An eight-week randomized intervention study on Korean adults to evaluate the effect of milk intake on obesity.

The anti-obesity effect of milk intake has been suggested via a variety of designed studies, but findings of obesity interventions for Korean adults are scarcely reported. The study aimed to investigate the anti-obesity effect of cow milk in Korean adults with an 8-wk randomized intervention. A total of 121 adults overweight aged 19 to 60 yr old were randomly assigned to 1 of the 2 groups: milk or control. During the intervention, both groups were encouraged 500 kcal of restriction a day, and the milk group consumed 200 mL of milk twice a day; the same energy intake as the control group, including milk intake, was recommended for 8 wk. We detected no significant differences in body weight (BW) and body mass index (BMI) between the milk and control groups during the 8-wk intervention, although the changes in BW and BMI of those within the milk group were significant. High-density lipoprotein cholesterol levels and serum calcium levels increased significantly in the milk group compared with the control group. Calcium, phosphorus, vitamin A, and riboflavin intakes increased significantly, when compared with the control. In conclusion, 8-wk milk consumption had no effect on weight loss and BMI change but improved some blood biomarkers and nutrient intake in Korean adults who were overweight. To evaluate the effect of milk on obesity reduction, well-designed, long-term, and large-scale studies are needed.

The QPLEX™ Plus Assay Kit for the Early Clinical Diagnosis of Alzheimer's Disease.

We recently developed a multiplex diagnostic kit, QPLEX™ Alz plus assay kit, which captures amyloid-ß1-40, galectin-3 binding protein, angiotensin-converting enzyme, and periostin simultaneously using microliters of peripheral blood and utilizes an optimized algorithm for screening Alzheimer's disease (AD) by correlating with cerebral amyloid deposition. Owing to the demand for early AD detection, we investigate the potential of our kit for the early clinical diagnosis of AD. A total of 1395 participants were recruited, and their blood samples were analyzed with the QPLEX™ kit. The average of QPLEX™ algorithm values in each group increased gradually in the order of the clinical progression continuum of AD: cognitively normal (0.382 ± 0.150), subjective cognitive decline (0.452 ± 0.130), mild cognitive impairment (0.484 ± 0.129), and AD (0.513 ± 0.136). The algorithm values between each group showed statistically significant differences among groups divided by Mini-Mental State Examination and Clinical Dementia Rating. The QPLEX™ algorithm values could be used to distinguish the clinical continuum of AD or cognitive function. Because blood-based diagnosis is more accessible, convenient, and cost- and time-effective than cerebral spinal fluid or positron emission tomography imaging-based diagnosis, the QPLEX™ kit can potentially be used for health checkups and the early clinical diagnosis of AD.

Infection and revision rates following primary total knee arthroplasty in patients with rheumatoid arthritis versus osteoarthritis: a meta-analysis.

PURPOSE: This meta-analysis compared infection and revision rates in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) who underwent total knee arthroplasty (TKA). Rates of superficial wound and deep periprosthetic infections were compared in the groups, as were whether revision rates associated with infectious and noninfectious causes differed in the RA and OA groups. METHODS: Studies were included in the meta-analysis if they (1) compared infection and revision rates after primary TKA in RA and OA patients; (2) directly compared superficial wound and deep periprosthetic infection rates in RA and OA patients who underwent primary TKA; and (3) reported the actual numbers of RA and OA patients who underwent TKA and developed postoperative infection and/or required revision. RESULTS: The rate of superficial wound infections after primary TKA was similar in the RA and OA groups (15/258 [5.8 %] vs. 77/1609 [4.7 %]; odds ratio [OR] 1.12, 95 % confidence interval [CI] 0.36-3.46; P = n.n.), but the deep infection rate was significantly higher in RA than in OA patients (229/7651 [3.0 %] vs. 642/68628 [0.9 %]; OR 2.04, 95 % CI 1.37-3.05; P < 0.001). The proportion of subjects who required revision resulting from infection after TKA was significantly higher in the RA than in the OA group (86/8201 [1.0 %] vs. 555/118755 [0.5 %]; OR 1.89, 95 % CI 1,34-2.66; P < 0.001), whereas the proportion of subjects requiring revision due to noninfectious causes did not differ significantly (46/594 [7.7 %] vs. 52/904 [5.7 %]; OR 1.22, 95 % CI 0.74-2.00; P = n.n.) CONCLUSION: Following primary TKA, RA patients had a significantly higher rate of deep periprosthetic infections than OA patients, but their superficial infection rates were similar. The revision rate due to infectious causes was significantly higher in RA than in OA patients, but their revision rates due to noninfectious causes did not differ. Therefore, the surgeon should fully explain to RA patients scheduled to undergo primary TKA that, compared to OA patients, they are more likely to experience a deep infection postsurgery. LEVEL OF EVIDENCE: Meta-analysis Level III.

Molecular insights into the evolutionary pathway of Vibrio cholerae O1 atypical El Tor variants.

Pandemic V. cholerae strains in the O1 serogroup have 2 biotypes: classical and El Tor. The classical biotype strains of the sixth pandemic, which encode the classical type cholera toxin (CT), have been replaced by El Tor biotype strains of the seventh pandemic. The prototype El Tor strains that produce biotype-specific cholera toxin are being replaced by atypical El Tor variants that harbor classical cholera toxin. Atypical El Tor strains are categorized into 2 groups, Wave 2 and Wave 3 strains, based on genomic variations and the CTX phage that they harbor. Whole-genome analysis of V. cholerae strains in the seventh cholera pandemic has demonstrated gradual changes in the genome of prototype and atypical El Tor strains, indicating that atypical strains arose from the prototype strains by replacing the CTX phages. We examined the molecular mechanisms that effected the emergence of El Tor strains with classical cholera toxin-carrying phage. We isolated an intermediary V. cholerae strain that carried two different CTX phages that encode El Tor and classical cholera toxin, respectively. We show here that the intermediary strain can be converted into various Wave 2 strains and can act as the source of the novel mosaic CTX phages. These results imply that the Wave 2 and Wave 3 strains may have been generated from such intermediary strains in nature. Prototype El Tor strains can become Wave 3 strains by excision of CTX-1 and re-equipping with the new CTX phages. Our data suggest that inter-chromosomal recombination between 2 types of CTX phages is possible when a host bacterial cell is infected by multiple CTX phages. Our study also provides molecular insights into population changes in V. cholerae in the absence of significant changes to the genome but by replacement of the CTX prophage that they harbor.

Dilated Virchow-Robin Space and Dopamine Transporter Imaging in the Striatum of Patients with Parkinsonism.

OBJECTIVE: The radiological and clinical significance of a dilated Virchow-Robin space (dVRS) in the striatum (STR) remains unclear. We investigated the role of dVRS in STR on parkinsonism and dopamine transporter positron emission tomography (DaT-PET) findings. METHODS: Patients with parkinsonism who underwent both brain magnetic resonance imaging and DaT-PET were included. Clinical status was evaluated by Hoehn and Yahr (HY) stage, Korean-Mini Mental Status Examination (K-MMSE), Montreal Cognitive Assessment Korea (MoCA-K), and Frontal Assessment Battery (FAB). dVRS was assessed by semi-quantitative and quantitative scales in each of the three segments of STR (caudate nuclei, anterior and posterior putamen) and was expressed as a dVRS score. DaT-PET was qualitatively assessed as either normal or abnormal in each segment. The relationship between dVRS and DaT-PET abnormality (ab-DaT-PET) was designated in each segment as either concordant or discordant. A concordant segment was defined by the presence of dVRS with ab-DaT-PET [Concordance rate (CR)=number of concordant segments/number of concordant and discordant segments]. RESULTS: Eleven patients were included. There was no significant correlation between the presence of dVRS and ab-DaT-PET. The mean CR was 0.39. CR was not significantly correlated with any clinical or neuroimaging scales. The dVRS score was significantly correlated with K-MMSE, MoCA-K, and FAB (r=-0.675, -0.847, and -0.868, respectively) but not with HY stage. CONCLUSION: dVRS in STR played no significant role on dopaminergic innervation revealed by DaT-PET and made little contribution to clinical parkinsonism; however, it was correlated with cognitive impairment.

Effects of uric acid levels on outcome in severe ischemic stroke patients treated with intravenous recombinant tissue plasminogen activator.

Uric acid (UA) has been known to be a neuroprotective antioxidant because of its free radical scavenger activity. We studied the influence of UA in patients with acute ischemic stroke after thrombolytic therapy. Two hundred eighteen consecutive patients treated with intravenous thrombolysis were included in this analysis. We analyzed the relationship between serum UA levels obtained at the emergency department and clinical outcomes. Early improvement and excellent functional outcomes were measured using the National Institutes of Health Stroke Scale (NIHSS) 24 h after onset and the modified Rankin scale after 3 months. There was no significant relationship between serum UA levels and early improvement or excellent functional outcome in the total patients (p = 0.583 and p = 0.082, respectively). However, in patients with severe baseline stroke deficits (NIHSS score ≥15), higher-tertile UA levels were significantly associated with excellent functional outcomes (p = 0.003). Excellent functional outcomes in patients with severe baseline disability might have a significant association with serum UA levels particularly in men but not in women (p = 0.007 in men and p = 0.621 in women). Increased serum UA levels might be associated with better outcomes in ischemic stroke patients treated with intravenous thrombolysis, but the effectiveness of UA can differ by initial stroke severity and gender.

Soil amendment with cow dung modifies the soil nutrition and microbiota to reduce the ginseng replanting problem.

Ginseng is a profitable crop worldwide; however, the ginseng replanting problem (GRP) is a major threat to its production. Soil amendment is a non-chemical method that is gaining popularity for alleviating continuous cropping obstacles, such as GRP. However, the impact of soil amendment with either cow dung or canola on GRP reduction and the associated soil microbiota remains unclear. In the present study, we evaluated the effect of soil amendment with cow dung, canola seed powder, and without amendment (control), on the survival of ginseng seedling transplants, the soil bacterial and fungal communities, and their associated metabolic functions. The results showed that cow dung increased ginseng seedling survival rate by 100 percent and had a remarkable positive effect on ginseng plant growth compared to control, whereas canola did not. Cow dung improved soil nutritional status in terms of pH, electrical conductivity, NO 3 - , total carbon, total phosphorus, and available phosphorus. The amplicon sequencing results using Illumina MiSeq showed that canola had the strongest negative effect in reducing soil bacterial and fungal diversity. On the other hand, cow dung stimulated beneficial soil microbes, including Bacillus, Rhodanobacter, Streptomyces, and Chaetomium, while suppressing Acidobacteriota. Community-level physiological profiling analysis using Biolog Ecoplates containing 31 different carbon sources showed that cow dung soil had a different metabolic activity with higher utilization rates of carbohydrates and polymer carbon sources, mainly Tween 40 and beta-methyl-d-glucoside. These carbon sources were most highly associated with Bacillota. Furthermore, predicted ecological function analyses of bacterial and fungal communities showed that cow dung had a higher predicted function of fermentation and fewer functions related to plant pathogens and fungal parasites, signifying its potential to enhance soil suppressiveness. Co-occurrence network analysis based on random matrix theory (RMT) revealed that cow dung transformed the soil microbial network into a highly connected and complex network. This study is the first to report the alleviation of GRP using cow dung as a soil amendment, and the study contributes significantly to our understanding of how the soil microbiota and metabolic alterations via cow dung can aid in GRP alleviation.

Spinach (Spinacia oleracea) as green manure modifies the soil nutrients and microbiota structure for enhanced pepper productivity.

Spinach has been suggested as a potential rotation crop for increasing crop yield by enhancing beneficial fungal microbes in continuous monocropping. However, no research on the use of spinach as a green manure has been reported. Thus, we tested the effects of spinach and Korean mustard cultivars (green and red mustards) (10 g pot -1) as green manure on soil chemical properties, pepper productivity, and soil microbiome of long-year pepper-monocropped soil. Spinach improved the soil nutrition (e.g., pH, SOM, TN, NH4+, and K), weed suppression, and pepper growth. Spinach had by far the highest fruit yield, over 100% pepper fruit yield increment over the mustard green manures and control. Our study showed that the major influencing factors to cause a shift in both bacterial and fungal community assemblies were soil pH, TC TN, and K. Following green manure amendment Bacillota, especially Clostridium, Bacillus and Sedimentibacter, were enriched, whereas Chloroflexi and Acidobacteriota were reduced. In addition, spinach highly reduced the abundance of Leotiomycetes and Fusarium but enriched Papiliotrema. FAPROTAX and FUNGuild analysis revealed that predicted functional profiles of bacterial and fungal communities in spinach-amended soil were changed. Spinach-treated soil was differentially abundant in function related to hydrocarbon degradation and functional guilds of symbiotrophs and ectomycorrhizal. This study contributes significantly to our understanding of how the soil fertility and soil microbiome alteration via spinach green manure application as a pre-plant soil treatment might help alleviate continuous cropping obstacles.

Pharmaceutical efficacy of novel human-origin Faecalibacterium prausnitzii strains on high-fat-diet-induced obesity and associated metabolic disorders in mice.

Introduction: Obesity and related metabolic issues are a growing global health concern. Recently, the discovery of new probiotics with anti-obesity properties has gained interest. Methods: In this study, four Faecalibacte-rium prausnitzii strains were isolated from healthy human feces and evaluated on a high-fat diet-induced mouse model for 12 weeks. Results: The F. prausnitzii strains reduced body weight gain, liver and fat weights, and calorie intake while improving lipid and glucose metabolism in the liver and adipose tissue, as evidenced by regulating lipid metabolism-associated gene expression, including ACC1, FAS, SREBP1c, leptin, and adiponectin. Moreover, the F. prausnitzii strains inhibited low-grade inflammation, restored gut integrity, and ameliorated hepatic function and insulin resistance. Interestingly, the F. prausnitzii strains modulated gut and neural hormone secretion and reduced appetite by affecting the gut-brain axis. Supplementation with F. prausnitzii strains noticeably changed the gut microbiota composition. Discussion: In summary, the novel isolated F. prausnitzii strains have therapeutic effects on obesity and associated metabolic disorders through modulation of the gut-brain axis. Additionally, the effectiveness of different strains might not be achieved through identical mechanisms. Therefore, the present findings provide a reliable clue for developing novel therapeutic probiotics against obesity and associated metabolic disorders.

Faecalibacterium prausnitzii prevents hepatic damage in a mouse model of NASH induced by a high-fructose high-fat diet.

Introduction: Nonalcoholic steatohepatitis (NASH) is an advanced nonalcoholic fatty liver disease characterized by chronic inflammation and fibrosis. A dysbiosis of the gut microbiota has been associated with the pathophysiology of NASH, and probiotics have proven helpful in its treatment and prevention. Although both traditional and next-generation probiotics have the potential to alleviate various diseases, studies that observe the therapeutic effect of next-generation probiotics on NASH are lacking. Therefore, we investigated whether a next-generation probiotic candidate, Faecalibacterium prausnitzii, contributed to the mitigation of NASH. Methods: In this study, we conducted 16S rRNA sequencing analyses in patients with NASH and healthy controls. To test F. prausnitzii could alleviate NASH symptoms, we isolated four F. prausnitzii strains (EB-FPDK3, EB-FPDK9, EB-FPDK11, and EB-FPYYK1) from fecal samples collected from four healthy individuals. Mice were maintained on a high-fructose high-fat diet for 16 weeks to induce a NASH model and received oral administration of the bacterial strains. Changes in characteristic NASH phenotypes were assessed via oral glucose tolerance tests, biochemical assays, and histological analyses. Results: 16S rRNA sequencing analyses confirmed that the relative abundance of F. prausnitzii reduced significantly in patients with NASH compared to healthy controls (p < 0.05). In the NASH mice, F. prausnitzii supplementation improved glucose homeostasis, prevented hepatic lipid accumulation, curbed liver damage and fibrosis, restored damaged gut barrier functions, and alleviated hepatic steatosis and liver inflammation. Furthermore, real-time PCR assays documented that the four F. prausnitzii strains regulated the expression of genes related to hepatic steatosis in these mice. Discussion: Our study, therefore, confirms that the administration of F. prausnitzii bacteria can alleviate NASH symptoms. We propose that F. prausnitzii has the potential to contribute to the next-generation probiotic treatment of NASH.

Antiviral activity of Bifidobacterium adolescentis SPM1005-A on human papillomavirus type 16.

BACKGROUND: Probiotic lactic acid bacteria (LAB) support a functional and balanced immune system, and contribute to immune modulatory effects in combatting microbial pathogens, including viruses. Most cervical cancers are associated with anogenital region infection with high-risk (HR) human papillomavirus (HPV). In this study, we analyzed the antiviral activity of Bifidobacterium adolescentis SPM1005-A in the SiHa cervical cancer cell line expressing HPV type 16. METHODS: We assessed the cellular toxicity of B. adolescentis SPM1005-A in SiHa cells by the Trypan blue dye exclusion assay. Cells (3.6 × 105) in culture plates with or without B. adolescentis SPM1005-A in the same type of medium, were incubated with HPV type 16 at a concentration of 5.1 × 107 cfu/ml. For antiviral analysis, we performed quantitative real-time PCR (qRT-PCR) for E6 and E7 oncogene expressions and observed protein levels by immunoblotting. RESULTS: The qRT-PCR results showed that E6 and E7 mRNA levels decreased simultaneously. Western blot analysis revealed that the E6 protein expression slightly decreased after 24 and 48 h, but the level of E7 protein expression appear unaffected compared with that in the control. Decreased HPV16 E6 and E7 mRNA transcript and protein levels were not associated with cell morphology or significant cytotoxic effects. CONCLUSIONS: This study showed that B. adolescentis SPM1005-A had antiviral activity through suppression E6 and E7 oncogene expression. The results suggest that B. adolescentis SPM1005-A could be potential applications of HPV-associated cervical cancer prevention.

Photovoltaic performance of dye-sensitized solar cell low temperature growth of ZnO nanorods using chemical bath deposition.

Nanostructured ZnO photoelectrodes were synthesized on fluorine-doped tin oxide (FTO) glass substrates that were spin-coated with a sol-gel based ZnO seed layer via a chemical bath deposition (CBD) method at varying times of 1, 2, 4, and 8 h. Then, TiO2 nanoparticulate electrodes were prepared on ZnO nanorods using the doctor blade technique. The uniformly grown ZnO nanorod layer had a length of approximately 710 nm on the FTO glass substrate with wurtzite structures which was confirmed through X-ray diffraction patterns. The length and diameter of the ZnO nanorods increased with an increase in the deposition time. The DSSCs fabricated with TiO2 nanoparticulate/grown ZnO nanorods and grown for 8 h showed the maximum efficiency (5.51%) with a short circuit current density (J(sc)) of 12.21 mA/cm2 and an open circuit voltage (V(oc)) of 0.70 at 100 mW/cm2 light intensity.

New Strains of Akkermansia muciniphila and Faecalibacterium prausnitzii are Effective for Improving the Muscle Strength of Mice with Immobilization-Induced Muscular Atrophy.

Muscular atrophy is a muscle disease in which muscle mass and strength decrease due to aging, injury, metabolic disorders, or chronic conditions. Proteins in muscle tissue are degraded by the ubiquitin-proteasome pathway, and atrophy accelerates this pathway. Akkermansia muciniphila and Faecalibacterium prausnitzii strains are effective agents against metabolic and inflammatory diseases in next-generation probiotic research. In this study, we evaluated the efficacy of A. muciniphila strain EB-AMDK19 and F. prausnitzii strain EB-FPDK11 in a mouse model of muscular atrophy, since atrophy inhibits energy metabolism and immune activation. After oral administration of each strain for 4 weeks, the hind legs of the mice were fixed with a plaster cast to immobilize them for a week. As a result, the administration of EB-AMDK19 and EB-FPDK11 strains improved grip strength but did not increase muscle mass. At the molecular level, A. muciniphila and F. prausnitzii treatments decreased the expression levels of ubiquitin-proteasome genes, atrogin-1, MuRF, and cathepsin L. They increased the expression level of the mitochondrial biogenesis regulatory gene, PGC-1α. The effect of the strains was confirmed by a decrease in myostatin. Furthermore, A. muciniphila and F. prausnitzii modulated the immune function by enhancing ZO-1 and inhibiting IL-6. In particular, EB-AMDK19 promoted the expression of IL-10, an anti-inflammatory cytokine. These results suggest that A. muciniphila and F. prausnitzii may have beneficial effects on muscular atrophy, verified by newly isolated EB-AMDK19 and EB-FPDK11 as potential next-generation probiotics.

Changes in Microbial Community Structure in Response to Gummosis in Peach Tree Bark.

Peach gummosis disease has been identified as a serious challenge in Korean agriculture and has developed to become a major cause of agricultural productivity losses. However, treatments for gummosis have not been systemically established and studies of the microbiome closely related to this plant disease are lacking. Therefore, we analyzed the bacterial and fungal communities in the bark and rhizosphere soil of healthy peach trees and those with gummosis. Through high-throughput sequencing, we obtained unprecedented insights into the bacterial and fungal dynamics of each group, including their diversity and taxonomic classification, as well as network analyses. We found that the presence of gummosis drives a significantly higher alpha diversity in the bark bacterial community. Peach gummosis bark mycobiomes included greater numbers of opportunistic pathogens such as Ascochyta, Botryosphaeria, Saccharomyces, Nectriaceae_NA, Trametes, and Valsaceae_NA. However, the microbiome also included bacteria beneficial to plant growth and the production of polysaccharides-namely, 1174-901-12, Catenibacterium, Cutibacterium, Friedmanniella, Methylobacterium-Methylorubrum, Pseudomonas, Rhodobacter, and Sphingomonas. Furthermore, we confirmed that gummosis induced a more complex structure in the bark microbiome network. We conclude that the findings of this study provide a valuable aid in profiling the overall peach tree microbial ecosystem, which can be utilized to develop precise biomarkers for the early diagnosis of gummosis.

Oral administration of Faecalibacterium prausnitzii and Akkermansia muciniphila strains from humans improves atopic dermatitis symptoms in DNCB induced NC/Nga mice.

Atopic dermatitis (AD) is a common inflammatory skin disease, and its pathogenesis is closely associated with microbial homeostasis in the gut, namely the gut-skin axis. Particularly, recent metagenomics studies revealed that the abundance of two major bacterial species in the gut, Faecalibacterium prausnitzii and Akkermansia muciniphila, may play a critical role in the pathogenesis of AD, but the effect of these species in AD has not yet been elucidated. To evaluate the potential beneficial effect of F. prausnitzii or A. muciniphila in AD, we conducted an animal model study where F. prausnitzii EB-FPDK11 or A. muciniphila EB-AMDK19, isolated from humans, was orally administered to 2,5-dinitrochlorobenzene (DNCB)-induced AD models using NC/Nga mice at a daily dose of 108 CFUs/mouse for six weeks. As a result, the administration of each strain of F. prausnitzii and A. muciniphila improved AD-related markers, such as dermatitis score, scratching behavior, and serum immunoglobulin E level. Also, the F. prausnitzii and A. muciniphila treatments decreased the level of thymic stromal lymphopoietin (TSLP), triggering the production of T helper (Th) 2 cytokines, and improved the imbalance between the Th1 and Th2 immune responses induced by DNCB. Meanwhile, the oral administration of the bacteria enhanced the production of filaggrin in the skin and ZO-1 in the gut barrier, leading to the recovery of functions. Taken together, our findings suggest that F. prausnitzii EB-FPDK11 and A. muciniphila EB-AMDK19 have a therapeutic potential in AD, which should be verified in humans.