Risk factors for scabies in hospital: a systematic review.

BACKGROUND: Annually, 175.4 million people are infected with scabies worldwide. Although parasitic infections are important nosocomial infections, they are unrecognized compared to bacterial, fungal, and viral infections. In particular, nonspecific cutaneous manifestations of scabies lead to delayed diagnosis and frequent nosocomial transmission. Hospital-based studies on the risk factors for scabies have yet to be systematically reviewed. METHODS: The study followed the PRISMA guidelines and was prospectively registered in PROSPERO (CRD42023363278). Literature searches were conducted in three international (PubMed, Embase, and CINAHL) and four Korean (DBpia, KISS, RISS, and Science ON) databases. We included hospital-based studies with risk estimates calculated with 95% confidence intervals for risk factors for scabies infection. The quality of the studies was assessed using the Joanna Briggs Institute critical appraisal tools. Two authors independently performed the screening and assessed the quality of the studies. RESULTS: A total of 12 studies were included. Personal characteristics were categorized into demographic, economic, residential, and behavioral factors. The identified risk factors were low economic status and unhygienic behavioral practices. Being a patient in a long-term care facility or institution was an important factor. Frequent patient contact and lack of personal protective equipment were identified as risk factors. For clinical characteristics, factors were categorized as personal health and hospital environment. People who had contact with itchy others were at higher risk of developing scabies. Patients with higher severity and those with a large number of catheters are also at increased risk for scabies infection. CONCLUSIONS: Factors contributing to scabies in hospitals range from personal to clinical. We emphasize the importance of performing a full skin examination when patients present with scabies symptoms and are transferred from settings such as nursing homes and assisted-living facilities, to reduce the transmission of scabies. In addition, patient education to prevent scabies and infection control systems for healthcare workers, such as wearing personal protective equipment, are needed.

PAR2-mediated cellular senescence promotes inflammation and fibrosis in aging and chronic kidney disease.

Cellular senescence contributes to inflammatory kidney disease via the secretion of inflammatory and profibrotic factors. Protease-activating receptor 2 (PAR2) is a key regulator of inflammation in kidney diseases. However, the relationship between PAR2 and cellular senescence in kidney disease has not yet been described. In this study, we found that PAR2-mediated metabolic changes in renal tubular epithelial cells induced cellular senescence and increased inflammatory responses. Using an aging and renal injury model, PAR2 expression was shown to be associated with cellular senescence. Under in vitro conditions in NRK52E cells, PAR2 activation induces tubular epithelial cell senescence and senescent cells showed defective fatty acid oxidation (FAO). Cpt1α inhibition showed similar senescent phenotype in the cells, implicating the important role of defective FAO in senescence. Finally, we subjected mice lacking PAR2 to aging and renal injury. PAR2-deficient kidneys are protected from adenine- and cisplatin-induced renal fibrosis and injury, respectively, by reducing senescence and inflammation. Moreover, kidneys lacking PAR2 exhibited reduced numbers of senescent cells and inflammation during aging. These findings offer fresh insights into the mechanisms underlying renal senescence and indicate that targeting PAR2 or FAO may be a promising therapeutic approach for managing kidney injury.

Adipose Tissue Macrophage Polarization Is Altered during Recovery after Exercise: A Large-Scale Flow Cytometric Study.

We performed a large-scale flow cytometric analysis to determine whether M1 macrophage (M1Ø) and M2 macrophage (M2Ø) polarization in white adipose tissue (WAT) was altered immediately after exercise. Additionally, we comprehensively investigated the effects of obesity, exercise intensity, and recovery time on macrophage polarization in WAT. A single exercise bout of various intensities (ND, non-exercise control; -LIE, low-intensity exercise; -MIE, mid-intensity exercise; -HIE, high-intensity exercise) was performed by normal mice (ND) and obese mice (HFD). To confirm differences in M1Ø/M2Ø polarization in WAT based on the recovery time after a single exercise bout, WAT was acquired at 2 h, 24 h, and 48 h after exercise (total n = 168, 7 mice × 4 groups × 2 diets × 3 recovery time). The harvested WAT was immediately analyzed by flow cytometry, and macrophages were fluorescently labeled using F4/80, as well as M1Ø with CD11c and M2Øs with CD206. After a single bout of exercise, the M2Ø/M1Ø polarization ratio of WAT increases in both normal and obese mice, but differences vary depending on recovery time and intensity. Regardless of obesity, our findings showed that there could be a transient increase in M1Ø in WAT over a short recovery time (24 h) post-exercise (in ND-MIE, ND-HIE, and HFD-HIE). Furthermore, it was observed that the greater the exercise intensity in obese mice, the more effective the induction of M2Ø polarization immediately after exercise, as well as the maintenance of high M2Ø polarization, even after a prolonged recovery time.

Correction: The amoebicidal effect of Torreya nucifera extract on Acanthamoeba lugdunensis.

[This corrects the article DOI: 10.1371/journal.pone.0281141.].

Extract of Torreya nucifera Pericarps Exhibits a Parasiticidal Effect on the Nematode Parasite, Trichinella spiralis.

Benzimidazole derivatives can effectively treat nematode parasitic infections; however, some derivatives demand distinct administrative strategies depending on plasma concentration and patient conditions. Numerous studies have examined the potential of natural extracts to exert parasiticidal activity with minimal side effects. Herein, we examined the potential parasiticidal effects of Torreya nucifera extract. The pericarps of T. nucifera were extracted with methanol, dried, and the pellet was dissolved in hot water (Tn-Phw). We designed four individual mouse experiments to clarify the prophylactic and therapeutic effects of Tn-Phw on Trichinella spiralis infection. Also, 100 L1 larvae were isolated and treated with Tn-Phw (10 mg/mL) in vitro to confirm the killing effect. Furthermore, we microscopically examined the morphology of L1 larvae to confirm the parasite-killing effect and analyzed the morphology using a scanning electron microscope (SEM). The expression of three molting-related genes was confirmed to determine whether Tn-Phw induced morphological changes in L1 larvae. Following treatment with Tn-Phw, L1 larvae death was observed after 16 h. Following SEM examination, the healthy muscle larvae showed striated ridges and wrinkles; this was not observed in extract-treated muscle larvae. Expression levels of the three molting-related genes did not differ between the Tn-Phw-treated and control groups. T. spiralis-infected mice pretreated with Tn-Phw showed significantly reduced muscle larva infection when compared with control mice. In all experiments, treatment with Tn-Phw afforded preventive and therapeutic effects against T. spiralis infection and parasitism. Natural substances against nematode parasites could be developed as therapeutic agents with few side effects and enhanced parasiticidal efficacy.

Evaluating the activity of N-89 as an oral antimalarial drug.

Despite the recent progress in public health measures, malaria remains a troublesome disease that needs to be eradicated. It is essential to develop new antimalarial medications that are reliable and secure. This report evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo. After a single oral dose (75 mg /kg) of N-89, its pharmacokinetic parameters were measured, and t1/2 was 0.97 h, Tmax was 0.75 h, and bioavailability was 7.01%. A plasma concentration of 8.1 ng/ml of N-89 was maintained for 8 h but could not be detected at 10 h. The dose inhibiting 50% of parasite growth (ED50) and ED90 values of oral N-89 obtained following a 4-day suppressive test were 20 and 40 mg/kg, respectively. Based on the plasma concentration of N-89, we evaluated the antimalarial activity and cure effects of oral N-89 at a dose of 75 mg/kg 3 times daily for 3 consecutive days in mice harboring more than 0.5% parasitemia. In all the N-89- treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days. Additionally, administering oral N-89 at a low dose of 50 mg/kg was sufficient to cure mice from day 6 without parasite recurrence. This work was the first to investigate the pharmacokinetic characteristics and antimalarial activity of N-89 as an oral drug. In the future, the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated.

Antimalarial effect of synthetic endoperoxide on synchronized Plasmodium chabaudi infected mice.

The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED50 values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

Pioneer Use of Antimalarial Transdermal Combination Therapy in Rodent Malaria Model.

We have previously reported 1,2,6,7-tetraoxaspiro [7.11]nonadecane (N-89) as a promising antimalarial compound. In this study, we evaluated the effect of transdermal therapy (tdt) of N-89 in combination (tdct) with other antimalarials as an application for children. We prepared ointment formulas containing N-89 plus another antimalarial drug, specifically, mefloquine, pyrimethamine, or chloroquine. In a 4-day suppressive test, the ED50 values for N-89 alone or combined with either mefloquine, pyrimethamine, or chloroquine were 18, 3, 0.1, and 3 mg/kg, respectively. Interaction assays revealed that N-89 combination therapy showed a synergistic effect with mefloquine and pyrimethamine, but chloroquine provoked an antagonistic effect. Antimalarial activity and cure effect were compared for single-drug application and combination therapy. Low doses of tdct N-89 (35 mg/kg) combined with mefloquine (4 mg/kg) or pyrimethamine (1 mg/kg) gave an antimalarial effect but not a cure effect. In contrast, with high doses of N-89 (60 mg/kg) combined with mefloquine (8 mg/kg) or pyrimethamine (1 mg/kg), parasites disappeared on day 4 of treatment, and mice were completely cured without any parasite recurrence. Our results indicated that transdermal N-89 with mefloquine and pyrimethamine provides a promising antimalarial form for application to children.

The amoebicidal effect of Torreya nucifera extract on Acanthamoeba lugdunensis.

As the number of contact lens users increases, contact lens induced corneal infection is becoming more common. Acanthamoeba keratitis (AK) is a type of those which is caused by Acanthamoeba species, and may cause severe ocular inflammation and visual loss. We evaluated whether Torreya nucifera (T. nucifera) extract has an anti-amoebic effect and studied its mechanism of action on Acanthamoeba lugdunensis (A. lugdunensis). Cell viability was tested using the alamarBlue™ method, and the cell death mechanism was confirmed using the Tali® Apoptosis Kit. The SYTOX® Green assay was performed to check the plasma membrane permeability. The JC-1 dye was used to measure the mitochondrial membrane potential. A CellTiter-Glo® Luminescent Assay was used to measure the adenosine-triphosphate (ATP) level. Morphological changes in the mitochondria were examined by transmission electron microscopy (TEM). Cystic changes and a decrease in cell viability after treatment with T. nucifera were observed. Both apoptotic and necrotic cells were found in the Tali® Apoptosis assay. There was no significant difference in plasma membrane permeability between the control and T. nucifera treated groups. The collapse of the mitochondrial membrane potential and reduced ATP level in A. lugdunensis was confirmed in the groups treated with T. nucifera. Structural damage to the mitochondria was observed on TEM in the groups treated with T. nucifera. T. nucifera showed an anti-amoebic effect on A. lugdunensis, by inducing the loss of mitochondrial membrane potential. Thus, it could be a future therapeutic agent for AK.

Changes in aquaporins expression due to acute water restriction in naturally aging mice

Aquaporins (AQPs) are water channels in the cell membrane that regulate osmosis in response to rapid changes in intracellular and extracellular fluid concentration caused by extrinsic factors. While there are so many studies on the association of AQPs with muscular atrophy, sarcopenia, and Duchenne muscular dystrophy (DMD), the expression of AQP has not been verified in naturally aging mice or humans. Notably, due to the characteristics of AQPs, the difference in function cannot be evaluated without extrinsic factors such as acute water restriction. The purpose of this study was to investigate the changes in AQPs expression and function due to natural aging under acute water restriction conditions in aging mice. The expression of AQP4 was shown to decrease with aging similar to previous studies. However, for the first time, this study results confirmed that AQP1 expression increased in aging mice. In addition, the expression of Aqp1 decreased in the acute water restricted group compared to the control group after acute water restriction in aging mice. These results suggest that although the expression of AQP1 increases with aging, its function is reduced. We also confirmed that overexpression of Aqp1 can inhibit myotube differentiation and that knockdown can promote myotube differentiation through in vitro experiments. In conclusion, based on our results, we suggest that the AQP1 is an important factor in sarcopenia caused by natural aging accompanied by chronic dehydration. (AU)

Toll-like receptor 2 mediates Acanthamoeba-induced allergic airway inflammatory response in mice.

BACKGROUND: Repeated intranasal exposure to Acanthamoeba has been revealed to induce allergic airway inflammatory responses in mice. Based on the role of toll-like receptors (TLRs) in the pathogenesis of allergic asthma, TLRs form a link between innate and adaptive immune responses, and play an important role in the activation of various cells in the innate immune system. METHODOLOGY/PRINCIPAL FINDINGS: To determine the TLRs that are related to these immune responses, we assessed the expression levels of inflammation-related genes in mouse lung epithelial (MLE)-12 cells treated with excretory-secretory proteins (ES-P) of the Acanthamoeba strain (KA/E2) with or without the TLR antagonists. The expression levels of inflammation-related genes, such as eotaxin, TARC, macrophage-derived chemokine (MDC), and TSLP, in the TLR2 and TLR9 antagonist treatment groups were decreased, compared to those in the ES-P alone or other TLR antagonist treatment groups. In particular, a greater decrease in the relevant gene expression levels was found in the TLR2 antagonist treatment group than in the TLR9 antagonist treatment group. Allergic airway inflammation was evaluated in the wild-type (WT) and TLR2 knockout (KO) groups following KA/E2 exposure. Based on the results, allergic airway inflammatory responses (airway resistance value, inflammatory cell infiltration, Th2-related cytokine expression, mucin production, and metaplasia of lung epithelial cells and goblet cells) by KA/E2 were reduced in the TLR2 KO groups. In addition, TLR2 knockout BMDCs displayed lower activation of surface markers owing to ES-P stimulation than normal BMDCs, and KA/E2 ES-P-treated TLR2-depleted BMDCs produced fewer Th2 cytokine-expressing cells from naïve T cells than WT BMDCs. When ES-P was administered after primary lung cells were obtained from WT and TLR2 KO mice, the expression levels of inflammation-related genes were found to be significantly decreased in TLR2 KO cells compared to those in WT cells. CONCLUSIONS: These results suggest that TLR2 is involved in lung inflammatory response activation in KA/E2 intranasal infection, especially in airway tissue.

Formulation and evaluation of the antimalarial N-89 as a transdermal drug candidate.

The discovery of new effective and safe antimalarial drugs is mandatory. In this report, we formulate and evaluate transdermal (td) 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the Plasmodium berghei rodent malaria parasite in vivo model. The selected solvent for the ointment type of td N-89 was polyethylene glycol (PEG) [PEG400:PEG 4000 = 8:1 (v/w)]. We tested different application areas of 4, 6, and 8 cm2 on the shaved backs of mice. Pharmacokinetic (PK) analysis of N-89 parameters after a single 4 cm2 transdermal application revealed that the Tmax was 2 h, the T1/2 was 1.9 h, and the AUC was 1951.1 ng.h/mL. More than 10 ng/mL of plasma concentration was maintained for 12 h. The ED50 values for the 4, 6, and 8 cm2 application areas in a 4-day suppressive test were 18.9, 25.1, and 26.8 mg/kg, respectively. We additionally tested the cure effect of td N-89 in mice at a dose of 60 mg/kg, twice daily for 4 days at 0.2% parasitemia. Parasites disappeared following day 7 post-treatment in all td N-89 treated groups. Mice were cured without any parasite recurrence or dermal irritation. In conclusion, this study determined for the first time the PK parameters and effect of a new ointment type of td N-89. This suggests that transdermal treatment with N-89 is an effective and safe alternative route for the treatment of malaria, especially in children.

Effect of parasitic infection on muscular function of dystrophin gene (Dmd) deficient mouse.

BACKGROUND: Previous studies have reported many cases of Trichinella spiralis (T. spiralis) infection in normal skeletal muscle but there is little research on T. spiralis infection in abnormal muscle tissue. OBJECTIVE: To identify the effect of T. spiralis infection on muscular dystrophy, this study compared aspects of infection between normal (C57BL/10) and dystrophin-deficient Duchenne muscular dystrophy (DMD) mdx mice. METHOD: Infection rate was found to be lower in mdx mice than in C57BL/10 mice at early stages of infection; however, infection and inflammation in mdx mice persisted at later stages of infection while the infection rate and inflammation in C57BL/10 mice decreased gradually. The inflammation area was proportional to the degree of infection in both groups. Muscle strength was measured by the time of latency to fall in the wire-hanging test. Hanging time was shorter in the infected group than in the uninfected group in both C57BL/10 and mdx mice. RESULTS: Muscle strength was also reduced in mdx mice compared with C57BL/10 mice in both the un-infected and infected groups. The muscle intracellular cytokines TGF-ß and IL-6 were continuously expressed from early stage to late-stage infection. IL-10 was strongly expressed at the early stage of infection but decreased as the infection progressed. TNF-α expression remained stable from early to late-stage infection in mdx mice, while TNF-α was elevated only during early-stage infection in C57BL/10 mice. The degree of muscle damage was significantly higher in mdx mice than in C57BL/10 mice because of the high level of serum creatine kinase (CK). CONCLUSION: These results suggest that mdx mice continued in infection and inflammation until the late stages of disease, which was in contrast to the C57BL/10 mice that recovered to some extent in the late stage of infection. In addition, that dystrophin-deficient mice are not suitable for T. spiralis infection compared to normal mice, and the degree of inflammation may be worse in mdx mice.

Changes in aquaporins expression due to acute water restriction in naturally aging mice.

Aquaporins (AQPs) are water channels in the cell membrane that regulate osmosis in response to rapid changes in intracellular and extracellular fluid concentration caused by extrinsic factors. While there are so many studies on the association of AQPs with muscular atrophy, sarcopenia, and Duchenne muscular dystrophy (DMD), the expression of AQP has not been verified in naturally aging mice or humans. Notably, due to the characteristics of AQPs, the difference in function cannot be evaluated without extrinsic factors such as acute water restriction. The purpose of this study was to investigate the changes in AQPs expression and function due to natural aging under acute water restriction conditions in aging mice. The expression of AQP4 was shown to decrease with aging similar to previous studies. However, for the first time, this study results confirmed that AQP1 expression increased in aging mice. In addition, the expression of Aqp1 decreased in the acute water restricted group compared to the control group after acute water restriction in aging mice. These results suggest that although the expression of AQP1 increases with aging, its function is reduced. We also confirmed that overexpression of Aqp1 can inhibit myotube differentiation and that knockdown can promote myotube differentiation through in vitro experiments. In conclusion, based on our results, we suggest that the AQP1 is an important factor in sarcopenia caused by natural aging accompanied by chronic dehydration.

Anti-obesity effects by parasitic nematode (Trichinella spiralis) total lysates.

Background: Obesity is an inducible factor for the cause of chronic diseases and is described by an increase in the size and number of adipocytes that differentiate from precursor cells (preadipocytes). Parasitic helminths are the strongest natural trigger of type 2 immune system, and several studies have showed that helminth infections are inversely correlated with metabolic syndromes. Methodology/Principal findings: To investigate whether helminth-derived molecules have therapeutic effects on high-fat diet (HFD)-induced obesity, we isolated total lysates from Trichinella spiralis muscle larvae. We then checked the anti-obesity effect after intraperitoneal administration and intraoral administration of total lysate from T. spiralis muscle larvae in a diet-induced obesity model. T. spiralis total lysates protect against obesity by inhibiting the proinflammatory response and/or enhancing M2 macrophages. In addition, we determined the effects of total lysates from T. spiralis muscle larvae on anti-obesity activities in 3T3-L1 preadipocytes by investigating the expression levels of key adipogenic regulators, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding protein alpha (C/EBPα) and adipocyte protein 2 (aP2). Oil Red O staining showed that the total lysates from T. spiralis muscle larvae decreased the differentiation of 3T3-L1 preadipocytes by decreasing the number of lipid droplets. In addition, the production levels of proinflammatory cytokines IL-1ß, IL-6, IFN-γ and TNF-α were examined by enzyme-linked immunosorbent assay (ELISA). T. spiralis total lysates decreased intracellular lipid accumulation and suppressed the expression levels of PPARγ, C/EBPα and aP2. Conclusion/Significance: These results show that T. spiralis total lysate significantly suppresses the symptoms of obesity in a diet- induced obesity model and 3T3-L1 cell differentiation and suggest that it has potential for novel anti-obesity therapeutics.

Phylogenetic Characteristics of Fasciola hepatica Isolated from a Korean Patient.

Fascioliasis is a parasitic infection caused by liver flukes. Although several cases have been reported in Korea, phylogenetic analysis of isolates is lacking. In this study, a 66-year-old woman with right upper quadrant (RUQ) abdominal pain was diagnosed as fascioliasis involving abdominal muscle by imaging study. She received praziquantel treatment, but symptoms were not improved. Lateral movement of the abscess lesion was followed. Trematode parasite was surgically removed from the patient's rectus abdominis muscle. The fluke was identified as Fasciola hepatica based on sequence analysis of 18S rDNA. To determine the phylogenetic position of this Fasciola strain (named Korean Fasciola 1; KF1), the cox1 gene (273 bp) was analyzed and compared with the genes of 17 F. hepatica strains isolated from cows, sheep, goats, and humans from various countries. Phylogenetic analysis showed that KF1 was closely related with the isolates from China goat.

Free-Living Amoeba Vermamoeba vermiformis Induces Allergic Airway Inflammation.

The high percentage of Vermamoeba was found in tap water in Korea. This study investigated whether Vermamoeba induced allergic airway inflammation in mice. We selected 2 free-living amoebas (FLAs) isolated from tap water, which included Korean FLA 5 (KFA5; Vermamoeba vermiformis) and 21 (an homolog of Acanthamoeba lugdunensis KA/ E2). We axenically cultured KFA5 and KFA21. We applied approximately 1 × 106 to mice's nasal passages 6 times and investigated their pathogenicity. The airway resistance value was significantly increased after KFA5 and KFA21 treatments. The eosinophil recruitment and goblet cell hyperplasia were concomitantly observed in bronchial alveolar lavage (BAL) fluid and lung tissue in mice infected with KFA5 and KFA21. These infections also activated the Th2-related interleukin 25, thymic stromal lymphopoietin, and thymus and activation-regulated chemokines gene expression in mouse lung epithelial cells. The CD4+ interleukin 4+ cell population was increased in the lung, and the secretion of Th2-, Th17-, and Th1-associated cytokines were upregulated during KFA5 and KFA21 infection in the spleen, lung-draining lymph nodes, and BAL fluid. The pathogenicity (allergenicity) of KFA5 and KFA21 might not have drastically changed during the long-term in vitro culture. Our results suggested that Vermamoeba could elicit allergic airway inflammation and may be an airway allergen.

Trichinella Infection Ameliorated Vincristine-Induced Neuroinflammation in Mice.

Vincristine (VCR) is a chemotherapeutic agent widely used in treatment of malignancies. However, VCR has a limitation in use since it commonly causes a painful neuropathy (VCR-induced peripheral neuropathy, VIPN). Inflammatory cytokines secreted by immune cells such as macrophages can exacerbate allodynia and hyperalgesia, because inhibiting the inflammatory response is a treatment target for VIPN. In this study, we investigated whether Trichinella spiralis, a widely studied helminth for its immunomodulatory abilities, can alleviate VCR-induced allodynia. Von Frey test showed that T. spiralis infection improved mechanical allodynia at 10 days after VCR injection. We further observed whether the difference was due to mitigated axon degeneration, but no significant difference between the groups in axonal degeneration in sciatic nerves and intra-epidermal nerve fibers was found. Conversely, we observed that number of infiltrated macrophages was decreased in the sciatic nerves of the T. spiralis infected mice. Moreover, treatment of T. spiralis excretory-secretory products caused peritoneal macrophages to secrete decreased level of IL-1ß. This study suggests that T. spiralis can relieve VCR-induced mechanical allodynia by suppressing neuroinflammation and that application of controllable degree of helminth may prove beneficial for VIPN treatment.

Activation of PAR2 promotes high-fat diet-induced renal injury by inducing oxidative stress and inflammation.

A high-fat diet (HFD) is a major risk factor for chronic kidney disease. Although HFD promotes renal injury, characterized by increased inflammation and oxidative stress leading to fibrosis, the underlying mechanism remains elusive. Here, we investigated the role and mechanism of protease-activating receptor 2 (PAR2) activation during HFD-induced renal injury in C57/BL6 mice. HFD for 16 weeks resulted in kidney injury, manifested by increased blood levels of blood urea nitrogen, increased levels of oxidative stress with inflammation, and structural changes in the kidney tubules. HFD-fed kidneys showed elevated PAR2 expression level in the tubular epithelial region. To elucidate the role of PAR2, PAR2 knockout mice and their littermates were administered HFD. PAR2 deficient kidneys showed reduced extent of renal injury. PAR2 deficient kidneys showed significantly decreased levels of inflammatory gene expression and macrophage infiltration, followed by reduced accumulation of extracellular matrix proteins. Using NRK52E kidney epithelial cells, we further elucidated the mechanism and role of PAR2 activation during renal injury. Palmitate treatment increased PAR2 expression level in NRK52E cells and scavenging of oxidative stress blocked PAR2 expression. Under palmitate-treated conditions, PAR2 agonist-induced NF-κB activation level was higher with increased chemokine expression level in the cells. These changes were attenuated by the depletion of oxidative stress. Taken together, our results suggest that HFD-induced PAR2 activation is associated with increased levels of renal oxidative stress, inflammatory response, and fibrosis.

Trichinella spiralis nurse cell formation is regulated via CCR7+ dendritic cells.

The chemokine receptor CCR7 is a well-established homing receptor for dendritic cells (DCs) and T-cells. Interaction with the CCL19 and CCL21 ligands promotes priming of immune responses in lymphoid tissues; however, the mechanism underlying CCR7-induced immune responses against helminth parasite infection remains unknown. Thus, we examined the role of CCR7 in generating protective immune responses against intracellular Trichinella spiralis infection. The results showed significantly increased CCR7, CCL19 and CCL21 expression in the muscle tissue compared to that in the intestinal tissue in T. spiralis-infected mice. The CCR7-expressing DC population increased in the mesenteric and peripheral lymph nodes (PLNs) during T. spiralis infection. Notably, the number of CCR7-expressing cells in PLNs increased by more than 30% at 28 days post-infection; however, this increase was significantly inhibited in CCR7-blocked mice treated with CCR7-specific antibodies. T helper 2 (Th2)-and regulatory T (Treg )-related cytokine levels were also reduced by CCR7-specific antibody treatment. CCR7-blocked mice lost their resistance to T. spiralis infection in the muscle phase but not in the intestinal phase. Furthermore, fewer eosinophils around the nurse cells and reduced total and T. spiralis-specific IgE in the serum were observed in CCR7-blocked mice compared to those infected with only T. spiralis. CCR7 blockade led to the T. spiralis infection-induced suppression of Th2- and Treg -related cytokine production in vitro. These results suggest that CCR7 in DCs might play an essential role in host defence mechanisms against T. spiralis infection, particularly in the muscle stage of the infection, by accelerating Th2 and Treg cell responses.