Flavor characteristics of garlic fish cakes using electronic nose and tongue analyses.

This study investigated the utility of garlic powder as a functional ingredient. The aim was to develop fish cakes with improved functionality and sensory preference based on the antioxidant activity and quality characteristics. Increasing amounts of garlic powder in the prepared fish cakes were associated with increasing total polyphenol and flavonoid contents, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazolin-6-sulfonic acid) (ABTS+) radical scavenging activity, and reducing power. Furthermore, electronic tongue and electronic nose analyses showed an increased the intensity of umami and sourness and increased the levels of volatile compounds. The lowest trimethylamine peak corresponded to the highest amount of garlic powder. Sensory evaluation indicated that 3% garlic powder had the highest score for all criteria. Fishy odor decreased as the proportion of garlic powder increased. These findings suggest that the addition of 3% garlic powder improves quality characteristics, sensory preference, and antioxidant activity of fish cakes.

C-Arm Computed Tomographic Image Fusion for Repetitive Transarterial Chemoembolization of Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the potential implications of fusion imaging with C-arm computed tomography (CACT) scans for repetitive conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma. MATERIALS AND METHODS: Fifty-six cTACE sessions were performed using fusion CACT images from September 2020 to June 2021 in a tertiary referral center, and the data were retrospectively analyzed. Fusion of unenhanced and enhanced CACT images was considered when previously accumulated iodized oil hampered the identification of local tumor progression or intrahepatic distant metastasis (indication A), when a tumor was supplied by multiple arteries with different origins from the aorta and missing tumor enhancement was suspected (indication B), or when iodized oil distribution on immediate post-cTACE CACT images needed to be precisely compared with the pre-cTACE images (indication C). Fusion image quality, initial tumor response, time to local progression (TTLP) of index tumors, and time to progression (TTP) were evaluated. RESULTS: The fusion quality was satisfactory with a mean misregistration distance of 1.4 mm. For the 40 patients with indication A, the initial tumor responses at 3 months were nonviable, equivocal, and viable in 27 (67.5%), 4 (10.0%), and 9 (22.5%) index tumors, respectively. The median TTLP and TTP were 14.8 months and 4.5 months, respectively. For 10 patients with indication B, the median TTLP and TTP were 8.3 months and 2.6 months, respectively. Among the 6 patients with indication C, 2 patients were additionally treated at the same cTACE session after confirming incomplete iodized oil uptake on fusion imaging. CONCLUSIONS: Fusion CACT images are useful in patients with hepatocellular carcinoma undergoing repetitive cTACE.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Management of the Underlying Etiologies and Comorbidities of Heart Failure.

Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, long-term anticoagulants are recommended according to the CHA2DS2-VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Management of the Underlying Etiologies and Comorbidities of Heart Failure.

Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, long-term anticoagulants are recommended according to the CHA2DS2-VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.

Iron Deficiency in Korean Patients With Heart Failure.

BACKGROUND: Although iron deficiency (ID) is an important and treatable risk factor for heart failure (HF), data on ID are scarce in Asian patients with HF. Therefore, we sought to determine the prevalence and clinical characteristics of ID in hospitalized Korean patients with HF. METHODS: In this prospective, multicenter cohort study, 461 patients with acute HF seen at five tertiary centers from January to November 2019 in Korea were enrolled. ID was defined as serum ferritin < 100 µg/L or ferritin 100-299 µg/L in combination with transferrin saturation < 20%. RESULTS: The patients' mean age was 67.6 ± 14.9 years, and 61.8% were male. Among total 461 patients, ID was present in 248 patients (53.8%). The prevalence of ID was significantly higher in women than in men (65.3% vs. 47.3%, P < 0.001). In a multivariable logistic regression analysis, the independent predictors of ID were female sex (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.47-3.30), valvular heart disease (OR, 2.10; 95% CI, 1.10-4.17), higher heart rate (OR, 1.10; 95% CI, 1.01-1.21), anemia (OR, 1.60; 95% CI, 1.07-2.40), and the use of clopidogrel (OR, 1.56; 95% CI, 1.00-2.45). Among women, the prevalence of ID did not significantly differ between younger and older women (< 65 years: 73.7% vs. ≥ 65 years: 63.0%, P = 0.222), those with low and high body mass index (BMI < 25 kg/m²: 66.2% vs. BMI ≥ 25 kg/m²: 69.6%, P = 0.703), or those with low and high natriuretic peptide (NP) levels (NP < median: 69.8% vs. NP ≥ median: 61.1%, P = 0.295). Only 0.2% patients with acute HF received intravenous iron supplementation in Korea. CONCLUSION: The prevalence of ID is high in hospitalized Korean patients with HF. Because ID cannot be diagnosed by clinical parameters, routine laboratory examinations are necessary to identify patients with ID. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04812873.

High-resolution pancreatic computed tomography for assessing pancreatic ductal adenocarcinoma resectability: a multicenter prospective study.

OBJECTIVE: This prospective multicenter study aimed to evaluate the diagnostic performance of 80-kVp thin-section pancreatic CT in determining pancreatic ductal adenocarcinoma (PDAC) resectability according to the recent National Comprehensive Cancer Network (NCCN) guidelines. METHODS: We prospectively enrolled surgical resection candidates for PDAC from six tertiary referral hospitals (study identifier: NCT03895177). All participants underwent pancreatic CT using 80 kVp tube voltage with 1-mm reconstruction interval. The local resectability was prospectively evaluated using NCCN guidelines at each center and classified into three categories: resectable, borderline resectable, and unresectable. RESULTS: A total of 138 patients were enrolled; among them, 60 patients underwent neoadjuvant therapy. R0 resection was achieved in 103 patients (74.6%). The R0 resection rates were 88.7% (47/53), 52.4% (11/21), and 0.0% (0/4) for resectable, borderline resectable, and unresectable disease, respectively, in 78 patients who underwent upfront surgery. Meanwhile, the rates were 90.9% (20/22), 76.7% (23/30), and 25.0% (2/8) for resectable, borderline resectable, and unresectable PDAC, respectively, in patients who received neoadjuvant therapy. The area under curve of high-resolution CT in predicting R0 resection was 0.784, with sensitivity, specificity, and accuracy of 87.4% (90/103), 48.6% (17/35), and 77.5% (107/138), respectively. Tumor response was significantly associated with the R0 resection after neoadjuvant therapy (odds ratio [OR] = 38.99, p = 0.016). CONCLUSION: An 80-kVp thin-section pancreatic CT has excellent diagnostic performance in assessing PDAC resectability, enabling R0 resection rates of 88.7% and 90.9% for patients with resectable PDAC who underwent upfront surgery and patients with resectable PDAC after neoadjuvant therapy, respectively. KEY POINTS: • The margin-negative (R0) resection rates were 88.7% (47/53), 52.4% (11/21), and 0.0% (0/4) for resectable, borderline resectable, and unresectable pancreatic ductal adenocarcinoma (PDAC), respectively, on 80-kVp thin-section pancreatic CT in the 78 patients who underwent upfront surgery. • Among the 60 patients who underwent neoadjuvant therapy, the R0 rates were 90.9% (20/22), 76.7% (23/30), and 25.0% (2/8) for resectable, borderline resectable, and unresectable PDAC, respectively. • Tumor response, along with the resectability status on pancreatic CT, was significantly associated with the R0 resection rate after neoadjuvant therapy.

Dermatophagoides farinae Extract Induces Interleukin 33-Mediated Atopic Skin Inflammation via Activation of RIP1.

Receptor-interacting protein kinase (RIP) family 1 signaling has complex effects on inflammatory processes and cell death, but little is known concerning allergic skin diseases. We examined the role of RIP1 in Dermatophagoides farinae extract (DFE)-induced atopic dermatitis (AD)-like skin inflammation. RIP1 phosphorylation was increased in HKCs treated with DFE. Nectostatin-1, a selective and potent allosteric inhibitor of RIP1, inhibited AD-like skin inflammation and the expression of histamine, total IgE, DFE-specific IgE, IL-4, IL-5, and IL-13 in an AD-like mouse model. The expression of RIP1 was increased in ear skin tissue from a DFE-induced mouse model with AD-like skin lesions and in the lesional skin of AD patients with high house dust mite sensitization. The expression of IL-33 was down-regulated after RIP1 inhibition, and the levels of IL-33 were increased by over-expression of RIP1 in keratinocytes stimulated with DFE. Nectostatin-1 reduced IL-33 expression in vitro and in the DFE-induced mouse model. These results suggest that RIP1 can be one of the mediators that regulate IL-33-mediated atopic skin inflammation by house dust mites.

Aerial part of Houttuynia cordata reverses memory impairment by regulating amyloid beta accumulation and neuroinflammation in Alzheimer's disease model.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by amyloid-ß (Aß) deposition, accompanied by neuroinflammation and memory dysfunction. Houttuyniae Herba (aerial parts of Houttuynia cordata, also known as fish mint; HH), an herbal medicine traditionally used to treat fever, urinary disorders, and pus, is revealed to protect neurons from Aß toxicity and regulate cholinergic dysfunction in AD models. In this study, we aimed to investigate the effects of HH on excessive accumulation of Aß followed by neuroinflammation, synaptic degeneration, and memory impairment. Two-month-old 5xFAD transgenic mice were administered HH at 100 mg/kg for 4 months. We observed that HH treatment ameliorated memory impairment and reduced Aß deposits in the brains of the mice. HH directly inhibited Aß aggregation in vitro using the Thioflavin T assay and indirectly suppressed the amyloidogenic pathway by increasing alpha-secretase expression in the mice brain. In addition, HH exerted antineuroinflammatory effects by reducing of glial activation and p38 phosphorylation. Moreover, HH treatment increased the expression of synaptophysin, a presynaptic marker protein. Overall, HH alleviates memory impairment in AD by facilitating nonamyloidogenic pathway and inhibiting neuroinflammation. Therefore, we suggest that HH can be a promising herbal drug for patients with AD requiring multifaceted improvement.

Comparative and expression analyses of AP2/ERF genes reveal copy number expansion and potential functions of ERF genes in Solanaceae.

BACKGROUND: The AP2/ERF gene family is a superfamily of transcription factors that are important in the response of plants to abiotic stress and development. However, comprehensive research of the AP2/ERF genes in the Solanaceae family is lacking. RESULTS: Here, we updated the annotation of AP2/ERF genes in the genomes of eight Solanaceae species, as well as Arabidopsis thaliana and Oryza sativa. We identified 2,195 AP2/ERF genes, of which 368 (17%) were newly identified. Based on phylogenetic analyses, we observed expansion of the copy number of these genes, especially those belonging to specific Ethylene-Responsive Factor (ERF) subgroups of the Solanaceae. From the results of chromosomal location and synteny analyses, we identified that the AP2/ERF genes of the pepper (Capsicum annuum), the tomato (Solanum lycopersicum), and the potato (Solanum tuberosum) belonging to ERF subgroups form a tandem array and most of them are species-specific without orthologs in other species, which has led to differentiation of AP2/ERF gene repertory among Solanaceae. We suggest that these genes mainly emerged through recent gene duplication after the divergence of these species. Transcriptome analyses showed that the genes have a putative function in the response of the pepper and tomato to abiotic stress, especially those in ERF subgroups. CONCLUSIONS: Our findings will provide comprehensive information on AP2/ERF genes and insights into the structural, evolutionary, and functional understanding of the role of these genes in the Solanaceae.

Trends of genital wart in Korea according to treatment method classification: Big data analysis of health care in 2010-2019.

PURPOSE: The purpose of this study is to investigate disease trend of genital wart through changes in each treatment method over the past 10 years in Korea. MATERIALS AND METHODS: From 2010 to 2019, surgical treatment including cauterization, excision, cryotherapy, and laser therapy, non-surgical treatment such as podophyllin, and surgical treatment for anorectal lesion were extracted and analyzed from 2010 to 2019. For each treatment method, characteristics such as sex, age, region, medical cost and average number of procedures were analyzed. RESULTS: The number of patients following all treatment modalities increased every year. Surgical treatment of genital wart and anorectal wart showed a significant increase in male patients. Number of non-surgical treatment decreased in males but increased in females. Surgical removal of the anorectal wart increased more than 250% in over 10 years, and males underwent surgery 4 times more than females. In both surgery and non-surgery, the mean session was higher in males. Most of them were carried out in primary medical institutions. In Seoul and Gyeonggi-do, the largest number of patients received treatment regardless of treatment method. CONCLUSIONS: Treatment for genital warts has increased rapidly over the past 10 years, and the increase in males is remarkable. The main treatment was surgery, and males mainly received surgical treatment, and females mainly received drug treatment. The primary medical institution was in charge of the most treatment. As the number of patients and related medical expenses are increasing rapidly, more attention and response to diseases are needed.

Greater Plasma Protein Adsorption on Mesoporous Silica Nanoparticles Aggravates Atopic Dermatitis.

Purpose: The protein corona surrounding nanoparticles has attracted considerable attention as it induces subsequent inflammatory responses. Although mesoporous silica nanoparticles (MSN) are commonly used in medicines, cosmetics, and packaging, the inflammatory effects of the MSN protein corona on the cutaneous system have not been investigated till date. Methods: We examined the greater plasma protein adsorption on MSN leads to serious inflammatory reactions in Dermatophagoides farinae extract (DFE)-induced mouse atopic dermatitis (AD)-like skin inflammation because of increased uptake by keratinocytes. Results: We compare the AD lesions induced by MSN and colloidal (non-porous) silica nanoparticles (CSN), which exhibit different pore architectures but similar dimensions and surface chemistry. MSN-corona treatment of severe skin inflammation in a DFE-induced in vivo AD model greatly increases mouse ear epidermal thickness and infiltration of immune cells compared with the CSN-corona treatment. Moreover, MSN-corona significantly increase AD-specific immunoglobulins, serum histamine, and Th1/Th2/Th17 cytokines in the ear and lymph nodes. MSN-corona induce more severe cutaneous inflammation than CSN by significantly decreasing claudin-1 expression. Conclusion: This study demonstrates the novel impact of the MSN protein corona in inducing inflammatory responses through claudin-1 downregulation and suggests useful clinical guidelines for MSN application in cosmetics and drug delivery systems.

Analysis of treatment outcomes according to the cycles of adjuvant chemotherapy in gastric cancer: a retrospective nationwide cohort study.

BACKGROUND: One-year S-1 or six-month capecitabine/oxaliplatin (CAPOX) has been the standard adjuvant chemotherapy for gastric cancer (GC). We investigated outcomes according to the cycles of adjuvant chemotherapy, using data from the Korean Health Insurance and Assessment Service. METHODS: A total of 20,552 patients, including 13,614 patients who received S-1 and 6,938 patients who received CAPOX extracted from 558,442 patients were retrospectively analyzed. The five-year overall survival rate was evaluated according to the duration of adjuvant chemotherapy. RESULTS: The five-year overall survival rate gradually increased according to the increase in adjuvant chemotherapy cycles in both the S-1 (≤ 5 cycles: 48.4%, hazard ratio [HR] 4.06, 95% confidence interval [CI] 3.74-4.40, P < 0.0001; 5 < cycles ≤ 6: 55.4%, HR 3.08, 95% CI 2.65-3.57, P < 0.0001; 6 < cycles ≤ 7: 64.1%, HR 2.11, 95% CI 1.84-2.41, P < 0.0001; 7 < cycles < 8: 71.1%, HR 1.60, 95% CI 1.39-1.84, P < 0.0001; ≥ 8 cycles: 77.9%) and the CAPOX groups (≤ 4 cycles: 43.5%, HR 3.20, 95% CI 2.84-3.61, P < 0.0001; 5 cycles: 45.3%, HR 2.63, 95% CI 2.11-3.27, P < 0.0001; 6 cycles: 47.1%, HR 2.09, 95% CI 1.76-2.49, P < 0.0001; 7 cycles: 55.3%, HR 1.63, 95% CI 1.35-1.96, P < 0.0001; ≥ 8 cycles: 67.2%). CONCLUSIONS: Reducing the treatment cycles of adjuvant chemotherapy in GC with S-1 or CAPOX showed inferior survival outcomes. Completing the standard duration of adjuvant chemotherapy with S-1 or CAPOX would be strongly recommended.

Zn-assisted modification of the chemical structure of N-doped carbon dots and their enhanced quantum yield and photostability.

This article presents the Zn-assisted synthesis of N-doped carbon dots (N-CDs) with an enhanced quantum yield (QY) and photostability. There have been intensive studies to improve or tune the optical properties of carbon dots (CDs) to meet the demand for luminescent materials in various fields, including energy conversion, photocatalysis, bioimaging, and phototherapy. For these applications, the photostability of the CDs is also a critical factor, but the related studies are relatively less common. The Zn-assisted N-CDs (denoted as Zn:N-CDs) obtained by the addition of Zn(OAc)2 to the precursors during the synthesis of N-CDs not only exhibited an enhanced quantum yield but also improved photostability compared to those of N-CDs. A comprehensive study of the chemical composition of Zn:N-CD and N-CD using X-ray photoelectron spectroscopy indicated a correlation between their chemical structure and photostability. Zn(OAc)2, which acts as a catalytic reagent, induced the modification of chemical structures at the edges of carbogenic sp2 domains, without being doped in N-CD, and the heteroatom-carbon bonds in Zn:N-CD seemed to be more resistant to light compared to those in N-CDs. The increased QY and photostability of Zn:N-CDs make them more suitable as an optical probe and they could be used in fingerprint identification. With Zn:N-CDs, the microstructure of fingerprints was confirmed clearly for a long duration effectively.

DA-9805, a Herbal Mixture, Restores Motor Manifestations in 6-Hydroxydopamine-induced Parkinson's Disease Mouse Model by Regulating Striatal Dopamine and Acetylcholine Levels.

Loss of dopamine (DA) is one of the primary features of Parkinson's disease (PD); however, imbalances of non-dopaminergic neurotransmitters significantly contribute to the disabilities noted in advanced PD patients. DA-9805 is the ethanolic extraction of the root bark of Paeonia × suffruticosa Andrews (Paeoniaceae), the root of Angelica dahurica (Hoffm.) Benth. and Hook.f. ex Franch. and Sav. (Apiaceae) and the root of Bupleurum falcatum L. (Apiaceae), which have been widely utilized as an enhancer of motor function in East Asia. This study aimed to investigate whether DA-9805 modified motor dysfunctions and imbalances associated with DA and other neurotransmitters in a 6-hydroxydopamine-induced PD mouse. We confirmed the expressions of proteins related with neurotransmissions in the striatum. In addition, we measured the striatal neurotransmitters using HPLC and analyzed their correlation. DA-9805 significantly improved motor impairments and restored the altered levels of neurotransmitters in the striatum. Moreover, DA-9805 improved the altered expressions of tyrosine hydroxylase (TH), DA transporter, and choline acetyltransferase (ChAT) in the ipsilateral part of mouse striatum or SNpc, which implies the neuroprotection. We also found that the level of striatal acetylcholine (Ach) has the moderate negative correlation with motor functions and TH expression in the SNpc. This study indicates that DA-9805 restores motor dysfunctions by normalizing the increased levels of striatal Ach via modulating DA transmission and ChAT expressions as well as its neuroprotective effects.

Efficacy and Safety of Bojungikgi-Tang for Persistent Allergic Rhinitis: A Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.

Background: Allergic rhinitis (AR) is a common disease, and conventional medications are often insufficient for treatment. Bojungikgi-tang (BJIGT) is an herbal medicine widely used in traditional medicine and has anti-inflammatory and immunoregulatory effects. We hypothesize that BJIGT would improve nasal symptoms in patients with persistent AR (PAR). Methods: This is a randomized, double-blind, placebo-controlled, phase II trial. A total of 105 patients, identified with perennial allergens, with a history of PAR and a mean total nasal symptom score (TNSS) ≥ 5 during the run-in period will be recruited from Daejeon Korean Medicine Hospital. Participants will be randomly assigned to a high-dose BJIGT group, standard-dose BJIGT group, or control group (placebo) in a 1 : 1 : 1 allocation ratio after a week run-in period. The treatment medication will be taken three times per day for 4 weeks. The primary outcome measure is the mean change in the TNSS before and after medication. The secondary outcome measures include the Korean Allergic Rhinitis-Specific Quality of Life Questionnaire, total IgE and eosinophil count, overall assessment of AR, pattern identification questionnaire for AR, and Sasang constitution. Discussion. The aim of this study is to investigate the efficacy and safety of BJIGT in the treatment of PAR and to determine the suitable dosage of BJIGT. Therefore, we planned a randomized, controlled, phase II trial of two different doses of BJIGT compared with placebo, and the results of this study are expected to provide evidence for the use of BJIGT as a treatment of PAR. Trial Registration. The National Clinical Trial Registry Clinical Research Information Service, CRIS, KCT0006616, https://cris.nih.go.kr/cris/search/detailSearch.do/20706.

The novel anti-neuroinflammatory functional food CCL01, a mixture of Cuscuta seed extracts and Lactobacillus paracasei NK112.

Neuroinflammation, which occurs due to microglia, is related to the pathogenesis of neurodegenerative disorders. Recently, the development of functional foods that down-regulate over-activated microglial cells to prevent the progression of neurodegenerative disorders has been proposed, since over-activated microglia induce a chronic source of neurotoxic factors and reduce neuronal survival. Thus, the anti-neuroinflammatory effects of a functional food mixture (CCL01) including Cuscuta seeds and Lactobacillus paracasei NK112 on lipopolysaccharide (LPS)-induced experimental models were investigated. In LPS-induced in vitro models, the expression levels of inflammatory mediators (e.g., inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2) and pro-inflammatory cytokines (e.g., tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6) were decreased upon CCL01 treatment. CCL01 showed an anti-neuroinflammatory effect in LPS-induced microglial cells via the inhibition of the mitogen-activated protein kinase (MAPK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and the activation of the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In the LPS-treated in vivo mouse models, the increased expression of ionized calcium binding adaptor molecule 1 (Iba-1), which indicates microglial activity, was markedly decreased upon treatment with CCL01 (50 and 200 mg kg-1) in the hippocampus and cortex areas of the mouse brains in comparison with the LPS-injected group. In addition, the groups to which CCL01 was administered had significantly decreased plasma levels of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 in the LPS-injected mouse models. Our data suggest that CCL01 may be a potential anti-neuroinflammatory agent that can prevent microglia overactivation, and it could be useful for developing functional foods.

DA-9801, a standardized Dioscorea extract, improves memory function via the activation of nerve growth factor-mediated signaling.

OBJECTIVES: Nerve growth factor (NGF) is a neurotrophin that plays a critical role in mammalian learning and memory functions. NGF also regulates neuronal cell differentiation and neurite outgrowth by activating ERK/CREB signaling. This present study examined the effects of a standardized Dioscorea extract (DA-9801), which is composed of Dioscorea japonica Thunb and Dioscorea nipponica Makino on memory function via its NGF-potentiating activities using an in vitro and in vivo paradigm. METHODS: Cells were incubated with or without different concentrations of DA-9801 (10, 25, and 50 µg/ml) extract for 24 h. The cultured conditioned medium from C6 glioma cells was used for NGF production assay, and neurite length in N2a cells was measured after every 2 h. Mice were orally treated with DA-9801 (10 and 100 mg/kg/day) once daily for 7 days. They were subjected to passive avoidance test to evaluate memory functions. The question of whether DA-9801 induced NGF synthesis was assessed by measuring the levels of NGF in the mouse cortical and hippocampal tissues. Hippocampal cell differentiation and NGF-mediated ERK/CREB signaling were evaluated by performing immunohistochemical analysis using BrdU, ki67, DCX, phosphorylated ERK and CREB in the mouse hippocampus. RESULTS: DA-9801 treatment increased the NGF contents and neurite length, respectively. Mice with DA-9801 administration showed memory enhancement in the passive avoidance test. DA-9801 also increased newborn cell differentiation, neurite length, NGF secretion, and ERK/CREB phosphorylation in the mouse hippocampus. DISCUSSION: These results suggest that DA-9801 treatment could improve memory function by inducing hippocampal NGF synthesis and ERK/CREB signaling.

A novel nutritional mixture, MBN, prevents memory impairment via inhibiting NLRP3 inflammasome formation in 5xFAD transgenic mice.

OBJECTIVES: Amyloid beta (Aß)-induced abnormal neuroinflammation is recognized as a major pathological factor of Alzheimer's disease (AD), which results in memory impairment. Inhibition of excessive neuroinflammation mediated by Aß is considered a promising strategy to ameliorate AD symptoms. To regulate the inflammatory response, nutritional and dietary supplements have been used for centuries. Based on this idea, we investigated whether MBN, a novel nutritional mixture including cassia bark, turmeric root, and ginkgo leaf, can prevent AD progression through neuroinflammatory regulation. METHODS: MBN (10, 30, or 100 µg/ml) and Aß1-42 monomer were incubated together, and the degree of Aß aggregation was measured using Thioflavin T assay. The effects of MBN on Aß pathology in vivo were evaluated by orally administering MBN (40 mg/kg/day for 16 weeks) to five familial AD (5xFAD) mice. RESULTS: We found that treatment with MBN inhibited Aß aggregation in vitro. Next, MBN treatment significantly inhibited the activation of microglia induced by aggregated Aß in 5xFAD mice. Caspase-1 activation, which plays an important role in the maturation of interleukin-1ß, was markedly reduced by MBN. We also found that oral administration of MBN in 5xFAD mice alleviated memory decline. Taken together, our findings demonstrate that MBN suppresses neuroinflammation by downregulating the caspase-1 expression, thereby ameliorating memory impairment in 5xFAD mice. DISCUSSION: Based on these results, we suggest that MBN may be a preventive and therapeutic supplement for AD through the regulation of neuroinflammation.

Complicated urinary tract infection in patients with benign prostatic hyperplasia.

Complicated urinary tract infection (UTI) is a symptomatic urinary infection accompanied by functional or structural abnormalities of the genitourinary tract. Benign prostatic hyperplasia (BPH) is a major cause of lower urinary tract obstruction in male patients, and bladder outlet obstruction (BOO) secondary to BPH can lead to UTIs in men. However, no evidence has clearly shown that UTI in the aging male population is associated with either post-void residual urine or BOO. Screening for the presence of bacteriuria is recommended prior to any procedure manipulating the urinary tract, and imaging studies of the upper urinary tract are recommended to identify underlying abnormalities. Recurrent or persistent UTI in men with BPH is an indication for surgical treatment. Asymptomatic bacteriuria should be screened for and treated before transurethral resection of the prostate (TURP). In addition, antibiotic prophylaxis reduced the risk of UTI in patients undergoing TURP. The choice of specific antimicrobial for prophylaxis should be based on local pathogen prevalence and individual antibiotic susceptibility. Patients with severe systemic infections require hospitalization, and empirical therapy should include an intravenous antimicrobial regimen. Further prospective studies are needed to refine the treatment process for complicated UTI in patients diagnosed with BPH.

Association Between Chronic Renal Disease and the Risk of Glaucoma Development: A 12-year Nationwide Cohort Study.

Purpose: The purpose of this study was to present the results of our investigation into the risk of glaucoma development in patients with chronic renal disease (CRD). Methods: The present retrospective cohort study used the Korean National Health Insurance Service data, which consisted of 1,025,340 random subjects who were tracked from 2002 to 2013. Newly diagnosed glaucoma and CRD were included on the basis of the Korean Classification of Disease codes. The CRD group consisted of patients who received an initial CRD diagnosis between January 2003 and December 2007 as an index period (n = 3640). The control group (n = 17,971) was selected using 1:5 propensity-score matching using social and demographic factors, along with the year of enrollment. Each group subject was followed until 2013. We used multivariate Cox proportional hazard regression analysis to compare the risk of glaucoma development between the two groups. Results: Glaucoma consecutively developed in 4.3% in the CRD group and 2.8% in the control group (P < 0.0001). CRD increased the risk of glaucoma development (hazard ratio [HR] = 1.63, 95% confidence interval [CI] = 1.34-1.98] after adjusting for age, sex, comorbidities, residence, household income, and the year of enrollment. In multivariate Cox regression analysis, patients with comorbidity of hypertension, diabetes mellitus, or aged ≥ 50 years showed a significantly higher risk of glaucoma development (all P < 0.008). Conclusions: A significant association between CRD and following development of glaucoma was revealed after adjusting the potential confounding factors.