Tenovin-1, a Selective SIRT1/2 Inhibitor, Attenuates High-fat Diet-induced Hepatic Fibrosis via Inhibition of HSC Activation in ZDF Rats.

Type 2 diabetes mellitus (T2DM) increases the risk of non-alcoholic fatty liver disease (NAFLD) progression to advanced stages, especially upon high-fat diet (HFD). HFD-induced hepatic fibrosis can be marked by oxidative stress, inflammation, and activation of hepatic stellate cells. Sirtuin 1/2 (SIRT1/2), NAD-dependent class III histone deacetylases, are involved in attenuation of fibrosis. In our conducted research, TGF-ß1-activated LX-2 cells, free fatty acid (FFA)-treated simultaneous co-culture (SCC) cells, and HFD-induced hepatic fibrosis in Zucker diabetic fatty (ZDF) rats, a widely used animal model in the study of metabolic syndromes, were used to evaluate the protective effect of Tenovin-1, a SIRT1/2 inhibitor. ZDF rats were divided into chow diet, HFD, and HFD + Tenovin-1 groups. Tenovin-1 reduced hepatic damage, inhibited inflammatory cell infiltration, micro/ macro-vesicular steatosis and prevented collagen deposition HFD-fed rats. Tenovin-1 reduced serum biochemical parameters, triglyceride (TG) and malondialdehyde (MDA) levels but increased glutathione, catalase, and superoxide dismutase levels. Tenovin-1 mitigated proinflammatory cytokines IL-6, IL-1ß, TNFα and fibrosis biomarkers in HFD rats, TGF-ß1-activated LX-2 and FFA treated SCC cells. Additionally, Tenovin-1 suppressed SIRT1/2 expression and inhibited JNK-1 and STAT3 phosphorylation in HFD rats and FFA-treated SCC cells. In conclusion, Tenovin-1 attenuates hepatic fibrosis by stimulating antioxidants and inhibiting inflammatory cytokines under HFD conditions in diabetic rats.

Clinicomicrobiological risk factors for infective endocarditis in viridans group streptococci bacteraemia.

BACKGROUND: When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear. OBJECTIVES: We aimed to identify independent risk factors for IE in patients with VGS BSI. METHODS: This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases. RESULTS: Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14-32.58; P < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03-12.94; P = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96-1.00; P = 0.015), solid cancer (aOR, 0.26; 95% CI, 0.13-0.53; P < 0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01-0.41; P = 0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87-14.68; P < 0.001). CONCLUSIONS: Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors.

Delay in the diagnosis of Brucella abortus bacteremia in a nonendemic country: a case report.

BACKGROUND: It is challenging to diagnose brucellosis in nonendemic regions because it is a nonspecific febrile disease. The accurate identification of Brucella spp. in clinical microbiology laboratories (CMLs) continues to pose difficulties. Most reports of misidentification are for B. melitensis, and we report a rare case of misidentified B. abortus. CASE PRESENTATION: A 67-year-old man visited an outpatient clinic complaining of fatigue, fever, and weight loss. The patient had a history of slaughtering cows with brucellosis one year prior, and his Brucella antibody tests were negative twice. After blood culture, the administration of doxycycline and rifampin was initiated. The patient was hospitalized due to a positive blood culture. Gram-negative coccobacilli were detected in aerobic blood culture bottles, but the CML's lack of experience with Brucella prevented appropriate further testing. Inaccurate identification results were obtained for a GN ID card of VITEK 2 (bioMérieux, USA) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using a MALDI Biotyper (Bruker, Germany). The strain showed 100.0% identity with Brucella spp. according to 16S rRNA sequencing. MALDI-TOF MS peaks were reanalyzed using the CDC MicrobeNet database to determine Brucella spp. (score value: 2.023). The patient was discharged after nine days of hospitalization and improved after maintaining only doxycycline for six weeks. The isolate was also identified as Brucella abortus by genomic evidence. CONCLUSION: Automated identification instruments and MALDI-TOF MS are widely used to identify bacteria in CMLs, but there are limitations in accurately identifying Brucella spp. It is important for CMLs to be aware of the possibility of brucellosis through communication with clinicians. Performing an analysis with an additional well-curated MALDI-TOF MS database such as Bruker security-relevant (SR) database or CDC MicrobeNet database is helpful for quickly identifying the genus Brucella.

Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions.

BACKGROUND: Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of UA's long-term treatment of AD and mechanisms of action are unknown. METHODS: We addressed these questions in three mouse models of AD with behavioral, electrophysiological, biochemical, and bioinformatic approaches. RESULTS: Long-term UA treatment significantly improved learning, memory, and olfactory function in different AD transgenic mice. UA also reduced amyloid beta (Aß) and tau pathologies and enhanced long-term potentiation. UA induced mitophagy via increasing lysosomal functions. UA improved cellular lysosomal function and normalized lysosomal cathepsins, primarily cathepsin Z, to restore lysosomal function in AD, indicating the critical role of cathepsins in UA-induced therapeutic effects on AD. CONCLUSIONS: Our study highlights the importance of lysosomal dysfunction in AD etiology and points to the high translational potential of UA. HIGHLIGHTS: Long-term urolithin A (UA) treatment improved learning, memory, and olfactory function in Alzheimer's disease (AD) mice. UA restored lysosomal functions in part by regulating cathepsin Z (Ctsz) protein. UA modulates immune responses and AD-specific pathophysiological pathways.

Exploring the Metabolic Effects of a Herbal Remedy of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia Extracts: Unraveling Its Therapeutic Potential as a Topical Application for Atopic Dermatitis Treatment.

Our previous study demonstrated that our novel herbal remedy, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum Cassia extracts, exhibits a therapeutic effect in 1-chloro-2,4-dinitrobenzene (DNCB)-induced mice by inhibiting the Th-2 inflammatory response upon oral administration. It also ameliorated imbalances in lipid metabolism related to the skin barrier function in keratinocytes, indicating its potential as a topical agent. This study aims to further investigate the therapeutic effects and metabolic mechanisms of its topical application. The anti-atopic effect was evaluated using dermatitis scores, histopathological analysis, and immune cell factors in DNCB-induced mice. Metabolomic profiling of serum and lesional skin was conducted to elucidate the metabolic mechanisms. The topical application significantly reduced dermatitis scores, mast cell infiltration, and serum levels of immunoglobulin E (IgE), IFN-γ, interleukin (IL)-4, IL-17, and thymic stromal lymphopoietin (TSLP), demonstrating its effectiveness in treating atopic dermatitis (AD). Serum metabolomics revealed alterations in fatty acid metabolism related to the pro-inflammatory response. In lesional skin, metabolic markers associated with oxidative stress, immune regulation, and AD symptoms were restored. This study demonstrated its potential as a topical agent in suppressing Th-2 inflammatory responses and improving metabolic abnormalities related to AD symptoms, providing crucial insights for developing natural AD treatments.

Memory-electroluminescence for multiple action-potentials combination in bio-inspired afferent nerves.

The development of optoelectronics mimicking the functions of the biological nervous system is important to artificial intelligence. This work demonstrates an optoelectronic, artificial, afferent-nerve strategy based on memory-electroluminescence spikes, which can realize multiple action-potentials combination through a single optical channel. The memory-electroluminescence spikes have diverse morphologies due to their history-dependent characteristics and can be used to encode distributed sensor signals. As the key to successful functioning of the optoelectronic, artificial afferent nerve, a driving mode for light-emitting diodes, namely, the non-carrier injection mode, is proposed, allowing it to drive nanoscale light-emitting diodes to generate a memory-electroluminescence spikes that has multiple sub-peaks. Moreover, multiplexing of the spikes can be obtained by using optical signals with different wavelengths, allowing for a large signal bandwidth, and the multiple action-potentials transmission process in afferent nerves can be demonstrated. Finally, sensor-position recognition with the bio-inspired afferent nerve is developed and shown to have a high recognition accuracy of 98.88%. This work demonstrates a strategy for mimicking biological afferent nerves and offers insights into the construction of artificial perception systems.

AI-based betting anomaly detection system to ensure fairness in sports and prevent illegal gambling.

This study develops a solution to sports match-fixing using various machine-learning models to detect match-fixing anomalies, based on betting odds. We use five models to distinguish between normal and abnormal matches: logistic regression (LR), random forest (RF), support vector machine (SVM), the k-nearest neighbor (KNN) classification, and the ensemble model-a model optimized from the previous four. The models classify normal and abnormal matches by learning their patterns using sports betting odds data. The database was developed based on the world football league match betting data of 12 betting companies, which offered a vast collection of data on players, teams, game schedules, and league rankings for football matches. We develop an abnormal match detection model based on the data analysis results of each model, using the match result dividend data. We then use data from real-time matches and apply the five models to construct a system capable of detecting match-fixing in real time. The RF, KNN, and ensemble models recorded a high accuracy, over 92%, whereas the LR and SVM models were approximately 80% accurate. In comparison, previous studies have used a single model to examine football match betting odds data, with an accuracy of 70-80%.

Early-Onset Hearing Loss in Mouse Models of Alzheimer's Disease and Increased DNA Damage in the Cochlea.

There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polß+/-. The 3xTgAD/Polß+/- mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polß+/- mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD.

Factors associated with sedentary behavior among community-dwelling breast cancer survivors aged 50 years or older.

Although increased sedentary behavior is associated with poor health outcomes among breast cancer survivors, the factors associated with high sedentary time in community-dwelling breast cancer survivors are unknown. This study aimed to identify factors associated with sedentary behavior in Korean community-dwelling breast cancer survivors aged ≥ 50 years. We included 205 breast cancer survivors from the Korea National Health and Nutrition Examination Survey. Total daily sedentary time was evaluated using questions from the Korean version of the Global Physical Activity Questionnaire. We used complex-sample multivariable-adjusted logistic regression analyses to analyze the associations between sociodemographic factors, medical factors, and health-related quality of life and high sedentary time (≥ 420 min/day). Among the Korean community-dwelling breast cancer survivors, 48.2% had a high daily sedentary time. Insufficient aerobic exercise (OR 2.29; 95% CI 1.12-4.69), diabetes (OR 3.37; 95% CI 1.22-9.33), and unemployed status (OR 2.29; 95% CI 1.05-5.02) were independently associated with high sedentary time after the adjustment for multiple sociodemographic and medical confounders. Participants with a low sedentary time (< 420 min/day) showed a significantly higher mean European Quality of Life 5-Dimensions (EQ-5D) index than those with a high sedentary time after adjusting for multiple confounders (0.89 ± 0.03 vs. 0.82 ± 0.04; P = 0.001). Among the EQ-5D dimensions, problems in mobility (OR 3.37; 95% CI 1.42-7.98) and pain/discomfort (OR 2.64; 95% CI 1.24-5.63) dimensions showed positive associations with high sedentary time. Middle- or older-aged breast cancer survivors with insufficient aerobic exercise, diabetes, unemployed status, and impaired quality of life are more likely to have a high sedentary time. Reducing sedentary behavior in this population requires a tailored approach that considers diverse sociodemographic, medical, and quality-of-life factors.

Differential association between physical activity behaviours and dynapenia by comorbid diseases in community-dwelling Korean older adults.

BACKGROUND: Physical activity (PA) behaviours and comorbid diseases are associated with muscle strength. However, the association between dynapenia and detailed PA behaviours, including participation in aerobic and resistance exercises and sedentary behaviour (SB), in relation to comorbid diseases has not yet been investigated. Using nationwide data, this study aimed to evaluate the independent association of dynapenia with detailed PA behaviour (participation in aerobic and resistance exercises and SB), and assess the differential associations of detailed PA behaviour with dynapenia according to comorbid diseases with prevalent sarcopenia. METHODS: A total of 7,558 community-dwelling older adults aged ≥ 65 years who were included in the Korea National Health and Nutrition Examination Survey from 2014 to 2019 were included in the present study. Cross-sectional associations between PA behaviours (participation in aerobic exercise, participation in resistance exercise, and SB) and dynapenia were analysed using complex-sample multivariable-adjusted logistic regression models according to the type of comorbid disease (cardiovascular disease [CVD], diabetes mellitus [DM], and chronic lung disease [CLD]). RESULTS: Sufficient aerobic exercise, sufficient resistance exercise, and low sedentary time of < 420 min/day showed independent negative associations with dynapenia (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.60-0.83; OR, 0.54; 95% CI, 0.42-0.69; and OR, 0.84; 95% CI, 0.72-0.97, respectively). Among the participants with CVD or CLD, the associations of sufficient resistance exercise (OR, 0.46; 95% CI, 0.26-0.82 and OR, 0.51; 95% CI, 0.35-0.75 for CVD and CLD, respectively) and low sedentary time (OR, 0.66; 95% CI, 0.45-0.98 and OR, 0.71; 95% CI, 0.55-0.93 for CVD and CLD, respectively) with dynapenia were significant, whereas the association of sufficient aerobic exercise with dynapenia was insignificant. Meanwhile, in participants with DM, sufficient aerobic exercise (OR, 0.70; 95% CI, 0.52-0.94) and sufficient resistance exercise (OR, 0.45; 95% CI, 0.29-0.70) were independently associated with dynapenia, whereas no association between SB and dynapenia was found. CONCLUSION: We observed an independent inverse association between PA behaviours and dynapenia. Disease-specific associations between each PA behaviour (sufficient aerobic exercise, sufficient resistance exercise, and low sedentary time) and dynapenia differed in the older adults. Therefore, these differences should be acknowledged during interventions for this population.

Efficacy of intradialytic neuromuscular electrical stimulation and oral nutritional supplementation in hemodialysis patients: a multicenter, randomized controlled trial.

Background: Sarcopenia is common in hemodialysis patients. This study aimed to evaluate the effect of simultaneous nutritional support and intradialytic neuromuscular electrical stimulation (NMES) in hemodialysis patients. Methods: We performed a 12-week, multicenter, randomized controlled trial. The participants were randomly assigned to the control group, the protein group (25 g of protein at every dialysis session), the NMES group (intradialytic NMES to quadriceps femoris muscles), and the NMES + P group (NMES with protein supplementation). The primary outcome was the difference in hand grip strength (HGS) and leg muscle strength (LMS) among groups. Secondary outcomes included body composition, physical performance (the 10-m walk test and the timed up and go test [TUG]), and questionnaires about quality of life (QoL), physical activity, and depression. In addition, subgroup analysis was performed by dividing NMES and NMES + P groups into high- and low-intensity NMES groups. Results: Fifty-nine patients completed all the study outcomes. There was no difference in muscle strength (HGS and LMS) and muscle mass among groups. Gait speed improved in NMES and NMES + P groups. Subscale scores for QoL (kidney disease effect, role limitations due to physical or emotional problems, and overall health ratings) improved in the NMES + P group. In subgroup analysis, LMS and TUG improved only in the high-intensity NMES group. Conclusion: In this study, NMES and-/or- protein supplementation did not make a significant difference in HGS and LMS. However, NMES or NMES + P improved functional capacity and QoL. Furthermore, higher NMES was superior in improving LMS and functional capacity.

Electron Oscillation-Induced Splitting Electroluminescence from Nano-LEDs for Device-Level Encryption.

Data security is a major concern in digital age, which generally relies on algorithm-based mathematical encryption. Recently, encryption techniques based on physical principles are emerging and being developed, leading to the new generation of encryption moving from mathematics to the intersection of mathematics and physics. Here, device-level encryption with ideal security is ingeniously achieved using modulation of the electron-hole radiative recombination in a GaN-light-emitting diode (LED). When a nano-LED is driven in the non-carrier injection mode, the oscillation of confined electrons can split what should be a single light pulse into multiple pulses. The morphology (amplitude, shape, and pulse number) of those history-dependent multiple pulses that act as carriers for transmitted digital information depends highly on the parameters of the driving signals, which makes those signals mathematically uncrackable and can increase the volume and security of transmitted information. Moreover, a hardware and software platform are designed to demonstrate the encrypted data transmission based on the device-level encryption method, enabling recognition of the entire ASCII code table. The device-level encryption based on splitting electroluminescence provides an encryption method during the conversion process of digital signals to optical signals and can improve the security of LED-based communication.

Chlorophyll a and novel synthetic derivatives alleviate atopic dermatitis by suppressing Th2 cell differentiation via IL-4 receptor modulation.

Atopic dermatitis (AD) treatment has largely relied on non-specific broad immunosuppressants despite their long-term toxicities until the approval of dupilumab, which blocks IL-4 signaling to target Th2 cell responses. Here, we report the discovery of compound 4aa, a novel compound derived from the structure of chlorophyll a, and the efficacy of chlorophyll a to alleviate AD symptoms by oral administration in human AD patients. 4aa downregulated GATA3 and IL-4 in differentiating Th2 cells by potently blocking IL-4 receptor dimerization. In the murine model, oral administration of 4aa reduced the clinical severity of symptoms and scratching behavior by 76% and 72%, respectively. Notably, the elevated serum levels of Th2 cytokines reduced to levels similar to those in the normal group after oral administration of 4aa. Additionally, the toxicological studies showed favorable safety profiles and good tolerance. In conclusion, 4aa may be applied for novel therapeutic developments for patients with AD.

Prosthetic valve endocarditis caused by Campylobacter fetus: a case report and literature review.

Campylobacter fetus is a Gram-negative bacillus typically associated with bacteremia in immunocompromised patients. Prosthetic valve endocarditis (PVE) is a serious complication of prosthetic valve surgery, with a high mortality rate if not treated promptly. We present a rare case of PVE caused by C. fetus. A man in his mid-60s presented to the Emergency Department with a fever and showed elevated C-reactive protein concentrations. He had prosthetic mitral and aortic valve replacement surgery 15 years previously. Gram-negative rods were detected in a blood culture. These rods were identified as C. fetus using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and confirmed by 16S rRNA sequencing. The patient was treated with gentamicin and imipenem, and underwent valve replacement surgery. C. fetus was isolated in a left atrial appendage swab obtained during the surgery. Follow-up blood cultures were negative after treatment. However, after a cardiac arrest event, the patient's general condition deteriorated, and he died. To the best of our knowledge, this is the first case of PVE caused by C. fetus in Korea and the second fatality to date. This case highlights the importance of considering C. fetus as a potential cause of PVE, even in patients without known risk factors.

Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice.

Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.

Effect of Wearing Personal Protective Equipment (PPE) for COVID-19 Treatment on Blood Culture Contamination: Implication for Optimal PPE Strategies.

The personal protective equipment (PPE) used to minimize exposure to hazards can hinder healthcare workers from performing sophisticated procedures. We retrospectively reviewed 77,535 blood cultures (202,012 pairs) performed in 28,502 patients from January 2020 to April 2022. The contamination rate of all blood cultures was significantly elevated in the coronavirus disease 2019 ward at 4.68%, compared to intensive care units at 2.56%, emergency rooms at 1.13%, hematology wards at 1.08%, and general wards at 1.07% (All of P < 0.001). This finding implies that wearing PPE might interfere with adherence to the aseptic technique. Therefore, a new PPE policy is needed that considers the balance between protecting healthcare workers and medical practices.

A Validation Study of a Deep Learning-Based Doping Drug Text Recognition System to Ensure Safe Drug Use among Athletes.

This study aimed to develop an English version of a doping drug-recognition system using deep learning-based optical character recognition (OCR) technology. A database of 336 banned substances was built based on the World Anti-Doping Agency's International Standard Prohibited List and the Korean Pharmaceutical Information Center's Drug Substance Information. For accuracy and validity analysis, 886 drug substance images, including 152 images of prescriptions and drug substance labels collected using data augmentation, were used. The developed hybrid system, based on the Tesseract OCR model, can be accessed by both a smartphone and website. A total of 5379 words were extracted, and the system showed character recognition errors regarding 91 words, showing high accuracy (98.3%). The system correctly classified all 624 images for acceptable substances, 218 images for banned substances, and incorrectly recognized 44 of the banned substances as acceptable. The validity analysis showed a high level of accuracy (0.95), sensitivity (1.00), and specificity (0.93), suggesting system validity. The system has the potential of allowing athletes who lack knowledge about doping to quickly and accurately check whether they are taking banned substances. It may also serve as an efficient option to support the development of a fair and healthy sports culture.

Lophomonas blattarum-like organism in bronchoalveolar lavage from a pneumonia patient: current diagnostic scheme and polymerase chain reaction can lead to false-positive results.

Lophomonas blattarum is an anaerobic protozoan living in the intestine of cockroaches and house dust mites, with ultramicroscopic characteristics such as the presence of a parabasal body, axial filament, and absence of mitochondria. More than 200 cases of Lophomonas infection of the respiratory tract have been reported worldwide. However, the current diagnosis of such infection depends only on light microscopic morphological findings from respiratory secretions. In this study, we attempted to provide more robust evidence of protozoal infection in an immunocompromised patient with atypical pneumonia, positive for Lophomonas-like protozoal cell forms. A direct search of bronchoalveolar lavage fluid via polymerase chain reaction (PCR), transmission electron microscopy (TEM), and metagenomic next-generation sequencing did not prove the presence of protozoal infection. PCR results were not validated with sufficient rigor, while de novo assembly and taxonomic classification results did not confirm the presence of an unidentified pathogen. The TEM results implied that such protozoal forms in light microscopy are actually non-detached ciliated epithelial cells. After ruling out infectious causes, the patient's final diagnosis was drug-induced pneumonitis. These findings underscore the lack of validation in the previously utilized diagnostic methods, and more evidence in the presence of L. blattarum is required to further prove its pathogenicity.

Anti-inflammatory effect and metabolic mechanism of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on atopic dermatitis in vivo and in vitro.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing skin disease accompanied by itchy and dry skin. AD is caused by complex interactions between innate and adaptive immune response. AD treatment include glucocorticoids and immunosuppressants. However, long-term treatment can have serious side effects. Thus, an effective AD treatment with fewer side effects is required. Natural materials, including herbal medicines, have potential applications. PURPOSE: This study evaluated the in vivo and in vitro therapeutic effects of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on AD and investigated the underlying metabolic mechanisms. METHODS: The anti-inflammatory effects of BS012 were assessed using a mouse model of AD induced by 1­chloro-2,4-dinitrobenzene (DNCB) and in tumor necrosis factor-alpha/interferon-gamma (TNF-α/IFN-γ) stimulated normal human epidermal keratinocytes (NHEKs). In DNCB-induced mice, total dermatitis score, histopathological analysis, and immune cell factors were assessed to evaluate the anti-atopic activity. In TNF-α/IFN-γ-stimulated NHEKs, pro-inflammatory cytokines, chemokines, and related signaling pathways were investigated. Serum and intracellular metabolomics were performed to identify the metabolic mechanism underlying the therapeutic effects of BS012 treatment. RESULTS: In DNCB-induced mice, BS012 showed potent anti-atopic activity, including reducing AD-like skin lesions and inhibiting the expression of Th2 cytokines and thymic stromal lymphopoietin. In TNF-α/IFN-γ-stimulated keratinocytes, BS012 dose-dependently inhibited the expression of pro-inflammatory cytokines and chemokines by blocking nuclear factor-kappa B and signal transducer and activator of transcription signaling pathways. Serum metabolic profiles of mice revealed significant changes in lipid metabolism related to inflammation in AD. Intracellular metabolome analysis revealed that BS012 treatment affected the metabolism associated with inflammation, skin barrier function, and lipid organization of the stratum corneum. CONCLUSION: BS012 exerts anti-atopic activity by reducing the Th2-specific inflammatory response and improving skin barrier function in AD in vivo and in vitro. These effects are mainly related to the inhibition of inflammation and recovery of metabolic imbalance in lipid organization. BS012, a novel combination with strong activity in suppressing the Th2-immune response, could be a potential alternative for AD treatment. Furthermore, the metabolic mechanism in vivo and in vitro using a metabolomics approach will provide crucial information for the development of natural products for AD treatment.