Acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP) is the most popular analgesic/antipyretic agent in the world. APAP has been regarded as a safer drug compared with non-steroidal anti-inflammatory drugs (NSAIDs) particularly in terms of lower risks of renal dysfunction, gastrointestinal injury, and asthma/bronchospasm induction, even in high-risk patients such as the elderly, children, and pregnant women. On the other hand, the recent increasing use of APAP has raised concerns about its toxicity. In this article, we review recent pharmacological and toxicological findings about APAP from basic, clinical, and epidemiological studies, including spontaneous drug adverse events reporting system, especially focusing on drug-induced asthma and pre-and post-natal closure of ductus arteriosus. Hepatotoxicity is the greatest fault of APAP and the most frequent cause of drug-induced acute liver failure in Western countries. However, its precise mechanism remains unclear and no effective cure beyond N-acetylcysteine has been developed. Recent animal and cellular studies have demonstrated that some cellular events, such as c-jun N-terminal kinase (JNK) pathway activation, endoplasmic reticulum (ER) stress, and mitochondrial oxidative stress may play important roles in the development of hepatitis. Herein, the molecular mechanisms of APAP hepatotoxicity are summarized. We also discuss the not-so-familiar “dark side” of APAP as an otherwise safe analgesic/antipyretic drug.

Endoplasmic reticulum aminopeptidase 1 (ERAP1) is well known as a processing enzyme of antigenic peptides, which are presented to major histocompatibility complex (MHC) class I molecules in the lumen of endoplasmic reticulum. Besides antigen processing, ERAP1 performs multiple functions in various cells depending on its intracellular and extracellular localization. Of note is the secretion of ERAP1 into the extracellular milieu in response to inflammatory stimuli, which further activates immune cells including macrophages and natural killer cells. Furthermore, secreted ERAP1 enhances the expression of pro-inflammatory cytokines like tumor necrosis factor-α, interleukin-1β, and interleukin-6. Such findings indicate that ERAP1 plays a significant role in the field of innate and acquired immunity. This review summarizes the functional analyses of ERAP1 that support our current understanding of its role as more than an antigenic peptide-processing enzyme, specifically emphasizing on its secretory form.

Drugs are developed through basic studies and clinical trials. In basic studies, researchers seek drug candidates using in vitro evaluation systems and subsequently examine their effectiveness in animal experiments as in vivo evaluations. Drug candidates identified in basic studies are tested to determine whether they are effective against human diseases in clinical trials. However, most drug candidates identified in in vitro evaluation systems do not show therapeutic effects in animal experiments due to pharmacokinetics and toxicity problems in the in vivo evaluations. This review outlines drug discovery using insect disease models that allow us to perform in vivo screening. Since insects have various advantages as experimental animals such as low cost for rearing and few ethical concerns, researchers can perform large-scale in vivo screening to find drug candidates. Silkworms are insects frequently used for studies of drug efficacy, pharmacokinetics, and toxicity. Based on silkworm research, I describe the benefits of using insect disease models for drug discovery. The use of insect disease models for in vivo screening is expected to facilitate drug discovery.

Low molecular weight metabolites produced by the intestinal microbiome that have been associated with health and disease as metabolites need to be constantly absorbed from the intestinal lumen and transported to intestinal epithelial cells and blood. Polyamines, especially spermidine and spermine, are bioactive chemicals which promote autophagy and suppress inflammation. The main source of exogenous polyamines is the intestinal lumen, where they are produced by intestinal microbiome. Considering the intestinal microbiome as a manufacturing plant for bioactive substances, we developed a novel hybrid putrescine biosynthesis system strategy, in which the simultaneous intake of Bifidobacterium animalis ssp. lactis LKM512 (Bifal) and arginine (Arg) upregulates the production of the putrescine, a precursor of spermidine and spermine, in the gut by controlling the bacterial metabolism beyond its vast diversity and inter-individual differences. In a clinical trial, healthy individuals with a body mass index near the maximum “healthy” range (25 kg/m³; n = 44) were randomized to consume either normal yogurt containing Bifal and Arg (Bifal + Arg YG) or placebo (normal yogurt) for 12 weeks. The change in reactive hyperemia index determined by EndoPAT from week 0 to 12 in the Bifal + Arg YG group was significantly higher than that in the placebo group, indicating that Bifal + Arg YG intake improved vascular endothelial function. In addition, the concentrations of fecal putrescine and serum spermidine in the Bifal+ Arg YG group were significantly higher than those in the placebo group. These findings suggest that consuming Bifal + Arg YG prevents or reduces atherosclerosis risk by upregulating blood spermidine levels, which subsequently induces autophagy.

Cryptococcosis is a potentially lethal disease caused by fungal pathogens including Cryptococcus neoformans and Cryptococcus gattii species complex. These fungal pathogens live in the environment and are associated with certain tree species and bird droppings. This infectious disease is not contagious, and healthy individuals may contract cryptococcal infections by inhaling the airborne pathogens from the environment. Although cleaning a contaminated environment is a feasible approach to control environmental fungal pathogens, prophylactic immunization is also considered a promising method to regulate cryptococcal infections. We review the history of the development of cryptococcal vaccines, vaccine components, and the various forms of immune memory induced by cryptococcal vaccines.

The diversity of advanced genetic engineering techniques that have become available in recent years has enabled a more precise manipulation of genes and genomes. Among these, bacteriophage genomes stand out as an interesting target due to their dependence on a host for replication, which previously complicated their manipulation, and due as well to the many possible fields in which they can be used. In this review, we highlight recent applications for which genetically modified bacteriophages are being employed: as phage therapy in medicine, animal industries and agricultural settings; as a source of new antimicrobials; as biosensors for research, health and environmental purposes; and as genetic engineering tools themselves.

Bacillus cereus is well known as a causative agent of food poisoning but it also causes bacteremia and endophthalmitis in nosocomial infections. However, as an environmental bacterium that lives in soil, it is often treated as simple contamination by hospitals. In recent years, highly pathogenic B. cereus strains that are similar to Bacillus anthracis have been detected in hospitals. The B. cereus sphingomyelinase contributes to its pathogenicity, as do sphingomyelinases produced by Staphylococcus aureus, Pseudomonas aeruginosa, Helicobacter pylori, and B. anthracis. Highly pathogenic B. cereus produces a large amount of sphingomyelinase. In this review, we describe the regulation of sphingomyelinase expression through the PlcR–PapR system, the pathogenicity of bacterial sphingomyelinases, and their potential as therapeutic drug targets.

The space habitat is a confined environment with a simple ecosystem that consists mainly of microorganisms and humans. Changes in the pathogenicity and virulence of bacteria, as well as in astronauts’ immune systems, during spaceflight may pose potential hazards to crew health. To ensure microbiological safety in the space habitat, a comprehensive analysis of environmental microbiota is needed to understand the overall microbial world in this habitat. The resulting data contribute to evidence-based microbial monitoring, and continuous microbial monitoring will provide information regarding changes in bioburden and microbial ecosystem; this information is indispensable for microbiological management. Importantly, the majority of microbes in the environment are difficult to culture under conventional culture conditions. To improve understanding of the microbial community in the space habitat, culture-independent approaches are required. Furthermore, there is a need to assess the bioburden and physiological activity of microbes during future long-term space habitation, so that the “alert” and/or “action” level can be assessed based on real-time changes in the microbial ecosystem. Here, we review the microbial monitoring in the International Space Station–Kibo, and discuss how these results will be adapted to the microbial control in space habitation and pharmaceutical and food processing industries.

Pterostilbene (PTE) has inhibitory effect on a wide array of tumors. However, the therapeutic potential of PTE in renal cancer cells and the underlying mechanisms have not been evaluated. In this study, the aim is to demonstrate the growth inhibitory and the underlying mechanisms of PTE on human renal cell carcinoma (RCC) cells in vitro. By cell viability, cell morphology and colony formation assays, we found that PTE significantly suppressed the proliferation of RCC cells, while had little toxicity to the normal renal cell line HK-2. Flow cytometry assay revealed that PTE potently induced the apoptosis of RCC cells in a concentration-dependent manner, which was also testified by up-regulation of the pro-apoptosis-related protein (Cyto C, Bad, Bak, Bax, Cleaved-caspase 3, Cleaved-caspase 9, Cleaved-poly(ADP-ribose)polymerase (PARP)) and down-regulation of the anti-apoptosis-related protein Bcl-2. Moreover, cell cycle being arrested in S phase and down-regulation of p-Akt and p-extracellular signal-regulated kinase (ERK)1/2 were observed following treatment with PTE in RCC cells, indicating that PTE exerted remarkable anti-tumor activity in RCC cells possibly via cell cycle arrest and inactivation of Akt and ERK1/2 signaling pathways. Immunofluorescence analysis of γH2AX and detecting the expression levels of γH2AX, proliferating cell nuclear antigen (PCNA) and Rad51 by Western blot showed that PTE induced the DNA damages response in RCC cells. Taken together, the results of the present study demonstrated that PTE was a potential preventive and therapeutic agent for human renal cell carcinoma.

Bleeding is a life-threating side effect of thromboprophylaxis with fondaparinux sodium (FPX) injection. The purpose of this retrospective study was to assess the risk factor for bleeding-related event following thromboprophylaxis with FPX after total knee arthroplasty (TKA) or total hip arthroplasty (THA). Adult patients undergoing TKA or THA at a single university hospital were administered FPX for thromboprophylaxis by subcutaneous injection of 1.5 or 2.5 mg per day. The risk factor for bleeding-related event was identified by propensity score-adjusted multivariate logistic analysis, and survival analysis was performed retrospectively in consideration of the identified risk factors. Two hundred and twenty-six patients who underwent TKA (n = 62) or THA (n = 164) were enrolled. Anaemia on postoperative day (POD) 1 was identified as a risk factor for bleeding-related event (odds ratio: 3.75, 95% confidence interval: 1.02–24.5, p = 0.04). Eighty of 226 patients were selected using a propensity score matching and patients with anaemia on POD1 in this population had a significantly higher incidence of bleeding-related event than those without anaemia (p = 0.0016, Ghen–Breslow–Wilcoxon test; p = 0.0015, log-rank test). These results suggest that anaemia on POD1 is an independent risk factor for bleeding-related event following thromboprophylaxis with FPX after TKA or THA.

Accumulating evidence suggests that the inhibition of neuroinflammation is a potential target for therapeutic or preventive strategies for Alzheimer’s disease (AD). Chemerin has attracted particular attention for its role in the regulation of inflammation. In addition, amyloid β_1–42 (Aβ_1–42) can interact with chemokine-like receptor 1 (CMKLR1), the receptor for chemerin, and induce microglial chemotaxis. Meanwhile, CMKLR1 is expressed in the brain, and both chemerin and Aβ_1–42 share the same receptor. Thus, we hypothesized that chemerin (C9), a chemerin-derived nonapeptide, may have the potential to ameliorate Aβ_1–42 mediated AD disease progression. The results showed that an intracerebroventricular (i.c.v.) injection of C9 (8 µg/kg) facilitated memory formation and improved memory retention, as evidenced by the results of both the novel object recognition test (NOR) and object location recognition (OLR) tasks. These memory-enhancing effects of C9 were also observed after C9 (2 µg/kg) was infused into the hippocampus. Moreover, we found that treatment with C9 reversed the deficits in memory and learning ability induced by oligomeric Aβ_1–42. Meanwhile, C9 also significantly inhibited Aβ_1–42-induced increases in the levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the hippocampus. The same results were obtained for Western blotting and enzyme-linked immunosorbent assay (ELISA) experiments. Finally, we observed that C9 did not affect locomotor activity, suggesting that its improvement of memory is not a false positive induced by hypolocomotion. In conclusion, C9 may facilitate memory formation, prolong memory retention, and ameliorate Aβ_1–42-induced memory impairment, suggesting that C9 may potentially represent a novel strategy for the treatment of AD.

Thiamine hydrochloride has been suggested as a natural, safe yet effective alternative for chemical insect repellents. However, there is a demand for a reassessment of the minimum required dose that is sufficient to perform a topical repellency on the human skin. Therefore, the purpose of the current work is to establish a dose–response curve from which the effective dose (ED) is calculated. A series of increasing concentrations of thiamine hydrochloride were applied to the forearm of adult volunteers, the number of bites was counted and the percent repellency calculated accordingly. Data of percent repellency were converted to probit values which were plotted against log doses. A linear relation was obtained from the dose–response curve with an r² = 0.958. Statistical validation of the equation was tested through linear regression analysis, where the slope and intercept were found significant from zero. No significant difference was shown between observed and expected responses (p > 0.05). ED 50 and 99.9% were computed from the linear equation and found to be 4.57 and 344 mg, respectively. This finding can be supported by future works in which a proper formulation of thiamine hydrochloride in the respective doses would be presented. One can get prolonged safe protection against insect bites.

According to the data, there are 387 million people with diabetes in the world, and the number of people with diabetes is expected to reach 600 million by 2035 (Nature Reviews Endocrinology, 14, 2018, Zheng et al.). At present, there are nearly 110 million diabetic patients in China, the incidence of which is increasing (Diabetologia, 61, 2018, Ma). Islet β cell apoptosis and proliferation is an important basis for the occurrence and development of diabetes. It has been reported that enhancing the activity of incretin–cAMP signaling pathway can also promote islet β cell proliferation, reduce β cell apoptosis and promote insulin secretion (Diabetologia, 59, 2016, Iida et al.). Tibetan medicine Triphala (THL) is a traditional national medicine, it plays a good role in anti-fatigue, antioxidation, prevention and treatment of polycythemia at high altitude. Research have shown that it can reduce blood glucose in patients with diabetes and inhibit the activity of glucosidase in the intestines (The Journal of Alternative and Complementary Medicine, 23, 2017, Peterson et al.). After the diabetic Wistar rat model induced by Streptozocin (STZ) was successfully duplicated, the positive drug sitagliptin tablet and THL were given and the changes of body weight and blood glucose were measured. After 6 weeks, the expression of related factors in serum and pancreas was observed. Compared with the model group, in the treatment group, blood glucose decreased, body weight increased, incretin–cAMP signaling pathway related factors glucose-dependent insulin-promoting polypeptide (GIP), glucagon-like peptide-1 (GLP-1), GLP-1R, cAMP, P-protein kinase A (PKA), AKT were up-regulated, insulin secretion was increased, liporing protein interaction protein (TXNIP) expression was down-regulated. In addition, in the treatment group, the degree of islet atrophy was alleviated and the number of islet β cells increased. This study shows that THL may enhance the activity of incretin–cAMP signal pathway and affect the proliferation and apoptosis of islet β cells, so as to achieve the effect of anti-diabetes.

Autophagy can remodel skeletal muscle in response to exercise. However, excessive autophagy can have adverse effects on skeletal muscle. Although Rhodiola crenulata (R. crenulata) is thought to regulate autophagy, its active ingredients and mechanisms of action remain unclear. In this study, molecular docking and network pharmacology were used to screen for autophagy-related targets of R. crenulata. Subsequently, protein–protein interaction (PPI) analysis was used to find the relationships between the inverse docking targets and autophagy-related targets and therefore highlight the key targets. And then the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database was recruited to explain the functions and enrichment pathways of the target proteins. Finally, the potential targets were validated by immunohistochemistry of a mouse model of exhaustive exercise-induced skeletal muscle injury. We found a network of 15 major constituents of R. crenulata with 30 autophagy-related and 105 inverse-docking targets by molecular docking and network pharmacology. The results of PPI analysis indicated that 16 inverse-docking targets interacted 8 autophagy-related proteins. Further pathway analysis showed that R. crenulata could regulate exercise-induced skeletal muscle autophagy through mammalian target of rapamycin (mTOR), AMP activated protein kinase (AMPK) and Forkhead box protein O (FoxO). The results of our animal experiments indicated that R. crenulata could suppress the expression of Ubiquitin-like protein ATG12 (ATG12), Beclin-1 (BECN1), and Serine/threonine-protein kinase ULK1 (ULK1), while increasing the expression of MTOR, NAD-dependent protein deacetylase sirtuin-1 (SIRT1), and Microtubule-associated protein tau (MAPT). In conclusion, this study demonstrated that R. crenulata may protect skeletal muscle injury induced by exhaustive exercise via regulating the mTOR, AMPK, and FoxO singling pathway.

This study focused on the differential metabolomic effects between water extracts of Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata in rats. The extracts were subsequently administered for 28 d. Serum biochemical indicators were tested, hematoxylin–eosin staining and immunohistochemistry staining were used to detect histopathological changes in the livers. Ultra-performance LC/quadrupole time-of-flight mass spectrometry was used to detect the changes in endogenous metabolites. Finally, we performed detailed analysis of the changes in metabolic pathways. Hematoxylin–eosin staining and immunohistochemistry staining results indicated that the water extracts of Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata had mild liver injury effect. Fifty-two differential endogenous biomarkers were confirmed as potential biomarkers between Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata groups. In the positive ion mode, the biomarkers included 31 Phosphatidyl cholines (PCs), six lysoPCs, and ceramide. In the negative ion mode, 12 biomarkers were confirmed, including glycodeoxycholic acid, chenodeoxycholic acid, and deoxycholic acid, etc. In Hydrophilic Interaction Liquid Chromatography (HILIC) mode, nine biomarkers were confirmed, including niacinamide, L-palmitoylcarnitine, and butyrylcarnitine, etc. Using MetaboAnalyst 4.0, six related metabolic pathways, including taurine and hypotaurine metabolism, sphingolipid metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, arginine and proline metabolism, and tryptophan metabolism and primary bile synthesis, were confirmed as the most differential pathways between the Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata groups.

We examined the influence of liver disease on the absorption from the liver surface of fluorescein isothiocyanate (FITC)-dextran 10 (FD-10, MW: 11000) and several marker compounds with different molecular weights. The purpose of this study was to determine the feasibility of liver surface application of macromolecular compounds in the disease state. We used male Wistar rats treated with carbon tetrachloride (CCl₄) or D-galactosamine (GAL). FD-10 and other marker compounds were applied to the liver surface using a cylindrical diffusion cell in liver-intoxicated rats. The blood, bile, urine, and the remaining solution in the diffusion cell were collected for assay. FD-10 was absorbed by first-order kinetics from the liver surface in the liver-intoxicated rat models. The calculated rate constant k_a values in the normal, CCl₄ and GAL groups were 0.000965, 0.00125 and 0.00104 min⁻¹, respectively. Increased absorption of FITC-dextrans in the liver-intoxicated rats was observed. In both CCl₄ and GAL groups, an inverse relationship was observed between the molecular weight and k_a from the rat liver surface of the marker compounds. The limits of the molecular weight absorbed from the liver surface were extrapolated to be 71200, 135000, and 105000 in the normal, CCl₄, and GAL groups, respectively. In conclusion, increased absorbability from the rat liver surface indicates that liver surface application for liver targeting of macromolecules in the diseased state is indeed feasible. Therefore, our findings can support further research on liver surface application of drugs under liver disease.

Colony stimulating factor 1 (CSF1) receptor (CSF1R) is a receptor protein-tyrosine kinase specifically expressed in monocyte-lineage cells, such as monocytes and macrophages. In this study, we characterized the pharmacological properties of an azetidine compound, JTE-952 ((2S)-3-{[2-({3-[4-(4-cyclopropylbenzyloxy)-3-methoxyphenyl]azetidine-1-yl}carbonyl)pyridin-4-yl]methoxy}propane-1,2-diol), which is a novel CSF1R tyrosine kinase inhibitor. JTE-952 potently inhibited human CSF1R kinase activity, with a half maximal inhibitory concentration of 11.1 nmol/L, and inhibited the phosphorylation of CSF1R in human macrophages and the CSF1-induced proliferation of human macrophages. It also inhibited human tropomyosin-related kinase A activity, but only at concentrations 200-fold higher than that required to inhibit the activity of CSF1R in inducing the proliferation of human macrophages. JTE-952 displayed no marked inhibitory activity against other kinases. JTE-952 potently inhibited lipopolysaccharide-induced proinflammatory cytokine production by human macrophages and in whole blood. JTE-952 (≥3 mg/kg given orally) also significantly attenuated the CSF1-induced priming of lipopolysaccharide-induced tumor necrosis factor-alpha production in mice and arthritis severity in a mouse model of collagen-induced arthritis. Taken together, these results indicate that JTE-952 is an orally available compound with potent and specific inhibitory activity against CSF1R, both in vitro and in vivo. JTE-952 is a potentially clinically useful agent for various human inflammatory diseases, including rheumatoid arthritis.

Benzoylaconitine (BAC), the main hydrolysate of aconitine, is a lower toxic monoester type alkaloid considered as the pharmacodynamic constituent in Aconitum species. In this study, the effects and mechanisms of BAC on production of inflammatory cytokines interleukin (IL)-6 and IL-8 were investigated in IL-1β-stimulated human synovial SW982 cells. The SW982 cells were incubated with BAC (0, 5 and 10 µM) before stimulating with IL-1β (10 ng/mL). The results revealed that BAC suppressed gene and protein expression of IL-6 and IL-8 induced by IL-1β. BAC decreased activation of mitogen-activated protein kinase (MAPK) and phosphorylation of Akt. BAC also inhibited degradation of inhibitor of kappaB (IκB)-α, phosphorylation and nuclear transposition of p65 protein. The results demonstrate that BAC exerts an anti-inflammatory effect dependent on MAPK, Akt and nuclear factor-κB (NF-κB) pathways in human synovial cells stimulated with IL-1β, suggesting that BAC may be exploited as a potential therapeutic agent for rheumatoid arthritis (RA) treatment.

Central nervous system (CNS) agents cause fractures among the elderly, but fracture risks of a wide range of CNS agent classes have not been analyzed in a study with the same population and definitions of variables. This study aimed to estimate the degree of fragility fracture risk of a wide range of CNS agent classes in elderly Japanese people. A case-crossover design study, with a case window and three control windows of 3 d each, as well as longer windows up to 15 d, was conducted among opioid non-users who lived without hospitalization for ≥13 months and incurred fragility fractures at ≥65 years of age, using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Conditional logistic regression estimated adjusted odds ratios (ORs) of CNS agent classes for fragility fractures for groups including and excluding users of pro re nata CNS agents (PRN-CNS agents) and for windows of 3–15 d. Antiepileptic agents had the highest adjusted ORs, 2.4 (95% confidence interval 2.3–2.5) for the group including PRN-CNS agent users (n = 446101). The next-highest classes were anti-dementia agents 1.5 (1.5–1.6), antipsychotics 1.5 (1.4–1.6), anti-Parkinson agents 1.3 (1.2–1.5), and antidepressants 1.1 (1.1–1.2). Similar ORs were found when PRN-CNS agent users were excluded (n = 352828), and slightly higher ORs were found for longer windows, with almost the same order of classes. Elderly individuals who use antiepileptic agents or a combination of antiepileptic agents and CNS agent classes with the next-highest ORs should be carefully monitored.

Oxaliplatin is a first-line clinical drug in cancer treatment and its side effects of peripheral neuropathic pain have also attracted much attention. Neuroinflammation induced by oxidative stress-mediated activation of nuclear factor-kappa B (NF-κB) plays an important role in the course. Current studies have shown that curcumin has various biological activities like antioxidant, anti-inflammatory, antitumor and so on, while few studies were conducted about its role in oxaliplatin-induced peripheral neuropathic pain. The aim of this study is to verify the mechanism of curcumin alleviating oxaliplatin-induced peripheral neuropathic pain. Intraperitoneal injection with oxaliplatin (4 mg/kg body weight) was given to the rats twice a week and last for four weeks to establish the model rats. Gavage administration of curcumin (12.5, 25, and 50 mg/kg body weight, respectively) was conducted for consecutive 28 d to explore the effects and potential mechanism. Our results showed that curcumin administration could increase mechanical withdrawal threshold and decrease the paw-withdrawal times of cold allodynia significantly; meanwhile, motor nerve conduction velocity (MNCV) and sense nerve conduction velocity (SNCV) were both increased and the injured neurons of the spinal cord were repaired. In addition, curcumin administration increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and reduced malondialdehyde (MDA). Moreover, the curcumin operation inhibited the activated of NF-κB and level of inflammatory factors like tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). In conclusion, these findings suggested that curcumin could alleviate oxaliplatin-induced peripheral neuropathic pain; the mechanism might be inhibiting oxidative stress-mediated activation of NF-κB and mitigating neuroinflammation.

Galectins are a group of animal lectins characterized by their specificity for β-galactosides. Of these, galectin-2 (Gal-2) is predominantly expressed in the gastrointestinal tract. In the current study, we used a mouse gastric mucous fraction to investigate whether Gal-2 is secreted from epithelial cells and identify its potential ligands in gastric mucus. Gal-2 was detected in the mouse gastric mucous fraction and could be eluted from it by the addition of lactose. Affinity chromatography using recombinant mouse galectin-2 (mGal-2)-immobilized adsorbent and subsequent LC-MS/MS identified MUC5AC, one of the major gastric mucin glycoproteins, as a potential ligand of mGal-2. Furthermore, MUC5AC was detected in the mouse gastric mucous fraction by Western blotting, and recombinant mGal-2 was adsorbed to this fraction in a carbohydrate-dependent manner. These results suggested that Gal-2 and MUC5AC in mouse gastric mucus interact in a β-galactoside-dependent manner, resulting in a stronger barrier structure protecting the mucosal surface.