Tanshinones and Salvianolic Acids of Danshen (Salvia miltiorrhiza Bunge).

As one of the traditional Chinese herbs, Danshen (Salvia miltiorrhiza Bunge) has been widely studied and widely used in the treatment of cardiovascular, cerebrovascular, and other immune diseases. Tanshinones and salvianolic acids isolated from Danshen are considered to be the main components of its biological activity and pharmacology that play important roles in increasing the index of immune organs, regulating the number and function of immune cells, and releasing immunoreactive substances. Especially tanshinone IIA, cryptotanshinone, salvianolic acid B, and rosmarinic acid show good biological activity in treating rheumatoid arthritis, some immune-mediated inflammatory diseases, psoriasis, and inflammatory bowel disease. In order to understand their pharmacological effects and provide references for future research and clinical treatment, the regulation of immune response by tanshinones and salvianolic acids is summarized in detail in this paper. In addition, the challenges in their pharmacological development and the opportunities to exploit their clinical potential have been documented.

Local Defense Factors in Cleft-Affected Palate in Children before and during Milk Dentition Age: A Pilot Study.

One of the most frequent congenital orofacial defects is the cleft lip and palate. Local tissue defense factors are known to be important in immune response and inflammatory and healing processes in the cleft tissue; however, they have only been researched in older children during mixed dentition. Thus, the aim of this study is to assess the distribution of LL-37, CD-163, IL-10, HBD-2, HBD-3, and HBD-4 in children before and during milk dentition. The unique and rare material of palate tissue was obtained from 13 patients during veloplastic surgeries during the time span of 20 years. Immunohistochemistry, light microscopy, semi-quantitative evaluation, and non-parametric statistical analysis were used. A significant decrease in HBD-3 and HBD-4 in the connective tissue was found, as well as several mutual statistically significant and strong correlations between HBD-2, HBD-3, HBD-4, and LL-37. Deficiency of HBD-3 and HBD-4 suggests promotion of chronic inflammation. The scarcity of HBD-4 could be connected to the different signaling pathways of dental pulp cells. Mutual correlations imply changes in the epithelial barrier, amplified healing efficiency, and increased antibacterial line of defense. Deprivation of changes in IL-10 quantity points to possible suppression of the factor. The presence of similar CD-163 immunoreactive substances produced by M2 macrophages was also observed.

Eucommia ulmoides Oliver repairs the disorder of intestinal microflora caused by high starch in Micropterus salmoides and improves resistance to pathogens.

Eucommia ulmoides Oliver (EuO) is a natural medicine that can improve the composition of intestinal flora in fish, but more experiments and data are needed to support whether it can effectively improve the changes of intestinal flora and intestinal damage caused by high starch. This study examined the changes in intestinal structure as well as intestinal flora before and after the addition of EuO to high-starch diets and analyzed the effects of such changes on immune and digestive functions. The results showed that EuO reduces mortality during Nocardia seriolae attack and can reduce starch-induced intestinal inflammation. Eucommia ulmoides Oliver supplementation was able to alter the changes of intestinal flora in fatty acid degradation, bacterial chemotaxis, porphyrin metabolism and flagella assembly caused by high starch. By analyzing the abundance and correlation of bacterial communities, three bacterial communities that were significantly related to the intervention effect of EuO were screened. Further analysis revealed that EuO supplementation reduced the increase in abundance of Limnochordaceae, Nitrolancea, Lysinibacillus, and Hydrogenispora induced by high starch, which were negatively correlated with levels of the immunoreactive substance LZM in fish. This study reveals the regulatory effects of EuO on the intestinal flora of Micropterus salmoides fed on high starch diets, and provides a theoretical basis for reducing starch damage to fish in production.

Effect of selected bioactive substances and nanoparticles on the immunoreactivity of edible packages containing chitosan, by the ELISA method

ABSTRACT The aim of this study was evaluated the effect of selected bioactive substances and nanoparticles on the immunoreactivity of edible packages based on chitosan using the ELISA. The analysed protein was the tropomyosin. The results confirmed the presence of the tropomyosin (3.77 ± 0.79–5.75 ± 0.01 µg/g) in control samples. This study demonstrated that the bioactive substances in the form of grape (0.61 ± 0.34–0.43 ± 0.16 µg/g), blueberry (0.58 ± 0.32–0.39 ± 0.27 µg/g), and parsley extracts (2.09 ± 1.28–0.79 ± 0.40 µg/g) reduces immunoreactivity (p < 0.05) of the tropomyosin. The elder pollen had no significant effect (p > 0.05) on immunoreactivity. ZnO and TiO2 nanoparticles also demonstrated immunoreactivity reduction (p < 0.05). The exception was silver nanoparticles, where the immunoreactivity increased with increasing concentration of grape extract (1.29 ± 0.01–5.47 ± 0.25 µg/g). The results confirmed the inhibitory effect of bioactive substances on the immunoreactivity of the used ELISA and also showed the need to consider immunoreactive substances when interpreting ELISA results.

Determining the Risk of Elevated Digoxin Concentrations Following Loading Dose in Patients With Acute and Chronic Kidney Disease.

The optimal loading dose of digoxin in patients with reduced kidney function is unknown. Tertiary references recommend reduced loading doses; however, these recommendations are based on immunoassays that are falsely elevated by the presence of digoxin-like immunoreactive substances, a problem that is minimized in modern assays. To determine whether chronic kidney disease (CKD) or acute kidney injury (AKI) is associated with supratherapeutic digoxin concentrations after a digoxin loading dose. A retrospective analysis on patients who received an intravenous loading dose of digoxin with a digoxin concentration collected 6 to 24 hours after the end of the dose. Patients were stratified into 3 groups: AKI, CKD, and non-AKI/CKD (NKI) based on glomerular filtration rate and serum creatinine. The primary outcome was frequency of supratherapeutic digoxin concentrations (>2 ng/mL) and secondary outcomes included frequency of adverse events. A total of 146 digoxin concentrations were included (AKI = 59, CKD = 16, NKI = 71). Frequencies of supratherapeutic concentrations were similar between groups (AKI: 10.2%, CKD: 18.8%, NKI: 11.3%; P = 0.61). Pre-planned logistic regression demonstrated no significant relationship between kidney function group and the development of a supratherapeutic concentration (AKI: odds ratio [OR]: 1.3, 95% confidence interval [CI]: 0.4-4.5; CKD: OR 4.3, 95% CI: 0.7-23). This is the first study in routine clinical practice evaluating the relationship between kidney function and digoxin peak concentrations that differentiates AKI from CKD. We did not find a relationship between kidney function and peak concentrations; however, the group with CKD was underpowered.

Significant Improvement in Digoxin Immunoassays Over Four Decades: Newer Assays are Less Affected by Interferences.

Digitalis glycosides derived from foxglove plants have been used for medicinal purposes since the 16th century. Currently, digoxin derived from foxgloves is used clinically. Owing to the narrow therapeutic range, therapeutic drug monitoring is essential; however, digoxin immunoassays suffer from interference. The issue of interference was reviewed for both older polyclonal antibody-based digoxin assays and newer monoclonal antibody-based digoxin assays. A literature search was conducted using PubMed, ScienceDirect, Scopus, Web of Science, and ResearchGate for studies on digoxin immunoassays published in the English language from 1969 to the present. Radioimmunoassays for digoxin in the 1970s and, later, first-generation nonradioimmunoassay methods were liable to several interferences, including digoxin-like immunoreactive substances, spironolactone, potassium canrenoate, and various digoxin metabolites. However, for the last 10-15 years, next next-generation digoxin immunoassays have been virtually free from such interferences. Nevertheless, certain herbal supplements, as well as both Digibind and DigiFab, interfere with serum digoxin measurement, even with the more recently developed digoxin assays. More recently introduced monoclonal antibody-based digoxin assays are superior to the older polyclonal antibody-based digoxin assays.

The central glial cell line-derived neurotrophic factor (GDNF) regulates pulmonary function in asthmatic rats.

Asthma is a common chronic inflammatory disease of the airway, but the mechanism is still not fully understood. This study aimed to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on asthma attacks. An asthmatic rat model was established. GDNF expression in the airway and brain was observed by immunohistochemistry (IHC), and the concentration of GDNF in bronchoalveolar lavage fluid (BALF) was detected by enzyme-linked immunosorbent assay (ELISA). After injection of GDNF and its antibody into the lateral ventricle of asthmatic rats, the pulmonary function was recorded, and the levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in BALF were tested. GDNF expressions were increased significantly in the lung tissues of asthmatic rats. In the central nervous system (CNS), GDNF-positive immunoreactive substances were observed in multiple brain regions, including the medial amygdala (MeA), paraventricular nucleus (PVN), cortex, and nucleus of solitary tract (NTS). After injection of GDNF into the lateral ventricles of asthmatic rats, the symptoms of asthma and airway inflammation were significantly aggravated, which could be improved by injection of GDNF antibody into the lateral ventricles. GDNF expression is increased in the lung and brain in asthmatic rats. During an asthma attack, the increased GDNF expressions in the rat brain remarkably aggravate the asthmatic symptoms.

Exosomes Derived from Immune Cells: The New Role of Tumor Immune Microenvironment and Tumor Therapy.

Exosomes are small vesicles secreted by living cells, with a typical lipid bilayer structure. They carry a variety of proteins, lipids, RNA and other important information, play an important role in the transmission of substances and information between cells, and gradually become a marker for early diagnosis of many diseases and an important tool in drug delivery system. Immune cells are an important part of tumor microenvironment, and they can affect tumor progression by secreting a variety of immunoreactive substances. This review focuses on the effects of various immune cell-derived exosomes on tumor cells, different immune cells and other stromal cells in tumor microenvironment. Exosomes derived from different immune cells can not only reshape a pro-inflammatory microenvironment to inhibit tumor progression, but also promote tumor progression by inhibiting the killing effect of NK cells, CD8+T cells and other cells or promoting tumor cells and immunosuppressive immune cells. In addition, we also discussed that some exosomes derived from immune cells (such as DC, M1 macrophages and neutrophils) play a tumor inhibitory role after being engineered.

Zearalenone promotes follicle development through activating the SIRT1/PGC-1α signaling pathway in the ovaries of weaned gilts.

This study aimed to investigate the effect of zearalenone (ZEA) exposure on follicular development in weaned gilts, and its mechanism based on the silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) signaling pathway. A total of 32 healthy female weaned piglets (Landrace × Yorkshire × Duroc) with an average body weight of 12.39±0.24kg were randomly allotted to a basal diet supplemented with 0, 0.15, 1.5, or 3.0mg/kg ZEA for a 32-d feeding test. Blood and ovarian samples were obtained at the end of the experiment to determine serum toxin concentrations, ovarian histology, and the expressions of proliferating cell nuclear antigen (PCNA) and SIRT1/PGC-1α signaling pathway-related genes. Results showed that the vulva area, serum concentrations of ZEA, α-zearalenol and β-zearalenol, the thickness of the growing follicular layer, and the diameter of the largest growing follicles, as well as the expressions of SIRT1, PGC-1α, estrogen-related receptor α (ERRα), ATP synthase subunit beta (ATP5B), and PCNA, increased linearly (P < 0.05) with increasing dietary ZEA, whereas the thickness of the primordial follicle layer decreased linearly (P < 0.05). Immunohistochemical analysis showed that the immunoreactive substances of SIRT1 and PGC-1α in the ovaries enhanced with the increasing dietary ZEA (P < 0.05). In addition, the thickness of the growing follicular layer and the diameter of the largest growing follicle were positively correlated with relative mRNA and protein expressions of SIRT1, PGC-1α, ERRα, ATP5B, and PCNA (P < 0.05). However, the thickness of the primordial follicle layer was negatively correlated with the mRNA and protein expression of SIRT1, PGC-1α, ERRα, ATP5B, and PCNA (P < 0.05). Interestingly, the 1.5mg/kg ZEA treatment had highly hyperplastic follicles, whereas 3.0mg/kg ZEA resulted in a large number of follicular atresia, which indicated that low-dose ZEA exposure accelerated follicular proliferation, while high-dose ZEA promoted follicular atresia, although the critical value interval needs further confirmation. Results provide a theoretical basis for finding the therapeutic target of ZEA-induced reproductive disorders in weaned gilts.

L-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats.

Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P <0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P <0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P <0.05), shortened colonic length (P <0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P <0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P <0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P <0.05), DAI (P <0.05), colonic length and enterocyte apoptosis (P <0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P <0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.

The Research Progress in Immunotherapy of Tuberculosis.

Tuberculosis (TB) is a serious public health problem worldwide. The combination of various anti-TB drugs is mainly used to treat TB in clinical practice. Despite the availability of effective antibiotics, effective treatment regimens still require long-term use of multiple drugs, leading to toxicity, low patient compliance, and the development of drug resistance. It has been confirmed that immune recognition, immune response, and immune regulation of Mycobacterium tuberculosis (Mtb) determine the occurrence, development, and outcome of diseases after Mtb infection. The research and development of TB-specific immunotherapy agents can effectively regulate the anti-TB immune response and provide a new approach toward the combined treatment of TB, thereby preventing and intervening in populations at high risk of TB infection. These immunotherapy agents will promote satisfactory progress in anti-TB treatment, achieving the goal of “ultra-short course chemotherapy.” This review highlights the research progress in immunotherapy of TB, including immunoreactive substances, tuberculosis therapeutic vaccines, chemical agents, and cellular therapy.

Effects of dietary tussah immunoreactive substances on the growth performance, physiological response and serum metabolome of shrimp ( Litopenaeus vannamei )

Immune enhancers as the substitute of antibiotics for controlling the diseases and promoting animals’ growth have been frequently used in the shrimp farming. In this study, two tussah immunoreactive substances (TIS) addition ratios (0.5% and 1.0%) in Litopenaeus vannamei culture were established and the effects of TIS on the growth performance, physiological responses and serum metabolome of L. vannamei were measured. Moreover, the resistance of L. vannamei to pathogenic bacteria after the TIS addition was evaluated. The results indicated that the improvement of growth performance was more effective with the higher addition rate of TIS. The higher weight gain rate induced by TIS addition could be due to the more powerful ability of lipid metabolism for producing more energy to promote the growth of L. vannamei. The increase in survival rate of L. vannamei could contribute by the higher serum immunity and disease resistance after the TIS addition for reducing the incidence of diseases. TIS addition also significantly changed the serum metabolome of L. vannamei, leading to the increases of vitamin B6 and vitamin E production, the improvement of environmental pressure resistance and the reduction of potential pathogen infection. The findings of this study showed the potential application of TIS in the shrimp farming, which could improve the growth performance and promote the lipid metabolism and immune capacity of shrimps.

Effects of microbial community and disease resistance against Vibrio splendidus of Yesso scallop (Patinopecten yessoensis) fed supplementary diets of tussah immunoreactive substances and antimicrobial peptides

This study was conducted to investigate the effects of dietary supplementation of tussah immunoreactive substances (TIS) and antimicrobial peptides (AMPs) on microbial community and resistance against Vibrio splendidus of Yesso scallop Patinopecten yessoensis. Scallops were fed with the basal diets supplemented with TIS (T group), AMPs (A group), or both of the two (TA group). After the feeding trial, the microbial community changes were evaluated, and the challenge test with V. splendidus was conducted, as well as the immune parameters and digestive enzyme activities were determined. The results revealed that the TA group was more capable of modulating the bacterial community composition of scallops by increasing the potentially beneficial bacteria and suppressing the pathogenic microorganism during the feeding trial. After injection, the cumulative mortality rate in TA group was notably lower than others. In addition, the TA group showed better digestive and immune parameters involved in digestive capacity, phagocyte function, phosphatase-responsiveness, and oxidation resistance. These results collectively confirmed that dietary TIS and AMPs in diet could effectively modulate the microflora structure and improve disease resistance against V. splendidus of scallop, and the positive effects were more obvious when dietary supplementation of them in combination.

Immunomodulatory functions of TRPM7 and its implications in autoimmune diseases.

An autoimmune disease is an inappropriate response to one's tissues due to a break in immune tolerance and exposure to self-antigens. It often leads to structural and functional damage to organs and systemic disorders. To date, there are no effective interventions to prevent the progression of autoimmune diseases. Hence, there is an urgent need for new treatment targets. TRPM7 is an enzyme-coupled, transient receptor ion channel of the subfamily M that plays a vital role in pathologic and physiologic conditions. While TRPM7 is constitutively activated under certain conditions, it can regulate cell migration, polarization, proliferation and cytokine secretion. However, a growing body of evidence highlights the critical role of TRPM7 in autoimmune diseases, including rheumatoid arthritis, multiple sclerosis and diabetes. Herein, we present (a) a review of the channel kinase properties of TRPM7 and its pharmacological properties, (b) discuss the role of TRPM7 in immune cells (neutrophils, macrophages, lymphocytes and mast cells) and its upstream immunoreactive substances, and (c) highlight TRPM7 as a potential therapeutic target for autoimmune diseases.

The Effects of Zearalenone on the Localization and Expression of Reproductive Hormones in the Ovaries of Weaned Gilts.

This study aims to investigate the effects of zearalenone (ZEA) on the localizations and expressions of follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), gonadotropin releasing hormone (GnRH) and gonadotropin releasing hormone receptor (GnRHR) in the ovaries of weaned gilts. Twenty 42-day-old weaned gilts were randomly allocated into two groups, and treated with a control diet and a ZEA-contaminated diet (ZEA 1.04 mg/kg), respectively. After 7-day adjustment, gilts were fed individually for 35 days and euthanized for blood and ovarian samples collection before morning feeding on the 36th day. Serum hormones of E2, PRG, FSH, LH and GnRH were determined using radioimmunoassay kits. The ovaries were collected for relative mRNA and protein expression, and immunohistochemical analysis of FSHR, LHR, GnRH and GnRHR. The results revealed that ZEA exposure significantly increased the final vulva area (p < 0.05), significantly elevated the serum concentrations of estradiol, follicle stimulating hormone and GnRH (p < 0.05), and markedly up-regulated the mRNA and protein expressions of FSHR, LHR, GnRH and GnRHR (p < 0.05). Besides, the results of immunohistochemistry showed that the immunoreactive substances of ovarian FSHR, LHR, GnRH and GnRHR in the gilts fed the ZEA-contaminated diet were stronger than the gilts fed the control diet. Our findings indicated that dietary ZEA (1.04 mg/kg) could cause follicular proliferation by interfering with the localization and expression of FSHR, LHR, GnRH and GnRHR, and then affect the follicular development of weaned gilts.

Effects of dietary Lactobacillus acidophilus and tussah immunoreactive substances supplementation on physiological and immune characteristics of sea cucumber (Apostichopus japonicus)

To investigate the effects of Lactobacillus acidophilus and tussah immunoreactive substances (TIS) supplementation alone or together on the growth performance, digestive and immune-related enzyme activities, and intestinal microbiota of the sea cucumber Apostichopus japonicus, a feeding experiment was conducted. The supplementation of L. acidophilus and TIS together produced the maximum digestive and immune activities, while the minimum values occurred in the control group. No remarkable differences in enzyme activities were observed when supplemented individually. Dietary L. acidophilus and TIS in combination might be more capable of improving digestive capacity, food utilization rate, phosphatase-responsiveness and antioxidants. Furthermore, the supplementation of L. acidophilus and TIS in combination demonstrated a greater ability to optimize the intestinal microbiota of A. japonicus by increasing the potentially beneficial bacteria involved in energy production and biosynthesis, and suppressing the opportunistic pathogens. These results collectively indicated that the combined supplementation of L. acidophilus and TIS has a synergistic effect on enhancing immunity and digestibility, and could improve the intestinal microbiota structure of A. japonicus, suggesting potential for industrial feeding applications.

Effects of Lactobacillus acidophilus and tussah immunoreactive substances on disease resistance of sea cucumber ( Apostichopus japonicus ) against Vibrio splendidus

Effects of dietary Lactobacillus acidophilus and tussah immunoreactive substances (TIS) on disease resistance of sea cucumber (Apostichopus japonicus) against Vibrio splendidus were investigated. Sea cucumbers were fed with a basal diet in the control group (CK group) or were supplemented with L. acidophilus (L group), TIS (T group) or both (LT group). The challenge test with V. splendidus was conducted after the feeding trial. The cumulative mortality rate in the LT group was significantly lower, while the highest mortality occurred in the control group. The LT group showed better digestive and immune parameters compared with the other treatments. Dietary L. acidophilus and TIS in combination could effectively enhance digestive function and food uptake, depress oxidative damage and improve the organismal defence capability. Regarding gut microbiota profiles, the LT group was more capable of inhibiting potentially opportunistic pathogens and regulating intestinal flora balance compared with the other groups. The administration of L. acidophilus and TIS in the diet could effectively improve disease resistance against V. splendidus of sea cucumbers by improving the immune and digestive enzyme activities and modulating intestinal microflora, signalling a potential role in the development and production of aquatic feed.

Dose-Effect of Zearalenone on the Localization and Expression of Growth Hormone, Growth Hormone Receptor, and Heat Shock Protein 70 in the Ovaries of Post-weaning Gilts.

Zearalenone (ZEA) has an estrogen-like effect, which can injure the reproductive system of animals, causing infertility, and abortion in sows. However, the underlying mechanisms are still not clear. The objective of this study was to assess the effects of ZEA on the localization and expression of growth hormone (GH), growth hormone receptor (GHR), and heat shock protein 70 (Hsp70) in the ovaries of post-weaning gilts. Forty healthy post-weaning gilts were randomly provided one of four diets: normal basal diet supplemented with 0 (control), 0.5 (ZEA0.5), 1.0 (ZEA1.0), and 1.5 (ZEA1.5) mg ZEA/kg. Gilts were housed and fed individually for 35 days; the ovaries were collected after euthanasia for antioxidant index, relative mRNA and protein expression, and immunohistochemical analyses of GH, GHR, and Hsp70. The results revealed that the glutathione peroxidase and total superoxide dismutase levels decreased (p < 0.05), whereas the malondialdehyde level increased (p < 0.05) with increasing ZEA content. The localization pattern of GH, GHR, and Hsp70 in ZEA-treated gilts was the same as that in the control; however, the localization of yellow and brown immunoreactive substances of GH, GHR, and Hsp70 was stronger in the ZEA groups than in the control. The relative mRNA and protein expression of GHR and Hsp70 was the highest in the ZEA1.0 group (p < 0.05), whereas that of GH was the highest in the ZEA0.5 group (p < 0.05). The mRNA and protein expression of GH was lower in the ZEA1.5 group than in the control (p < 0.05). Hsp70 results showed adverse responses to increasing ZEA levels in gilt ovaries, suggesting that Hsp70 played an important role in alleviating ZEA-induced oxidative stress.

Enhanced protein phosphorylation in Apostichopus japonicus intestine triggered by tussah immunoreactive substances might be involved in the regulation of immune-related signaling pathways

The sea cucumber Apostichopus japonicus is an economically important species owing to its high nutritive and medicinal value. In order to avoid the pollution resulting from the overuse of antibiotics in A. japonicus aquaculture, various immunostimulants have been used as an alternative to improve the efficiency of A. japonicus farming. Our previous proteomic investigation has shown that several proteins participating in the immune-related physiology of A. japonicus were differentially expressed in the intestinal tissue in response to tussah immunoreactive substances (TIS). This study further explored the immunostimulation mechanism of TIS in A. japonicus. Phosphoproteomics technology was used to investigate the effect of TIS on protein phosphorylation in the intestine of A. japonicus following feeding with a TIS-supplemented diet. A total of 213 unique phosphoproteins were detected from 225 unique phosphopeptides. KEGG pathway analysis showed that majority of the phosphoproteins are involved in endocytosis, carbon metabolism and spliceosome functional group. Sixteen of the phosphoproteins exhibited differential phosphorylation in response to TIS and 12 of these were found to associate with biological functions. Of these 12 phosphoproteins, eight exhibited enhanced phosphorylation while four displayed reduced phosphorylation. These 12 proteins were further analyzed and all were found to play a role in regulating some aspects of the immune system and the growth of sea cucumbers, especially in phagocytosis, energy metabolism and disease resistance. The findings of this study could therefore shed new light on the immune pathways of sea cucumber that are affected by TIS. This could help us to better understand the underlying mechanism linked to the immunoenhancement of A. japonicus in response to TIS, one that is associated with the change in protein phosphorylation.

Interference of enzalutamide on digoxin immunoassay: A case report

Androgen sensitive prostate cancer is a malignancy that may be treated with hormonal therapy. Enzalutamide, an androgen receptor antagonist, is indicated in patients with metastatic castration-resistant prostate cancer. The drug inhibits translocation of activated androgen receptors into the cell nucleus and prevents DNA binding, thereby inducing cell death and tumour regression. Digoxin is a widely used cardiac glycoside to treat heart failure and reduce ventricular rate in atrial fibrillation. Therapeutic drug monitoring is essential due to its narrow therapeutic index. However, digoxin assays can be affected by many substances including digoxin-like immunoreactive substances (DLIS), medications such as spironolactone, canrenoate, various Chinese medicines and anti-digoxin antibody. We present a case of falsely elevated digoxin levels due to enzalutamide interaction with the chemiluminescent microparticle immunoassay.