Deletion of PD-1 destabilizes the lineage identity and metabolic fitness of tumor-infiltrating regulatory T cells.

Regulatory T (Treg) cells have an immunosuppressive function and highly express the immune checkpoint receptor PD-1 in the tumor microenvironment; however, the function of PD-1 in tumor-infiltrating (TI) Treg cells remains controversial. Here, we showed that conditional deletion of PD-1 in Treg cells delayed tumor progression. In Pdcd1fl/flFoxp3eGFP-Cre-ERT2(+/-) mice, in which both PD-1-expressing and PD-1-deficient Treg cells coexisted in the same tissue environment, conditional deletion of PD-1 in Treg cells resulted in impairment of the proliferative and suppressive capacity of TI Treg cells. PD-1 antibody therapy reduced the TI Treg cell numbers, but did not directly restore the cytokine production of TI CD8+ T cells in TC-1 lung cancer. Single-cell analysis indicated that PD-1 signaling promoted lipid metabolism, proliferation and suppressive pathways in TI Treg cells. These results suggest that PD-1 ablation or inhibition can enhance antitumor immunity by weakening Treg cell lineage stability and metabolic fitness in the tumor microenvironment.

Subtherapeutic hydroxychloroquine concentration is associated with increased disease activity and greater organ damage in lupus.

OBJECTIVE: To investigate the effects of the serum HCQ concentration on clinical manifestations, disease activity and organ damage in a longitudinal cohort of SLE patients. METHODS: The 338 SLE patients were assessed with respect to their demographic data, clinical and laboratory findings, Physician's Global Assessment (PGA), adjusted mean SLEDAI-2000 (AMS) and SLICC Damage Index (SDI) annually for 5 consecutive years. Patients were divided into two groups according to their serum HCQ concentration at baseline: subtherapeutic (<500 ng/ml) and therapeutic (≥500 ng/ml) groups. The impact of the HCQ concentration on the clinical outcomes was evaluated in a longitudinal analysis using a generalized estimating equation (GEE). RESULTS: Of the 338 patients, 287 (84.9%) were in the subtherapeutic group at baseline. This group had a higher incidence of newly developed LN (P = 0.036) and had been prescribed higher mean and cumulative doses of prednisolone (P = 0.003 and P = 0.013, respectively) than the therapeutic group. In multivariable analyses based on GEE, the subtherapeutic group had a higher AMS score (ß = 1.398, 95% CI 0.607, 2.189; P < 0.001), higher PGA score (ß = 0.328, 95% CI 0.215, 0.441; P < 0.001) and higher SDI score (ß = 0.366, 95% CI 0.061, 0.671; P = 0.019) across all 5 years. CONCLUSION: The subtherapeutic HCQ concentration was associated with the development of new-onset LN, and had significant associations with disease activity and cumulative organ damage in SLE patients over time.

Ramosetron as an add-on therapy for refractory fibromyalgia: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study aimed to assess the efficacy and safety of intravenous ramosetron for pain relief in patients with fibromyalgia (FM) unresponsive to conventional treatments. METHODS: . In this prospective, double-blind, placebo-controlled trial, 80 FM patients were randomly allocated to receive either placebo (n = 40) or ramosetron (n = 40) at a dosage of 0.3 mg/day intravenously for five consecutive days. The primary outcome was the reduction in pain intensity at the end of the treatment period, evaluated using a visual analogue scale (VAS). Secondary outcome measures included the FM Impact Questionnaire, Beck Depression Inventory (BDI), Multi-Dimensional Health Assessment Questionnaire (MDHAQ), EQ-5D, and State-Trait Anxiety Inventory on days 5 (end of treatment), 7, 10, and 28. Safety was continuously monitored throughout the study. RESULTS: . At the end of the treatment phase, the ramosetron group demonstrated a significantly greater reduction in VAS pain scores compared with the placebo group (1.18 ± 1.60 vs 0.54 ± 1.59, p< 0.05). Additionally, the ramosetron group exhibited significant improvements in BDI (4.42 ± 5.18 vs 1.33 ± 4.87, p< 0.05) and MDHAQ pain scale (0.37 ± 0.74 vs 0.04 ± 0.52, p< 0.05) scores. However, these improvements in pain VAS and BDI scores were not sustained through day 28. The safety profile of ramosetron was favorable, with gastrointestinal symptoms, particularly constipation, being the most commonly reported adverse events. CONCLUSIONS: . Intravenous administration of ramosetron provided safe and effective short-term relief of pain intensity in FM patients with inadequate response to standard treatments.

Deep learning approach for early prediction of COVID-19 mortality using chest X-ray and electronic health records.

BACKGROUND: An artificial-intelligence (AI) model for predicting the prognosis or mortality of coronavirus disease 2019 (COVID-19) patients will allow efficient allocation of limited medical resources. We developed an early mortality prediction ensemble model for COVID-19 using AI models with initial chest X-ray and electronic health record (EHR) data. RESULTS: We used convolutional neural network (CNN) models (Inception-ResNet-V2 and EfficientNet) for chest X-ray analysis and multilayer perceptron (MLP), Extreme Gradient Boosting (XGBoost), and random forest (RF) models for EHR data analysis. The Gradient-weighted Class Activation Mapping and Shapley Additive Explanations (SHAP) methods were used to determine the effects of these features on COVID-19. We developed an ensemble model (Area under the receiver operating characteristic curve of 0.8698) using a soft voting method with weight differences for CNN, XGBoost, MLP, and RF models. To resolve the data imbalance, we conducted F1-score optimization by adjusting the cutoff values to optimize the model performance (F1 score of 0.77). CONCLUSIONS: Our study is meaningful in that we developed an early mortality prediction model using only the initial chest X-ray and EHR data of COVID-19 patients. Early prediction of the clinical courses of patients is helpful for not only treatment but also bed management. Our results confirmed the performance improvement of the ensemble model achieved by combining AI models. Through the SHAP method, laboratory tests that indicate the factors affecting COVID-19 mortality were discovered, highlighting the importance of these tests in managing COVID-19 patients.

Folate deficiency is associated with increased radiographic severity of osteoarthritis in knee joints but not in hand joints.

OBJECTIVES: No previous studies have explored the effect of folate deficiency on the severity of osteoarthritis (OA). Therefore, we investigated the relationship between folate level and features on knee and hand radiographs in a large, population-based OA cohort. METHODS: Among 9,260 subjects enrolled in the Dong-gu study, 2,489 who had knee and hand joint radiographs were included. Of these, subjects with a history of amputation or total knee replacement were excluded. Serum folate levels were measured using blood samples collected at the time of enrolment and stored. A semi-quantitative system was used to grade the severity of hand and knee x-ray changes. Linear regression was performed to assess relationships between serum folate levels and knee and hand radiographic scores after adjusting for age, sex, body mass index, smoking, alcohol consumption, education, physical activity, occupation, vitamin D, and ferritin. RESULTS: A total of 2,322 subjects were recruited. After adjusting for confounders, participants with folate deficiency (<4 ng/mL) had higher total (p<0.001), osteophyte (p<0.001), joint space narrowing (p=0.002), tibial attrition (p<0.001), and sclerosis (p=0.005) scores for knee joint radiographs compared to participants with a normal folate level. After adjusting for confounders, the radiographic scores for hand joints did not differ between the groups. CONCLUSIONS: Folate deficiency is associated with increased radiographic severity of OA in knee joints, but not in hand joints. Further studies are needed to explore the differential effects of folate on the severity of knee and hand OA.

Solihabitans fulvus gen. nov., sp. nov., a member of the family Pseudonocardiaceae isolated from soil.

A polyphasic taxonomic study was carried out on an actinobacterial strain (AN110305T) isolated from soil sampled in the Republic of Korea. Cells of the strain were Gram-stain-positive, aerobic, non-motile and rod-shaped. Comparative 16S rRNA gene sequence studies showed a clear affiliation of strain AN110305T with Actinomycetia, with highest pairwise sequence similarities to Goodfellowiella coeruleoviolacea DSM 43935T (97.6%), Umezawaea tangerina MK27-91F2T (97.0%), Kutzneria chonburiensis NBRC 110610T (96.9%), Kutzneria buriramensis A-T 1846T (96.8%), Umezawaea endophytica YIM 2047XT (96.8%), Kutzneria albida NRRL B-24060T (96.7%) and Saccharothrix coeruleofusca NRRL B-16115T (96.6%). Cells of strain AN110305T formed pale-yellow colonies on Reasoner's 2A agar. MK-9 (H4) (68%) and MK-10 (H4) (32%) were the predominant menaquinones. Diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethyl ethanolamine, hydroxy-phosphatidylethanolamine, an unidentified aminolipid and an unidentified aminophospholipid were major polar lipids. Iso-C16:0 (24.5%), anteiso-C15:0 (19.3%), anteiso-C17:0 (15.7%) and iso-C15:0 (15.2%) were the major fatty acids and meso-diaminopimelic acid was the pepdidoglycan. The cell-wall sugars were composed of galactose, glucose, mannose and ribose. The genomic DNA G+C content was 70.7 mol%. Based on genotypic and phenotypic data, strain AN110305T could be distinguished from all genera within the family Pseudonocardiaceae and represents a novel genus and species named Solihabitans fulvus gen. nov., sp nov. The type strain is AN110305T (=KCTC 39307T =DSM 103572T).

Salinarimonas soli sp. nov., isolated from soil.

A light pink coloured bacterium, designated strain BN140002T, was isolated from a soil sample collected in Goesan-gun, Chungcheongbuk-do, Republic of Korea. Cells of strain BN140002T were Gram-stain-negative, aerobic, motile and rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences showed 94.7, 94.7, 93.9, 93.3, 93.4 and 93.0% similarities to Salinarimonas rosea KCTC 22346T, Salinarimonas ramus DSM 22962T, Saliniramus fredricksonii HL-109T, Microvirga soli R491T, Chelatococcus caeni EBR-4-1T and Chelatococcus composti PC-2T, respectively. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. The major cellular fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and summed feature 1 (C12 : 0 aldehyde and/or unknown 10.98) and the predominant ubiquinone was Q-10. The genomic DNA G+C content of strain BN140002T was 70.1 mol%. The genomic orthoANI values between strain BN140002T and Salinarimonas rosea KCTC 22346T and Salinarimonas ramus DSM 22962T were 75.0 and 74.8 %, respectively. Strain BN140002T had a class I-C type CRISPR-Cas system (CRISPR-associated helicase Cas3, CRISPR-associated protein Cas8c, CRISPR-associated protein Cas7, CRISPR-associated RecB family exonuclease Cas4, CRISPR-associated protein 1, 2). Based on phenotypic, chemotaxonomic and phylogenetic data, strain BN140002T should be assigned as a novel species of the genus Salinarimonas, for which the name Salinarimonas soli sp. nov. is proposed. The type strain is BN140002T (=KCTC 42643T=CCTCC AB 2017173T).

Nocardioides humilatus sp. nov., isolated from farmland soil in the Republic of Korea.

A Gram-stain positive, aerobic, irregularly rod-shaped, non-spore-forming bacterium, designated as BN130099T, was isolated from farmland soil sampled in Goesan-gun, Chungbuk, Republic of Korea. Phylogenetic analysis of its 16S rRNA gene sequence showed that the strain is closely related to Nocardioides pelophilus KACC 19192T with 98.11 % similarity. The DNA G+C content of strain BN130099T was 68.84 mol% (draft genome sequence). The genome sequence of BN130099T displayed key enzymes involved in bioremediation of organic pollutants and biosynthetic clusters of saquayamycin. The strain contained ll-2,6-diaminopimelic acid in the cell-wall peptidoglycan and MK-8(H4) as the major respiratory quinone. The predominant fatty acid was iso-C16 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and phosphatidylinositol. The results of physiological and biochemical characterization allowed the phenotypic differentiation of strain BN130099T from N. pelophilus KACC 19192T. The strain represents a novel species of the genus Nocardioides, for which we propose the name Nocardioides humilatus sp. nov. The type strain is BN130099T (=KCTC 49079T=CCTCC AB 2018135T).

Non-adherence to methotrexate was associated with high disease activity and poor health-related outcomes during a 4-year follow-up of rheumatoid arthritis patients.

OBJECTIVES: Although methotrexate (MTX) is the first-line drug for management of rheumatoid arthritis (RA), non-adherence to MTX is highly prevalent and under-recognised. Here, we investigated adherence to MTX and its impact on clinical outcomes during follow-up in patients with RA. METHODS: In total, 367 RA patients were included in this study, with patient visits conducted annually for 4 consecutive years. Adherence was defined by the medication possession ratio during the follow-up period. We divided the patients into two groups; patients who took ≥80% of their prescribed MTX doses and those who did not. In a prospective cohort, the generalised estimating equations were used to identify longitudinal associations between drug adherence and clinical outcomes including disease activity, physical function, and quality of life. RESULTS: Of the 367 RA patients, 8.7% were found to have taken MTX <80% during the period of follow up. After adjustment for confounders, non-adherence to MTX was significantly associated with higher DAS28-ESR during the follow-up period (coefficient ß=0.989, 95%; CI: 0.603-1.375; p<0.001). In addition, non-adherence to MTX was a significant predictor of RAPID3 (coefficient ß=1.847; 95% CI: 0.221-3.472; p=0.026) and EQ-5D (coefficient ß= -0.051; 95% CI: -0.090-0.012; p=0.010) after adjustment for confounding factors. CONCLUSIONS: Non-adherence to MTX was significantly associated with worse clinical outcomes, as evidenced by higher disease activity, poorer physical function, and lower health-related quality of life during a 4-year follow-up of RA patients.

Comparison of three different definitions of low disease activity in patients with systemic lupus erythematosus and their prognostic utilities.

OBJECTIVES: Three definitions of low-level disease activity in patients with SLE have been proposed by different groups. These include minimal disease activity (MDA), low disease activity (LDA) and the lupus low disease activity state (LLDAS). We investigated the performance of these definitions in SLE patients. METHODS: We recruited 299 SLE patients who were followed up annually for 4 consecutive years. We compared the three definitions of low disease activity via longitudinal analysis; we used a generalized, linear-mixed effects model and generalized estimating equations. RESULTS: The LLDAS was significantly associated with a lower SLICC/ACR damage index (ß coefficient=-0.064, 95% CI: -0.129, -0.002, P=0.050), reduced flare (odds ratio = 0.090, 95% CI: 0.034, 0.239, P<0.001), an improved SF-36 physical component score (ß coefficient=0.782, 95% CI: 0.046, 1.519, P=0.037), and an improved SF-36 mental component score (ß coefficient=1.522, 95% CI: 0.496, 2.547, P=0.004). Neither the MDA nor the LDA were associated with these variables. CONCLUSION: The LLDAS definition performs better than the MDA and LDA definitions, showing that LLDAS is associated with less organ damage and flare, and a better quality of life, during follow-up.

Uric acid as a risk factor for progression to chronic kidney disease in patients with lupus nephritis: results from the KORNET registry.

OBJECTIVES: Little is known regarding the effect of hyperuricaemia on the progression of kidney function in patients with lupus nephritis (LN). Thus, we investigated the effect of uric acid (UA) on the long-term outcome of patients with biopsy-proven LN. METHODS: Data were obtained from KORNET, a prospective longitudinal systemic lupus erythematosus registry in the Republic of Korea. All 137 patients with LN included in this study had undergone a kidney biopsy and were subsequently treated with immunosuppressants. The patients were divided into two groups: UA ≤7 mg/dL and >7 mg/dL; their sociodemographic, clinical, treatment-related data, and outcomes were compared. Cox-proportional regression analyses were performed to identify independent predictors of renal outcome in patients with LN. RESULTS: Among the 137 patients, 37 (27.0%) had UA >7 mg/dL. This higher UA group included fewer women, but more patients with hypertension, proliferative type LN, and a chronicity index >12. The 24-h urinary protein excretion and the creatinine level were higher in this group; haemoglobin, platelet, and albumin levels were lower. During 85.0 months of follow-up, complete remission at 1 year was less frequent in the higher UA group, whereas chronic kidney disease (CKD) and end-stage renal disease were more prevalent. In the Cox proportional hazards regression analysis, UA >7 mg/dL was a signi cant predictor of progression to CKD in patients with LN (hazard ratio=2.437; p=0.020). CONCLUSIONS: Our findings suggest that hyperuricaemia at LN onset is an independent risk factor that predicts the development of CKD in patients with LN.

Biosynthesis of Nonimmunosuppressive ProlylFK506 Analogues with Neurite Outgrowth and Synaptogenic Activity.

Separating the immunosuppressive activity of FK506 (1) from its neurotrophic activity is required to develop FK506 analogues as drugs for the treatment of neuronal diseases. Two new FK506 analogues, 9-deoxo-36,37-dihydro-prolylFK506 (2) and 9-deoxo-31-O-demethyl-36,37-dihydro-prolylFK506 (3) containing a proline moiety instead of the pipecolate ring at C-1 and modifications at the C-9/C-31 and C-36-C-37 positions, respectively, were biosynthesized, and their biological activities were evaluated. The proline substitution in 9-deoxo-36,37-dihydroFK506 and 9-deoxo-31-O-demethyl-36,37-dihydroFK506 reduced immunosuppressive activity by more than 120-fold, as previously observed. Compared with FK506 (1), 2 and 3 exhibited ∼1.2 × 105- and 2.2 × 105-fold reductions in immunosuppressive activity, respectively, whereas they retained almost identical neurite outgrowth activity. Furthermore, these compounds significantly increased the strength of synaptic transmission, confirming that replacement of the pipecolate ring with a proline is critical to reduce the strong immunosuppressive activity of FK506 (1) while enhancing its neurotrophic activity.

Description of desferrioxamine-producing bacterium Chitinophaga agrisoli sp. nov., isolated from soil.

A Gram-stain-negative, non-motile, yellow-pigmented and non-spore forming rod-shaped bacterium, designated strain BN140078T, was isolated from farmland soil, Chungbuk, Republic of Korea. It was able to grow aerobically at 10-40 °C (optimum 28 °C), pH 5.5-7.5 (optimum pH 7.0) and with 0-2.0% (w/v) NaCl concentration (optimum 1.0%) on Reasoner's 2A (R2A) agar medium. Comparative 16S rRNA gene sequence analysis showed that the strain BN140078T had 96.9%, 96.5% and 96.1% 16S rRNA gene similarities with Chitinophaga ginsengihumi KACC 17604T, Chitinophaga rupis KACC 14521T and Chitinophaga japonensis KACC 12057T, respectively. The predominant respiratory quinone was menaquinone MK-7 and the major fatty acids (≥ 5%) were C16:1 ω5c, iso-C15:0, iso-C17:0 3-OH and Summed Feature 3 (C16:1 ω7c and/or C16:1 ω6c). The polar lipids were composed of phosphatidylethanolamine, four unidentified amino lipids and six unidentified lipids. The genomic DNA G+C content was 49.5 mol%. The genome of strain BN140078T comprises a number of biosynthetic gene clusters for secondary metabolites, in particular those for non-ribosomal peptide products. The polyphasic taxonomic study clearly distinguished this strain from its closest phylogenetic neighbors. Thus, we propose that the BN140078T represents a novel species of the genus Chitinophaga, for which the name Chitinophaga agrisoli sp. nov. was proposed. The type strain is BN140078T (=KCTC 62555T = CCTCC AB 2018162T).

Nocardioides antri sp. nov., Isolated from Soil in a Rock Cave.

A Gram-positive, aerobic, rod-shaped, non-spore-forming bacterium, designated as BN140041T, was isolated from cave soil at Gubyeongsan Mountain, Boeun-gun, Chungbuk province in Republic of Korea. Phylogenetic analysis of the 16S rRNA gene sequence showed that the strain is closely related to Nocardioides silvaticus S-34 T, N. pelophilus THG-T63T, and N. immobilis FLL521T with 97.4%, 97.1%, and 96.8% similarity. The draft genome length was 4.27 Mb containing 424 contigs with a DNA G + C content of 70.5 mol%. The ANI value between strain BN140044T and its closely related species N. silvaticus S-34 T was 82.6%. The genome sequence of BN140041T displayed a key enzyme involved in the bioremediation of organic pollutants. The diagnostic diamino acid of peptidoglycan was LL-2,6-diaminopimelic acid. The major respiratory quinone was MK-8(H4), and the major fatty acids (> 5% of the total fatty acids) were iso-C16:0 (55.3%), C18:1ω9c (7.7%) and iso-C17:0 (5.7%). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, and phosphatidylinositol. The results of genotypical, physiological, and biochemical characterization allow the phenotypic differentiation of strain BN140041T from related the Nocardioides strains. Therefore, strain BN140041T represents a novel species of the genus Nocardioides, for which we propose the name Nocardioides antri sp. nov. The type strain is BN140041T (= KCTC 49080 T = CCTCC AB 2018226 T).

Altered distribution and enhanced osteoclastogenesis of mucosal-associated invariant T cells in gouty arthritis.

OBJECTIVE: This study was designed to investigate the role of mucosal-associated invariant T (MAIT) cells in gouty arthritis (GA) and their effects on osteoclastogenesis. METHODS: Patients with GA (n = 61), subjects with hyperuricaemia (n = 11) and healthy controls (n = 30) were enrolled in this study. MAIT cells, cytokines, CD69, programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells in the presence of M-CSF and RANK ligand. RESULTS: Circulating MAIT cell levels were significantly reduced in GA patients. However, their capacities for IFN-γ, IL-17 and TNF-α production were preserved. Expression levels of CD69, PD-1 and LAG-3 in MAIT cells were found to be elevated in GA patients. In particular, CD69 expression in circulating MAIT cells was increased by stimulation with MSU crystals, suggesting that deposition of MSU crystals might contribute to MAIT cell activation. Interestingly, MAIT cells were found to be accumulated in synovial fluid and infiltrated into gouty tophus tissues within joints. Furthermore, activated MAIT cells secreted pro-resorptive cytokines (i.e. IL-6, IL-17 and TNF-α) and facilitated osteoclastogenesis. CONCLUSION: This study demonstrates that circulating MAIT cells are activated and numerically deficient in GA patients. In addition, MAIT cells have the potential to migrate to inflamed tissues and induce osteoclastogenesis. These findings provide an important role of MAIT cells in the pathogenesis of inflammation and bone destruction in GA patients.

Nutritional safety of oncometabolic surgery for early gastric cancer patients: a prospective single-arm pilot study using a historical control group for comparison.

BACKGROUND: Oncometabolic surgery (OS) is a modification of the Roux-en Y reconstruction method, in which the lengths of the biliopancreatic and Roux limbs are longer than that with conventional surgery (CS). Although OS is performed to improve postoperative glycemic control in gastric cancer patients with type 2 diabetes mellitus (T2DM), its postoperative nutritional safety has not been clarified. This prospective pilot study evaluated the safety and feasibility of OS in early gastric cancer patients. METHODS: This study evaluated 20 patients with clinical T1N0 stage and preoperative body mass index (BMI) ≥ 32.5 kg/m2, or ≥ 27.5 kg/m2 with comorbidities, who underwent OS. Primary outcomes were cumulative incidences of anemia and deficiencies in iron and vitamin B12 after 1 year. The outcomes were compared to those of a matched historical control group. RESULTS: The cumulative incidences of anemia (15.0% vs. 10.0%, P = 0.99), iron deficiency (15.0% vs. 10.0%, P = 0.99), and vitamin B12 deficiency (10.0% vs. 0%, P = 0.47) did not differ significantly in the OS and CS groups. However, median vitamin B12 concentration tended to be lower (395.8 vs. 493.7 pg/mL, P = 0.06) and reductions in vitamin B12 concentration tended to be greater (174.7 vs. 123.0 pg/mL, P = 0.07) in the OS group. BMI loss was similar in the two groups (2.9 vs. 2.8 kg/m2, P = 0.80). Remission rates of hypertension (68.8% vs. 41.2%, P = 0.22) and T2DM (77.8% vs. 50.0%, P = 0.58) were higher in the OS group. CONCLUSION: Nutritional parameters did not differ significantly in the OS and CS groups. Vitamin B12 levels should be carefully monitored after OS.

Efficacy and safety of mycophenolate mofetil and tacrolimus combination therapy in patients with lupus nephritis: a nationwide multicentre study.

OBJECTIVES: Recent studies have shown that a combination treatment of mycophenolate mofetil (MMF) and tacrolimus (TAC) may be an option for lupus nephritis (LN) patients that do not adequately respond to initial treatment. We evaluated the efficacy and safety of the combination treatment of MMF and TAC in LN patients with suboptimal response to prior MMF or TAC treatments. METHODS: In this multicentre study, we retrospectively enrolled 62 patients with class III, IV, or V LN who inadequately responded to MMF or TAC treatment. Those patients were then treated with a combination of MMF and TAC for 6 months. The primary outcome was complete remission (CR) at 6 months, and secondary outcomes included overall response and adverse events. RESULTS: After 6 months of treatment with the drug combination, CR was achieved in 14 of 62 patients (22.6%), and 35 (56.5%) patients responded. A significant reduction in proteinuria and lupus disease activity score was observable after 3 months. After 1 year, the CR rate increased to 36.4% (20 of 55 patients), and the overall response rate (n=38, 69.1%) also increased from 6 months. Twenty-one patients reported 29 adverse events, including severe infection requiring hospitalisation (n=3, 10.3%), infection not requiring hospitalisation (n=2, 6.9%), and herpes zoster (n=4, 13.8%). CONCLUSIONS: Our findings suggest that a combined MMF and TAC treatment, with a favourable adverse-event profile, may be a beneficial option for LN patients with inadequate response to either MMF or TAC treatments.

Flavitalea flava sp. nov., a bacterium isolated from a soil sample, and emended description of the genus Flavitalea.

A Gram-stain negative strain, designated AN120636T, was isolated from a soil sample collected from Goesan-gun, Chungbuk, South Korea. The strain was strictly aerobic, with golden yellow-pigmented colonies on R2A agar. Cells were non-motile, long or short rods and some were observed to be coccal. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain AN120636T belongs to the genus Flavitalea in the family of Chitinophagacea, with Flavitalea populi (95.4%), Pseudoflavitalea soli (95.0%), Flavitalea gansuensis (94.7%) and Pseudoflavitalea rhizosphaerae (94.7%) as its close relatives. Growth was observed at 15-32 °C, pH 5.0-7.0 and in the absence of NaCl. The strain contained iso-C17:0 3-OH, iso-C15:1 G and iso-C15:0 as its major cellular fatty acids; phosphatidylethanolamine as the major polar lipid; MK-7 as its respiratory quinone; and the polyamine was homospermidine. The genomic DNA G+C content was 44.8 mol%. On the basis of the polyphasic evidence, strain AN120636T is considered to represent a novel species, for which the name Flavitalea flava sp. nov. is proposed. The type strain is AN120636T (=KCTC 52346T=CCTCC AB 2017174T).

Root Bark of Paeonia suffruticosa Extract and Its Component Methyl Gallate Possess Peroxynitrite Scavenging Activity and Anti-inflammatory Properties through NF-κB Inhibition in LPS-treated Mice.

A peroxynitrite (ONOO-)-generating system induced by 3-morpholinosydnonimine, was used to evaluate the ONOO- scavenging properties of plants that have been widely used as traditional medicine in Korea for the treatment of several diseases. The most effective medicinal plants were Paeonia suffruticosa Andrew, followed in order by Lonicera japonica Thunb., Curcuma zedoaria (Christm.) Roscoe, and Pueraria thunbergiana Benth. In addition, root bark of P. suffruticosa was partitioned with organic solvents of different polarities, and the ethyl acetate (EtOAc) fraction showed the strongest ONOO- scavenging activity. Methyl gallate, a plant-derived phenolic compound identified from the EtOAc fraction, exerted strong ONOO- scavenging activity. The in vivo therapeutic potential of methyl gallate was investigated using lipopolysaccharide-treated mice. Oral administration of methyl gallate protected against acute renal injury and exhibited potential anti-inflammatory properties through an increase in antioxidant activity and decrease in nuclear factor-kappa B activity.

Aurantisolimonas haloimpatiens gen. nov., sp. nov., a bacterium isolated from soil.

A Gram-stain negative, strictly aerobic and non-motile bacterium, designated strain BN130233T, was isolated from a soil sample collected from Gyeongsangbuk-do, Republic of Korea. Colonies were orange in colour, with wet and smooth surfaces. Phylogenetic analyses based on the 16S rRNA gene sequences resulted in strain BN130233T forming a cluster with members of the family Chitinophagaceae Kämpfer et al. 2011, while sharing the highest sequence identity of 91.2 % with Chitinophaga niastensis JS16-4T. Good growth was observed at 20-28 °C, pH 7.0 and in the absence of NaCl. The major fatty acids were summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH. The respiratory quinone was MK-7. Major polar lipids contained phosphatidylethanolamine, an unidentified phospholipid, three unidentified aminolipids and eight unidentified lipids. The genomic DNA G+C content was 40.6 mol%. Phenotypic and chemotaxonomic characteristics together with 16S rRNA gene sequence analyses showed that strain BN130233T was distinct from its close phylogenetic relatives in the family ChitinophagaceaeKämpfer et al. 2011. The strain is, therefore, proposed as a representative of a new genus and new species with the name Aurantisolimonas haloimpatiens. The type strain of Aurantisolimonas haloimpatiens is BN130233T (=CCTCC AB 2017051T=KCTC 42642T).