A role of anterior cingulate cortex in the emergence of worker-parasite relationship.

We studied the brain mechanisms underlying action selection in a social dilemma setting in which individuals' effortful gains are unfairly distributed among group members. A stable "worker-parasite" relationship developed when three individually operant-conditioned rats were placed together in a Skinner box equipped with response lever and food dispenser on opposite sides. Specifically, one rat, the "worker," engaged in lever-pressing while the other two "parasitic" rats profited from the worker's effort by crowding the feeder in anticipation of food. Anatomically, c-Fos expression in the anterior cingulate cortex (ACC) was significantly higher in worker rats than in parasite rats. Functionally, ACC inactivation suppressed the worker's lever-press behavior drastically under social, but only mildly under individual, settings. Transcriptionally, GABAA receptor- and potassium channel-related messenger RNA expressions were reliably lower in the worker's, relative to parasite's, ACC. These findings indicate the requirement of ACC activation for the expression of exploitable, effortful behavior, which could be mediated by molecular pathways involving GABAA receptor/potassium channel proteins.

A Bioinformatics Investigation of Hub Genes Involved in Treg Migration and Its Synergistic Effects, Using Immune Checkpoint Inhibitors for Immunotherapies.

This study aimed to identify hub genes involved in regulatory T cell (Treg) function and migration, offering insights into potential therapeutic targets for cancer immunotherapy. We performed a comprehensive bioinformatics analysis using three gene expression microarray datasets from the GEO database. Differentially expressed genes (DEGs) were identified to pathway enrichment analysis to explore their functional roles and potential pathways. A protein-protein interaction network was constructed to identify hub genes critical for Treg activity. We further evaluated the co-expression of these hub genes with immune checkpoint proteins (PD-1, PD-L1, CTLA4) and assessed their prognostic significance. Through this comprehensive analysis, we identified CCR8 as a key player in Treg migration and explored its potential synergistic effects with ICIs. Our findings suggest that CCR8-targeted therapies could enhance cancer immunotherapy outcomes, with breast invasive carcinoma (BRCA) emerging as a promising indication for combination therapy. This study highlights the potential of CCR8 as a biomarker and therapeutic target, contributing to the development of targeted cancer treatment strategies.

Retrospective comparison of the effects of remimazolam and dexmedetomidine on postoperative delirium in elderly patients undergoing orthopedic surgery of the lower extremities under spinal anesthesia.

PURPOSE: Remimazolam is often used for perioperative sedation due to its rapid onset and offset. However, the possible association between remimazolam and postoperative delirium (POD) remains undetermined. The present study evaluated whether remimazolam increased the incidence of POD compared with dexmedetomidine in elderly patients undergoing orthopedic surgery of the lower extremities. METHODS: This retrospective study included patients aged ≥ 65 years who had undergone orthopedic surgery of the lower extremities under spinal anesthesia from January 2020 to November 2022 and were sedated with continuous intravenous infusion of dexmedetomidine or remimazolam. The incidence of POD was assessed through a validated comprehensive review process of each patient's medical records. The effect of remimazolam on the occurrence of POD compared with dexmedetomidine was evaluated by propensity score weighted multivariable logistic models. RESULTS: A total of 447 patients were included in the final analysis. The crude incidence of POD within 3 days after surgery was 7.5% (17/226) in the dexmedetomidine group and 11.8% (26/221) in the remimazolam group, increasing to 9.7% (22/226) and 15.8% (35/221), respectively (p = 0.073), within 5 days. The multivariable models showed that, compared with dexmedetomidine, intraoperative sedation with remimazolam significantly increased the occurrence of POD within 3 days (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.31 to 3.82, p = 0.003) and 5 days (OR 2.10, 95% CI 1.32 to 3.40, p = 0.002). CONCLUSION: Compared with dexmedetomidine, remimazolam infusion may be associated with a higher risk of POD in elderly patients undergoing orthopedic surgery of the lower extremities under spinal anesthesia.

Continuous cardiac output estimation using a new modified Fick method during off-pump coronary artery bypass graft surgery: a retrospective observational study.

PURPOSE: Several technical aspects of the Fick method limit its use intraoperatively. A data-driven modification of the Fick method may enable its use in intraoperative settings. METHODS: This two-center retrospective observational study included 57 (28 and 29 in each center) patients who underwent off-pump coronary artery bypass graft (OPCAB) surgery. Intraoperative recordings of physiological data were obtained and divided into training and test datasets. The Fick equation was used to calculate cardiac output (CO-Fick) using ventilator-determined variables, intraoperative hemoglobin level, and SvO2, with continuous thermodilution cardiac output (CCO) used as a reference. A modification CO-Fick was derived and validated: CO-Fick-AD, which adjusts the denominator of the original equation. RESULTS: Increased deviation between CO-Fick and CCO was observed when oxygen extraction was low. The root mean square error of CO-Fick was decreased from 6.07 L/min to 0.70 L/min after the modification. CO-Fick-AD showed a mean bias of 0.17 (95% CI 0.00-0.34) L/min, with a 36.4% (95% CI 30.6-44.4%) error. The concordance rates of CO-Fick-AD ranged from 73.3 to 87.1% depending on the time interval and exclusion zone. CONCLUSIONS: The original Fick method is not reliable when oxygen extraction is low, but a modification using data-driven approach could enable continuous estimation of cardiac output during the dynamic intraoperative period with minimal bias. However, further improvements in precision and trending ability are needed.

Targeting FAK/PYK2 with SJP1602 for Anti-Tumor Activity in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) presents significant challenges due to its aggressive nature and limited treatment options. Focal adhesion kinase (FAK) has emerged as a critical factor promoting tumor growth and metastasis in TNBC. Despite encouraging results from preclinical and early clinical trials with various FAK inhibitors, none have yet achieved clinical success in TNBC treatment. This study investigates the therapeutic potential of a novel dual inhibitor of FAK and PYK2, named SJP1602, for TNBC. In vitro experiments demonstrate that SJP1602 effectively inhibits FAK and PYK2 activities, showing potent effects on both kinases. SJP1602 shows concentration-dependent inhibition of cell growth, migration, invasion, and 3D spheroid formation in TNBC cell lines, surpassing the efficacy of other FAK inhibitors. Pharmacokinetic studies in rats indicate favorable bioavailability and sustained plasma concentrations of SJP1602, supporting its potential as a therapeutic agent. Furthermore, in TNBC xenograft models, SJP1602 exhibits significant dose-dependent inhibition of tumor growth. These promising results emphasize the potential of SJP1602 as a potent dual inhibitor of FAK and PYK2, deserving further investigation in clinical trials for TNBC treatment.

Errors in pressure measurements due to changes in pressure transducer levels during adult cardiac surgery: a prospective observational study.

BACKGROUND: Blood pressure measurement is an essential element during intraoperative patient management. However, errors caused by changes in transducer levels can occur during surgery. METHODS: This single center, prospective, observational study enrolled 25 consecutive patients scheduled for elective cardiac surgery with invasive arterial and central venous pressure (CVP) monitoring. Hydrostatic pressures caused by level differences (leveling pressure) between a reference point (on the center of the left biceps brachii muscle) and the transducers (fixed on the right side of the operating table) for arterial and central lines were continuously measured using a leveling transducer. Adjusted pressures were calculated as measured pressure - leveling pressure. Hypotension (mean arterial pressure < 80, <70, and < 60 mmHg), and CVP (< 6, ≥6 and < 15, or ≥ 15 mmHg) and pulmonary artery pressure (PAP, mean > 20 mmHg) levels were determined using unadjusted and adjusted pressures. RESULTS: Twenty-two patients were included in the analysis. Leveling pressure ≥ 3 mmHg and ≥ 5 mmHg observed at 46.0 and 18.7% of pooled data points, respectively. Determinations of hypotension using unadjusted and adjusted pressures showed disagreements ranging from 3.3 to 9.4% depending on the cutoffs. Disagreements in defined levels of CVP and PAP were observed at 23.0 and 17.2% of the data points, respectively. CONCLUSIONS: The errors in pressure measurement due to changes in transducer level were not trivial and caused variable disagreements in the determination of MAP, CVP, and PAP levels. To prevent distortions in intraoperative hemodynamic management, strategies should be sought to minimize or adjust for these errors in clinical practice. TRIAL REGISTRATION: cris.nih.go.kr (KCT0006510).

DDM-HSA: Dual Deterministic Model-Based Heart Sound Analysis for Daily Life Monitoring.

A sudden cardiac event in patients with heart disease can lead to a heart attack in extreme cases. Therefore, prompt interventions for the particular heart situation and periodic monitoring are critical. This study focuses on a heart sound analysis method that can be monitored daily using multimodal signals acquired with wearable devices. The dual deterministic model-based heart sound analysis is designed in a parallel structure that uses two bio-signals (PCG and PPG signals) related to the heartbeat, enabling more accurate heart sound identification. The experimental results show promising performance of the proposed Model III (DDM-HSA with window and envelope filter), which had the highest performance, and S1 and S2 showed average accuracy (unit: %) of 95.39 (±2.14) and 92.55 (±3.74), respectively. The findings of this study are anticipated to provide improved technology to detect heart sounds and analyze cardiac activities using only bio-signals that can be measured using wearable devices in a mobile environment.

Monitoring trafficking and expression of hemagglutinin-tagged transient receptor potential melastatin 4 channel in mammalian cells.

The TRPM4 gene encodes a Ca2+-activated monovalent cation channel called transient receptor potential melastatin 4 (TRPM4) that is expressed in various tissues. Dysregulation or abnormal expression of TRPM4 has been linked to a range of diseases. We introduced the hemagglutinin (HA) tag into the extracellular S6 loop of TRPM4, resulting in an HA-tagged version called TRPM4-HA. This TRPM4-HA was developed to investigate the purification, localization, and function of TRPM4 in different physiological and pathological conditions. TRPM4-HA was successfully expressed in the intact cell membrane and exhibited similar electrophysiological properties, such as the current-voltage relationship, rapid desensitization, and current size, compared to the wild-type TRPM4. The presence of the TRPM4 inhibitor 9-phenanthrol did not affect these properties. Furthermore, a wound-healing assay showed that TRPM4-HA induced cell proliferation and migration, similar to the native TRPM4. Co-expression of protein tyrosine phosphatase, non-receptor type 6 (PTPN6 or SHP-1) with TRPM4-HA led to the translocation of TRPM4-HA to the cytosol. To investigate the interaction between PTPN6 and tyrosine residues of TRPM4 in enhancing channel activity, we generated four mutants in which tyrosine (Y) residues were substituted with phenylalanine (F) at the N-terminus of TRPM4. The YF mutants displayed properties and functions similar to TRPM4-HA, except for the Y256F mutant, which showed resistance to 9-phenanthrol, suggesting that Y256 may be involved in the binding site for 9-phenanthrol. Overall, the creation of HA-tagged TRPM4 provides researchers with a valuable tool to study the role of TRPM4 in different conditions and its potential interactions with other proteins, such as PTPN6.

Transtibial pull-out repair of lateral meniscus posterior root is beneficial for graft maturation after anterior cruciate ligament reconstruction: a retrospective study.

PURPOSE: To determine the repair of LMPR lesions would improve the ACL graft maturation. METHOD: A total of 49 patients underwent ACL reconstruction were included in this study. Patients were furtherly sub-grouped according to the status of LMPR: intact (17), repair (16) and resected (16). Assessments performed pre- and 2 years post-operatively included patients-reported scores and arthrometer side-to-side difference. Magnetic resonance imaging was used 2 years after the surgery to compare the lateral meniscal extrusion (LME), anterior tibial subluxation of the medial compartment (ATSMC), anterior tibial subluxation of the lateral compartment (ATSLC), the difference of ATSMC and ATSLC, and signal/noise quotient (SNQ) of ACL graft. RESULTS: In LMPR resected group, it showed greater post-operative ATSMC-ATSLC difference when compared with pre-operatively (P = 0.006) and with the other 2 groups (intact: P = 0.031; repair: P = 0.048). SNQ of ACL graft was higher in LMPR resected group than those in LMPR intact (P = 0.004) and repair group (P = 0.002). The LMPR repair group showed significant reduction in LME post-operatively (P = 0.001). Post-operative measures on ATSLC-ATSMC difference (ß = 0.304, P = 0.049) and LME (ß = 0.492, P = 0.003) showed significant association with graft SNQ. CONCLUSIONS: Transtibial repair of LMPR concomitant with ACL reconstruction restored translational stability, reduced meniscus extrusion, making it beneficial for ACL graft maturation.

Novel Design of a Multimodal Technology-Based Smart Stethoscope for Personal Cardiovascular Health Monitoring.

Heart sounds and heart rate (pulse) are the most common physiological signals used in the diagnosis of cardiovascular diseases. Measuring these signals using a device and analyzing their interrelationships simultaneously can improve the accuracy of existing methods and propose new approaches for the diagnosis of cardiovascular diseases. In this study, we have presented a novel smart stethoscope based on multimodal physiological signal measurement technology for personal cardiovascular health monitoring. The proposed device is designed in the shape of a compact personal computer mouse for easy grasping and attachment to the surface of the chest using only one hand. A digital microphone and photoplehysmogram sensor are installed on the bottom and top surfaces of the device, respectively, to measure heart sound and pulse from the user's chest and finger simultaneously. In addition, a high-performance Bluetooth Low Energy System-on-Chip ARM microprocessor is used for pre-processing of measured data and communication with the smartphone. The prototype is assembled on a manufactured printed circuit board and 3D-printed shell to conduct an in vivo experiment to test the performance of physiological signal measurement and usability by observing users' muscle fatigue variation.

Depressed Mood Prediction of Elderly People with a Wearable Band.

Depression in the elderly is an important social issue considering the population aging of the world. In particular, elderly living alone who has narrowed social relationship due to bereavement and retirement are more prone to be depressed. Long-term depressed mood can be a precursor to eventual depression as a disease. Our goal is how to predict the depressed mood of single household elderly from unobtrusive monitoring of their daily life. We have selected a wearable band with multiple sensors for monitoring elderly people. Depression questionnaire has been surveyed periodically to be used as the labels. Instead of working with depression patients, we recruited 14 single household elderly people from a nearby community. The wearable band provided daily activity and biometric data for 71 days. From the data, we generate a depressed mood prediction model. Multiple features from the collected sensor data are exploited for model generation. One general model is generated to be used as the baseline for the initial model deployment. Personal models are also generated for model refinement. The general model has a high recall of 80% in an MLP model. Individual models achieved an average recall of 82.7%. In this study, we have demonstrated that we can generate depressed mood prediction models with data collected from real daily living. Our work has shown the feasibility of using a wearable band as an unobtrusive depression monitoring sensor even for elderly people.

Is measurement of central venous pressure required to estimate systemic vascular resistance? A retrospective cohort study.

BACKGROUND: The clinical range of central venous pressure (CVP) (typically 5 to 15 mmHg) is much less than the range of mean arterial blood pressure (60 to 120 mmHg), suggesting that CVP may have little impact on estimation of systemic vascular resistance (SVR). The accuracy and feasibility of using an arbitrary CVP rather than actual CVP for the estimation of SVR during intraoperative period is not known. METHODS: Using vital records obtained from patients who underwent neurological and cardiac surgery, the present study retrospectively calculated SVR using fixed values of CVP (0, 5, 10, 15, and 20 mmHg) and randomly changing values of CVP (5 to 15 mmHg) and compared these calculated SVRs with actual SVR, calculated using actual CVP. Differences between actual SVR and SVRs based on fixed and random CVPs were quantified as root mean square error (RMSE) and mean absolute percentage error (MAPE). Bland-Altman analysis and four-quadrant plot analysis were performed. RESULTS: A total of 34 patients are included, including 18 who underwent neurosurgery and 16 who underwent cardiac surgery; 501,380 s (139.3 h) of data was analyzed. The SVR derived from a fixed CVP of 10 mmHg (SVRf10) showed the highest accuracy (RMSE: 115 and 104 [dynes/sec/cm- 5] and MAPE: 6.3 and 5.7% in neurological and cardiac surgery, respectively). The 95% limits of agreement between SVRf10 and actual SVR were - 208.5 (95% confidence interval [CI], - 306.3 to - 148.1) and 242.2 (95% CI, 181.8 to 340.0) dynes/sec/cm- 5 in neurosurgery and - 268.1 (95% CI, - 367.5 to - 207.7) and 163.2 (95% CI, 102.9 to 262.6) dynes/sec/cm- 5 in cardiac surgery. All the SVRs derived from the fixed CVPs (regardless of its absolute value) showed excellent trending ability (concordance rate > 0.99). CONCLUSIONS: SVR can be estimated from a fixed value of CVP without causing significant deviation or a loss of trending ability. However, caution is needed when using point estimates of SVR when the actual CVP is expected to be out of the typical clinical range. TRIAL REGISTRATION: This study was registered Clinical Research Information Service, a clinical trial registry in South Korea ( KCT0006187 ).

Effect of silicon-doped calcium phosphate cement on angiogenesis based on controlled macrophage polarization.

Vascularization is an important early indicator of osteogenesis involving biomaterials. Bone repair and new bone formation are associated with extensive neovascularization. Silicon-based biomaterials have attracted widespread attention due to their rapid vascularization. Although calcium phosphate cement (CPC) is a mature substitute for bone, the application of CPC is limited by its slow degradation and insufficient promotion of neovascularization. Calcium silicate (CS) has been shown to stimulate vascular endothelial proliferation. Thus, CS may be added to CPC (CPC-CS) to improve the biocompatibility and neovascularization of CPC. In the early phase of bone repair (the inflammatory phase), macrophages accumulate around the biomaterial and exert both anti- and pro-inflammatory effects. However, the effect of CPC-CS on macrophage polarization is not known, and it is not clear whether the effect on neovascularization is mediated through macrophage polarization. In the present study, we explored whether silicon-mediated macrophage polarization contributes to vascularization by evaluating the CPC-CS-mediated changes in the immuno-environment under different silicate ion contents both in vivo and in vitro. We found that the silicon released from CPC-CS can promote macrophage polarization into the M2 phenotype and rapid endothelial neovascularization during bone repair. Dramatic neovascularization and osteogenesis were observed in mouse calvarial bone defects implanted with CPC-CS containing 60% CS. These findings suggest that CPC-CS is a novel biomaterial that can modulate immune response, promote endothelial proliferation, and facilitate neovascularization and osteogenesis. Thus, CPC-CS shows potential as a bone substitute material.

Development of a Finger-Ring-Shaped Hybrid Smart Stethoscope for Automatic S1 and S2 Heart Sound Identification.

Cardiac auscultation is one of the most popular diagnosis approaches to determine cardiovascular status based on listening to heart sounds with a stethoscope. However, heart sounds can be masked by visceral sounds such as organ movement and breathing, and a doctor's level of experience can more seriously affect the accuracy of auscultation results. To improve the accuracy of auscultation, and to allow nonmedical staff to conduct cardiac auscultation anywhere and anytime, a hybrid-type personal smart stethoscope with an automatic heart sound analysis function is presented in this paper. The device was designed with a folding finger-ring shape that can be worn on the finger and placed on the chest to measure photoplethysmogram (PPG) signals and acquire the heart sound simultaneously. The measured heart sounds are detected as phonocardiogram (PCG) signals, and the boundaries of the heart sound variation and the peaks of the PPG signal are detected in preprocessing by an advanced Shannon entropy envelope. According to the relationship between PCG and PPG signals, an automatic heart sound analysis algorithm based on calculating the time interval between the first and second heart sounds (S1, S2) and the peak of the PPG was developed and implemented via the manufactured prototype device. The prototype device underwent accuracy and usability testing with 20 young adults, and the experimental results showed that the proposed smart stethoscope could satisfactorily collect the heart sounds and PPG signals. In addition, within the developed algorithm, the device was as accurate in start-points of heart sound detection as professional physiological signal-acquisition systems. Furthermore, the experimental results demonstrated that the device was able to identify S1 and S2 heart sounds automatically with high accuracy.

Using Twitter to Understand the Effects of the Cameroon Anglophone Crisis on Social Determinants of Health.

Insufficient opportunities to collect data on public health exist in armed conflict regions. Increased use of social media during war and conflict has allowed for data collection in situations where information is usually difficult to obtain. In this study, Twitter, a public social media platform, was used as a source of data and information to gain insight into how the Cameroon Anglophone Crisis impacts public health in the population. Our findings revealed that Twitter was being used to share information and call for action. Analysis of tweets revealed 8 distinct themes, which illustrated the impact of the crisis on the social determinants of health: neglect from government related to the social determinants of health; education; loss of employment; increased poverty; housing and homelessness; social exclusion and oppression; women and gender inequality; and health services. This study provides insight into the significant impact on public health in Cameroon caused by the Anglophone Crisis, and demonstrates the potential benefits of social media for gathering information about public health in crisis situations.

FCHO1560-571 peptide, a PKB kinase motif, inhibits tumor progression.

BACKGROUND: Cell division is regulated by protein kinase B (PKB)-mediated FCH domain only 1 (FCHO1) phosphorylation. METHODS: FCHO1560-571, a synthetic water-soluble peptide, was generated from the PKB substrate motif 560PPRRLRSRKVSC571 found in the human FCHO1 protein. RESULTS: In this study, we found that in vitro FCHO1560-571 inhibits cell proliferation via PKB/ERK/SMAD4 pathways in KRAS-mutated A549 lung cancer cells. In addition, FCHO1560-571, at effective doses of 15 and 30 mg/kg, significantly suppressed tumor growth and decreased the size and weight of tumors in A549-xenograft mice. CONCLUSION: These results suggest that the FCHO1560-571 peptide could be a potential therapy for lung cancer.

Complete genome sequence and comparative genomic analysis of hyper-aerotolerant Campylobacter lari strain SCHS02 isolated from duck for its potential pathogenicity.

Campylobacter lari strain SCHS02, a novel hyper-aerotolerant strain that survives under aerobic conditions, was isolated from retail duck meat. The genome is a single chromosome of 1,520,838 base pairs, with a mean GC content of 29.7%. It harbors 1546 protein-coding sequences and 45 tRNA and 9 rRNA genes. Genes associated with the oxidative stress response, including perR, bcp, ahpC, and sodB, were identified in the genome. Furthermore, 68 virulence-related genes were identified and sorted into 9 classes and 14 subclasses. The virulence gene profile of SCHS02 was similar to those of two human clinical C. lari isolates. Comparative genomic analysis of strain SCHS02 and 18 C. lari strains retrieved from a public database revealed the core and accessory gene profiles of C. lari strains, as well as putative core gene involved in halotolerance. Phylogenetic analysis revealed that strain SCHS02 is genetically related to isolates from bird samples and human clinical isolates, rather than to isolates from other environmental sources. These findings reveal essential genomic information about the newly identified hyper-aerotolerant C. lari strain isolated from a duck source, providing a basis for future studies of the strain considering its potential threat to public health and further research of the pathogenicity of C. lari.

Combined Enrichment and Quantitative Polymerase Chain Reaction to Improve Sensitivity and Reduce Time of Detection of Listeria monocytogenes in Mushrooms.

This study evaluated a combined method for the detection of Listeria monocytogenes in mushrooms, involving enrichment and quantitative real-time polymerase chain reaction (qPCR), to improve sensitivity and reduce detection time. The growth of L. monocytogenes was evaluated in Listeria enrichment broth (LEB) with modified carbon and nitrogen sources, increasing sodium concentrations, and added micronutrients. Primers targeting the L. monocytogenes iap (iap1 and iap2), hlyA (hlyA1-hlyA6), and prfA (prfA1-prfA4) genes were developed and their sensitivity and specificity were evaluated. The greatest increase in L. monocytogenes cell count was observed after 6-h incubation at 30°C in LEB+2 × FAC (LEB plus 20 mL/L ferric ammonium citrate), where cell count increased by 1.4 log CFU (colony-forming unit)/mL, compared with 0.9 log CFU/mL in LEB (p < 0.05). iap2 primers targeting the iap gene showed high specificity and were the most sensitive among those tested, with a detection limit of 2 log CFU/mL in LEB medium, 3.1 log CFU/g in golden needle mushroom, and 3.5 log CFU/g in large oyster mushroom. When applied to detection in golden needle mushrooms, a combination of 3-h incubation in LEB+2 × FAC medium and qPCR analysis with iap2 primers permitted detection of L. monocytogenes, even at an inoculum of 1 log CFU/g. Similarly, in large oyster mushrooms, 10-h enrichment in LEB+2 × FAC medium resulted in a cell count of 3.7 log CFU/g. These results indicate that a combined detection method, using LEB+2 × FAC medium for enrichment followed by qPCR with iap2 primer pair, can reduce enrichment time and improve the sensitivity and specificity of L. monocytogenes detection in mushrooms.

Asymptomatic Clostridium perfringens Inhabitation in Intestine Can Cause Inflammation, Apoptosis, and Disorders in Brain.

Clostridium perfringens (CP) is a foodborne pathogen. The bacterium can also inhabit human gut without symptoms of foodborne illness. However, the clinical symptoms of long-term inhabitation have not been known yet. Therefore, the objective of this study was to elucidate the relationship between intestinal CP and other internal organs. Phosphate-buffered saline (PBS) and CP were orally injected into 5-week-old (YOUNG) and 12-month-old C57BL6/J (ADULT) mice. Gene expression levels related to inflammation (tumor necrosis factor-α [TNF-α], interleukin [IL]-1ß, and IL-6) and oxidative stress (superoxide dismutase [SOD]1, SOD2, SOD3, glutathione reductase [GSR], glutathione peroxidase [GPx]3, and catalase [CAT]) responses were evaluated in the brain, small intestine, and liver. In addition, apoptosis-related (BCL2-associated X [BAX]1 and high-mobility group box-1 [HMGB1]) and brain disorder-related genes (CCAAT-enhancer-binding protein [C/EBP]-ß, C/EBPδ, C/EBP homologous protein [CHOP], and amyloid precursor protein [APP]) as brain damage markers were examined. The protein expressions in the brain were also measured. Gene expression levels of inflammation and oxidative stress responses were higher (p < 0.05) in brains of CP-YOUNG and CP-ADULT mice, compared with PBS-YOUNG and PBS-ADULT, and the gene expression levels were higher (p < 0.05) in brains of CP-ADULT mice than CP-YOUNG mice. Apoptosis-related (BAX1 and HMGB1) and brain disorder-related genes (C/EBPß, C/EBPδ, CHOP, and APP) were higher (p < 0.05) in brains of CP-challenged mice, compared with PBS-challenged mice. Even oxidative stress response (GPx and SOD2), cell damage-related (HMGB1), and ß-amyloid proteins were higher (p < 0.05) in brains of CP- than in PBS-challenged mice. C/EBP protein was higher (p < 0.05) in CP-YOUNG, compared with PBS-YOUNG mice. However, these clinical symptoms were not observed in small intestine and liver. These results indicate that although asymptomatic intestinal CP do not cause foodborne illness, their inhabitation may cause brain inflammation, oxidative stress, apoptosis, and cell damage, which may induce disorders, especially for the aged group.

Vitamin E (α-tocopherol) consumption influences gut microbiota composition.

This study evaluated if vitamin E consumption affects gut microbiota. Mice were grouped into control, low vitamin E (LV), and high vitamin E (HV). LV and HV were fed DL-α-tocopherol at 0.06 mg/20 g and 0.18 mg/20 g of body weight per day, respectively, for 34 days. Body weight of mice was measured before and after vitamin E treatment. Animals were sacrificed, liver, spleen, small intestine and large intestine collected, and weight and length were measured. Composition of gut microbiota was determined by microbiome analysis. Spleen weight index of LV was the highest. However, liver weight indices and intestinal lengths were not different. Body weights of LV group were higher than those of control. Ratio of Firmicutes to Bacteroidetes was different in LV compared to control and HV. These results indicate that low-level consumption of vitamin E increases spleen and body weight, and changes gut microbiota.