Screening and rational identification of a novel angiotensin-converting enzyme C-domain inhibitory peptide from Fabaceae food peptide library.

Angiotensin-converting enzyme (ACE), consisting of N-domain and C-domain, is a key regulator of blood pressure. The use of cACE-specific inhibitors helps minimize side effects in clinical applications. Legumes are a good source of proteins containing ACE inhibitory peptides; however, no studies have reported the identification of cACE-specific inhibitory peptides from Fabaceae. In this study, thermal hydrolysates from seeds, sprouts, pods, seedlings, and flowers of legumes were analyzed. Flowers of legumes exhibited a C-domain-preference ACE inhibition and anti-hypertensive effect in rats. Screening the legume peptide library identified a novel cACE inhibitory peptide, SJ-1. This study reported the first identification of cACE inhibitory peptide from Fabaceae foods. SJ-1, identified from the legume flowers, interacted with active site residues of cACE, leading to the inhibition of ACE activity, downregulation of bradykinin levels, and reduction of blood pressure. These findings also suggested the potential of legume proteins as a source of cACE inhibitory peptides.

[Using Multiple Strategies to Improve the Accuracy of Hemodynamic Monitoring].

BACKGROUND & PROBLEMS: Hemodynamic monitoring is an important part of nursing care in the intensive care unit. Recent advances in medical technology and the diversification of intensive care equipment have increased the variety of instruments used in clinical hemodynamic monitoring. Many nurses who use new hemodynamic monitors are not familiar with instrument care, resulting in patient safety incidents caused by nurses not identifying warnings of hemodynamic data change and notifying doctors to provide treatment. The accuracy of hemodynamic monitoring care in our ward of 74.0% motivated this improvement project. PURPOSE: To improve the accuracy of hemodynamic monitoring care to 98.3%. RESOLUTION: Conduct educational training and plan professional education; establish an audit system to regularly monitor the accuracy of nursing care; provide tips to make the operation manual easier to read and understand; establish mobile learning to make learning immediate and more accessible; hold instrument operation practice sessions to improve nursing staff proficiency; monitor and upload data to the hospital information system. RESULTS: After the improvement project, the accuracy of hemodynamic monitoring care increased to 98.7%. CONCLUSIONS: The impact achieved met expectations, and the improvement project will be extended to other intensive care units in the hospital. Our nurses are now more familiar with the operation methods and the significance of monitoring values and interpretation of data. Also, when a value changes or becomes abnormal, they immediately notify the doctor for further evaluation and interventions to improve patient safety.

Analysis of target organs of Houttuynia cordata: A study on the anti-inflammatory effect of upper respiratory system.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (HC) is a traditional anti-pyretic herb that is classified as the lung meridian in traditional Chinese medicine. However, no articles have explored the main organs responsible for the anti-inflammatory activities of HC. AIM OF THE STUDY: The aim of the study was to investigate the meridian tropism theory of HC in lipopolysaccharide (LPS)-induced pyretic mice, as well as to identify the underlying mechanisms. MATERIALS AND METHODS: Transgenic mice carrying the luciferase gene driven by nuclear factor-κB (NF-κB) were intraperitoneally injected with LPS and orally administered standardized concentrated HC aqueous extract. The phytochemicals present in the HC extract were analyzed using high-performance liquid chromatography. In vivo and ex vivo luminescent imaging from transgenic mice was used to investigate the meridian tropism theory and anti-inflammatory effects of HC. Microarray analysis of gene expression patterns was used to elucidate the therapeutic mechanisms of HC. RESULTS: HC extract was found to contain phenolic acids, such as protocatechuic acid (4.52%) and chlorogenic acid (8.12%), as well as flavonoids like rutin (2.05%) and quercitrin (7.73%). The bioluminescent intensities induced by LPS in the heart, liver, respiratory system, and kidney were significantly suppressed by HC, while the maximal decrease (about 90% reduction) of induced luminescent intensity was observed in the upper respiratory tract. These data suggested that upper respiratory system might be the target for HC anti-inflammatory abilities. HC affected the processes involved in innate immunity, such as chemokine-mediated signaling pathway, inflammatory response, chemotaxis, neutrophil chemotaxis, and cellular response to interleukin-1 (IL-1). Moreover, HC significantly reduced the proportions of p65-stained cells and the amount of IL-1ß in trachea tissues. CONCLUSION: Bioluminescent imaging coupled with gene expression profile was used to demonstrate the organ selectivity, anti-inflammatory effects, and therapeutic mechanisms of HC. Our data demonstrated for the first time that HC displayed lung meridian-guiding effects and exhibited great anti-inflammatory potential in the upper respiratory tract. The NF-κB and IL-1ß pathways were associated with the anti-inflammatory mechanism of HC against LPS-provoked airway inflammation. Moreover, chlorogenic acid and quercitrin might be involved in the anti-inflammatory properties of HC.

[Using Multiple Strategies to Reduce the Incidence of Delirium in Older Adult Patients Receiving Surgery].

BACKGROUND & PROBLEMS: Older adult patients receiving surgery experience a relatively high rate of developing acute delirium due to factors related to the environment, surgery and anesthesia, pain, and indwelling line, which puts these patients at higher risk of patient safety incidents. The incidence of delirium among older patients receiving surgery in our ward was 12.3%. Moreover, in our ward, delirium-attributed self-extraction accounted for 84.2% of the "tubing events" reported via the Taiwan Patient-safety Reporting System and delirium-attributed falls accounted for 33.3% of the "fall events". Thus, delirium in this patient population had a serious effect on patient safety and increased medical expenses. PURPOSE: Reduce the incidence of delirium in older adult patients receiving surgery from 12.3% to 6.6%. METHODS: Strategies used included providing delirium care education and training to improve the delivery of delirium preventive treatments and the care implementation rate by care teams; formulating a surgical delirium high-risk factor assessment scale for the early screening of high-risk patients; adopting the "RADAR" delirium identification method for the rapid identification of cognition changes; establishing delirium prevention and treatment care guidelines for quality-of-care improvement; introducing bedside exercise equipment to increase patient mobility; and designating a dedicated delirium ward for these patients to provide high-quality delirium care services. RESULTS: The incidence rate of delirium in older adult patients receiving surgery was reduced to 6.5%. In addition, the implementation rate of delirium prevention treatment was increased to 98% in physicians and 100% in nurses. CONCLUSIONS: This project resulted in significantly improved outcomes and was expanded to the other surgical wards. The innovative concept of incorporating a designated delirium ward for older patients receiving surgery into other wards may be referenced in future ward planning and strategies for improving the quality of medical care.

[Using Creative Thinking Teaching to Improve Abdominal Drainage Tube Care Integrity Among Two-Year Post Graduate Nurses (PGNs)].

BACKGROUND & PROBLEMS: The abdominal drainage tube is an important device used in disease treatment and life maintenance. Drainage tube slippage leads to complications that increase both length of stay and costs of care. Four and seven cases of drainage tube slippage were reported, respectively, in 2018 and 2019 in our trauma wards. Among these, 9 cases were under the care of nurses in their post graduate year (PGY) training program. PURPOSE: To increase to 94% the abdominal drainage tube care-completeness rate of nurses in the PGY program. METHODS: Methods used included: establishing a standardized care module for abdominal drainage tube in the trauma wards, using the "drainage tube model" and multimedia teaching material in education to enhance skill proficiency, flexibly adjusting education schedules, using a creative-thinking teaching model in education, employing direct observation to evaluate PGY nurses' abdominal drainage tube skills; and establishing a drainage tube skill proficiency audit mechanism. RESULTS: After the intervention, the rate of care completeness for the abdominal drainage tube rose to 98.1%, participant awareness rose to 100%, and the rate of abdominal drainage tube slippage reduced to 0%. CONCLUSIONS: This project achieved good outcomes that may be expanded horizontally to other surgical wards. The use of the creative-thinking teaching model in training activities received good feedback from the nurse participants and will be incorporated into in-service education standards along with the computerized direct observation of procedural skills in the PGY e-learning passport to strengthen the completeness of learning processes.

Rosmarinic acid ameliorated psoriatic skin inflammation in mice through the novel inhibition of the interleukin-17A/interleukin-17A receptor interaction.

The interaction between interleukin-17A (IL-17A) and IL-17A receptor (IL-17RA) is a crucial target of psoriasis. Several natural compounds from foods or herbs have displayed efficacies on the amelioration of psoriasis. However, the anti-psoriatic mechanisms are mostly through the common anti-inflammatory effects and rarely via the blockage of the IL-17A/IL-17RA interaction. In this study, the IL-17A/IL-17RA-targeting effects of phenylpropanoids, a large class of secondary metabolites in plants, were analyzed. By screening 17 phenylpropanoids, we found that top four compounds with IL-17A/IL-17RA-blocking abilities were rosmarinic acid, eugenol, syringic acid, and gallic acid, with inhibitory concentrations at 50% of 2.14 ± 0.35 mM, 6.35 ± 0.1 mM, 4.79 ± 0.2 mM, and >10 mM, respectively. The oral administration of rosmarinic acid ameliorated redness and scaling on the dorsal skin of imiquimod-induced psoriatic mice in a dose-dependent manner. Rosmarinic acid suppressed the production of IL-23 and IL-17A and the infiltration of granulocyte subsets in skin tissues. Docking analysis showed that rosmarinic acid docked into IL-17A/IL-17RA interaction regions and exhibited hydrogen bonding with Arg-61, Glu-68, Arg-100, and Ser-118 of IL-17A, which are located in the epitope regions recognized by IL-17A neutralizing antibodies Fab6785 and Fab6468. In conclusion, this is the first study reporting that rosmarinic acid is an IL-17A-targeting agent that ameliorates psoriatic skin inflammation in mice via blocking the IL-17A/IL-17RA interaction.

The novel anti-inflammatory activity of mcIRBP from Momordica charantia is associated with the improvement of diabetic nephropathy.

Diabetic nephropathy is an inflammatory immune disorder accompanying diabetes. A trypsin inhibitor of Momordica charantia, mcIRBP, is an abundant 68 amino acid residue protein that interacts with the insulin receptor. Here the long-term effects of mcIRBP on the improvement of diabetic nephropathy were determined. Type 2 diabetic mice (db/db) were given mcIRBP administered orally for 12 consecutive weeks. Histological changes relating to the kidney were evaluated using Periodic Acid Schiff and Sirius Red staining. The mcIRBP-affected gene expression profile in the kidney was determined using RNA-Seq. The renoprotective mechanism of mcIRBP was elucidated based on ex vivo imaging and immunohistochemistry staining. Data showed that the administration of mcIRBP significantly decreased fasting blood glucose and glycated hemoglobin A1c (HbA1c) levels by 61% and 27.92%, respectively, suggesting that mcIRBP exhibited HbA1c-lowering abilities in diabetic mice. RNA sequencing (RNA-Seq) analysis showed that the majority of the mcIRBP-affected biological pathways were associated with inflammation and immunity, and the nuclear factor-κB (NF-κB) signaling pathway was significantly affected by mcIRBP. Ex vivo imaging showed that mcIRBP significantly decreased NF-κB-driven bioluminescence in the kidney by 46 ± 23%. The levels of the renal function indices, Evans blue dye content, fibrosis lesions, and cytokine expression were significantly decreased by mcIRBP, suggesting that mcIRBP improved vascular leakage and the pathological and inflammatory characteristics of diabetic nephropathy. This is the first study reporting that, in addition to blood glucose regulation, mcIRBP can act as a novel renoprotective and anti-inflammatory polypeptide, thereby improving diabetic nephropathy in db/db mice. In addition, this study suggested that there was a potential medicinal use of mcIRBP for the management of diabetes and its complications.

Correction: The novel anti-inflammatory activity of mcIRBP from Momordica charantia is associated with the improvement of diabetic nephropathy.

Correction for 'The novel anti-inflammatory activity of mcIRBP from Momordica charantia is associated with the improvement of diabetic nephropathy' by Pei-Yung Liao et al., Food Funct., 2022, DOI: 10.1039/d1fo03620c.

A gastro-resistant peptide from Momordica charantia improves diabetic nephropathy in db/db mice via its novel reno-protective and anti-inflammatory activities.

Diabetic nephropathy (DN), a principal diabetic microvascular complication, is a chronic inflammatory immune disorder. A gastro-resistant peptide mcIRBP-9 from Momordica charantia has shown modulation of blood glucose homeostasis in diabetic mice. Here we conducted a long-term experiment to evaluate the therapeutic effects and mechanisms of mcIRBP-9 on DN. Type 2 diabetic mice (db/db mice) were orally given mcIRBP-9 once daily for 12 consecutive weeks. The amelioration of DN was evaluated by renal function indexes, vascular leakage, and pathological lesions. Possible effective mechanisms of mcIRBP-9 on DN were analyzed by gene expression profiles. A pharmacokinetic study in rats was carried out to evaluate the oral bioavailability of mcIRBP-9. Our data showed that mcIRBP-9 was able to enter systemic circulation in rats after oral administration. In comparison with mock, long-term administration of mcIRBP-9 significantly decreased blood glucose (572.25 ± 1.55 mg dL-1vs. 213.50 ± 163.39 mg dL-1) and HbA1c levels (13.58 ± 0.30% vs. 8.23 ± 2.98%) and improved the survival rate (85.7% vs. 100%) in diabetic mice. mcIRBP-9 ameliorated DN by reducing renal vascular leakage and histopathological changes. mcIRBP-9 altered the pathways involved in inflammatory and immune responses, and the nuclear factor-κB played a central role in the regulation of mcIRBP-9-affected pathways. Moreover, mcIRBP-9 improved the inflammatory characteristic of DN in diabetic and non-diabetic mice. In conclusion, mcIRBP-9 displayed a novel anti-inflammatory activity and exhibited a reno-protective ability in addition to controlling the blood glucose and HbA1c levels. These findings suggested the role of mcIRBP-9 from M. charantia as a nutraceutical agent for diabetes and subsequent DN.

Positive association of Parkinson's disease with ankylosing spondylitis: a nationwide population-based study.

BACKGROUND: Ankylosing spondylitis (AS) is characterized by excessive production of inflammatory cytokines. Recent evidence suggests that inflammation underlies the neurodegenerative process of Parkinson's disease (PD). Whether AS has an influence on the development of PD is unclear. We aimed to examine a relationship, if any exists between AS and PD. METHODS: A population-based matched cohort study was performed using data from the 2000-2010 Taiwan National Health Insurance database. 6440 patients with AS and 25,760 randomly selected, age- and sex-matched controls were included in this study. The risk of PD in the AS cohort was evaluated by using a Cox model. RESULTS: This study revealed a positive association between AS and the risk of PD regardless of sex and age (aHR 1.75, p < .001). Particularly, AS cohort to non-AS cohort relative risk of PD significantly increased for the patients aged below 49 and above 65 years (aHR 4.70, p < .001; aHR 1.69, p < .001, respectively) and the patients with and without comorbidities (aHR 1.61, p < .001; aHR 2.71, p < .001, respectively). Furthermore, NSAID use was associated with lower risk of PD (aHR 0.69, p < .05). However, the risk of PD was higher (aHR 2.40, p < .01) in patients with AS receiving immunosuppressants than in those not receiving (aHR 1.70, p < .001). CONCLUSIONS: Patients with AS had an increased risk of PD which might be related to underlying chronic inflammation. Further research is required to elucidate the underlying mechanism.

The protective effect of quercetin on retinal inflammation in mice: the involvement of tumor necrosis factor/nuclear factor-κB signaling pathways.

Quercetin is a natural flavonoid that occurs in fruits and vegetables. Retinal inflammation is an important cause of vision loss. This study was aimed to analyze the effects of oral administration of quercetin on retinal inflammation. Transgenic mice, carrying nuclear factor-κB (NF-κB)-driven luciferase genes, were injected with 1 mg per kg body weight of lipopolysaccharide (LPS). Various amounts (1, 10, and 100 mg per kg body weight) of quercetin were orally given to mice. LPS-induced retinal inflammation was evaluated by bioluminescence imaging and histological examination 4 hours later. RNA-Seq analysis of gene expression profiles was performed to explain the mechanisms of quercetin on eye inflammation. Our data showed that LPS enhanced luminescent signals on ocular tissues, while LPS-induced luminescence intensities were significantly suppressed by quercetin by 73.61 ± 21.74%. LPS significantly increased the thickness of retinal tissues by 1.52 ± 0.37 fold, in comparison with the mock, while quercetin reduced the LPS-induced retinal thickness and decreased the accumulation of infiltrating granulocytes. Biological pathway analysis showed that tumor necrosis factor (TNF), cytokine, and NF-κB signaling pathways were involved in the anti-inflammatory mechanisms of quercetin. Immunohistochemical staining further showed that quercetin reduced the activation of NF-κB, the expression of interleukin-1ß and TNF-α, and the infiltration of granulocytes in retinal tissues. In conclusion, this is the first study reporting the effects and mechanisms of orally administered quercetin against LPS-induced retinal inflammation in mice. Due to its safety, our study suggested that supplementation of quercetin has beneficial effects on the eyes.

Anti-hypertensive and angiotensin-converting enzyme inhibitory effects of Radix Astragali and its bioactive peptide AM-1.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypertension is one of the common chronic health problems in the world. Astragalus membranaceus root (AM), also known as Huangqi, is a popular medicinal herb traditionally used to reinforce vital energy and modulate hypertension. AIM OF THE STUDY: This study was to reveal the anti-hypertensive activities and mechanisms of AM in spontaneously hypertensive rats (SHRs). Moreover, the presence of bioactive components in AM was further identified. MATERIALS AND METHODS: We analyzed the effects of aqueous extract of AM (AME) on the regulation of blood pressure and angiotensin converting enzyme (ACE), the major target of anti-hypertensive drugs. Proteomic, bioinformatics, and docking analyses were performed to identify the anti-hypertensive bioactive peptides in AME. RESULTS: Our data showed that AME inhibited ACE activities in a dose-dependent manner, with an IC50 of 1.85 ± 0.01 µg/ml. In comparison with mock, oral administration of AME reduced systolic blood pressure (SBP) levels in SHRs, and the level of SBP was decreased by 22.33 ± 3.61 mmHg at 200 mg/kg AME. Proteomic analysis identified that an abundant 152-amino-acid putative protein kinase fragment accounted for approximately 11.7% of protein spots in AME. AM-1 (LVPPHA), a gastrointestinal enzyme-resistant peptide cleaved from putative protein kinase fragment, inhibited ACE activities, with an IC50 value of 414.88 ± 41.88 µM. Moreover, oral administration of AM-1 significantly decreased SBP levels by 42 ± 2.65 mmHg at 10 µmol/kg. Docking analysis further showed that AM-1 docked into the active site channel of ACE and interacted with Ala-354 in the active site pocket of ACE. CONCLUSIONS: the ACE inhibitory effect of AM and the presence of ACE inhibitory phytopeptide in AME supported the ethnomedical use of AM on hypertension.

A Potential Herbal Adjuvant Combined With a Peptide-Based Vaccine Acts Against HPV-Related Tumors Through Enhancing Effector and Memory T-Cell Immune Responses.

Viral infection is associated with many types of tumorigenesis, including human papillomavirus (HPV)-induced cervical cancer. The induction of a specific T-cell response against virus-infected cells is desired to develop an efficient therapeutic approach for virus-associated cancer. Chinese herbal medicine (CHM) has a long history in the treatment of cancer patients in Asian countries. Hedyotis diffusa Willd (Bai Hua She She Cao, BHSSC) is frequently used clinically and has been shown to inhibit tumor growth in vitro. However, in vivo data demonstrating the antitumor efficacy of BHSSC are still lacking. We showed that BHSSC induces murine and human antigen-presenting cell (APC) activation via the MAPK signaling pathway and enhances antigen presentation in bone marrow-derived dendritic cells (BMDCs) in vitro. Furthermore, we identified that treatment with BHSSC leads to improved specific effector and memory T-cell responses in vivo. Variant peptide-based vaccines combined with BHSSC improved antitumor activity in preventive, therapeutic, and recurrent HPV-related tumor models. Furthermore, we showed that rutin, one of the ingredients in BHSSC, induces a strong specific immune response against HPV-related tumors in vivo. In summary, we demonstrated that BHSSC extract and its active compound, rutin, can be used as adjuvants in peptide-based vaccines to increase immunogenicity and to bypass the requirement of a conditional adjuvant.

Regulation effect and mechanism of Sheng-Hua-Tang on female reproductive system: From experimental transcriptomic analysis to clinical applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-Hua-Tang (SHT) is commonly used to treat female illnesses, especially postpartum conditioning. However, its effects and mechanisms on female reproductive system remain unclear. The aim of the present study was to investigate the effect of SHT on female brain-ovary-uterus axis from bench to clinic. MATERIALS AND METHODS: Mice were administrated SHT (200 mg/kg) orally for seven consecutive days. Brain, ovary, and uterus tissues were then collected for microarray analysis. A nationwide database analysis and a pilot randomized, open-label clinical trial were further applied to evaluate the clinical application and effects of SHT on postpartum women. RESULTS: Microarray analysis showed that oral administration of SHT induced a cascade reaction of gene expression, with 17, 883, and 1592 genes were significantly regulated by SHT in brain, ovary, and uterus, respectively. Population-based analysis of one million subjects in Taiwan's National Health Insurance Research Database between 1997 and 2013 showed that SHT was commonly used in menstrual disorders in female population, especially dysmenorrhea, abnormal uterine bleeding, and variation of menstrual cycle. Clinical trial on postpartum women showed that oral administration SHT for one week alleviated uterine contraction pain and breast swelling pain. Furthermore, Mmp2, Mmp3, Mmp9, Mmp11, Mmp15, Oxtr, Plrl, and Tph2 gene expression affected by SHT in mice were correlated with clinical effects of SHT in human subjects. CONCLUSION: This report provided the scientific evidences of mechanisms and clinical efficacies of SHT. Moreover, our findings might afford insights for clinical doctors in terms of SHT prescription.

Antihypertensive Effects of Corn Silk Extract and Its Novel Bioactive Constituent in Spontaneously Hypertensive Rats: The Involvement of Angiotensin-Converting Enzyme Inhibition.

Corn silk tea has been used in folk medicine for anti-hypertensive healthcare. Angiotensin-converting enzyme (ACE) plays a crucial role on the homeostasis of blood pressure. However, effects of corn silk tea on ACE activity and the presence of ACE inhibitory constituents in corn silk are still unknown. Here we applied proteomics and bioinformatics approaches to identify corn silk bioactive peptides (CSBps) that target ACE from the boiling water extract of corn silk (CSE). CSE significantly reduced systolic blood pressure (SBP) levels in spontaneously hypertensive rats and inhibited the ACE activity. By proteomics coupled with bioinformatics analyses, we identified a novel ACE inhibitory peptide CSBp5 in CSE. CSBp5 significantly inhibited the ACE activity and decreased SBP levels in a dose-dependent manner. Docking analysis showed that CSBp5 occupied the substrate-binding channel of ACE and interacted with ACE via hydrogen bonds. In conclusion, we identified that CSE exhibited anti-hypertensive effects in SHRs via the inhibition of ACE, the target of most anti-hypertensive drugs. In addition, an ACE inhibitory phytopeptide CSBp5 that decreased SBP levels in rats was newly identified. Our findings supported the ethnomedical use of corn silk tea on hypertension. Moreover, the identification of ACE inhibitory phytopeptide in corn silk further strengthened our findings.

Ferulic acid altered IL-17A/IL-17RA interaction and protected against imiquimod-induced psoriasis-like skin injury in mice.

Ferulic acid (FA), a phenolic phytochemical, is commonly found in grains, vegetables, and fruits. Interleukin-17A (IL-17A) and IL-17 receptor A (IL-17RA) interaction is one of important therapeutic targets for psoriasis. Here we analyzed the FA effects on IL-17A/IL-17RA interaction and psoriasis-like skin injury induced by imiquimod (IMQ). IL-17A-blocking assay and docking analysis showed that FA interacted with Trp-67, Gln-94, and Glu-95 residues of IL-17A via hydrogen bonds and consequently abolished the binding of IL-17RA to IL-17A. Mice were topically given with IMQ and orally given with various amounts of FA for 14 consecutive days. FA attenuated IMQ-induced psoriasis-like skin lesions in a dose-dependent manner, and the epidermal thickness of mice treated with 100 mg/kg FA was reduced by 53.48 ±â€¯4.44% in comparison with sham. Global analysis of differentially expressed genes showed that IMQ and FA significantly affected immune response, metabolism, and mitogen-activated protein kinase signaling pathways. Immunohistochemical staining showed that FA inhibited the infiltration and the cytokine secretion of Th17 cell, dendritic cell, and granulocyte subsets in psoriatic skin tissues. In conclusion, we newly identified that oral administration of FA protected against IMQ-induced psoriatic skin injury in mice. Moreover, its protection was associated with the interference of IL-17A/IL-17RA interaction.

Adjunctive Chinese herbal medicine therapy for nasopharyngeal carcinoma: Clinical evidence and experimental validation.

BACKGROUND: To investigate the benefits of adjunctive Chinese herbal medicine (CHM) for patients with nasopharyngeal carcinoma (NPC). METHODS: We included all patients diagnosed with NPC during 1997-2009 and followed until 2011 in Taiwan. We used 1:1 frequency matching by age, sex, comorbidity, conventional treatment, and index year to compare the CHM users and non-CHM users (n = 2542 each). The prescribed CHM was further investigated with regard to its cytotoxicity. RESULTS: Compared with non-CHM users, adjunctive CHM users had a lower hazard ratio of mortality risk, and a better survival probability. Gan-Lu-Yin (GLY) was the most commonly prescribed CHM, and it reduced cell viability, inhibited tumor proliferation, and induced apoptosis through the poly (ADP-ribose) polymerase and caspase-3-dependent pathway in human NPC TW01 cells. Oral administration of GLY retarded NPC-TW01 tumor growth in the xenograft nude mouse model. CONCLUSION: Real-world data and laboratory experiments implied that adjunctive CHM might be beneficial for NPC patients.

Does nephrotic syndrome without chronic kidney disease increase the risk of Parkinson's disease and secondary parkinsonism? A nationwide population-based study in Taiwan.

OBJECTIVES: Previous research has shown that patients with nephrotic syndrome (NS) have a higher risk of cognitive impairment, dementia or neurodegenerative disorder. The present study aimed to examine a relationship, if any exists between NS and Parkinson's disease (PD), a neurodegenerative disorder and secondary parkinsonism (sPS). METHODS: A nationwide retrospective observational study conducted using data from the 2000-2010 Taiwan National Health Insurance Research Database. This study included 3663 patients with NS and 14 652 randomly selected, age-matched and sex-matched patients without NS. A Cox multivariable proportional hazards model was used to evaluate the risk of PD and sPS (PDsPS) in the NS cohort. RESULTS: This study identified a positive association between NS and the risk of PDsPS in both men and women and in all age groups (adjusted HR 1.51; 95% CI 1.37 to 1.66). Compared with patients without NS and comorbidities, those with NS with two or more comorbidities exhibited an 8.23-fold higher risk of PDsPS (95% CI 6.22 to 10.9) and patients with NS and one comorbidity exhibited a 2.93-fold higher risk of PDsPS (95% CI 2.37 to 3.63). CONCLUSIONS: Patients with NS have an increased risk of PDsPS. This increased risk may be related to brain vascular damage or blood-brain barrier impairment. Further research is necessary to explore the underlying relationship between NS and PDsPS.

Vanillin-Ameliorated Development of Azoxymethane/Dextran Sodium Sulfate-Induced Murine Colorectal Cancer: The Involvement of Proteasome/Nuclear Factor-κB/Mitogen-Activated Protein Kinase Pathways.

Vanillin is a natural dietary flavoring widely used in the food industry. Colorectal cancer (CRC) is one of the common malignancies in the world. Chronic intestinal inflammation is a risk factor for the development of CRC. We have previously found that vanillin improves and prevents colitis in mice. Here we evaluated the inhibitory activities of vanillin on a mouse model of colitis-induced CRC. Mice were challenged intraperitoneally with azoxymethane (AOM) and orally with dextran sodium sulfate (DSS). Various dosages of vanillin were orally administered for 13 consecutive weeks. Vanillin alleviated the development of tumors in AOM/DSS-induced mice. The total number of tumors in 100 mg/kg vanillin group was significantly reduced by 57.14 ± 7.67%, compared with sham group. Gene expression analysis showed that vanillin downregulated the expression levels of proteasome genes in colon tissues. Moreover, vanillin at 10 mM significantly suppressed proteasome activities in HCT-116 cells by 41.27 ± 0.41%. Furthermore, vanillin diminished the phosphorylation of mitogen-activated protein kinases (MAPKs) and reduced the number of p65-positive cells, proliferating cells, and granulocytes in colon tissues with statistical significance. In conclusion, our data suggested that vanillin was a bioactive compound that ameliorated the development of AOM/DSS-induced colon cancer in mice. Moreover, the amelioration of vanillin might be associated with the downregulation of proteasome, nuclear factor-κB, and MAPK pathways.

Oral Administration of Vanillin Improves Imiquimod-Induced Psoriatic Skin Inflammation in Mice.

Vanillin is one of the most widely used flavoring products worldwide. Psoriasis is a chronic inflammatory skin disorder. The interleukin-23 (IL-23)/interleukin-17 (IL-17) axis plays a critical role in psoriasis. Here, we analyzed the effect of vanillin on imiquimod (IMQ)-induced psoriatic skin inflammation in mice. Mice were treated topically with IMQ on the back skin and orally with various amounts of vanillin for 7 consecutive days. Vanillin significantly improved IMQ-induced histopathological changes of skin in a dose-dependent manner. The thickness and number of cell layers of epidermis were reduced by 29 ± 14.4 and 27.8 ± 11%, respectively, in mice given 100 mg/kg of vanillin. A microarray showed that a total of 9042 IMQ-upregulated genes were downregulated by vanillin, and the biological pathways involved in the immune system and metabolism were significantly altered by vanillin. The upregulated expressions of IL-23, IL-17A, and IL-17F genes were suppressed by vanillin, with fold changes of -3.07 ± 0.08, -2.06 ± 0.21, and -1.62 ± 0.21, respectively. Moreover, vanillin significantly decreased both the amounts of IL-17A and IL-23 and the infiltration of immune cells in the skin tissues of IMQ-treated mice. In conclusion, our findings suggested that vanillin was an effective bioactive compound against psoriatic skin inflammation. Moreover, the downregulation of IL-23 and IL-17 expression suggested that vanillin was a novel regulator of the IL-23/IL-17 axis.