A Study of the Wound Healing Mechanism of a Traditional Chinese Medicine, Angelica sinensis, Using a Proteomic Approach

Angelica sinensis (AS) is a traditional Chinese herbal medicine that has been formulated clinically to treat various form of skin trauma and to help wound healing. However, the mechanism by which it works remains a mystery. In this study we have established a new platform to evaluate the pharmacological effects of total AS herbal extracts as well as its major active component, ferulic acid (FA), using proteomic and biochemical analysis. Cytotoxic and proliferation-promoting concentrations of AS ethanol extracts (AS extract) and FA were tested, and then the cell extracts were subject to 2D PAGE analysis. We found 51 differentially expressed protein spots, and these were identified by mass spectrometry. Furthermore, biomolecular assays, involving collagen secretion, migration, and ROS measurements, gave results that are consistent with the proteomic analysis. In this work, we have demonstrated a whole range of pharmacological effects associated with Angelica sinensis that might be beneficial when developing a wound healing pharmaceutical formulation for the herbal medicine

CRONOS: Colorization and Contrastive Learning for Device-Free NLoS Human Presence Detection using Wi-Fi CSI

In recent years, the demand for pervasive smart services and applications has increased rapidly. Device-free human detection through sensors or cameras has been widely adopted, but it comes with privacy issues as well as misdetection for motionless people. To address these drawbacks, channel state information (CSI) captured from commercialized Wi-Fi devices provides rich signal features for accurate detection. However, existing systems suffer from inaccurate classification under a non-line-of-sight (NLoS) and stationary scenario, such as when a person is standing still in a room corner. In this work, we propose a system called CRONOS (Colorization and Contrastive Learning Enhanced NLoS Human Presence Detection), which generates dynamic recurrence plots (RPs) and color-coded CSI ratios to distinguish mobile people from vacancy in a room, respectively. We also incorporate supervised contrastive learning to retrieve substantial representations, where consultation loss is formulated to differentiate the representative distances between dynamic and stationary cases. Furthermore, we propose a self-switched static feature enhanced classifier (S3FEC) to determine the utilization of either RPs or color-coded CSI ratios. Our comprehensive experimental results show that CRONOS outperforms existing systems that apply machine learning, non-learning based methods, as well as non-CSI based features in open literature. CRONOS achieves the highest presence detection accuracy in vacancy, mobility, line-of-sight (LoS), and NLoS scenarios

Attention-based Learning for Sleep Apnea and Limb Movement Detection using Wi-Fi CSI Signals

Wi-Fi channel state information (CSI) has become a promising solution for non-invasive breathing and body motion monitoring during sleep. Sleep disorders of apnea and periodic limb movement disorder (PLMD) are often unconscious and fatal. The existing researches detect abnormal sleep disorders in impractically controlled environments. Moreover, it leads to compelling challenges to classify complex macro- and micro-scales of sleep movements as well as entangled similar waveforms of cases of apnea and PLMD. In this paper, we propose the attention-based learning for sleep apnea and limb movement detection (ALESAL) system that can jointly detect sleep apnea and PLMD under different sleep postures across a variety of patients. ALESAL contains antenna-pair and time attention mechanisms for mitigating the impact of modest antenna pairs and emphasizing the duration of interest, respectively. Performance results show that our proposed ALESAL system can achieve a weighted F1-score of 84.33, outperforming the other existing non-attention based methods of support vector machine and deep multilayer perceptron

Major interventions are associated with survival of out of hospital cardiac arrest patients - a population based survey

Background. The overall survival rate of out-of-hospital cardiac arrest (OHCA) in Taiwan or even in the whole of Asia is relatively low. Major interventions, such as target temperature management (TTM), coronary artery angiography, and extracorporeal membrane oxygenation (ECMO), have been associated with better patient outcome. However, studies in Taiwan revealing evidence of the benefits of these interventions are limited. Methods. A population-based study used an 8-year database to analyze overall survival and risk factors ˝among OHCA patients. All adult non-trauma OHCA patients were identified through diagnostic and procedure codes. Hospital survival and return of spontaneous circulation (ROSC) were primary and secondary outcomes. Logistic regression and Cox regression analyses were conducted. Results. There was a relationship between major interventions (including TTM, coronary artery angiography, and ECMO) and better hospital survival. Age, income, major interventions, and acute myocardial infarction history were associated with hospital survival. The adjusted hazard ratios (HRs) were 0.406 (95% CI, 0.295 to 0.558), 1.109 (95% CI, 1.027 to 1.197), 1.075 (95% CI, 1.002 to 1.154), 1.097 (95% CI, 1.02 to 1.181) and 0.799(95% CI, 0.677 to 0.942) for patients with major interventions, age≥50, medium low and low income, middle income, and acute myocardial infarction history, respectively. Conclusion. This population-based study in Taiwan revealed that older age (≥50), medium low and low income were associated with a lower rate of survival. Major interventions, including TTM, coronary angiography, and ECMO, were related to better survival

Combined Application Therapies of Stem Cells and Drugs in the Neurological Disorder Attenuation

Neurological disorders (NDs) are diseases of the central and peripheral nervous system that affected the hundreds of millions of people worldwide. Temporal lobe epilepsy (TLE) is a common NDs with hallucinations and disturbance of consciousness that cause the abnormal neurological activity in any part of brain. Neuroinflammation (NI) has been identified in epilepsy-related tissue from both experimental and clinical evidence and suspected to participate in the formation of neuronal cell death, reactive gliosis and neuroplastic changes in the hippocampus, may contribute to epileptogenesis. The NI is tightly regulated by microglia, but it is thought that excessive or chronic microglial activation can contribute to neurodegenerative processes. Therefore, the modulation of microglia responses may provide a therapeutic target for the treatment of severe or chronic NI conditions. Although the condition responds well to antiepileptic drugs (AEDs), there are still unresponsive to AEDs in about 1/3 of cases. Neural stem cells are the origin of various types of neural cells during embryonic development. Currently, many results of stem cell therapies in the animal experiments and clinical trials were demonstrated the efficacious therapeutic effects in the attenuated symptoms of ND. Therefore, the combined application therapies of stem cells and drugs may be a promising candidate for the therapeutic strategies of NDs, especially TLE

The Arabidopsis Malectin-Like/LRR-RLK IOS1 is Critical for BAK1-Dependent and BAK1-Independent Pattern-Triggered Immunity

Plasma membrane-localized pattern recognition receptors (PRRs) such as FLAGELLIN SENSING2 (FLS2), EF-TU RECEPTOR (EFR) and CHITIN ELICITOR RECEPTOR KINASE 1 (CERK1) recognize microbe-associated molecular patterns (MAMPs) to activate pattern-triggered immunity (PTI). A reverse genetics approach on genes responsive to the priming agent beta-aminobutyric acid (BABA) revealed IMPAIRED OOMYCETE SUSCEPTIBILITY1 (IOS1) as a critical PTI player. Arabidopsis thaliana ios1 mutants were hyper-susceptible to Pseudomonas syringae bacteria. Accordingly, ios1 mutants showed defective PTI responses, notably delayed up-regulation of the PTI-marker gene FLG22-INDUCED RECEPTOR-LIKE KINASE1 (FRK1), reduced callose deposition and mitogen-activated protein kinase activation upon MAMP treatment. Moreover, Arabidopsis lines over-expressing IOS1 were more resistant to bacteria and showed a primed PTI response. In vitro pull-down, bimolecular fluorescence complementation, co-immunoprecipitation, and mass spectrometry analyses supported the existence of complexes between the membrane-localized IOS1 and BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1 (BAK1)-dependent PRRs FLS2 and EFR, as well as with the BAK1-independent PRR CERK1. IOS1 also associated with BAK1 in a ligand-independent manner, and positively regulated FLS2-BAK1 complex formation upon MAMP treatment. In addition, IOS1 was critical for chitin-mediated PTI. Finally, ios1 mutants were defective in BABA-induced resistance and priming. This work reveals IOS1 as a novel regulatory protein of FLS2-, EFR- and CERK1-mediated signaling pathways that primes PTI activation

Hypokalemia, Its Contributing Factors and Renal Outcomes in Patients with Chronic Kidney Disease

Background: In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated. Design, Participants & Measurements 2500 participants with CKD stage 1–4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used. Results: The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m2. Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03–3.22) in sK 5 mEq/L conferred 1.6-fold (95% CI,1.09–2.34) increased risk of ESRD compared with sK = 4.5–5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range. Conclusion: In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes

The SAR analysis of dietary polyphenols and their antagonistic effects on bortezomib at physiological concentrations

Background: Bortezomib (BTZ), a primary treatment for MM, but its effectiveness can be reduced by interactions with vicinal diol moieties (VDMs) in polyphenols. Despite this, it’s debated whether BTZ therapy necessitates avoiding polyphenol-rich products, given the low bioavailability of polyphenols. Additionally, it remains unclear whether the structure of polyphenols contributes to their BTZ antagonism. Therefore, our study aims to unravel the structure-activity relationship of dietary polyphenols and their BTZ antagonism at daily diet-achievable physiological concentrations.Methods: We assessed the antagonistic effects of 25 polyphenols against BTZ using cell viability assays in RPMI 8226 cells. ChemGPS-NP helped analyze the structural similarity. Additionally, long-term cytotoxicity assays evaluated these effects at physiologically relevant concentrations.Results: By cell viability assays, we found a positive correlation between the number of VDMs in gallotannins and their BTZ antagonism. Moreover, the origin and configuration of VDMs, rather than the total VDM concentration, play a pivotal role in the combined antagonistic effects against BTZ in gallotannins. Additionally, ChemGPS-NP analysis indicated that the aromaticity and C-3 hydroxyl group in flavonoids’ C-rings enhance their BTZ antagonism. Finally, long-term cytotoxicity assays reveal that gallic acid (GA), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), at their physiological concentrations—attainable through tea consumption—significantly and synergistically antagonize BTZ.Conclusion: Due to the potential for these polyphenols to reduce the effectiveness of BTZ, it is advisable for MM patients undergoing BTZ treatment to reduce their consumption of foods high in VDM-containing polyphenols