A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of Well Parent Japan in routine care in Japan: The training and nurturing support for mothers (TRANSFORM) study.

BACKGROUND: Well Parent Japan (WPJ) is a new hybrid group parent training programme combining sessions to improve mothers' psychological well-being with a culturally adapted version of the New Forest Parenting Programme (NFPP). This study investigates the effectiveness and cost-effectiveness of WPJ against treatment as usual (TAU) within Japanese child mental health services. METHODS: TRANSFORM was a pragmatic multi-site randomised controlled trial (RCT) with two parallel arms. Altogether 124 mothers of 6-12-year-old children with DSM-5 ADHD were randomised to WPJ (n = 65) or TAU (n = 59). Participants were assessed at baseline, post-treatment and three-month follow-up. The primary outcome was parent-domain stress following intervention. Secondary outcomes included maternal reports of child-domain stress, parenting practices, parenting efficacy, mood, family strain, child behaviour and impairment. Objective measures of the parent-child relationship were collected at baseline and post-treatment. Data analysis was intention to treat (ITT) with treatment effects quantified through analysis of covariance (ANCOVA) via multilevel modelling. An incremental cost-effectiveness ratio (ICER) assessed WPJ's cost-effectiveness. RESULTS: WPJ was superior to TAU in reducing parent-domain stress post-treatment (adjusted mean difference = 5.05, 95% CI 0.33 to 9.81, p = .036) and at follow-up (adjusted mean difference 4.82, 95% CI 0.09 to 9.55, p = .046). Significant WPJ intervention effects were also observed for parenting practices, parenting efficacy and family strain. WPJ and TAU were not significantly different post-intervention or at follow-up for the other secondary outcomes. The incremental cost of WPJ was 34,202 JPY (315.81 USD). The probability that WPJ is cost-effective is 74% at 10,000 JPY (USD 108.30) per one-point improvement in parenting stress, 92% at 20,000 JPY (216.60 USD). The programme was delivered with high fidelity and excellent retention. CONCLUSIONS: WPJ can be delivered in routine clinical care at modest cost with positive effects on self-reported well-being of the mothers, parenting practices and family coping. WPJ is a promising addition to psychosocial interventions for ADHD in Japan.

Oral Administration of Lipopolysaccharide Enhances Insulin Signaling-Related Factors in the KK/Ay Mouse Model of Type 2 Diabetes Mellitus.

Lipopolysaccharide (LPS), an endotoxin, induces systemic inflammation by injection and is thought to be a causative agent of chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). However, our previous studies found that oral LPS administration does not exacerbate T2DM conditions in KK/Ay mice, which is the opposite of the response from LPS injection. Therefore, this study aims to confirm that oral LPS administration does not aggravate T2DM and to investigate the possible mechanisms. In this study, KK/Ay mice with T2DM were orally administered LPS (1 mg/kg BW/day) for 8 weeks, and blood glucose parameters before and after oral administration were compared. Abnormal glucose tolerance, insulin resistance progression, and progression of T2DM symptoms were suppressed by oral LPS administration. Furthermore, the expressions of factors involved in insulin signaling, such as insulin receptor, insulin receptor substrate 1, thymoma viral proto-oncogene, and glucose transporter type 4, were upregulated in the adipose tissues of KK/Ay mice, where this effect was observed. For the first time, oral LPS administration induces the expression of adiponectin in adipose tissues, which is involved in the increased expression of these molecules. Briefly, oral LPS administration may prevent T2DM by inducing an increase in the expressions of insulin signaling-related factors based on adiponectin production in adipose tissues.

Classification of grazing-incidence small-angle X-ray scattering patterns by convolutional neural network.

Grazing-incidence small-angle X-ray scattering (GISAXS) patterns have multiple superimposed contributions from the shape of the nanoscale structure, the coupling between the particles, the partial pair correlation, and the layer geometry. Therefore, it is not easy to identify the model manually from the huge amounts of combinations. The convolutional neural network (CNN), which is one of the artificial neural networks, can find regularities to classify patterns from large amounts of combinations. CNN was applied to classify GISAXS patterns, focusing on the shape of the nanoparticles. The network found regularities from the GISAXS patterns and showed a success rate of about 90% for the classification. This method can efficiently classify a large amount of experimental GISAXS patterns according to a set of model shapes and their combinations.

Carbohydrate-restricted diet promotes skin senescence in senescence-accelerated prone mice.

This study used senescence-accelerated prone mice (SAMP8) to examine the effects of a carbohydrate-restricted diet on aging and skin senescence, to determine how long-term carbohydrate restriction affects the aging process. Three-week-old male SAMP8 mice were divided into three groups after 1 week of preliminary feeding: one was given a controlled diet, the other was given a high-fat diet, and the third was given a carbohydrate-restricted diet. Ad libitum feeding was administered until the mice reached 50 weeks of age. Before the end of the test period, a grading test was used to evaluate visible aging in the mice. After the test period, serum and skin samples in mice were obtained and submitted for analysis. As a result, the grading test demonstrated that there was significant progression of visible aging in the carbohydrate-restricted group, as well as a decreased survival rate. Histological examination of the skin revealed that the epidermis and dermis in the carbohydrate-restricted group had become thinner. Analysis of the mechanisms involved demonstrated an increase in serum interleukin-6, aggravated skin senescence, inhibition of skin autophagy and activation of skin mTOR. Therefore, this study proved that a carbohydrate-restricted diet promoted skin senescence in senescence-accelerated mice.

The effect of dietary lipid on gut microbiota in a senescence-accelerated prone mouse model (SAMP8).

Gut microbiota change with aging and diet. In a previous study, it was shown that a moderate-fat diet enriched with fish oil had beneficial effects for elderly patients, so we examined the effect of this diet on aging-related changes in gut microbiota in this study. We used 3-month-old male senescence-accelerated prone mice (SAMP8). The mice were fed a normal diet containing 4 g soybean oil/100 g of diet for 6 months and then divided into 4 groups: (1) the Baseline group, ended breeding at 6 months old; (2) the Control group, continued on a normal diet until 15 months old; (3) the MF group, switched to a moderate-fat diet until 15 months old; and (4) the MF + FO group, switched to a moderate-fat diet enriched with fish oil until 15 months old. When mice were 6 or 15 months old, fecal samples were collected and gut microbiota analysis was performed. Gut microbiota analysis at the genus level showed that bacteria known to increase in association with fatty liver and intestinal inflammation increased with aging. However, this alteration was largely inhibited by the moderate-fat diet enriched with fish oil. On the other hand, there was a decrease with aging in the bacteria that play a role in energy consumption, but this alteration was inhibited by the moderate-fat diet enriched with fish oil. These results suggest that a moderate-fat diet enriched with fish oil has beneficial effects on gut microbiota in aging.

Effect of the Japanese diet during pregnancy and lactation or post-weaning on the risk of metabolic syndrome in offspring.

We examined the effects on offspring of ingestion of the 1975 Japanese diet during pregnancy and lactation and after weaning in mice. Pregnant dams were divided into groups that were fed the Japanese diet or a control diet and raised until offspring were weaned. The offspring after weaning were further divided into groups that were raised on the Japanese diet or the control diet. Ingestion of the Japanese diet after weaning suppressed accumulation of visceral fat in offspring, and reduced the amount of lipids in serum and liver. This effect was weakened if the Japanese diet was only ingested during pregnancy and lactation. Therefore, it was suggested that ingestion of the Japanese diet of mothers during pregnancy and lactation weakens the lipid accumulation inhibitory effect of the Japanese diet in children.

The 1975 Japanese diet has a stress reduction effect in mice: search for physiological effects using metabolome analysis.

We aimed to find new physiological effects of the Japanese diet. First, to determine the key components in serum from mice fed the 1975 diet, serum from mice fed the 1960, 1975, 1990 or 2005 Japanese diet was analyzed using CE-TOFMS and LC-TOFMS. Based on these results, the key components were determined by principal component analysis. Among the identified compounds, GABA was included. Therefore, a stress reduction effect was inferred as a novel physiological effect of this diet. Next, we tested whether the 1975 diet had an actual stress reduction effect in mice. Mice were given the 1975 diet or a control diet for 4 weeks, after which they were divided into restraint stress and non-stress groups. Mice fed the 1975 diet had significantly decreased stress parameters compared with those fed the control diet. These results provide the first evidence that the 1975 Japanese diet has a stress reduction effect.

Standardisation of the Japanese diet for use in animal experiments.

The aim of this study was to develop a purified diet that mimics the characteristics of the Japanese diet using readily available materials with a simpler composition and a focus on quality, with the goal of facilitating performance of studies on the Japanese diet worldwide. The utility of the new diet was examined as a mimic of the standard Japanese diet for use in animal experiments. We examined whether a key characteristic of the Japanese diet of being less likely to cause obesity could be reproduced. The mimic diet had a balance of protein, fat and carbohydrate based on the 1975 Japanese diet, which is the least likely to cause obesity, and materials chosen with reference to the National Health and Nutrition Survey (NHNS). To examine similarities of the mimic diet with the model 1975 Japanese diet, we created a menu of the 1975 diet based on the NHNS and prepared the freeze-dried and powdered diet. The mimic diet, the 1975 Japanese diet, a control AIN-93G diet and a Western diet were fed to mice for 4 weeks. As a result, the mimic diet and the 1975 diet resulted in less accumulation of visceral fat and liver fat. Mice given these two diets showed similar effects. This indicates that the mimic diet used in this study has characteristics of the 1975 Japanese diet and could be used as a standard Japanese diet in animal experiments.

Intake of mulberry 1-deoxynojirimycin prevents colorectal cancer in mice.

The effect of 1-deoxynojirimycin, a caloric restriction mimetic, was examined in ICR mice with azoxymethane dextran sodium sulfate-induced colorectal cancer. Azoxymethane is a carcinogen (10 mg/kg body weight), and 2% dextran sodium sulfate (w/v) used as a colitis-inducing agent. Mice were separated into 5 groups: a group without colorectal cancer fed a normal diet (CO- group), and groups with colorectal cancer fed a normal diet (CO+ group), a calorie-restricted diet (caloric restriction group), and diets including 0.02% and 0.1% 1-deoxynojirimycin (l-1-deoxynojirimycin and H-1-deoxynojirimycin groups). The tumor incidence and number were reduced significantly in the caloric restriction group compared to the CO+ group, and were also suppressed in a dose-dependent manner by 1-deoxynojirimycin. mRNA for anti-apoptotic Bcl-2 was decreased and that for pro-apoptotic Bax was increased in the carcinoma tissue of CR, l-1-deoxynojirimycin and H-1-deoxynojirimycin groups. These results suggest that caloric restriction and 1-deoxynojirimycin inhibit growth of colorectal cancer by inducing apoptosis in an induced cancer model in mice.

High-fat diet intake from senescence inhibits the attenuation of cell functions and the degeneration of villi with aging in the small intestine, and inhibits the attenuation of lipid absorption ability in SAMP8 mice.

We examined the effect of a high-fat diet from senescence as a means of preventing malnutrition among the elderly. The senescence-accelerated mouse P8 was used and divided into three groups. The 6C group was given a normal diet until 6 months old. The 12N group was given a normal diet until 12 months old. The 12F group was given a normal diet until 6 months old and then a high-fat diet until 12 months old. In the oral fat tolerance test, there was a decrease in area under the curve for serum triacylglycerol level in the 12N group and a significant increase in the 12F group, suggesting that the attenuation of lipid absorption ability with aging was delayed by a high-fat diet from senescence. To examine this mechanism, histological analysis in the small intestine was performed. As a result, the degeneration of villi with aging was inhibited by the high-fat diet. There was also a significant decrease in length of villus in the small intestine in the 12N group and a significant increase in the 12F group. The high-fat diet from senescence inhibited the degeneration of villi with aging in the small intestine, and inhibited the attenuation of lipid absorption ability.

Decreased lipid absorption due to reduced pancreatic lipase activity in aging male mice.

Malnutrition due to aging is partly caused by decreased absorption of nutrients by the gastrointestinal tract. However, the underlying mechanism is unclear and changes in lipid absorption with aging are poorly understood. In this study, changes in lipid absorption with aging were examined in mice aged 3 and 25 months. After overnight fasting, blood samples were collected from snipped tails and then soybean oil was administered orally. Three hours later, mice were sacrificed by decapitation and the liver, pancreas, small intestine and blood were collected. The increase in serum triacylglycerol after soybean oil administration was significantly lower in the older mice, indicating a decrease in lipid absorption with aging. Measurement of mRNA levels for triacylglycerol absorption-related genes showed that mRNA for pancreatic lipase tended to decrease in 25-month-old mice. There was no significant difference in the protein level of pancreatic lipase, but the enzyme activity showed a significant decrease in the older mice. To examine this mechanism, expression levels of mRNA for protein turnover-related genes in the pancreas were measured. The level of a proteasomal mRNA showed a significant decrease in 25-month-old mice. This suggests that the ability to degrade unfolded protein decreases in the aging pancreas, and that this leads to reduction of pancreatic lipase activity and a decrease in lipid absorption.

Anti-inflammatory and Insulin Signaling Phenotype Induced by Repeated Lipopolysaccharide Stimulation in 3T3-L1 Adipocytes.

BACKGROUND/AIM: Lipopolysaccharide (LPS) is thought to be a causative agent of type 2 diabetes, because it has been shown that a single LPS stimulation in vitro induces chronic inflammation and reduces insulin signaling in adipocytes. However, oral LPS administration prevents type 2 diabetes, and this effect does not correspond to a single LPS adipocyte stimulation. In this study, the response of adipocytes to single and repeated stimulation with LPS was examined. MATERIALS AND METHODS: 3T3-L1 cells were differentiated into adipocytes and stimulated with LPS once or thrice every 24 h. The expression levels of inflammatory and anti-inflammatory factors and insulin sensitivity-related factors were measured. RESULTS: Single stimulation with LPS increased the mRNA and protein expression of inflammatory factors (interleukin-6 and monocyte chemotactic protein 1), but this increase was inhibited by repeated stimulation. In contrast, the mRNA expression levels of anti-inflammatory factors (proliferator-activated receptor γ and peroxisome proliferator-activated receptor gamma coactivator1 α) were increased by repeated LPS stimulation. Additionally, the mRNA expression levels of insulin sensitivity-related factors (glucose transporter type 4, insulin receptor, insulin receptor substrate 1 and thymoma viral proto-oncogene 2) in adipocytes were increased upon repeated LPS stimulation. CONCLUSION: Repetitive LPS stimulation, unlike single stimulation of adipocytes, upregulates anti-inflammatory and insulin signaling-related factors.

Real-world evidence of the impact of obesity on residual teeth in the Japanese population: A cross-sectional study.

BACKGROUND: Tooth loss is associated with nutritional status and significantly affects quality of life, particularly in older individuals. To date, several studies reveal that a high BMI is associated with tooth loss. However, there is a lack of large-scale studies that examined the impact of obesity on residual teeth with respect to age and tooth positions. OBJECTIVE: We assessed the impact of obesity on the number and position of residual teeth by age groups using large scale of Japanese database. METHODS: This was a cross-sectional study of 706150 subjects that were included in the database that combined the data from health insurance claims and health check-up, those lacking information about BMI, HbA1c level, smoking status, and the number of residual teeth were excluded. Thus, a total of 233517 aged 20-74 years were included. Subjects were classified into 4 categories based on BMI, and the number of teeth was compared between age-groups. The percentage of subjects with residual teeth in each position was compared between groups with obesity (BMI ≥25.0 kg/m2) and non-obesity. Logistic regression analysis was performed to clarify whether obesity predicts having <24 teeth. RESULTS: Higher BMI was associated with fewer teeth over 40s (P for trend <0.0001 when <70s). Obesity was associated with the reduction of residual teeth in the maxillary; specifically, the molars were affected over the age 30. Smoking status further affected tooth loss at positions that were not affected by obesity alone. After adjusting for age, sex, smoking status, and HbA1c ≥6.5%, obesity remained an independent predictive factor for having <24 teeth (ORs: 1.35, 95% CIs: 1.30-1.40). CONCLUSIONS: We found that an increase in BMI was associated with a decrease in the number of residual teeth from younger ages independently of smoking status and diabetes in the large scale of Japanese database.

The Effectiveness and Cost-effectiveness of Well Parent Japan for Japanese Mothers of Children With ADHD: Protocol for a Randomized Controlled Trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder associated with numerous functional deficits and poor long-term outcomes. Internationally, behavioral interventions are recommended as part of a multimodal treatment approach for children with ADHD. Currently, in Japan, there are limited interventions available to target ADHD. Well Parent Japan (WPJ), a new hybrid parent-training program, provides a culturally acceptable and effective way to help support Japanese children with ADHD and their parents. OBJECTIVE: This pragmatic multicenter randomized controlled trial aims to provide preliminary evidence about the effectiveness and cost-effectiveness of WPJ evaluated against treatment as usual (TAU) within routine Japanese mental health services. METHODS: Mothers of children (aged 6-12 years) diagnosed with ADHD were recruited from child and adolescent mental health care services at three hospital sites across Japan (Fukui, Fukuoka, and Okinawa). The mothers were randomized to receive immediate treatment or TAU. The effectiveness and cost-effectiveness of WPJ over TAU at the end of the intervention and at 3-month follow-up will be evaluated. The primary outcome is maternal parent domain stress in the parenting role. The following secondary outcomes will be explored: child behavior, including severity of ADHD symptoms; parenting practices; emotional well-being; and the parent-child relationship and maternal child domain parenting stress. Data analysis will follow intention-to-treat principles with treatment effects quantified through analysis of covariance using multilevel modeling. An incremental cost-effectiveness ratio will be used to analyze the cost-effectiveness of the WPJ intervention. RESULTS: Study funding was secured through a proof-of-concept grant in July 2018. Approval by the institutional review board for the data collection sites was obtained between 2017 and 2019. Data collection began in August 2019 and was completed in April 2022. Participant recruitment (N=124) was completed in May 2021. Effectiveness and cost-effectiveness analyses are expected to be completed by July 2022 and December 2022, respectively. These timelines are subject to change owing to the COVID-19 pandemic. CONCLUSIONS: This is the first multisite pragmatic trial of WPJ based on the recruitment of children referred directly to routine clinical services in Japan. This multisite randomized trial tests the effectiveness of WPJ in children and families by comparing WPJ directly with the usual clinical care offered for children diagnosed with ADHD in Japan. We also seek to assess and compare the cost-effectiveness of WPJ with TAU in Japan. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN66978270; https://www.isrctn.com/ISRCTN66978270. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32693.

Virucidal activity of oral care products against SARS-CoV-2 in vitro.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) caused by infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Since reducing the amount of virus in saliva is considered to prevent broader infection, the Center for Disease Control (CDC) and American Dental Hygienists' Association (ADHA) have recommended use of CPC- or CHX-containing oral care products before the dental procedure. However, there is no certified evidence. So, we examined inactivation of SARS-CoV-2 by oral care products in several countries in vitro. METHODS: 0.05 % Cetylpyridinium chloride (CPC) mouthwash, 0.05 % CPC toothpaste and 0.30 % CPC spray in Japan; 0.06 % chlorhexidine gluconate (CHX) + 0.05 % CPC mouthwash and 0.12 % CHX + 0.05 % CPC mouthwash in Europe; 0.075 % CPC mouthwash, 0.12 % CHX mouthwash, and 0.20 % delmopinol hydrochloride mouthwash in the USA; and 0.04 % CPC mouthwash in China were assessed for their virucidal activity with ASTM E1052. RESULTS: The virus was inactivated in vitro by the contact time in directions for use of all oral care products containing CPC or delmopinol hydrochloride as anticeptics. CONCLUSIONS: These results suggest that these oral care products in each country may reduce the viral load in the mouth.

Oral Administration of Lipopolysaccharide Prevents Cognitive Impairment in Streptozotocin-induced Diabetic Mice in a Blood Glucose-independent Manner.

BACKGROUND/AIM: Diabetes is a risk factor for dementia. However, no radical preventive method for diabetes-associated dementia has yet been developed. Our previous study revealed that oral administration of lipopolysaccharide (LPS) prevents high-fat diet-induced cognitive impairment. Therefore, we investigated here whether oral administration of LPS (OAL) could also prevent diabetes-associated dementia. MATERIALS AND METHODS: Diabetic mice were produced by intraperitoneal administration of streptozotocin (STZ), and then mice were orally administered LPS. Cognitive ability was evaluated using the Morris water maze, and gene expression was analyzed in isolated microglia. RESULTS: OAL prevented STZ-induced diabetic cognitive impairment, but did not affect blood glucose levels. Moreover, OAL promoted the expression of neuroprotective genes in microglia, such as heat shock protein family 40 (HSP40) and chemokine CCL7. CONCLUSION: OAL prevents diabetes-associated dementia, potentially via promotion of HSP40 and CCL7 expression in microglia.

Prevention of streptozotocin­induced Neuro­2a cell death by C8­B4 microglia transformed with repetitive low­dose lipopolysaccharide.

Diabetes­associated neuronal dysfunction (DAND) is one of the serious complications of diabetes, but there is currently no remedy for it. Streptozotocin [2­deoxy­2­(3­methy1­3­nitrosoureido) D­glucopyranose; STZ] is one of the most well­established diabetes inducers and has been used in vivo and in vitro DAND models. The aim of the present study was to demonstrate that C8­B4 microglia transformed by the stimulus of repetitive low­dose lipopolysaccharide (LPSx3­microglia) prevent STZ­induced Neuro­2a neuronal cell death in vitro. The ELISA results showed that neurotrophin­4/5 (NT­4/5) secretion was promoted in LPSx3­microglia and the cell viability assay with trypan blue staining revealed that the culture supernatant of LPSx3­microglia prevented STZ­induced neuronal cell death. In addition, reverse transcription­quantitative PCR showed that neurons treated with the culture supernatant of LPSx3­microglia promoted the gene expression of B­cell lymphoma­extra large and glucose­dependent insulinotropic polypeptide receptor. Furthermore, the inhibition of tyrosine kinase receptor B, a receptor of NT­4/5, suppressed the neuroprotective effect of LPSx3­microglia. Taken together, the present study demonstrated that LPSx3­microglia prevent STZ­induced neuronal death and that NT­4/5 may be involved in the neuroprotective mechanism of LPSx3­microglia.

Prevention of Diabetes-Associated Cognitive Dysfunction Through Oral Administration of Lipopolysaccharide Derived From Pantoea agglomerans.

Diabetes-related cognitive dysfunction (DRCD) is a serious complication induced by diabetes. However, there are currently no specific remedies for DRCD. Here, we show that streptozotocin-induced DRCD can be prevented without causing side effects through oral administration of lipopolysaccharide (LPS) derived from Pantoea agglomerans. Oral administration of LPS (OAL) prevented the cerebral cortex atrophy and tau phosphorylation induced by DRCD. Moreover, we observed that neuroprotective transformation of microglia (brain tissue-resident macrophages) is important for preventing DRCD through OAL. These findings are contrary to the general recognition of LPS as an inflammatory agent when injected systemically. Furthermore, our results strongly suggest that OAL promotes membrane-bound colony stimulating factor 1 (CSF1) expression on peripheral leukocytes, which activates the CSF1 receptor on microglia, leading to their transformation to the neuroprotective phenotype. Taken together, the present study indicates that controlling innate immune modulation through the simple and safe strategy of OAL can be an innovative prophylaxis for intractable neurological diseases such as DRCD. In a sense, for modern people living in an LPS-depleted environment, OAL is like a time machine that returns microglia to the good old LPS-abundant era.

A Novel Anti-inflammatory Phenotype Transformed by Repetitive Low-dose Lipopolysaccharide in Primary Peritoneal Tissue-resident Macrophages.

BACKGROUND/AIM: Our previous studies suggested that oral administration of lipopolysaccharide (LPS) regulates the progression of various diseases via transformation of tissue-resident macrophages (MΦ). Recently, we characterized microglia transformed by repetitive low-dose LPS treatment (REPELL-microglia) in vitro, and this response was similar to that observed in response to oral administration of LPS in vivo. Here, we examined the characteristics of peritoneal tissue-resident MΦ (pMΦ) transformed by repetitive low-dose LPS treatment (REPELL-pMΦ). MATERIALS AND METHODS: Primary pMΦ were treated with low-dose LPS (1 ng/ml) three times; subsequently, phagocytic activity and gene expression were evaluated. RESULTS: REPELL-pMΦ exhibited high phagocytic activity and elevated expression of Arg1, Gipr, Gdnf, and Fpr2. The gene expression profiles observed in REPELL-pMΦ were distinct from those of REPELL-microglia. CONCLUSION: REPELL-pMΦ have the potential to promote clearance of xenobiotics and to suppress inflammation. The present study also demonstrates the diversity of tissue-resident MΦ transformation that reflect their tissue origin.