Immune-inflammatory biomarkers for the occurrence of MACE in patients with myocardial infarction with non-obstructive coronary arteries.

Background: Neutrophil-to-high-density lipoprotein cholesterol ratio (NHR), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), lymphocyte-to-high-density lipoprotein cholesterol ratio (LHR), platelet-to-high-density lipoprotein cholesterol ratio (PHR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) have been identified as immune-inflammatory biomarkers associated with the prognosis of cardiovascular diseases. However, the relationship of these biomarkers with the prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) remains unclear. Method: Patients with MINOCA who underwent coronary angiography at the 920th Hospital of Joint Logistics Support Force were included in our study. Clinical baseline characteristics and laboratory testing data were collected from the hospital record system. The patients were divided into two groups on the basis of major adverse cardiovascular events (MACE) occurrence. Multiple logistic regression analysis was conducted to assess the relationship between NHR, MHR, LHR, PHR, SII, SIRI, AISI, and MACE. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of NHR, MHR, LHR, PHR, SII, SIRI, and AISI for MACE in patients with MINOCA. The accuracy of the prediction was indicated by the area under the curve (AUC) value. Results: The study included 335 patients with MINOCA. (81 in the MACE group and 254 in the No-MACE group). The MACE group had higher levels of NHR, MHR, LHR, PHR, SII, SIRI, and AISI than the No-MACE group. Multiple logistic regression analysis adjusted for confounding factors indicated that the higher levels of NHR, MHR, PHR, SII, SIRI, and AISI were associated with the occurrence of MACE in patients with MINOCA (P < 0.001). The AUC values for NHR, MHR, PHR, SII, SIRI, and AISI were 0.695, 0.747, 0.674, 0.673, 0.688, and 0.676, respectively. The combination of NHR, MHR, PHR, SII, SIRI, and AISI improved the accuracy of predicting MACE in patients with MINOCA (AUC = 0.804). Conclusion: Higher levels of NHR, MHR, PHR, SII, SIRI, and AISI were associated with the occurrence of MACE, and the combination of NHR, MHR, PHR, SII, SIRI, and AISI improved the accuracy for predicting the incidence of MACE events in patients with MINOCA.

Effect of cellulase on antioxidant activity and flavor of Rosa roxburghii Tratt.

Cellulase can increase the soluble dietary fiber (SDF) content in Rosa roxburghii Tratt (RRT), but the effects on polyphenol content, bioactivity, and flavor are unknown. This study analyzed the changes in SDF content, total phenolic content, antioxidant activity and flavor before and after cellulase treatment. Cellulase treatment increased the SDF and total phenolic content of RRT by 13 % (P < 0.05) and 25.68 % (P < 0.05), respectively, and increased the antioxidant activity. HS-GC-IMS identified a total of 42 volatile compounds present, and ROAV analysis revealed that the characteristic aroma compounds of RRT were mainly aldehydes, alcohols, and ethers. The electronic nose and tongue results were consistent with the HS-GC-IMS analysis, indicating the positive effect of cellulase on the quality of RRT. Cellulase treatment significantly improved the oxidative activity and flavor performance of RRT. These results of RRT, providing practical guidance for improving the flavor and product quality.

Simulated space environmental factors of weightlessness, noise and low atmospheric pressure differentially affect the diurnal rhythm and the gut microbiome.

The circadian clock extensively regulates physiology and behavior. In space, astronauts encounter many environmental factors that are dramatically different from those on Earth; however, the effects of these factors on circadian rhythms and the mechanisms remain largely unknown. The present study aimed to investigate the changes in the mouse diurnal rhythm and gut microbiome under simulated space capsule conditions, including microgravity, noise and low atmospheric pressure (LAP). Noise and LAP were loaded in the capsule while the conditions in the animal room remained constant. The mice in the capsule showed disturbed locomotor rhythms and faster adaptation to a 6-h phase advance. RNA sequencing of hypothalamus samples containing the suprachiasmatic nucleus (SCN) revealed that microgravity simulated by hind limb unloading (HU) and exposure to noise and LAP led to decreases in the quantities of differentially expressed genes (DEGs), including circadian clock genes. Changes in the rhythmicity of genes implicated in pathways of cardiovascular deconditioning and more concentrated phases were found under HU or noise and LAP. Furthermore, 16S rRNA sequencing revealed dysbiosis in the gut microbiome, and noise and LAP may repress the temporal discrepancy in the microbiome community structure induced by microgravity. Changes in diurnal oscillations were observed in a number of gut bacteria with critical physiological consequences on metabolism and immunodefense. We also found that the superimposition of noise and LAP may repress normal changes in global gene expression and adaptation in the gut microbiome. Our data demonstrate that in addition to microgravity, exposure to noise and LAP affect the robustness of circadian rhythms and the community structure of the gut microbiome, and these factors may interfere with each other in their adaptation to respective conditions. These findings are important for furthering our understanding of the alterations in circadian rhythms in the complex environment of space.

Serum food specific IgG antibodies are associated with small bowel inflammation in patients with Crohn's disease.

BACKGROUND/AIMS: Food antigens are thought to play a vital role in the initiation and perpetuation of Crohn's disease (CD). The main purpose of this study was to evaluate the potential association of serum food specific IgG antibodies and small bowel (SB) inflammation in CD patients. METHODS: We conducted a prospective observational study with 96 CD patients. Demographic, disease-related data and inflammatory parameters were collected. Serum food IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Capsule endoscopy was performed to detect SB inflammation quantified by the Lewis Score. RESULTS: Seventy-eight of (81.3%) CD patients were detected positive for at least one food-specific antibody. The five most prevalent food antibodies in CD patients were tomato, egg, corn, rice, and soybean. Patients with SB inflammation had a higher positive rate of food IgG antibodies (P = 0.010) and more IgG-positive food items (P = 0.010) than those without. Specifically, patients with SB inflammation were more likely to have positive food-specific IgG against egg (P = 0.014), corn (P = 0.014), and wheat (P = 0.048). Additionally, the number of positive food IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation (P = 0.015 and P = 0.013, respectively). CONCLUSION: Our study confirmed that CD patients with SB inflammation had a higher positive rate of food IgG antibodies and more IgG-positive food items. The number of food positive IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation.

Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury.

Background: Allograft lung ischemia-reperfusion injury (ALIRI) is a major cause of early primary graft dysfunction and poor long-term survival after lung transplantation (LTx); however, its pathogenesis has not been fully elucidated. Cell death is a mechanism underlying ALIRI. Cuproptosis is a recently discovered form of programmed cell death. To date, no studies have been conducted on the mechanisms by which cuproptosis-related genes (CRGs) regulate ALIRI. Therefore, we explored the potential biomarkers related to cuproptosis to provide new insights into the treatment of ALIRI. Materials and methods: Datasets containing pre- and post-LTx lung biopsy samples and CRGs were obtained from the GEO database and previous studies. We identified differentially expressed CRGs (DE-CRGs) and performed functional analyses. Biomarker genes were selected using three machine learning algorithms. The ROC curve and logistic regression model (LRM) of these biomarkers were constructed. CIBERSORT was used to calculate the number of infiltrating immune cells pre- and post-LTx, and the correlation between these biomarkers and immune cells was analyzed. A competing endogenous RNA network was constructed using these biomarkers. Finally, the biomarkers were verified in a validation set and a rat LTx model using qRT-PCR and Western blotting. Results: Fifteen DE-CRGs were identified. GO analysis revealed that DE-CRGs were significantly enriched in the mitochondrial acetyl-CoA biosynthetic process from pyruvate, protein lipoylation, the tricarboxylic acid (TCA) cycle, and copper-transporting ATPase activity. KEGG enrichment analysis showed that the DE-CRGs were mainly enriched in metabolic pathways, carbon metabolism, and the TCA cycle. NFE2L2, NLRP3, LIPT1, and MTF1 were identified as potential biomarker genes. The AUC of the ROC curve for each biomarker was greater than 0.8, and the LRM provided an excellent classifier with an AUC of 0.96. These biomarkers were validated in another dataset and a rat LTx model, which exhibited good performance. In the CIBERSORT analysis, differentially expressed immune cells were identified, and the biomarkers were associated with the immune cells. Conclusion: NFE2L2, NLRP3, LIPT1, and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of cuproptosis in ALIRI.

Differential regulation of phosphorylation, structure, and stability of circadian clock protein FRQ isoforms.

Neurospora crassa is an important model organism for circadian clock research. The Neurospora core circadian component FRQ protein has two isoforms, large FRQ (l-FRQ) and small FRQ (s-FRQ), of which l-FRQ bears an additional N-terminal 99-amino acid fragment. However, how the FRQ isoforms operate differentially in regulating the circadian clock remains elusive. Here, we show l-FRQ and s-FRQ play different roles in regulating the circadian negative feedback loop. Compared to s-FRQ, l-FRQ is less stable and undergoes hypophosphorylation and faster degradation. The phosphorylation of the C-terminal l-FRQ 794-aa fragment was markedly higher than that of s-FRQ, suggesting the l-FRQ N-terminal 99-aa region may regulate the phosphorylation of the entire FRQ protein. Quantitative label-free LC/MS analysis identified several peptides that were differentially phosphorylated between l-FRQ and s-FRQ, which were distributed in FRQ in an interlaced fashion. Furthermore, we identified two novel phosphorylation sites, S765 and T781; mutations S765A and T781A showed no significant effects on conidiation rhythmicity, although T781 conferred FRQ stability. These findings demonstrate that FRQ isoforms play differential roles in the circadian negative feedback loop and undergo different regulations of phosphorylation, structure, and stability. The l-FRQ N-terminal 99-aa region plays an important role in regulating the phosphorylation, stability, conformation, and function of the FRQ protein. As the FRQ circadian clock counterparts in other species also have isoforms or paralogues, these findings will also further our understanding of the underlying regulatory mechanisms of the circadian clock in other organisms based on the high conservation of circadian clocks in eukaryotes.

Comprehensive detrimental effects of a simulated frequently shifting schedule on diurnal rhythms and vigilance.

Accumulating data have demonstrated that shift work causes a disturbance in circadian rhythms, which is detrimental to physiology and performance. However, the detailed effects of shift work and especially the underlying mechanisms remain to be further investigated. Frequently shifting schedules are widely used in industries, e.g., maritime tasks, oil mining, and aviation. In this work, we investigated the physiological changes and vigilance of 12 subjects who lived on a 30-day frequent shift working schedule in a confined environment, which mimics the common maritime schedules. Elevated and decreased cortisol levels were observed at different stages during the shift, suggesting the occurrence of stress and fatigue. The results of the Karolinska Sleepiness Scale (KSS) indicate increased sleepiness and a changed pattern of the rhythmicity of sleepiness during the shift. The tests of the Psychomotor Vigilance Task (PVT) reveal that the shift led to a continuously decreasing alertness as the shift working schedule progressed, which is prevalently due to the increasingly slower reaction speed. The PVT time-out errors were significantly increased in the early period but decreased in the late period. In addition, we found recoupling of the correlations between multiple physiological and cognitive variables. For instance, heartbeat rate (HR) and breath rate (BR) showed moderate correlations in the control and early periods but little in the late period. Together, these results reveal substantial alterations in diurnal rhythms, affected vigilance and changed coupling of the correlations of diurnal rhythms, physiology and cognition caused by a shift schedule. Our findings may help in the recognition of the detrimental effects of such working schedules and provide clues for the development of potential mitigations.

Multi-omics analysis of biomarkers and molecular mechanism of rheumatoid arthritis with bone destruction.

OBJECTIVES: Our study aimed to elucidate the role of metabolites, bacteria, and fungi in rheumatoid arthritis (RA) patients with bone destruction (BD(+)) and identify some biomarkers to predicate bone progression of RA. METHODS: Plasma metabolites of the 127 RA patients and 69 healthy controls were conducted by using nontargeted liquid chromatography-mass spectrometry (LC-MS). The gut bacteria and fungi were assessed by 16S rRNA and internal transcribed spacer (ITS). RESULTS: Compared with RA patients without bone destruction (BD(-)), some metabolites, bacteria, and fungi were altered in BD(+). Seven metabolites were selected as key metabolites for classifying the BD(+) and BD(-) groups with moderate accuracy (AUC=0.71). Metabolites-groups, metabolites-metabolites, and metabolites-clinical factors had a certain correlation, and 7 metabolites were enriched in glycerophospholipid metabolism and L-arginine and proline metabolism pathways. The bacteria and fungi of the BD(+) group showed significant differences in composition and function compared with BD(-) group. The changed 4 bacteria and 12 fungi yielded accuracy (AUC=0.74 and AUC=0.87, respectively) for the two groups. Taking 7 metabolites, 4 bacteria, and 12 fungi as a panel for AUC analysis, an improved AUC of 0.99 significantly discriminated the two groups. The changed metabolites, gut bacteria, and fungi may affect the pathway related to L-arginine. CONCLUSIONS: Our nontargeted LC-MS, 16S rRNA, and ITS highlighted a novel link among the metabolites, bacteria, fungi, and pathology of BD(+), which could contribute to our understanding of the role of metabolites, bacteria, and fungi in BD(+) etiology and offered some novel biomarkers to predict the bone progression of RA.

Investment Behavior Related to Automated Machines and Biased Technical Change: Based on Evidence From Listed Manufacturing Companies in China.

This paper studies the impact of a recent increase in the ratio of automated machines to ordinary capital (RAMOC) on the bias of technical change in the manufacturing industry and the mechanism influencing this. Using panel data of A-share listed manufacturing companies on the Shanghai and Shenzhen stock exchanges from 2012 to 2019, combined with the Xtfrontier model and trans-log production function, we measure the index of the bias of technical change of the manufacturing industry in China. Furthermore, we adopt a fixed effects model to test the impact of an increase of investment in automated machines on the bias of technical change. We also use an intermediary effect model to examine the intermediate mechanism from the perspectives of capital and skill matching. The results show that technical change in the manufacturing industry is biased toward automated machine capital. An incremental increase in RAMOC leads to technical change in the manufacturing industry becoming biased toward automated machine capital, wherein the intermediary mechanism is the labor structure effect. Based on industrial linkage, the investment in automated machines in the upstream (downstream) manufacturing industry increases, the technical change of the downstream (upstream) manufacturing industry is biased toward automated machine capital, and the forward linkage effect is greater than the backward linkage effect. This research enhances understanding of (1) the direction and characteristics of technical change in China, (2) how to improve the output efficiency of automated machines, (3) differences in factor revenue distribution, and (4) how new growth points in the economy can be cultivated. They show that we should encourage and support investment in automated machines, vigorously promote technical change to bias toward automated machine capital, improve the skill level of the labor force, and strengthen the match between automated machines and labor.

An adaptive hybrid XdeepFM based deep Interest network model for click-through rate prediction system.

Recent advances in communication enable individuals to use phones and computers to access information on the web. E-commerce has seen rapid development, e.g., Alibaba has nearly 12 hundred million customers in China. Click-Through Rate (CTR) forecasting is a primary task in the e-commerce advertisement system. From the traditional Logistic Regression algorithm to the latest popular deep neural network methods that follow a similar embedding and MLP, several algorithms are used to predict CTR. This research proposes a hybrid model combining the Deep Interest Network (DIN) and eXtreme Deep Factorization Machine (xDeepFM) to perform CTR prediction robustly. The cores of DIN and xDeepFM are attention and feature cross, respectively. DIN follows an adaptive local activation unit that incorporates the attention mechanism to adaptively learn user interest from historical behaviors related to specific advertisements. xDeepFM further includes a critical part, a Compressed Interactions Network (CIN), aiming to generate feature interactions at a vectorwise level implicitly. Furthermore, a CIN, plain DNN, and a linear part are combined into one unified model to form xDeepFM. The proposed end-to-end hybrid model is a parallel ensemble of models via multilayer perceptron. CIN and xDeepFM are trained in parallel, and their output is fed into a multilayer perceptron. We used the e-commerce Alibaba dataset with the focal loss as the loss function for experimental evaluation through online complex example mining (OHEM) in the training process. The experimental result indicates that the proposed hybrid model has better performance than other models.

Circadian misalignment leads to changes in cortisol rhythms, blood biochemical variables and serum miRNA profiles.

The circadian clock plays a critical role in synchronizing the inner molecular, metabolic and physiological processes to environmental cues that cycle with a period of 24 h. Non-24 h and shift schedules are commonly used in maritime operations, and both of which can disturb circadian rhythms. In this study, we first conducted an experiment in which the volunteers followed a 3-d rotary schedule with consecutive shift in sleep time (rotatory schedule), and analyzed the changes in salivary cortisol rhythms and blood variables. Next we conducted another experiment in which the volunteers followed an 8 h-on and 4-h off schedule (non-24-h schedule) to compare the changes in blood/serum variables. The rotatory schedule led to elevated levels of serum cortisol during the early stage, and the phase became delayed during the early and late stages. Interestingly, both of the schedules caused comprehensive changes in blood/serum biochemical variables and increased phosphate levels. Furthermore, transcriptomic analysis of the plasma miRNAs from the volunteers following the rotatory schedule identified a subset of serum miRNAs targeting genes involved in circadian rhythms, sleep homeostasis, phosphate transport and multiple important physiological processes. Overexpression of miRNAs targeting the phosphate transport associated genes, SLC20A1 and SLC20A2, showed altered expression due to rotary schedule resulted in attenuated cellular levels of phosphate, which might account for the changed levels in serum phosphate. These findings would further our understanding of the deleterious effects of shift schedules and help to optimize and enhance the performances and welfare of personnel working on similar schedules.

ClusterMap Building and Relocalization in Urban Environments for Unmanned Vehicles.

Map building and map-based relocalization techniques are important for unmanned vehicles operating in urban environments. The existing approaches require expensive high-density laser range finders and suffer from relocalization problems in long-term applications. This study proposes a novel map format called the ClusterMap, on the basis of which an approach to achieving relocalization is developed. The ClusterMap is generated by segmenting the perceived point clouds into different point clusters and filtering out clusters belonging to dynamic objects. A location descriptor associated with each cluster is designed for differentiation. The relocalization in the global map is achieved by matching cluster descriptors between local and global maps. The solution does not require high-density point clouds and high-precision segmentation algorithms. In addition, it prevents the effects of environmental changes on illumination intensity, object appearance, and observation direction. A consistent ClusterMap without any scale problem is built by utilizing a 3D visual-LIDAR simultaneous localization and mapping solution by fusing LIDAR and visual information. Experiments on the KITTI dataset and our mobile vehicle illustrates the effectiveness of the proposed approach.

DlICE1, a stress-responsive gene from Dimocarpus longan, enhances cold tolerance in transgenic Arabidopsis.

ICE1 (inducer of CBF expression 1) encodes a typical MYC-like basic helix-loop- helix (bHLH) transcription factor that acts as a pivotal component in the cold signalling pathway. In this study, DlICE1, a novel ICE1-like gene, was isolated from the southern subtropical fruit tree longan (Dimocarpus longan Lour.). DlICE1 encodes a nuclear protein with a highly conserved bHLH domain. DlICE1 expression was slightly upregulated under cold stress. Overexpression of DlICE1 in Arabidopsis conferred enhanced cold tolerance via increased proline content, decreased ion leakage, and reduced malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation. Expression of the ICE1-CBF cold signalling pathway genes, including AtCBF1/2/3 and cold-responsive genes (AtRD29A, AtCOR15A, AtCOR47 and AtKIN1), was also significantly higher in DlICE1-overexpressing lines than in wild-type (WT) plants under cold stress. In conclusion, these findings indicate that DlICE1 is a member of the bHLH gene family and positively regulates cold tolerance in D. longan.

Sleep deprivation and a non-24-h working schedule lead to extensive alterations in physiology and behavior.

Most organisms on Earth possess circadian rhythms in their physiology and behaviors that allow them to resonate with the cycling environment over a 24-h period. However, in human society, a substantial quantity of jobs requires non-24-h working and rest or shift schedules, which causes more or less misalignment in circadian rhythms and disorders as a consequence. In this work, we conducted a sleep deprivation (SD) and non-24-h working and rest schedule (8 h on and 4 h off) experiment over 10 d in total and measured the changes in a series of physiologic and cognitive parameters. The results show that although the subjects could sleep during the schedule, their sleepiness increased significantly. Actigraphy data suggest that a 12-h schedule might result in chronic SD. Along with the increased sleepiness revealed by the Karolinska Sleepiness Scale questionnaire, the neurobehavioral psychomotor vigilance test data reveal that, compared with the control period, the reaction time of the subjects was significantly delayed. The saliva insulin levels were significantly changed in the morning in SD and non-24-h cycles. Salivary biochemical parameters were also altered, including aspartate aminotransferase and K+. 16S rRNA-based analysis of the salivary microbiota showed differentially changed patterns in bacteria composition and concentration. Together, these data demonstrate that an abnormal working and rest schedule might produce comprehensive interference with circadian rhythms, metabolism, and cognition.-Ma, H., Li, Y., Liang, H., Chen, S., Pan, S., Chang, L., Li, S., Zhang, Y., Liu, X., Xu, Y., Shao, Y., Yang, Y., Guo, J. Sleep deprivation and a non-24-h working schedule lead to extensive alterations in physiology and behavior.

Vitamin B1 Helps to Limit Mycobacterium tuberculosis Growth via Regulating Innate Immunity in a Peroxisome Proliferator-Activated Receptor-γ-Dependent Manner.

It is known that vitamin B1 (VB1) has a protective effect against oxidative retinal damage induced by anti-tuberculosis drugs. However, it remains unclear whether VB1 regulates immune responses during Mycobacterium tuberculosis (MTB) infection. We report here that VB1 promotes the protective immune response to limit the survival of MTB within macrophages and in vivo through regulation of peroxisome proliferator-activated receptor γ (PPAR-γ). VB1 promotes macrophage polarization into classically activated phenotypes with strong microbicidal activity and enhanced tumor necrosis factor-α and interleukin-6 expression at least in part by promoting nuclear factor-κB signaling. In addition, VB1 increases mitochondrial respiration and lipid metabolism and PPAR-γ integrates the metabolic and inflammatory signals regulated by VB1. Using both PPAR-γ agonists and deficient mice, we demonstrate that VB1 enhances anti-MTB activities in macrophages and in vivo by down-regulating PPAR-γ activity. Our data demonstrate important functions of VB1 in regulating innate immune responses against MTB and reveal novel mechanisms by which VB1 exerts its function in macrophages.

Tsantan Sumtang Alleviates Chronic Hypoxia-Induced Pulmonary Hypertension by Inhibiting Proliferation of Pulmonary Vascular Cells.

Hypoxia-induced pulmonary hypertension (HPH) is a severe condition associated with significant morbidity and mortality in people living at high altitude. Tsantan Sumtang, a traditional Tibetan medicine, has been routinely used for the treatment of cardiopyretic disease, as well as stenocardia. Interestingly, our previous research found that Tsantan Sumtang improved HPH in rats maintaining in a hypobaric chamber. We performed a series of experiments to test the indexes of vasoconstriction and vascular remodeling, the key pathophysiological characteristics of HPH. Our results showed that Tsantan Sumtang relaxed noradrenaline (NE)-precontracted rat pulmonary artery rings in a concentration-dependent manner in vitro. The PGI2-cAMP (prostaglandin I2-cyclic adenosine monophosphate) pathway, NO-cGMP (nitric oxide-cyclic guanosine monophosphate) pathway, and the opening of K+ channels (inward rectifier K+ channels, large conductance Ca2+-activated K+ channels, and voltage-dependent K+ channels) might play major roles in the vasorelaxation effect. In vivo, the administration of Tsantan Sumtang resulted in a substantial decrease in the rat mean pulmonary artery pressure (mPAP) and the right ventricular hypertrophy index (RVHI). The reduction of thickness of small pulmonary arterial wall and the WT% (the ratio of the vascular wall thickness to the vascular diameter) were observed. The smooth muscle muscularization of the arterials was alleviated by Tsantan Sumtang treatment at the same time. Tsantan Sumtang also reduced remodeling of pulmonary arterioles by suppressing the expression of proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (α-SMA), cyclin D1, and cyclin-dependent kinase 4 (CDK4) through inhibition of p27Kip1 degradation. Therefore, Tsantan Sumtang could be applied as a preventative medication for HPH, which would be a new use for this traditional medicine.

IPEX Syndrome, FOXP3 and Cancer.

In this review, we introduce the IPEX syndrome and its relationship with germline mutations of the FOXP3 gene. We then describe the multiple functional roles of FOXP3 in regulatory T cells and epithelial cells as well as in IPEX syndrome and tumor progression. Potential mechanisms of FOXP3 inactivation and transcriptional regulation are discussed with recent advances. Finally, we point out current issues and a potential FOXP3-mediated therapeutic strategy as well as the reactivation of FOXP3 in patients with IPEX syndrome and cancer.