POLArIS, a versatile probe for molecular orientation, revealed actin filaments associated with microtubule asters in early embryos.

Biomolecular assemblies govern the physiology of cells. Their function often depends on the changes in molecular arrangements of constituents, both in the positions and orientations. While recent advancements of fluorescence microscopy including super-resolution microscopy have enabled us to determine the positions of fluorophores with unprecedented accuracy, monitoring the orientation of fluorescently labeled molecules within living cells in real time is challenging. Fluorescence polarization microscopy (FPM) reports the orientation of emission dipoles and is therefore a promising solution. For imaging with FPM, target proteins need labeling with fluorescent probes in a sterically constrained manner, but because of difficulties in the rational three-dimensional design of protein connection, a universal method for constrained tagging with fluorophore was not available. Here, we report POLArIS, a genetically encoded and versatile probe for molecular orientation imaging. Instead of using a direct tagging approach, we used a recombinant binder connected to a fluorescent protein in a sterically constrained manner that can target specific biomolecules of interest by combining with phage display screening. As an initial test case, we developed POLArISact, which specifically binds to F-actin in living cells. We confirmed that the orientation of F-actin can be monitored by observing cells expressing POLArISact with FPM. In living starfish early embryos expressing POLArISact, we found actin filaments radially extending from centrosomes in association with microtubule asters during mitosis. By taking advantage of the genetically encoded nature, POLArIS can be used in a variety of living specimens, including whole bodies of developing embryos and animals, and also be expressed in a cell type/tissue specific manner.

Chloroquine regulates the lipopolysaccharide-induced inflammatory response in RAW264.7 cells.

INTRODUCTION AND OBJECTIVES: Macrophage-induced inflammation plays a key role in defense against injury and harmful pathogens. Autophagy and the inflammatory response are associated; however, the relationship between the autophagy pathway and lipopolysaccharide (LPS)- induced inflammatory responses remains unknown. We aimed to determine the effect of autophagy on the LPS-induced myeloid differentiation factor 88 (MyD88)/nuclear transcription factor kB (NF-kB) pathway-mediated inflammatory response in RAW264.7 cells. MATERIALS AND METHODS: To determine the effect of autophagy on the LPS-induced inflammatory response, using various in vitro assays, we determined the effect of autophagy inhibitors and inducers on the inflammatory response in RAW264.7 cells. RESULTS: Chloroquine (CQ), an autophagy inhibitor, suppressed pro-inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNFα) in LPS-stimulated RAW264.7 cells. CQ also affected inflammatory mediators such as myeloid differentiation factor 88 and NF-kB in LPS-stimulated RAW264.7 cells. CONCLUSION: This study demonstrated that CQ regulates the LPS-induced inflammatory response in RAW264.7 cells. We propose that targeting the regulation of pro-inflammatory cytokine levels and inflammatory mediators using CQ is a promising therapeutic approach for preventing inflammatory injury. CQ serves as a potential therapeutic target for treating various inflammatory diseases.

Reduced Cross-Sectional Area of the Gluteus Medius Muscle is Associated With Decreased Activities of Daily Living in Older Adult Patients With Hip Fractures.

We investigated the association between the cross-sectional area (CSA) of the gluteus medius muscle (GMM) and activities of daily living in patients with hip fractures. This retrospective cohort study comprised 111 patients aged ≥65 years who underwent hip fracture rehabilitation. The CSA of the GMM was measured using computed tomography scans in the early stages of hospitalization. The group with decreased CSA of the GMM had a median GMI ≤17 cm2/m2 for male patients and ≤16 cm2/m2 for female patients. Patients in the group with decreased CSA of the GMM had lower functional independence measure gains than those in the control group. After adjusting for confounders, we found that decreased CSA of the GMM was significantly associated with lower functional independence measure gains (ß: -0.432, p < .001). In patients with hip fractures, decreased CSA of the GMM was associated with decreased activities of daily living.

Oxytocin receptor-expressing neurons in the medial preoptic area are essential for lactation, whereas those in the lateral septum are not critical for maternal behavior.

INTRODUCTION: In nurturing systems, the oxytocin (Oxt)-oxytocin receptor (Oxtr) system is important for parturition, and essential for lactation and parental behavior. Among the nerve nuclei that express Oxtr, the lateral septal nucleus (LS) and medial preoptic area (MPOA) are representative regions that control maternal behavior. METHODS: We investigated the role of Oxtr- and Oxtr-expressing neurons, located in the LS and MPOA, in regulating maternal behavior by regulating Oxtr expression in a region-specific manner using recombinant mice and adeno-associated viruses. We quantified the prolactin (Prl) concentrations in the pituitary gland and plasma when Oxtr expression in the MPOA was reduced. RESULTS: The endogenous Oxtr gene in the neurons of the LS did not seem to play an essential role in maternal behavior. Conversely, decreased Oxtr expression in the MPOA increased the frequency of pups being left outside the nest and reduced their survival rate. Deletion of Oxtr in MPOA neurons prevented elevation of Prl levels in plasma and pituitary at postpartum day 2. DISCUSSION/CONCLUSION: Oxtr-expressing neurons in the MPOA are involved in the postpartum production of Prl. We confirmed the essential functions of Oxtr-expressing neurons and the Oxtr gene itself in the MPOA for the sustainability of maternal behavior, which involved Oxtr-dependent induction of Prl.

Catheter Intervention for Flow Regulatory Clips on Palliative Shunts and Conduits in Patients with Congenital Heart Disease.

Catheter intervention (CI) for a Blalock-Taussig shunt (BTS) or a ventricle-to-pulmonary artery conduit (VPC) is often required after a palliative surgery for congenital heart disease. Flow regulatory clips help improve interstage mortality; their use necessitates CIs to prevent cyanosis. To study the CI outcomes in patients who underwent palliative surgery with either BTSs or VPCs with flow regulatory clips. This single-center retrospective study evaluated demographic characteristics and interventional outcomes of 49 consecutive pediatric patients who required CI for BTS (BTS group) or VPC (VPC group) between January 2008 and September 2018. Overall, 34 and 18 procedures were performed in the BTS and VPC groups, respectively. Moreover, 19/32 (59.3%) and 12/17 (70.1%) patients from the BTS and VPC groups had flow regulatory clips, respectively. All clips were unclipped successfully; one patient in each group underwent staged unclipping. A higher proportion of "clipped patients" underwent CI due to desaturation [clipped vs. non-clipped: BTS, 10/20 (50.0%) vs. 3/14 (21.4%), p = 0.092; VPC, 9/13 (69.2%) vs. 1/5 (20.0%), p = 0.060]. Most clipped patients successfully progressed to the next stage [BTS, 19/20 (95.0%); VPC, 12/13 (92.3%)]. Severe adverse events (SAEs) were more frequent in the VPC group than in the BTS group [3/13 (23.1%) vs. 0/20 (0%), p = 0.024]. Two patients developed an atrioventricular block (requiring an atropine infusion), while one died due to pulmonary overcirculation. While the indication of CI was cyanosis for a higher proportion of clipped patients, all clips were unclipped successfully. The incidence of CI-related SAEs was higher in the VPC group than in the BTS group.

Cardiac MRI for Fontan candidates after intrapulmonary-artery septation.

Intrapulmonary-artery septoplasty may be effective for establishing two-lung Fontan circulation in patients with unilateral pulmonary circulation. However, evaluation of the function of each lung by conventional modalities can be challenging in these patients due to differing sources of blood flow to the left and right lungs following intrapulmonary-artery septation. Herein, we report a case in which two-lung Fontan circulation was successfully achieved after using cardiac MRI along with conventional modalities to evaluate pulmonary circulation.

Indicators of Improvement in Performing Activities of Daily Living Among Older Patients Undergoing Rehabilitation Following Hip Fractures.

This study aimed to evaluate the relationship between improvement in activities of daily living (ADL) and cognitive status during rehabilitation and assess factors associated with ADL improvement among older patients undergoing rehabilitation after hip fractures. This retrospective cohort study comprised 306 patients aged ≥80 years who underwent hip fracture rehabilitation. The functional independence measure gain during rehabilitation was significantly lower in the group with abnormal cognition than in the group with normal cognition. Mini-Mental State Examination, Charlson Comorbidity Index, daily duration of rehabilitation, and length of hospitalization for rehabilitation were independent factors associated with functional independence measure gain during rehabilitation in the multivariate regression analysis. Although older patients with cognitive impairment had lower ADL improvements during hip fracture rehabilitation, such patients may be able to improve their ADL by undergoing intensive and long rehabilitation programs. They should not refrain from such rehabilitation programs due to older age, fracture, and cognitive impairment.

Determination of a Low Skeletal Muscle Mass Index Using the Mass of the Gluteus Medius in Older Patients With Hip Fractures.

This study evaluated the relationship between the muscle mass of the gluteus medius (GM) and skeletal muscle mass index (SMI) measured in patients with hip fractures. In this study, 141 patients with hip fractures were divided into those with high or low SMI. The GM index (GMI) was calculated by dividing the GM by the square of the height in meters. The correlation between GMI and SMI was subsequently analyzed, and cutoff values for determining the loss of skeletal muscle mass were calculated using the receiver operating characteristic curve. GMI and SMI showed a positive correlation for both sexes (male: r = .890, female: r = .626, p < .001). The GMI cutoff values were 19.460 cm2/m2 for males and 17.850 cm2/m2 for females. Skeletal muscle mass evaluation of the GM could contribute to hip fracture recovery by improving mobility and facilitating the early diagnosis of loss of SMM.

Changes in subcellular structures and states of pumilio 1 regulate the translation of target Mad2 and cyclin B1 mRNAs.

Temporal and spatial control of mRNA translation has emerged as a major mechanism for promoting diverse biological processes. However, the molecular nature of temporal and spatial control of translation remains unclear. In oocytes, many mRNAs are deposited as a translationally repressed form and are translated at appropriate times to promote the progression of meiosis and development. Here, we show that changes in subcellular structures and states of the RNA-binding protein pumilio 1 (Pum1) regulate the translation of target mRNAs and progression of oocyte maturation. Pum1 was shown to bind to Mad2 (also known as Mad2l1) and cyclin B1 mRNAs, assemble highly clustered aggregates, and surround Mad2 and cyclin B1 RNA granules in mouse oocytes. These Pum1 aggregates were dissolved prior to the translational activation of target mRNAs, possibly through phosphorylation. Stabilization of Pum1 aggregates prevented the translational activation of target mRNAs and progression of oocyte maturation. Together, our results provide an aggregation-dissolution model for the temporal and spatial control of translation.

First case of a renal cyst infection caused by Desulfovibrio: a case report and literature review.

BACKGROUND: Genus Desulfovibrio species is a sulphate-reducing anaerobic gram-negative rod that resides in the human oral cavity and intestinal tract. It was reported as the causative pathogen of bacteraemia and abdominal infections, but not renal cyst infection, and Desulfovibrio fairfieldensis has higher pathogenicity than other Desulfovibrio species. CASE PRESENTATION: A 63-year-old man was on haemodialysis for end-stage renal failure due to autosomal dominant polycystic kidney disease. On admission, he had a persistent high-grade fever, right lumbar back pain, and elevated C-reactive protein levels. His blood and urine cultures were negative. He received ciprofloxacin and meropenem; however, there was no clinical improvement. Contrast-enhanced computed tomography and plain magnetic resonance imaging revealed a haemorrhagic cyst at the upper pole of the right kidney. The lesion was drained. Although the drainage fluid culture was negative, D. fairfieldensis was detected in a renal cyst using a polymerase chain reaction. After the renal cyst drainage, he was treated with oral metronidazole and improved without any relapse. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a renal cyst infection with Desulfovibrio species. D. fairfieldensis is difficult to detect, and polymerase chain reaction tests can detect this bacterium and ensure better management for a successful recovery.

Angiographic diagnosis for accurate assessment of congenital porto-systemic shunt and extrahepatic portal vein obstruction in children.

BACKGROUND: Congenital porto-systemic shunt (CPSS) is a rare disease and can cause fatal complications. Accurate angiographic assessment is mandatory for proper treatment. Although technically difficult, we developed assessment techniques and assessed their accuracy. One technique came from evaluating patients with extrahepatic portal vein obstruction (EHPVO). METHODS: We conducted a single center retrospective study to evaluate the efficacy of angiographic diagnostic procedure for the assessment of CPSS and EHPVO, and its impact on patients' subsequent interventions and clinical course. Eight patients with CPSS and two patients with EHPVO who underwent diagnostic angiography were included. Assessment of the intrahepatic portal vein was performed in all patients. The route of the shunt, and portal vein pressure under shunt occlusion, were also evaluated for patients with CPSS. Evaluation was first attempted with a balloon angiographic catheter (standard method). Three additional techniques were performed as needed: (i) direct wedge-catheter injection without balloon inflation, (ii) use of occlusion balloon in two patients, and (iii) hybrid angiography with sheath placement directly into the superior mesenteric vein. RESULTS: The standard method was sufficient in four patients. On the other hand, all three techniques were required in two patients each. One lost contact during follow up, but all other patients underwent optimal intervention. There were no complications related to the angiographic procedure. CONCLUSIONS: Use of direct wedge-catheter injection without balloon inflation, occlusion balloon, and hybrid catheterization improved the diagnostic yield in patients with CPSS or EHPVO.

Recovery Strategy for Overturned Wheeled Vehicle Using a Mobile Robot and Experimental Validation.

This paper describes mobile robot tactics for recovering a wheeled vehicle that has overturned. If such a vehicle were to tip over backward off its wheels and be unable to recover itself, especially in areas where it is difficult for humans to enter and work, overall work efficiency could decline significantly, not only because the vehicle is not able to perform its job, but because it becomes an obstacle to other work. Herein, the authors propose a robot-based recovery method that can be used to recover such overturned vehicles, and the authors evaluate its effectiveness. The recovery robot, which uses a mounted manipulator and hand to recover the overturned vehicle, is also equipped with a camera and a personal computer (PC). The ARToolKit software package installed on the PC detects AR markers attached to the overturned vehicle and uses the information they provide to orient itself in order to perform recovery operations. A statics analysis indicates the feasibility of the proposed method. To facilitate these operations, it is also necessary to know the distance between the robotic hand and the target position for grasping of vehicle. Therefore, a theoretical analysis is conducted, and a control system based on the results is implemented. The experimental results obtained in this study demonstrate the effectiveness of the proposed system.

Factors in the acquisition of independent walking in patients with cerebral infarction using decision tree analysis.

OBJECTIVES: Independent walking is considered a rehabilitation factor for patients with stroke. There are no reports examining the predictors of independent walking at approximately one month after stroke onset. We aimed to examine factors related to the degree of independent walking, using a decision tree analysis, in patients with stroke. MATERIALS AND METHODS: This retrospective, observational study was conducted on patients with cerebral infarction. The study period was from May 2017 to October 2021. Patients were categorized into independent (≥ 6; N=88) and dependent (≤ 5; N=98) groups based on the Functional Independence Measure locomotion scale at discharge. A decision tree analysis was performed to identify factors related to independent walking. RESULTS: Overall, 186 participants (mean age, 77.8 ± 9.6 years; 104 men and 82 women) were included. The independent group had higher scores in Functional Assessment for Control of Trunk (14.7 ± 4.6 vs. 7.8 ± 6.0, p <.001), Berg Balance Scale (35.5 ± 15.1 vs. 17.9 ± 15.4, p <.001) and Mini Mental State Examination-Japanese (22.6 ± 5.2 vs. 16.1 ± 7.3, p <.001) on admission than the dependent group. Decision tree analysis identified the Functional Assessment for Control of Trunk score on admission as the best discriminator for independent walking. CONCLUSIONS: The interrelationship between trunk function, cognitive function, and balance function may influence the acquisition of independent walking in patients with stroke.

Undernutrition at Admission Suppresses Post-Stroke Recovery of Trunk Function.

OBJECTIVES: Malnutrition and decreased trunk function have a negative influence on the activities of daily living (ADL) prognosis after stroke. However, the relationship between malnutrition and improvement in trunk function has not been clarified. We aimed to examine the influence of malnutrition on the improvement in trunk function in stroke patients. MATERIALS AND METHODS: This retrospective, observational study was conducted with cerebral infarction patients aged ≥ 65 years with stroke. The study period was from May 2018 to September 2020. Patients were divided into malnutrition and intact groups according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. The primary outcome was the change in the Functional Assessment for Control of Trunk (FACT) score (FACT score at discharge - FACT score at admission). RESULTS: A total of 183 participants (mean age, 79.7 ± 7.5 years; males, 56.3%) were included. A total of 79 (43%) and 104 (57%) patients were divided into the malnutrition and intact groups, respectively. The malnutrition group had a lower FACT score at admission (7.7 ± 7.3 vs. 11.9 ± 6.3, P < 0.001) and a lower FACT score at discharge (8.0 ± 7.7 vs. 13.3 ± 6.1, P < 0.001) than the intact group. After adjustment for the confounding factors, malnutrition was associated with a smaller change in the FACT score (coefficient = -1.871, 95% CI = -3.401 to -0.340, P = 0.017). CONCLUSIONS: Malnutrition has a negative influence on the recovery of trunk function in post-stroke patients. This finding should be verified through additional prospective studies.

Early Wearing of Knee-Ankle-Foot Orthosis Improves Functional Prognosis in Patients after Stroke.

OBJECTIVES: Knee-ankle-foot orthosis (KAFO) is sometimes used for gait training in stroke patients. The impact of the time of wearing KAFO on activities of daily living (ADL) recovery has not been clarified. This study aimed to examine the relationship between the days from onset to KAFO wearing and functional prognosis in patients after stroke. MATERIALS AND METHODS: This retrospective, observational study was conducted with stroke patients who were prescribed a KAFO. Patients were divided into early and delayed groups according to the median days from onset to KAFO wearing. Baseline characteristics were evaluated at the initiation of KAFO wearing. The primary outcome was the Functional Independence Measure (FIM) gain, which was scored by the nurse at baseline and discharge. RESULTS: 112 participants (mean age 67.9 ± 14.0 years, 51.8% male) were included. The time period measure from day of onset to KAFO wearing for the early group was significantly shorter than the delayed group (35.8 ± 6.6 days vs. 73.5 ± 28.9 days). The early group had a higher FIM at discharge (84.9 ± 28.0% vs. 65.1 ± 29.0%, P < 0.001) and higher FIM gain (36.9 ± 19.8% vs. 26.8 ± 22.3, P = 0.013) than did the delayed group. Multiple regression analysis showed that the early group was associated with FIM gain (coefficient = 8.607, P = 0.032). CONCLUSIONS: Early wearing of KAFO, irrespective of the difference in ADL at the time of KAFO wearing, may have a positive impact on the improvement of ADL in patients after stroke.

Development of nanobody-based POLArIS orientation probes enabled multi-color/multi-target orientation imaging in living cells.

Fluorescence polarization microscopy (FPM) can visualize the dipole orientation of fluorescent molecules and has been used for analyzing architectural dynamics of biomolecules including cytoskeletal proteins. To monitor the orientation of target molecules by FPM, target molecules need to be labeled with fluorophores in a sterically constrained manner, so that the fluorophores do not freely rotate. Recently, a versatile probe for such labeling using fluorescent proteins, POLArIS (Probe for Orientation and Localization Assessment, recognizing specific Intracellular Structures of interest), was reported. POLArIS is a fusion protein consisting of a non-immunoglobulin-based recombinant binder Affimer and a green fluorescent protein (GFP), where the Affimer and GFP are rigidly connected to each other. POLArIS probe for molecules of interest can be developed through phage display screening of Affimer. This screening is followed by the rigid connection of fluorescent proteins to the selected Affimers. The Affimer-based POLArIS, however, cannot be used with animal immune libraries for selecting specific binder clones. In addition, multi-color FPM by POLArIS was not available due to the lack of color variations of POLArIS. In this study, we have developed new versions of POLArIS with nanobodies, which are compatible with animal immune libraries, and expanded color variations of POLArIS with cyan/green/yellow/red fluorescent proteins, enabling multi-color orientation imaging for multiple targets. Using nanobody-based POLArIS orientation probes, we performed two-color FPM of F-actin and vimentin in living cells. Furthermore, we made nanobody-based POLArIS probes that have different dipole orientations for adjusting the orientation of fluorescence polarization with respect to the target molecules. These nanobody-based POLArIS with options of colors and dipole orientations will enhance the performance of this probe for broader applications of fluorescence polarization imaging in living cells, tissues, and whole organisms.

Epalrestat suppresses inflammatory response in lipopolysaccharide-stimulated RAW264.7 cells.

INTRODUCTION AND OBJECTIVES: Lipopolysaccharide (LPS) is a potent inducer of inflammatory response. Inflammation is a major risk factor for many diseases. Regulation of inflammatory mediator and pro-inflammatory cytokine levels could be a potential therapeutic approach to treat inflammatory injury. The purpose of the present study was to determine whether epalrestat (EPS), which is used for the treatment of diabetic neuropathy, suppresses inflammatory response in LPS-stimulated RAW264.7 cells. MATERIAL AND METHODS: The effects of EPS at near-plasma concentration on the levels of pro-inflammatory cytokines and inflammatory mediators was examined using by MTS assay, quantitative RT-PCR analysis, and western blotting in LPS-stimulated RAW264.7 cells. RESULTS: EPS suppressed mRNA and protein expression levels of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNFα, in RAW264.7 cells stimulated with LPS. EPS also affected inflammatory mediators such as iNOS and NF-κB in LPS-stimulated RAW264.7 cells. CONCLUSIONS: In this study, we demonstrated for the first time that EPS suppresses inflammatory response in LPS-stimulated RAW264.7 cells. From these results, we propose that targeting the regulation of pro-inflammatory cytokine levels and inflammatory mediators by EPS is a promising therapeutic approach to treat inflammatory injury. It is expected that EPS, whose safety and pharmacokinetics have been confirmed clinically, would be useful for the treatment of inflammatory diseases.

[Pulmonary Epithelioid Hemangioendothelioma:Report of a Case].

A 54-year-old woman with a lung tumor was admitted to our hospital for surgical treatment. Chest computed tomography (CT) showed a 16×14×10 mm nodule in left upper lobe. Flurodeoxyglucose (FDG)-positron emission tomography (PET)/CT revealed increased uptake in the nodule. We diagnosed the tumor as lung cancer preoperatively, and performed surgery. Frozen section diagnosis after partial lung resection was lung cancer and we performed left upper lobectomy. The tumor was histopathologically diagnosed as pulmonary epithelioid hemangioendothelioma( PEH).

[Primary Pulmonary Paraganglioma:Report of a Case].

A 60-year-old woman with a lung tumor was admitted to our hospital for surgical treatment. Chest computed tomography (CT) showed a 23×21×20 mm nodule in the right lower lobe. Although the lung nodule was thought to be benign due to CT image findings, its size was apparently larger than that of CT image at four years ago. So, we decided to resect the nodule and performed a partial lung resection under video-assisted thoracic surgery. The tumor was histopathologically diagnosed as a paraganglioma and scored 0 point in pheochromocytoma of the adrenal gland score( PASS). Since no abnormal uptake that indicates primary site was not found on fluorodeoxyglucose-positron emission tomography (FDGPET) performed after surgery, we diagnosed this tumor as a primary pulmonary paraganglioma. She is still alive without recurrence.

Orally administered pathobionts and commensals have comparable and innocuous systemic effects on germ-free mice.

BACKGROUND AND OBJECTIVES: Recent evidence suggests that oral bacteria can affect extra-oral diseases by modulating aspects of the gut environment such as the microbiome, metabolome, and immune profiles. However, differences in the effects of different types of oral bacteria, particularly periodontopathic and health-associated bacteria, remain elusive. MATERIALS AND METHODS: Five-week-old germ-free mice were orally administered with either periodontopathic bacteria as oral pathobionts (Porphyromonas gingivalis, Filifactor alocis, and Fusobacterium nucleatum) or bacteria associated with periodontal health (Actinomyces naeslundii, Streptococcus mitis, and Veillonella rogosae) twice a week for five weeks. The presence of all bacterial species in the feces and the livers of the mice was analyzed via polymerase chain reaction (PCR), using specific primers for 16S rRNA genes. Alveolar bone resorption was evaluated histologically. The expression profiles of various genes in the liver and small intestine were analyzed using real-time PCR. Sera were analyzed to determine the levels of antibodies and endotoxin. The proportions of T helper 17 (Th17) and regulatory T (Treg) cells in mesenteric lymph nodes and Peyer's patches were analyzed using flow cytometry. RESULTS: Neither of the types of bacteria administered in this experiment induced alveolar bone resorption. All bacteria elicited some degree of systemic antibody response in the mice, although the response to S. mitis was not obvious. The response to P. gingivalis and V. rogosae was strongest. Generally, the health-associated bacteria but not the periodontitis-associated bacteria were detected in fecal samples. Interestingly, only Fusobacterium nucleatum DNA was detected in the liver, despite that live Fusobacterium nucleatum were not detected in the liver. The levels of interleukin-17 in the intestine and genes related to lipid accumulation in the liver were significantly higher in the mice that received periodontitis-associated bacteria. In addition, expression of the gene associated with endoplasmic reticulum stress was higher and that of the gene controlling circadian rhythm was lower in the periodontitis group. There was no difference in serum endotoxin, T-cell phenotypes in the lymphatic tissues, or genes related to the gut barrier. CONCLUSION: Oral administration of periodontitis-associated bacteria can induce pathological changes in the liver and intestine that are implicated in the process of periodontitis. These findings further support the importance of the oral-gut connection.