The m6A writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism.

N6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.

Ramelteon alleviates myocardial ischemia/reperfusion injury (MIRI) through Sirt3--dependent regulation of cardiomyocyte apoptosis.

Reperfusion stands as a pivotal intervention for ischemic heart disease. However, the restoration of blood flow to ischemic tissue always lead to further damage, which is known as myocardial ischemia/reperfusion injury (MIRI). Ramelteon is an orally administered drug used to improve sleep quality, which is famous for its high bioadaptability and absence of notable addictive characteristics. However, the specific mechanism by which it improves MIRI is still unclear. Sirtuin-3 (Sirt3), primarily located in mitochondria, is crucial in mitigating many cardiac diseases, including MIRI. Based on the structure of Sirt3, we simulated molecular docking and identified several potential amino acid binding sites between it and ramelteon. Therefore, we propose a hypothesis that ramelteon may exert cardioprotective effects by activating the Sirt3 signaling pathway. Our results showed that the activation levels and expression level of Sirt3 were significantly decreased in MIRI tissue and H2O2 stimulated H9C2 cells, while ramelteon treatment upregulated Sirt3 activity and expression. After treat with 3-TYP, a classic Sirt3 activity inhibitor, we constructed myocardial ischemia/reperfusion surgery in vivo and induced H9C2 cells with H2O2 in vitro. The results showed that the myocardial protection and anti-apoptotic effects of ramelteon were antagonized by 3-TYP, indicating that the activation of Sirt3 is a key mechanism for ramelteon to exert myocardial protection. In summary, our results confirm a novel mechanism by which ramelteon improves MIRI by activating Sirt3 signaling pathway, providing strong evidence for the treatment of MIRI with ramelteon.

Berberine inhibits NLRP3 inflammasome activation by regulating mTOR/mtROS axis to alleviate diabetic cardiomyopathy.

Diabetes cardiomyopathy (DCM) refers to myocardial dysfunction and disorganization resulting from diabetes. In this study, we investigated the effects of berberine on cardiac function in male db/db mice with metformin as a positive control. After treatment for 8 weeks, significant improvements in cardiac function and a reduction in collagen deposition were observed in db/db mice. Furthermore, inflammation and pyroptosis were seen to decrease in these mice, as evidenced by decreased expressions of p-mTOR, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), IL-1ß, IL-18, caspase-1, and gasdermin D (GSDMD). In vitro experiments on H9C2 cells showed that glucose exposure at 33 mmol/L induced pyroptosis, whereas berberine treatment reduced the expression of p-mTOR and NLRP3 inflammasome components. Moreover, berberine treatment was seen to inhibit the generation of mitochondrial reactive oxygen species (mtROS) and effectively improve cell damage in high glucose-induced H9C2 cells. The mTOR inhibitor, Torin-1, showed a therapeutic effect similar to that of berberine, by reducing the expression of NLRP3 inflammasome components and inhibiting mtROS generation. However, the activation of mTOR by MHY1485 partially nullified berberine's protective effects during high glucose stress. Collectively, our study reveals the mechanism that berberine regulates the mTOR/mtROS axis to inhibit pyroptosis induced by NLRP3 inflammasome activation, thereby alleviating DCM.

Differential Regulation of Intracisternally Injected Angiotensin II-Induced Mechanical Allodynia and Thermal Hyperalgesia in Rats.

The present study examined the underlying mechanisms of mechanical allodynia and thermal hyperalgesia induced by the intracisternal injection of angiotensin (Ang) II. Intracisternal Ang II injection decreased the air puff threshold and head withdrawal latency. To determine the operative receptors for each distinct type of pain behavior, we intracisternally injected Ang II receptor antagonists 2 h after Ang II injection. Losartan, an Ang II type 1 receptor (AT1R) antagonist, alleviated mechanical allodynia. Conversely, PD123319, an Ang II type 1 receptor (AT2R) antagonist, blocked only thermal hyperalgesia. Immunofluorescence analyses revealed the co-localization of AT1R with the astrocyte marker GFAP in the trigeminal subnucleus caudalis and co-localization of AT2R with CGRP-positive neurons in the trigeminal ganglion. Intracisternal pretreatment with minocycline, a microglial inhibitor, did not affect Ang II-induced mechanical allodynia, whereas L-α-aminoadipate, an astrocyte inhibitor, significantly inhibited Ang II-induced mechanical allodynia. Furthermore, subcutaneous pretreatment with botulinum toxin type A significantly alleviated Ang II-induced thermal hyperalgesia, but not Ang II-induced mechanical allodynia. These results indicate that central Ang II-induced nociception is differentially regulated by AT1R and AT2R. Thus, distinct therapeutic targets must be regulated to overcome pain symptoms caused by multiple underlying mechanisms.

Stakeholders' Perceptions Regarding Digital Therapeutics Reimbursement in South Korea: Qualitative Study.

Background: Digital therapeutics (DTx) are therapeutic interventions driven by software and directly provided to patients, allowing them to manage their health with ease in any setting. A growing interest in DTx has spurred a discussion concerning their reimbursement pathways. However, DTx are still at a premature stage, with insufficient evidence on effectiveness, efficiency, and safety. Currently, although industries desire to quickly enter the market, especially by getting their products reimbursed by the National Health Insurance (NHI) fund, the NHI is cautious about DTx due to their uncertainties. Thus, public discussion and social consensus are crucial in deciding whether to reimburse DTx by the NHI fund. Objective: This study examined multiple stakeholders' awareness and attitudes toward DTx and perceptions of regulatory pathways for adopting DTx. Methods: In-depth interviews were conducted with 11 stakeholders in South Korea (industry: n=4, health care: n=3, academia: n=2, and consumer: n=2) using semistructured guidelines. They were purposively sampled to identify individuals with expertise in DTx and NHI policies. The interviews were conducted either in person or via a videoconference for 45-70 minutes. Qualitative data were analyzed using directed content analysis, which uses interview guidelines as an analytical framework. Results: Findings were divided into three categories: (1) awareness and attitude toward DTx, (2) perception of whether DTx are worth entering the market and being reimbursed by the NHI fund, and (3) perception of how to enter the market and how to reimburse DTx by the NHI fund if they are worth it. Although consumer stakeholders were not familiar with the basic concept of DTx, the other stakeholders understood it thoroughly. However, all participants showed positive attitudes and acceptance of DTx. Most of them responded that DTx are worth entering the market, but they could not reach an agreement on the pathways for DTx to enter the market. Although participants were in favor of the reimbursement of DTx in principle, they responded that a conservative approach is required due to insufficient clinical evidence for DTx. Conclusions: We found that stakeholders in South Korea had positive attitudes toward DTx, perceived them as worth using, and agreed to allow them to enter the market. The main issue was not the problem of the technology itself but the difference in opinion as to the pathways for reimbursement. Therefore, this study concluded that the NHI fund, which is operated very conservatively, is insufficient to quickly adopt and implement DTx. Various reimbursement methods, including tax-based financing, raising innovation funds for new technologies, and pilot studies using the NHI fund, should be used to rapidly generate clinical evidence and reduce the uncertainties of DTx to secure a stable market.

Preventive effects of Ramelteon on bleomycin-induced pulmonary fibrosis in mice.

Pulmonary fibrosis (PF) is a devastating lung disease that leads to impaired lung function and ultimately death. Several studies have suggested that melatonin, a hormone involved in regulating sleep-wake cycles, may be effective in improving PF. Ramelteon, an FDA-approved melatonin receptor agonist, has shown promise in exerting an anti-PF effect similar to melatonin. However, further investigations are required for illuminating the extent on its therapeutic benefits and the underlying molecular mechanisms. In this work, a mouse lung fibrosis model was built through intratracheal administration of bleomycin (BLM). Subsequently, the mice were administrated Ramelteon for a duration of 3 weeks to explore its efficacy and mechanism of action. Additionally, we utilized a TGF-ß1-induced MRC-5 cell model to further investigate the molecular mechanism underlying ramelteon's effects. Functionally, Ramelteon partially abrogated TGF-ß1-induced pulmonary fibrosis and reduced fibroblast proliferation, extracellular matrix deposition, and differentiation into myofibroblasts. In vivo experiments, ramelteon attenuated BLM-induced pulmonary fibrosis and collagen deposition. Mechanistically, ramelteon exerts its beneficial effect by alleviating translocation and expression of YAP1, a core component of Hippo pathway, from cytoplasm to nucleus; however, overexpression of YAP1 reversed this effect. In conclusion, our findings indicate that ramelteon can improve PF by regulating Hippo pathway and may become a potential candidate as a therapy to PF.

Analysis of the prescription trends of potentially inappropriate medications in Korean older outpatients by sex: A retrospective study using data from the health insurance review and assessment service.

This study aimed to determine the policy implications for drug management by identifying the prescription trends of potentially inappropriate medications (PIMs) in older outpatients. Considering the Drug Utilization Review and Korean version of the standards for PIMs based on the Beers Criteria, 141 ingredients were selected that spanned over 7 years of health insurance claims data analysis. During the study period, the number of patients and claims related to PIMs increased. Although the number of health insurance claims decreased in 2020 owing to coronavirus disease (COVID-19), it increased again in 2021. Tamsulosin was the most frequently prescribed drug for male patients, followed by alprazolam and zolpidem. For female patients, eperisone was the most frequently prescribed drug, followed by alprazolam, zolpidem, and etizolam. In Korea, health insurance claims for PIMs decreased in 2020 owing to the COVID-19 pandemic. However, an overall increasing trend was observed from 2015 to 2021. Moreover, during this period, the prescription trend of benzodiazepine-type drugs and zolpidem increased in both male and female patients. Therefore, management policies regarding PIMs and drug ingredients, such as benzodiazepines and zolpidem, are required.

Clinicogenomic characteristics and synthetic lethal implications of germline homologous recombination-deficient hepatocellular carcinoma.

BACKGROUNDS AND AIMS: We performed an in-depth examination of pathogenic germline variants (PGVs) and somatic variants in DNA damage response (DDR) genes in hepatocellular carcinoma (HCC) to explore their clinical and genomic impacts. APPROACH AND RESULTS: We used a merged whole-exome or RNA sequencing data set derived from in-house ( n = 230) and The Cancer Genome Atlas ( n = 362) databases of multiethnic HCC samples. We also evaluated synthetic lethal approaches targeting mutations in homologous recombination (HR) genes using HCC cells selected from five genomic databases of cancer cell lines. A total of 110 PGVs in DDR pathways in 96 patients were selected. Of the PGV carriers, 44 were HR-altered and found to be independently associated with poorer disease-free survival after hepatectomy. The most frequently altered HR gene in both germline and somatic tissues was POLQ , and this variant was detected in 22.7% (10/44) and 23.8% (5/21) of all the corresponding carriers, respectively. PGVs in HR were significantly associated with upregulation of proliferation and replication-related genes and familial risk of HCC. Samples harboring PGVs in HR with loss of heterozygosity were most strongly correlated with the genomic footprints of deficient HR, such as mutation burden and denovoSig2 (analogous to Catalogue of Somatic Mutations in Cancer [COSMIC] 3), and poor outcome. Pharmacologic experiments with HCC cells defective in BRCA2 or POLQ suggested that tumors with this phenotype are synthetic lethal with poly(ADP-ribose) polymerase inhibitors. CONCLUSIONS: Our findings suggest that germline HR defects in HCC tend to confer a poor prognosis and result in distinctive genomic scarring. Tests of the clinical benefits of HR-directed treatments in the affected patients are needed.

Clinical Practice Guidelines for Oropharyngeal Dysphagia / 대한연하장애학회지

Objective@#Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one’s physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. @*Methods@#Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. @*Results@#Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. @*Conclusion@#This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Developmental comparison between cerebral organoids in vitro and body's cortices in vivo / 解剖学报

Objective To understand the characteristics and developmental differences between cerebral organoids in vitro and normal cerebral cortices in vivo. Methods 1. Grouping: cerebral cortices in vivo group and cultured cerebral organoids in vitro group. 2. Sample collection: cortical tissues were collected from Kunming mouse embryos at embryonic day 7.5(E7.5), E9.5, E11.5, E14.5, and postnatal day 3 (P3) or P7. Three specimens were taken from each group. Meanwhile, cerebral organoids were cultured with mouse induced pluripotent stem cells (iPSCs), and samples at different culture time point were collected, and more than 3 samples were collected at each time point. 3. Detection method: the distribution of different types of cells in each group of specimens was analyzed by immunofluorescent staining. Results While relative similarities between in vivo cerebral cortical development and the cerebral organoids in vitro were observed, including the histogenesis, and the morphological differentiation of nerve cells and glial cells, the lamellar architecture of cerebral cortex in mouse brain was not observed in cerebral organoids. Conclusion The development of cerebral organoids in vitro has some similarity with body's cortical development. Therefore, cerebral organoids can be used to a substitution of cortex and diseases' models, but improvement of the existing technologies is necessary.

Gate-voltage-induced reversible electrical phase transitions in Mo0.67W0.33Se2 devices.

Tunable electrical phase transitions based on the structural and quantum-state phase transitions in two-dimensional transition-metal dichalcogenides have attracted attention in both semiconducting electronics and quantum electronics applications. Here, we report gate-voltage-induced reversible electrical phase transitions in Mo0.67W0.33Se2 (MoWSe) field-effect transistors prepared on SiO2/Si substrates. In gate-induced depletion regions of the 2H phase, an electrical current resumes flow at 150 K < T < 200 K with decreasing T irrespective of the layer number (n) for MoWSe when n < 20. The newly appearing electron-doped-type conducting channel again enters the 2H-phase region when the back-gate voltage increases, accompanied by the negative differential transconductance for four-layer and monolayer devices or by a deflection point in the transfer curves for a multilayer device. The thermal activation energies of the new conducting and 2H-phase branches differ by one order of magnitude at the same gate voltage for both the four-layer and monolayer cases, indicating that the electrical band at the Fermi level was modified. The hysteresis measurements for the gate voltage were performed with a five-layer device, which confirms the reversible electrical transition behavior. The possible origins of the nucleated conducting phase in the depletion region of the 2H phase of MoWSe are discussed.

Cellular Mechanisms Mediating the Antinociceptive Effect of Botulinum Toxin A in a Rodent Model of Trigeminal Irritation by a Foreign Body.

Although numerous studies have described botulinum toxin type A (BTX-A) efficacy against trigeminal neuralgia (TN), the underlying cellular mechanisms remain unclear. We have investigated cellular mechanisms that mediate the antinociceptive effect of BTX-A in a rodent model of TN produced by compression of the trigeminal nerve root (TNR). Anesthetized male Sprague-Dawley rats were fixed in a stereotaxic instrument and compression of the TNR was then achieved with a 4% agar solution. This model produced a significant mechanical allodynia and increased the expression of hypoxia-inducible factor (HIF)-1α and cytokines levels including interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the trigeminal ganglion (TG) by postoperative day (POD) 7. Single or double treatments with a high BTX-A dose (3 U/kg) led to significantly prolonged antinociceptive effects. Furthermore, a single treatment with BTX-A (3 U/kg) significantly suppressed the upregulation of HIF-1α expression and IL-1ß, IL-6, and TNF-α concentrations in the TG. Intraganglionic injection of PX-12, a HIF-1α inhibitor, led to significant anti-allodynic effects and lowered the IL-1ß, IL-6, and TNF-α levels in the TG. These findings indicate that the antinociceptive effect of BTX-A is mediated via HIF-1α associated cytokines modulation in the TG and is therefore a potentially relevant treatment strategy for TN. PERSPECTIVE: The antinociceptive properties of BTX-A in a rat model of trigeminal neuralgia are mediated through the regulation of the HIF-1α associated cytokine pathway in the trigeminal ganglion. BTX-A is therefore a potentially effective treatment strategy for trigeminal neuralgia.

Theragnostic 64Cu/67Cu Radioisotopes Production With RFT-30 Cyclotron.

64Cu and 67Cu are theragnostic pair radionuclides with promising application in the nuclear medicine. 64Cu is PET nuclide for the non-invasive diagnosis and 67Cu is beta emitter for therapy of various cancers. This study discusses optimization efforts in the production of these radioactive coppers carried out with 30 MeV cyclotron. Optimized conditions include target preparation, chemical separation, and quality control. The production routes of 64Cu and 67Cu were studied based on the nuclear reactions of 64Ni(p,n)64Cu and 70Zn(p,α)67Cu. The produced 64Cu and 67Cu have >99.9% of the radionuclidic purity. The yield at the end of bombardment (EOB) of 64Cu and 67Cu is 28.5 MBq/µAh and 67Cu is 0.58 MBq/µAh, respectively.

Erratum: Serum Prohibitin 2/PHB2 in Parkin-Mediated Mitophagy: A Potential Therapeutic Target for Non-Small Cell Lung Carcinoma.

The authors requested replacing Figure 2 as there was an error. The details of this error are as follows: Representative picture of transwell migration assay, A549 control group (Figure 2E). Representative picture of wound healing assay, 24h, A549 negative control group (Figure 2C). The above pictures were repeated within their own group (control group and negative control group). Representative picture of wound healing assay, 0h, A549 si-PHB2 group (Figure 2C). The authors used the wrong picture during data handling. Changes do not influence the results of the paper. In the original experiment, H1299 and A549 cells were divided into 4 groups (Control, si-PHB2, +PHB2, and negative control). Transwell migration assay and wound healing assay were performed 5 times. In addition, these results have been repeated by another research group (PHB2 promotes tumorigenesis via RACK1 in non-small cell lung cancer, Theranostics 2021, Vol. 11, Issue 7). Reference: Han Zhang, Chuntong Yin, Xin Liu, Xue Bai, Lei Wang, Honglin Xu, Jin Ju, Linyou Zhang. Prohibitin 2/PHB2 in Parkin-Mediated Mitophagy: A Potential Therapeutic Target for Non-Small Cell Lung Carcinoma.  Med Sci Monit. 2020; 26: e923227. DOI: 10.12659/MSM.923227.

Reimbursement of Digital Therapeutics: Future Perspectives in Korea.

Digital health is rapidly growing worldwide and its area is expanding from wellness to treatment due to digital therapeutics (DTx). This study compared DTx in the Korean context with other countries to better understand its political and practical implications. DTx is generally the same internationally, often categorized as software as a medical device. It provides evidence-based therapeutic interventions for medical disabilities and diseases. Abroad, DTx support entailed state subsidies and fundraising and national health insurance coverage. In the case of national health insurance coverage, most cases were applied to mental diseases. Moreover, in Japan, DTx related to hypertension will possibly be under discussion for national health insurance coverage in 2022. In overseas countries, coverage was decided only when the clinical effects were equivalent to those provided by existing technology, and in the UK, real usage data for DTx and associated evaluations were reflected by national health coverage determination. Prices were either determined through closed negotiations with health insurance operating agencies and manufacturers or established based on existing technology. Concerning the current situation, DTx dealing with various diseases including hypertension are expected to be developed near in the future, and the demand for use and compensation will likely increase. Therefore, it is urgent to define and prepare for DTx, relevant support systems, and health insurance coverage listings. Several support systems must be considered, including government subsidies, science/technology funds, and health insurance.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) modulates the proliferation and apoptosis of acute lymphoblastic leukemia cells by sponging miR-486-5p.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) is related to the progress of various cancers. Here, we illuminated the role of PVT1 in acute lymphoblastic leukemia (ALL) cell proliferation and apoptosis. PVT1 was upregulated in plasma samples from patients with ALL and ALL cell lines. PVT1 silencing repressed cell viability and enhanced cell apoptosis in Jurkat and SUP-B15 cells. PVT1 targeted microRNA-486-5p (miR-486-5p) and negatively modulated miR-486-5p expression. Upregulation of miR-486-5p decreased cell viability and increased ALL cell apoptosis. Mastermind Like Transcriptional Coactivator 3 (MAML3) was a downstream molecule of miR-486-5p and miR-486-5p mimic transfection weakened its expression in ALL cells. Rescue experiments proved that reintroduction of PVT1 counteracted the impacts of miR-486-5p in ALL cell proliferation and apoptosis. In vivo, PVT1 silencing repressed the tumor growth of SUP-B15 cells and reduced the expression of MAML3. Altogether, silencing of PVT1 inhibited ALL cell growth and induced cell apoptosis through sponging miR-486-5p.

TNF-α-Mediated RIPK1 Pathway Participates in the Development of Trigeminal Neuropathic Pain in Rats.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) participates in the regulation of cellular stress and inflammatory responses, but its function in neuropathic pain remains poorly understood. This study evaluated the role of RIPK1 in neuropathic pain following inferior alveolar nerve injury. We developed a model using malpositioned dental implants in male Sprague Dawley rats. This model resulted in significant mechanical allodynia and upregulated RIPK1 expression in the trigeminal subnucleus caudalis (TSC). The intracisternal administration of Necrosatin-1 (Nec-1), an RIPK1 inhibitor, blocked the mechanical allodynia produced by inferior alveolar nerve injury The intracisternal administration of recombinant rat tumor necrosis factor-α (rrTNF-α) protein in naive rats produced mechanical allodynia and upregulated RIPK1 expression in the TSC. Moreover, an intracisternal pretreatment with Nec-1 inhibited the mechanical allodynia produced by rrTNF-α protein. Nerve injury caused elevated TNF-α concentration in the TSC and a TNF-α block had anti-allodynic effects, thereby attenuating RIPK1 expression in the TSC. Finally, double immunofluorescence analyses revealed the colocalization of TNF receptor and RIPK1 with astrocytes. Hence, we have identified that astroglial RIPK1, activated by the TNF-α pathway, is a central driver of neuropathic pain and that the TNF-α-mediated RIPK1 pathway is a potential therapeutic target for reducing neuropathic pain following nerve injury.

The role of pyroptosis in endothelial dysfunction induced by diseases.

Most organs in the body rely on blood flow, and vesicular damage is the leading cause of injury in multiple organs. The endothelium, as the barriers of vessels, play a critical role in ensuring vascular homeostasis and angiogenesis. The rapid development of risk factors in endothelial injuries has been seen in the past decade, such as smoking, infectious, and diabetes mellites. Pyroptotic endothelium is an inflammatory mode of governed endothelial cell death that depend on the metabolic disorder and severe infectious such as atherosclerosis, and sepsis-related acute lung injury, respectively. Pyroptotic endothelial cells need GSDMD cleaved into N- and C-terminal by caspase1, and the cytokines are released by a pore constructed by the N-terminal of GSDMD in the membrane of ECs, finally resulting in severe inflammation and pyroptotic cell death. This review will focus on the patho-physiological and pharmacological pathways of pyroptotic endothelial metabolism in diseases. Overall, this review indicates that pyroptosis is a significant risk factor in diseases and a potential drug target in related diseases.

Standardization of FEES Evaluation for the Accurate Diagnosis of Dysphagia / 대한연하장애학회지

Objective@#Fiberoptic endoscopic evaluation of swallowing (FEES) is a standard diagnostic tool for swallowing disorders. However, it has not been used frequently in Korea because of the long test time, low cost, and the absence of a standard evaluation system. The purpose of this study was to suggest a standard fill-out form for the FEES result. @*Methods@#From February 2019 to June 2020, a total of 98 FEES tests were performed by an otolaryngologist (JYJ) at the Wonkwang University Hospital. After the exclusion of 68 cases, 30 cases were analyzed twice by 4 raters with over 5 years of experience as otolaryngologists working in various hospitals. The results were measured for the rater’s test-retest reliability and inter-rater consistency. @*Results@#Cohen’s kappa values for measuring the intra-rater consistency of the four raters were 0.984, 0.887, 0.848, and 0.930, respectively, meaning very good alignment of 0.8 or more, respectively. The Fleiss Kappa value for measuring inter-rater consistency was 0.276, meaning ‘fair’ for values of 0.2 or more. To examine consistency, an intraclass correlation coefficient (ICC) analysis conducted by assuming the grading score to be a constant continuous variable gave an ICC value of 0.729 (P＜0.001), showing a very reliable tendency. @*Conclusion@#In this study, all the items of the fill-out form were rated using a three-step grading scale, so the degree of agreement was high when performed twice by the same rater, but the degree of agreement among raters was relatively low. Therefore, our fill-out form for FEES will be useful in evaluating the improvement of a patient over the course of clinical treatment.

A proposed mechanism by which Qishen Yiqi dropping pill improves cardiac energy metabolism in rats with heart failure based on metabolomics and network pharmacology / 药学学报

"Omics" and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). 1H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.