Pharmacologic management of trigeminal nerve injury after endodontic treatment: A retrospective analysis.

BACKGROUND: Trigeminal nerve injury following endodontic treatment, leading to unpleasant sensations or partial sensory loss in the face or oral mucosa, is uncommon but significant when it occurs. OBJECTIVE: This study analysed the pharmacological management of trigeminal nerve injuries (TNI) in a university-based hospital. METHODS: We conducted a retrospective analysis of 47 patients who visited the Department of Orofacial Pain and Oral Medicine at Yonsei University Dental Hospital, Seoul, Korea, after TNI following endodontic procedures in primary clinics. Both objective tests and subjective evaluations, assessed the extent and duration of sensory injury during the initial visit. The patient's initial symptoms, presumed cause of TNI, referral delay (time interval between TNI and the first visit to our clinic), and medications were analysed to determine whether these factors affected the outcomes. RESULTS: Most patients with TNI experienced dysesthesia with hypoesthesia (70.2%). The mandibular molars were predominantly affected (72.3%), with the inferior alveolar nerve (IAN), lingual nerve (LN), both IAN and LN, and maxillary nerve compromised in 83.0, 12.8, 2.1, and 2.1% of cases, respectively. Causes of TNI included local anaesthesia (29.8%), overfilling/over-instrumentation (25.5%), endodontic surgery (17.0%), and unknown factors (27.7%). A shorter referral delay was associated with better outcomes, with an average delay of 8.6 weeks for symptom improvement compared with 44.1 weeks for no change. The medication regimens included steroids, NSAIDs, topical lidocaine, vitamin B complex, Adenosine Triphosphate (ATP), antiepileptics, antidepressants, and opioids administered alone or in combination, with a mean duration of 20.7 weeks. 53.2% of the patients reported improvement in their symptoms, 27.7% experienced no significant change, and 19.1% had unknown outcomes. CONCLUSIONS: Swift referral to an orofacial pain specialist is recommended for effective recovery in cases of TNI arising from endodontic treatment.

Artificial intelligence in diagnosing dens evaginatus on periapical radiography with limited data availability.

This study aimed to develop an artificial intelligence (AI) model using deep learning techniques to diagnose dens evaginatus (DE) on periapical radiography (PA) and compare its performance with endodontist evaluations. In total, 402 PA images (138 DE and 264 normal cases) were used. A pre-trained ResNet model, which had the highest AUC of 0.878, was selected due to the small number of data. The PA images were handled in both the full (F model) and cropped (C model) models. There were no significant statistical differences between the C and F model in AI, while there were in endodontists (p = 0.753 and 0.04 in AUC, respectively). The AI model exhibited superior AUC in both the F and C models compared to endodontists. Cohen's kappa demonstrated a substantial level of agreement for the AI model (0.774 in the F model and 0.684 in C) and fair agreement for specialists. The AI's judgment was also based on the coronal pulp area on full PA, as shown by the class activation map. Therefore, these findings suggest that the AI model can improve diagnostic accuracy and support clinicians in diagnosing DE on PA, improving the long-term prognosis of the tooth.

Orofacial Pain with Cardiac Origin of Coronary Artery Disease: A Case Report and Literature Review.

When diagnosing orofacial pain, clinicians should also consider non-odontogenic origin and systemic diseases as possible etiological factors, along with odontogenic origin. This case report aimed to provide information for early detection of orofacial pain of cardiac origin by dentists, when pain due to coronary artery disease is the only presenting symptom. A 60-year-old male patient with unexplained isolated bilateral jaw pain that had persisted for the past 5 years was referred to a dentist by an anesthesiologist who suspected temporomandibular joint disorder. In oral examination, no specific pathological changes were observed in the oral cavity, including teeth, surrounding alveolar bone, and buccal mucosa. Magnetic resonance imaging and conventional radiography showed no pathological destruction or abnormalities of bone and soft tissue in the temporomandibular joint region. However, pain was precipitated by ordinary daily activities, and the pain alleviating factor was rest. Eventually, the patient was referred to a cardiologist for further evaluation since his pain was induced by physical activity. Coronary artery disease (CAD) was diagnosed using coronary computed tomography angiography, and the pain was considered to be angina pectoris. Percutaneous coronary intervention was successfully done for the patient, after which his orofacial symptoms disappeared. To conclude, isolated craniofacial pain of cardiac origin may lead to patients seeking dental care or visiting orofacial pain clinics. In these settings, dentists and orofacial pain specialists may contribute to the diagnosis of CAD and refer patients for cardiac evaluation and appropriate management.

Preclinical investigation of patient-derived cervical cancer organoids for precision medicine.

OBJECTIVE: Advanced cervical cancer is still difficult to treat and in the case of recurrent cancer, it is desirable to utilize personalized treatment rather than uniform treatment because the type of recurrence is different for each individual. Therefore, this study aimed to establish a patient-derived organoid (PDO) platform to determine the effects of chemotherapy, radiation therapy, and targeted therapy in cervical cancer. METHODS: We established organoids from 4 patients with various types of cervical cancer. The histopathological and gene profiles of these organoid models were compared to determine their characteristics and the maintenance of the patient phenotype. Each type of organoid was also subjected to anticancer drug screening and radiation therapy to evaluate its sensitivity. RESULTS: We established PDOs to recapitulate the main elements of the original patient tumors, including the DNA copy number and mutational profile. We selected 7 drugs that showed growth inhibition in cervical cancer organoids out of 171 using an Food and Drug Administration -approved drug library. Moreover, adenocarcinoma and large-cell neuroendocrine carcinoma showed resistance to radiation therapy. whereas squamous cell carcinoma and villoglandular carcinoma showed a significant response to radiotherapy. CONCLUSION: Our results showed that patient-derived cervical cancer organoids can be used as a platform for drug and radiation sensitivity testing. These findings suggest that patient-derived cervical cancer organoids could be used as a personalized medicine platform and may provide the best treatment options for patients with various subtypes of cervical cancer.

Game-based digital therapeutics for children and adolescents: Their therapeutic effects on mental health problems, the sustainability of the therapeutic effects and the transfer of cognitive functions.

Mental health problems in childhood and adolescence (e. g., attention deficits, problems in emotional understanding and subclinical levels of anxiety) are reported to develop further in adulthood and/or to increase the risk of developing mental health disorders in adulthood. Although it is important to provide treatment or prevention interventions for children and adolescents in order to reduce the risk of the further development of mental health problems, the pharmacological and behavioral treatments for this age group have limitations (e.g., limited access, unsustainable treatment effects and the lack of engagement in intervention). In order to overcome the limitations of conventional treatments, the use of digital technology, especially video games for this age group, is suggested. In order to be accepted as clinical interventions, objective evidence for the therapeutic effects of digital therapeutic that used video games to treat or prevent targeted mental health problems are required. Thus, this review aims to explore whether game-based digital therapeutics (DTx) for children and adolescents showed therapeutic effects on targeted mental health problems. As game-based DTx are suggested to show sustained therapeutic effects and the transfer of cognitive functions, it also reviews the maintenance of the therapeutic effects of DTx and the extent of the transfer of cognitive functions. Game-based DTx that are developed to treat or prevent mental health problems (e.g., attention deficit, depression) in children and adolescents are found to show therapeutic effects on targeted mental health problems despite the limitations (e.g., small sample size, limited investigation of the sustainability). This review would contribute to the understanding of whether there is objective evidence of the therapeutic effects of digital therapeutics using video games that deliver treatment or prevention interventions for mental health problems in children and adolescents.

Glucocerebroside-Containing Milk Concentrated Powder Suppresses Oxidative Stress and Photoaging in the Skin of Hairless Mice.

This study investigated the protective effects of glucocerebroside-containing buttermilk concentrated powder (GCBM) on oxidative stress and photoaging in ultraviolet B (UVB)-irradiated hairless mice. We measured antioxidant enzyme activities, collagen synthesis-related pathways, and moisturizing-related factors in the dorsal skin of mice. We observed that dietary supplementation with GCBM increased antioxidant enzyme activity and decreased pro-inflammatory cytokine expression in the UVB-irradiated dorsal skin. Furthermore, dietary supplementation with GCBM inhibited wrinkle formation by suppressing the JNK/c-FOS/c-Jun/MMP pathway and stimulating the TGF-ßRI/Smad3/procollagen type I pathway. Dietary supplementation with GCBM also increased skin moisturization by stimulating hyaluronic acid and ceramide synthesis in the dorsal skin. Therefore, buttermilk powder supplementation helps prevent photoaging and can be used as an effective component in developing anti-photoaging products.

Short Term Isocaloric Ketogenic Diet Modulates NLRP3 Inflammasome Via B-hydroxybutyrate and Fibroblast Growth Factor 21.

A ketogenic diet (KD) is known to have beneficial health effects. Various types of KD interventions have been applied to manage metabolic syndrome based on modification of diet parameters such as duration of intervention, macronutrient components, and total calories. Nevertheless, the beneficial health impact of isocaloric KD is largely unknown, especially in healthy subjects. The present study investigated the acute effects of a 3-day isocaloric KD. In this non-randomized intervention study, we recruited 15 healthy volunteers aged 24-38 years (7 men and 8 women) and placed them on an isocaloric KD restricting intake of carbohydrates but not energy (75% fat, 20% protein, 5% carbohydrate) for 3 days. Biochemical profiles and laboratory measurements were performed. Peripheral blood monocular cells were cultured, and measured cell stimulated cytokines. After short-term isocaloric KD, subjects lost body weight and serum free fatty acid levels were increased. These results accompanied elevated serum ß-hydroxybutyrate (BHB) concentration and fibroblast growth factor 21 (FGF21) levels and improved insulin sensitivity. Regarding the direct effect of BHB on inflammasome activation, interleukin-1ß (IL-1ß) and tumor necrosis factor-α secretion in response to adenosine triphosphate or palmitate stimulation in human macrophages decreased significantly after isocaloric KD. In ex-vivo experiments with macrophages, both FGF21 and BHB further reduced IL-1ß secretion compared to either BHB or FGF21 alone. The inhibitory effect of FGF21 on IL-1ß secretion was blunted with bafilomycin treatment, which blocked autophagy flux. In conclusion, isocaloric KD for 3 days is a promising approach to improve metabolic and inflammatory status. Clinical Trial Registration: clinicaltrials.gov (NCT02964572).

Artificial intelligence in positioning between mandibular third molar and inferior alveolar nerve on panoramic radiography.

Determining the exact positional relationship between mandibular third molar (M3) and inferior alveolar nerve (IAN) is important for surgical extractions. Panoramic radiography is the most common dental imaging test. The purposes of this study were to develop an artificial intelligence (AI) model to determine two positional relationships (true contact and bucco-lingual position) between M3 and IAN when they were overlapped in panoramic radiographs and compare its performance with that of oral and maxillofacial surgery (OMFS) specialists. A total of 571 panoramic images of M3 from 394 patients was used for this study. Among the images, 202 were classified as true contact, 246 as intimate, 61 as IAN buccal position, and 62 as IAN lingual position. A deep convolutional neural network model with ResNet-50 architecture was trained for each task. We randomly split the dataset into 75% for training and validation and 25% for testing. Model performance was superior in bucco-lingual position determination (accuracy 0.76, precision 0.83, recall 0.67, and F1 score 0.73) to true contact position determination (accuracy 0.63, precision 0.62, recall 0.63, and F1 score 0.61). AI exhibited much higher accuracy in both position determinations compared to OMFS specialists. In determining true contact position, OMFS specialists demonstrated an accuracy of 52.68% to 69.64%, while the AI showed an accuracy of 72.32%. In determining bucco-lingual position, OMFS specialists showed an accuracy of 32.26% to 48.39%, and the AI showed an accuracy of 80.65%. Moreover, Cohen's kappa exhibited a substantial level of agreement for the AI (0.61) and poor agreements for OMFS specialists in bucco-lingual position determination. Determining the position relationship between M3 and IAN is possible using AI, especially in bucco-lingual positioning. The model could be used to support clinicians in the decision-making process for M3 treatment.

The Association Between Hippocampal Volume and Level of Attention in Children and Adolescents.

The hippocampus, which engages in the process of consolidating long-term memories and learning, shows active development during childhood and adolescence. The hippocampus also functionally influences attention. Based on the influence of hippocampal function on attention, it was expected that the volume of the hippocampus would be associated with the difference in attention during childhood and adolescence, in which the brain develops actively. Thus, this study examined the association between hippocampal volume and attention metrics measured by the continuous performance test (CPT) in 115 children and adolescents (mean age = 12.43 ± 3.0, 63 male and 52 female). In association studies with both auditory and visual attention, we found that the bilateral hippocampal volumes showed negative relationships with auditory omission errors. A smaller volume of the left hippocampus also led to a longer auditory response time. However, visual attention did not show any significant relationship with the hippocampal volume. These findings were consistent even after adjusting for the effects of the related covariates (e.g., age, insomnia, and depression). Taken together, this study suggested that the increase in hippocampal volume during childhood and adolescence was associated significantly with better auditory attention.

Association of Extensive Video Gaming and Cognitive Function Changes in Brain-Imaging Studies of Pro Gamers and Individuals With Gaming Disorder: Systematic Literature Review.

BACKGROUND: The World Health Organization announced the inclusion of gaming disorder (GD) in the International Classification of Diseases, 11th Revision, despite some concerns. However, video gaming has been associated with the enhancement of cognitive function. Moreover, despite comparable extensive video gaming, pro gamers have not shown any of the negative symptoms that individuals with GD have reported. It is important to understand the association between extensive video gaming and alterations in brain regions more objectively. OBJECTIVE: This study aimed to systematically explore the association between extensive video gaming and changes in cognitive function by focusing on pro gamers and individuals with GD. METHODS: Studies about pro gamers and individuals with GD were searched for in the PubMed and Web of Science databases using relevant search terms, for example, "pro-gamers" and "(Internet) gaming disorder." While studies for pro gamers were searched for without date restrictions, only studies published since 2013 about individuals with GD were included in search results. Article selection was conducted by following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: By following the PRISMA guidelines, 1903 records with unique titles were identified. Through the screening process of titles and abstracts, 86 full-text articles were accessed to determine their eligibility. A total of 18 studies were included in this systematic review. Among the included 18 studies, six studies included pro gamers as participants, one study included both pro gamers and individuals with GD, and 11 studies included individuals with GD. Pro gamers showed structural and functional alterations in brain regions (eg, the left cingulate cortex, the insula subregions, and the prefrontal regions). Cognitive function (eg, attention and sensorimotor function) and cognitive control improved in pro gamers. Individuals with GD showed structural and functional alterations in brain regions (eg, the striatum, the orbitofrontal cortex, and the amygdala) that were associated with impaired cognitive control and higher levels of craving video game playing. They also showed increased cortical thickness in the middle temporal cortex, which indicated the acquisition of better skills. Moreover, it was suggested that various factors (eg, gaming expertise, duration or severity of GD, and level of self-control) seemed to modulate the association of extensive video game playing with changes in cognitive function. CONCLUSIONS: Although a limited number of studies were identified that included pro gamers and/or individuals who reported showing symptoms of GD for more than 1 year, this review contributed to the objective understanding of the association between extensive video game playing and changes in cognitive function. Conducting studies with a longitudinal design or with various comparison groups in the future would be helpful in deepening the understanding of this association.

Artificial intelligence in detecting temporomandibular joint osteoarthritis on orthopantomogram.

Orthopantomogram (OPG) is important for primary diagnosis of temporomandibular joint osteoarthritis (TMJOA), because of cost and the radiation associated with computed tomograms (CT). The aims of this study were to develop an artificial intelligence (AI) model and compare its TMJOA diagnostic performance from OPGs with that of an oromaxillofacial radiology (OMFR) expert. An AI model was developed using Karas' ResNet model and trained to classify images into three categories: normal, indeterminate OA, and OA. This study included 1189 OPG images confirmed by cone-beam CT and evaluated the results by model (accuracy, precision, recall, and F1 score) and diagnostic performance (accuracy, sensitivity, and specificity). The model performance was unsatisfying when AI was developed with 3 categories. After the indeterminate OA images were reclassified as normal, OA, or omission, the AI diagnosed TMJOA in a similar manner to an expert and was in most accord with CBCT when the indeterminate OA category was omitted (accuracy: 0.78, sensitivity: 0.73, and specificity: 0.82). Our deep learning model showed a sensitivity equivalent to that of an expert, with a better balance between sensitivity and specificity, which implies that AI can play an important role in primary diagnosis of TMJOA from OPGs in most general practice clinics where OMFR experts or CT are not available.

Effects of Lactobacillus plantarum CJLP55 on Clinical Improvement, Skin Condition and Urine Bacterial Extracellular Vesicles in Patients with Acne Vulgaris: A Randomized, Double-Blind, Placebo-Controlled Study.

Lactobacillus plantarum CJLP55 has anti-pathogenic bacterial and anti-inflammatory activities in vitro. We investigated the dietary effect of CJLP55 supplement in patients with acne vulgaris, a prevalent inflammatory skin condition. Subjects ingested CJLP55 or placebo (n = 14 per group) supplements for 12 weeks in this double-blind, placebo-controlled randomized study. Acne lesion count and grade, skin sebum, hydration, pH and surface lipids were assessed. Metagenomic DNA analysis was performed on urine extracellular vesicles (EV), which indirectly reflect systemic bacterial flora. Compared to the placebo supplement, CJLP55 supplement improved acne lesion count and grade, decreased sebum triglycerides (TG), and increased hydration and ceramide 2, the major ceramide species that maintains the epidermal lipid barrier for hydration. In addition, CJLP55 supplement decreased the prevalence of Proteobacteria and increased Firmicutes, which were correlated with decreased TG, the major skin surface lipid of sebum origin. CJLP55 supplement further decreased the Bacteroidetes:Firmicutes ratio, a relevant marker of bacterial dysbiosis. No differences in skin pH, other skin surface lipids or urine bacterial EV phylum were noted between CJLP55 and placebo supplements. Dietary Lactobacillus plantarum CJLP55 was beneficial to clinical state, skin sebum, and hydration and urine bacterial EV phylum flora in patients with acne vulgaris.

Genome-wide functional analysis of hot pepper immune receptors reveals an autonomous NLR clade in seed plants.

Plants possess hundreds of intracellular immune receptors encoding nucleotide-binding domain leucine-rich repeat (NLR) proteins. Full-length NLRs or a specific domain of NLRs often induce plant cell death in the absence of pathogen infection. In this study we used genome-wide transient expression analysis to identify a group of NLRs (ANLs; ancient and autonomous NLRs) carrying autoactive coiled-coil (CCA ) domains in pepper (Capsicum annuum). CCA -mediated cell death mimics hypersensitive cell death triggered by the interaction between NLRs and pathogen effectors. Sequence alignment and mutagenesis analyses revealed that the intact α1 helix of CCA s is critical for both CCA - and ANL-mediated cell death. Cell death induced by CCA s does not require NRG1/ADR1 or NRC type helper NLRs, suggesting ANLs may function as singleton NLRs. We also found that CCA s localize to the plasma membrane, as demonstrated for Arabidopsis singleton NLR ZAR1. Extended studies revealed that autoactive CCA s are well conserved in other Solanaceae plants as well as in rice, a monocot plant. Further phylogenetic analyses revealed that ANLs are present in all tested seed plants (spermatophytes). Our study not only uncovers the autonomous NLR clade in plants but also provides powerful resources for dissecting the underlying molecular mechanism of NLR-mediated cell death in plants.

SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1ß release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1ß secretion compared to sulfonylurea accompanied by increased serum ß-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.

Commercial video games and cognitive functions: video game genres and modulating factors of cognitive enhancement.

BACKGROUND: Unlike the emphasis on negative results of video games such as the impulsive engagement in video games, cognitive training studies in individuals with cognitive deficits showed that characteristics of video game elements were helpful to train cognitive functions. Thus, this study aimed to have a more balanced view toward the video game playing by reviewing genres of commercial video games and the association of video games with cognitive functions and modulating factors. Literatures were searched with search terms (e.g. genres of video games, cognitive training) on database and Google scholar. RESULTS: video games, of which purpose is players' entertainment, were found to be positively associated with cognitive functions (e.g. attention, problem solving skills) despite some discrepancy between studies. However, the enhancement of cognitive functions through video gaming was limited to the task or performance requiring the same cognitive functions. Moreover, as several factors (e.g. age, gender) were identified to modulate cognitive enhancement, the individual difference in the association between video game playing and cognitive function was found. CONCLUSION: Commercial video games are suggested to have the potential for cognitive function enhancement. As understanding the association between video gaming and cognitive function in a more balanced view is essential to evaluate the potential outcomes of commercial video games that more people reported to engage, this review contributes to provide more objective evidence for commercial video gaming.

The difference in sleep, depression, anxiety, and Internet addiction between Korean adolescents with different circadian preference.

OBJECTIVES: Compared to adults, adolescents tend to prefer evening times developmentally. The orientation toward evening times is associated with behavioral and emotional problems. Thus, this study examined the association of circadian preference with sleep-related variables, depression, anxiety, and Internet addiction in Korean adolescents. MATERIALS AND METHODS: Participants completed the questionnaires measuring sleep pattern, sleep problem, depression, anxiety, and Internet addiction. RESULTS: Among 765 students (age range: 13-17 years), 211 students (N male= 134) were allocated into morning types (MT) and 258 adolescents (N male= 147) were allocated into evening types (ET) based on scores of the Morningness-Eveningness Scale. Adolescents without circadian preference (N = 296) were defined as neither type (NT). ET, compared to MT and NT, woke up later in the weekend, showed delays in bedtimes, and spent shorter time sleeping. They also reported a higher level of daytime sleepiness, insomnia, and depression than NT. However, the group difference in wake time on school days was not significant, and adolescents showed mild insomnia regardless of their circadian preference. Although smartphone using time in the weekend was significantly different between groups, group difference in Internet addiction was significant only when gender was adjusted. CONCLUSION: Circadian preference was associated with sleep patterns and sleep problems in Korean adolescents. ET showed significantly different sleep patterns compared to MT and NT. ET not only reported a higher level of daytime sleepiness and insomnia but also more depressive symptoms compared to NT. These findings suggest that the uniqueness of adolescence and environmental factors seemed to influence the association of circadian preference with mental problem.

Effect of catechins and high-temperature-processed green tea extract on scavenging reactive oxygen species and preventing Aß1-42 fibrils' formation in brain microvascular endothelium.

The present study investigated the effect of high-temperature-processed green tea extract (HTP_GTE) and its bioactive components on the reduction of reactive oxygen species (ROS) and amyloid-beta (Aß) protein in human microvascular endothelial cells. Compared to Aß1-42-only treatment, pretreatment of HTP_GTE was revealed to effectively inhibit ROS generation (P<0.05). HTP_GTE and catechins not only inhibit Aß1-42 fibril formation but also destabilize preformed Aß1-42 fibrils. The presence of HTP_GTE, Aß1-42 fibril formation was significantly inhibited in a dose-dependent manner at 12.5-100 µg/ml of HTP_GTE, showing 86-56%, respectively. Treatment of various concentrations of HTP_GTE and catechins steadily destabilized the preformed Aß1-42 fibrils for 24 h in a dose-dependent manner. It was observed that the gallated groups such as epigallocatechin gallate, epicatechin gallate, gallocatechin gallate, and catechin gallate more effectively disturbed Aß1-42 fibril formation and destabilized the preformed Aß1-42 fibrils than the non-gallated group. Taken together, these findings supported that sterilized green tea could be promising natural anti-amyloidogenic agents associated with therapeutic approaches in Alzheimer's disease by scavenging ROS generation and Aß fibril in the brain tissue.

Increased Intestinal Absorption of Vitamin U in Steamed Graviola Leaf Extract Activates Nicotine Detoxification.

Graviola leaves contain much vitamin U (vit U), but their sensory quality is not good enough for them to be developed as food ingredients. Addition of excipient natural ingredients formulated alongside vit U as active ingredients could enhance not only its sensory quality but also its bioavailability. The objectives of this study were to measure the bioaccessibility and intestinal cellular uptake of bioactive components, including rutin, kaempferol-rutinoside, and vit U, from steamed extract of graviola leaves (SGV) and SGV enriched with kale extract (SGK), and to examine how much they can detoxify nicotine in HepG2 cells. The bioaccessibility of vit U from SGV and SGK was 82.40% and 68.03%, respectively. The cellular uptake of vit U in SGK by Caco-2 cells was higher than that in SGV. Cotinine content converted from nicotine in HepG2 cells for 120 min was 0.22 and 0.25 µg/mg protein in 50 µg/mL of SGV and SGK, respectively, which were 2.86 and 3.57 times higher than the no-treatment control. SGK treatment of HepG2 cells upregulated CYP2A6 three times as much as did that of SGV. Our results suggest that graviola leaf extract enriched with excipient ingredients such as kale could improve vit U absorption and provide a natural therapy for detoxifying nicotine.

Tamoxifen-induced acute eosinophilic pneumonia in a breast cancer patient.

INTRODUCTION: Tamoxifen is often used as antihormonal therapy in patients with breast cancer. However, it has various side effects, of which pneumonia is a rare occurrence. PRESENTATION OF CASE: A 46-year-old female patient with breast cancer underwent surgical treatment. Tamoxifen was administered as adjuvant therapy on post-operative day 14; 2 days after administration of tamoxifen, the patient developed high fever of more than 39 °C and cough with dyspnea. Based on chest computed tomography findings of ground glass opacity, interlobular septal thickening, and mild pleural effusion in both lungs, eosinophilic pneumonia was suspected. Tamoxifen was discontinued and methylprednisolone injection was administered; the patient showed improvement of symptoms and radiographic findings. DISCUSSION: Tamoxifen was suspected as the cause of eosinophilic pneumonia since the patient developed high-grade fever at the time of tamoxifen administration, which subsided after discontinuation of the treatment. Other factors considered as the cause of pneumonia were examined, but all showed negative results. In order to confirm tamoxifen as the cause of pneumonia, tamoxifen treatment was restarted at follow-up (post-operative day 47); however, after 1 month, regular administration was not possible due to the development of itching symptom and difficulty in obtaining the patient's cooperation. CONCLUSION: The study highlights that if the patient on tamoxifen develops high fever and cough with dyspnea at 2-3days after the first administration, tamoxifen-induced pneumonia should be suspected.

Two Clade A Phosphatase 2Cs Expressed in Guard Cells Physically Interact With Abscisic Acid Signaling Components to Induce Stomatal Closure in Rice.

BACKGROUND: The core ABA signaling components functioning in stomatal closure/opening, namely ABA receptors, phosphatases, SnRK2s and SLAC1, are well characterized in Arabidopsis, but their functions in guard cells of rice have not been extensively studied. RESULTS: In this study, we confirmed that OsSLAC1, the rice homolog of AtSLAC1, is specifically expressed in rice guard cells. Among the rice SAPKs, SAPK10 was specifically expressed in guard cells. In addition, SAPK10 phosphorylated OsSLAC1 in vitro and transgenic rice overexpressing SAPK10 or OsSLAC1 showed significantly less water loss than control. Thus, those might be major positive signaling components to close stomata in rice. We identified that only OsPP2C50 and OsPP2C53 among 9 OsPP2CAs might be related with stomatal closure/opening signaling based on guard cell specific expression and subcellular localization. Transgenic rice overexpressing OsPP2C50 and OsPP2C53 showed significantly higher water loss than control. We also characterized the interaction networks between OsPP2C50 and OsPP2C53, SAPK10 and OsSLAC1 and found two interaction pathways among those signaling components: a hierarchical interaction pathway that consisted of OsPP2C50 and OsPP2C53, SAPK10 and OsSLAC1; and a branched interaction pathway wherein OsPP2C50 and OsPP2C53 interacted directly with OsSLAC1. CONCLUSION: OsPP2C50 and OsPP2C53 is major negative regulators of ABA signaling regarding stomata closing in rice. Those can regulate the OsSLAC1 directly or indirectly thorough SAPK10.