Association between breastfeeding duration and diabetes mellitus in menopausal women: a machine-learning analysis using population-based retrospective study.

BACKGROUND: Breastfeeding resets insulin resistance caused by pregnancy however, studies on the association between breastfeeding and diabetes mellitus (DM) have reported inconsistent results. Therefore, we aimed to investigate the risk of DM according to breastfeeding duration in large-scale population-based retrospective study. In addition, machine-learning prediction models for DM and hemoglobin A1c (HbA1c) were developed to further evaluate this association. METHODS: We used the Korean National Health and Nutrition Examination Surveys database, a nationwide and population-based health survey from 2010 to 2020. We included 15,946 postmenopausal women with a history of delivery, whom we divided into three groups according to the average breastfeeding duration: (1) no breastfeeding, (2) < 12 months breastfeeding, and (3) ≥ 12 months breastfeeding. Prediction models for DM and HbA1c were developed using an artificial neural network, decision tree, logistic regression, Naïve Bayes, random forest, and support vector machine. RESULTS: In total, 2248 (14.1%) women had DM and 14,402 (90.3%) had a history of breastfeeding. The prevalence of DM was the lowest in the < 12 breastfeeding group (no breastfeeding vs. < 12 months breastfeeding vs. ≥ 12 months breastfeeding; 161 [10.4%] vs. 362 [9.0%] vs. 1,725 [16.7%], p < 0.001). HbA1c levels were also the lowest in the < 12 breastfeeding group (HbA1c: no breastfeeding vs. < 12 months breastfeeding vs. ≥ 12 months breastfeeding; 5.9% vs. 5.9% vs. 6.1%, respectively, p < 0.001). After adjustment for covariates, the risk of DM was significantly increased in both, the no breastfeeding (adjusted odds ratio [aOR] 1.29; 95% CI 1.29, 1.62]) and ≥ 12 months of breastfeeding groups (aOR 1.18; 95% CI 1.01, 1.37) compared to that in the < 12 months breastfeeding group. The accuracy and the area under the receiver-operating-characteristic curve of the DM prediction model were 0.93 and 0.95, respectively. The average breastfeeding duration was ranked among the top 15 determinants of DM, which supported the strong association between breastfeeding duration and DM. This association was also observed in a prediction model for HbA1c. CONCLUSIONS: Women who did not breasted had a higher risk of developing DM than those who breastfed for up to 12 months.

Labdane-Type Diterpenoids from Streptomyces griseorubens and Their Antimicrobial and Cytotoxic Activities.

Chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces griseorubens, resulted in the discovery of five new labdane-type diterpenoids: chlorolabdans A-C (1-3), epoxylabdans A and B (4 and 5), along with one known analog (6). The structures of the new compounds were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and by comparing their experimental data with those in the literature. The new compounds were evaluated for their antimicrobial activity, and 2 displayed significant activity against Gram-positive bacteria, with minimum inhibitory concentration (MIC) values ranging from 4 to 8 µg/mL. Additionally, 1, 2, and 4 were tested for their cytotoxicity against seven blood cancer cell lines by CellTiter-Glo (CTG) assay and six solid cancer cell lines by sulforhodamine B (SRB) assay; 1, 2, and 4 exhibited cytotoxic activities against some blood cancer cell lines, with concentration causing 50% cell growth inhibition (IC50) values ranging from 1.2 to 22.5 µM.

Machine learning analysis for the association between breast feeding and metabolic syndrome in women.

This cross-sectional study aimed to develop and validate population-based machine learning models for examining the association between breastfeeding and metabolic syndrome in women. The artificial neural network, the decision tree, logistic regression, the Naïve Bayes, the random forest and the support vector machine were developed and validated to predict metabolic syndrome in women. Data came from 30,204 women, who aged 20 years or more and participated in the Korean National Health and Nutrition Examination Surveys 2010-2019. The dependent variable was metabolic syndrome. The 86 independent variables included demographic/socioeconomic determinants, cardiovascular disease, breastfeeding duration and other medical/obstetric information. The random forest had the best performance in terms of the area under the receiver-operating-characteristic curve, e.g., 90.7%. According to random forest variable importance, the top predictors of metabolic syndrome included body mass index (0.1032), medication for hypertension (0.0552), hypertension (0.0499), cardiovascular disease (0.0453), age (0.0437) and breastfeeding duration (0.0191). Breastfeeding duration is a major predictor of metabolic syndrome for women together with body mass index, diagnosis and medication for hypertension, cardiovascular disease and age.

Meirols A-C: Bioactive Catecholic Compounds from the Marine-Derived Fungus Meira sp. 1210CH-42.

Three new catecholic compounds, named meirols A-C (2-4), and one known analog, argovin (1), were isolated from the marine-derived fungus Meira sp. 1210CH-42. Their structures were determined by extensive analysis of 1D, 2D NMR, and HR-ESIMS spectroscopic data. Their absolute configurations were elucidated based on ECD calculations. All the compounds exhibited strong antioxidant capabilities with EC50 values ranging from 6.01 to 7.47 µM (ascorbic acid, EC50 = 7.81 µM), as demonstrated by DPPH radical scavenging activity assays. In the α-glucosidase inhibition assay, 1 and 2 showed potent in vitro inhibitory activity with IC50 values of 184.50 and 199.70 µM, respectively (acarbose, IC50 = 301.93 µM). Although none of the isolated compounds exhibited cytotoxicity against one normal and six solid cancer cell lines, 1 exhibited moderate cytotoxicity against the NALM6 and RPMI-8402 blood cancer cell lines with GI50 values of 9.48 and 21.00 µM, respectively. Compound 2 also demonstrated weak cytotoxicity against the NALM6 blood cancer cell line with a GI50 value of 29.40 µM.

Ultrasonographic assessment of abnormal fetal growth related to uteroplacental-fetal biometrics and Doppler (U-AID) indices: Protocol for multicenter retrospective cohort study trial.

Fetal growth restriction (FGR) is one of the leading causes of perinatal morbidity and mortality. Many studies have reported an association between FGR and fetal Doppler indices focusing on umbilical artery (UA), middle cerebral artery (MCA), and ductus venosus (DV). The uteroplacental-fetal circulation which affects the fetal growth consists of not only UA, MCA, and DV, but also umbilical vein (UV), placenta and uterus itself. Nevertheless, there is a paucity of large-scale cohort studies that have assessed the association between UV, uterine wall, and placental thickness with perinatal outcomes in FGR, in conjunction with all components of the uteroplacental-fetal circulation. Therefore, this multicenter study will evaluate the association among UV absolute flow, placental thickness, and uterine wall thickness and adverse perinatal outcome in FGR fetuses. This multicenter retrospective cohort study will include singleton pregnant women who undergo at least one routine fetal ultrasound scan during routine antepartum care. Pregnant women with fetuses having structural or chromosomal abnormalities will be excluded. The U-AID indices (UtA, UA, MCA, and UV flow, placental and uterine wall thickness, and estimated fetal body weight) will be measured during each trimester of pregnancy. The study population will be divided into two groups: (1) FGR group (pregnant women with FGR fetuses) and (2) control group (those with normal growth fetus). We will assess the association between U-AID indices and adverse perinatal outcomes in the FGR group and the difference in U-AID indices between the two groups.

Streptinone, a New Indanone Derivative from a Marine-Derived Streptomyces massiliensis, Inhibits Particulate Matter-Induced Inflammation.

Inflammatory diseases caused by air pollution, especially from particulate matter (PM) exposure, have increased daily. Accordingly, attention to treatment or prevention for these inflammatory diseases has grown. Natural products have been recognized as promising sources of cures and prevention for not only inflammatory but also diverse illnesses. As part of our ongoing study to discover bioactive compounds from marine microorganisms, we isolated streptinone, a new indanone derivative (1), along with three known diketopiperazines (2-4) and piericidin A (5), from a marine sediment-derived Streptomyces massiliensis by chromatographic methods. The structure of 1 was elucidated based on the spectroscopic data analysis. The relative and absolute configurations of 1 were determined by 1H-1H coupling constants, 1D NOESY, and ECD calculation. The anti-inflammatory activities of 1 were evaluated through enzyme-linked immunosorbent assay (ELISA), Western blot, and qPCR. Compound 1 suppressed the production of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, by inhibiting the Toll-like receptor (TLR)-mediated nuclear factor kappa B (NF-κB) signaling pathway. Therefore, compound 1 could potentially be used as an agent in the prevention and treatment of diverse inflammatory disorders caused by particulate matter.

Rifamycin-Related Polyketides from a Marine-Derived Bacterium Salinispora arenicola and Their Cytotoxic Activity.

Eight rifamycin-related polyketides were isolated from the culture broth of a marine-derived bacterium Salinispora arenicola, including five known (2-5 and 8) and three new derivatives (1, 6, and 7). The structures of the new compounds were determined by means of spectroscopic methods (HRESIMS and 1D, 2D NMR) and a comparison of their experimental data with those previously reported in the literature. The isolated compounds were evaluated for their cytotoxicity against one normal, six solid, and seven blood cancer cell lines and 1 showed moderate activity against all the tested cell lines with GI50 values ranging from 2.36 to 9.96 µM.

Sesquiterpenes from Streptomyces qinglanensis and Their Cytotoxic Activity.

Nine sesquiterpenes, including eight pentalenenes (1-8) and one bolinane derivative (9), were isolated from the culture broth of a marine-derived actinobacterium Streptomyces qinglanensis 213DD-006. Among them, 1, 4, 7, and 9 were new compounds. Their planar structures were determined by spectroscopic methods (HRMS, 1D, and 2D NMR), and the absolute configuration was established by biosynthesis consideration and electronic-circular-dichroism (ECD) calculations. All the isolated compounds were screened for their cytotoxicity against six solid and seven blood cancer cell lines. Compounds 4-6 and 8 showed a moderate activity against all of the tested solid cell lines, with GI50 values ranging from 1.97 to 3.46 µM.

Thiolactones and Δ8,9-Pregnene Steroids from the Marine-Derived Fungus Meira sp. 1210CH-42 and Their α-Glucosidase Inhibitory Activity.

The fungal genus Meira was first reported in 2003 and has mostly been found on land. This is the first report of second metabolites from the marine-derived yeast-like fungus Meira sp. One new thiolactone (1), along with one revised thiolactone (2), two new Δ8,9-steroids (4, 5), and one known Δ8,9-steroid (3), were isolated from the Meira sp. 1210CH-42. Their structures were elucidated based on the comprehensive spectroscopic data analysis of 1D, 2D NMR, HR-ESIMS, ECD calculations, and the pyridine-induced deshielding effect. The structure of 5 was confirmed by oxidation of 4 to semisynthetic 5. In the α-glucosidase inhibition assay, compounds 2-4 showed potent in vitro inhibitory activity with IC50 values of 148.4, 279.7, and 86.0 µM, respectively. Compounds 2-4 exhibited superior activity as compared to acarbose (IC50 = 418.9 µM).

Association between Consumption of Dietary Supplements and Chronic Kidney Disease Prevalence: Results of the Korean Nationwide Population-Based Survey.

Despite the enormous global market of dietary supplements, the impact of dietary supplements on kidney disease is still unclear. Based on the National Health and Nutrition Examination Survey from 2015 to 2017, this study evaluated the association between dietary supplement and chronic kidney disease (CKD) in 13,271 Korean adults. Among the dietary supplements, vitamin and mineral intake was the highest at 61.41%, followed by omega-3 fatty acids at 11.85%, and ginseng at 7.99%. The prevalence of CKD was significantly higher in those who consumed amino acids and proteins, ginseng and red ginseng, and herbal medicine (plant extract)-berries than in those who did not. Conversely, patients who consumed probiotic supplements had a significantly lower prevalence of CKD than those who did not. In the population without CKD risk factors or history of CKD, the prevalence of CKD was high in the group consuming ginseng and red ginseng. After adjusting for covariates, the herbal medicine (plant extract)-berry group showed an independent association with CKD incidence. In conclusion, it is suggested that dietary supplements may affect kidney function. Further large-scale cohort studies are required to elucidate the exact effects of each dietary supplement on CKD.

TcPO2 Value Can Predict Wound Healing Time in Clinical Practice of CLTI Patients.

BACKGROUND: Transcutaneous oxygen pressure (TcPO2) is a noninvasive, nonradiological test to measure local oxygen released from capillaries through the skin. Since it reflects the metabolic state of the lower limb, it can predict wound healing in patients with critical limb threatening ischemia (CLTI). The purpose of this study was to determine the effectiveness of TcPO2 test in evaluating wound healing potential of patients with CLTI. METHODS: This was a retrospective, single-center, nonrandomized, and observational study. A prospectively registered database of patients who visited Vascular Surgery Department of St. Mary's Hospital for CLTI and underwent TcPO2 tests from October 1, 2015 to July 1, 2021 was reviewed. Patients were divided into 2 groups: (1) those who had amputation only; and (2) those who underwent revascularization procedures. Patients whose wound healing status could not be determined were excluded. The clinical characteristics of patients, patient characteristics related to lower TcPO2 value, treatment success rate, and time for the wound to be healed were analyzed. RESULTS: A total of 84 patients were included in this study. There was no difference in background patient characteristics between the 2 groups despite better survival within 12 months and shorter healing time in the revascularization group. A total of 76 patients survived 12 months after surgery, and 63 patients were healed. Higher HbA1c, higher serum creatinine, history of stroke, and history of coronary artery disease were related to lower TcPO2 value on multiple linear regression. The cutoff value of TcPO2 was determined to be 40 mm Hg for predicting wound healing. This value was similar to those of previous studies. In addition, there was a negative correlation between TcPO2 and wound healing time. Correlations among the anklebrachial index (ABI), toe-brachial index (TBI), and TcPO2 were not determined because ABI and TBI for some patients could not be obtained due to wound condition. CONCLUSIONS: The TcPO2 value can predict the wound healing process of ischemic lower extremity injury.

New Angucycline Glycosides from a Marine-Derived Bacterium Streptomyces ardesiacus.

Chemical investigation of the ethyl acetate extract from the culture broth of the marine-derived actinobacterium Streptomyces ardesiacus 156VN-095 led to the isolation of three hitherto undescribed angucycline glycosides, including urdamycins W and X (1 and 2) and grincamycin U (9), as well as their seven known congeners. The structures of the new compounds were elucidated by means of spectroscopic methods (HRESIMS, 1D and 2 D NMR) and comparison of their experimental data with literature values. Compounds 1-3 and 9 were evaluated for their anti-Gram-positive bacterial effect and cytotoxicity against six cancer cell lines. Compound 1 displayed significant cytotoxicity against all the tested cell lines with GI50 values of 0.019-0.104 µM. Collectively, these findings highlight the potential of angucycline glycosides as leading structures for the development of new anti-cancer drugs.

Aspersterols A-D, Ergostane-Type Sterols with an Unusual Unsaturated Side Chain from the Deep-Sea-Derived Fungus Aspergillus unguis.

Four previously undescribed ergostane-type sterols, aspersterols A-D (1-4), were isolated from a deep-sea-derived fungus, Aspergillus unguis IV17-109. The structures of the new compounds were determined by extensive analyses of their spectroscopic data, pyridine-induced deshielding effect, Mosher's method, and electronic circular dichroism calculations. The key feature of these sterols is the presence of a rare unsaturated side chain with conjugated double bonds at Δ17 and Δ22. The absolute configuration of C-24 in the side chain was determined by hydrogenation and comparing 13C NMR chemical shifts of the hydrogenated products with literature values. In addition, aspersterol A (1) is the second representative of anthrasteroids with a hydroxy group at the C-2 position. Compound 1 showed cytotoxicity against six cancer cell lines, with GI50 values of 3.4 ± 0.3 to 4.5 ± 0.7 µM, while 2-4 showed anti-inflammatory activity, with IC50 values ranging from 11.6 ± 1.6 to 19.5 ± 1.2 µM.

New Glycosylated Secondary Metabolites from Marine-Derived Bacteria.

Three new glycosylated secondary metabolites, including a new indole alkaloid, pityriacitrin D (1), and two new trehalose lipids (2 and 3), together with three known compounds (4-6) were isolated from two marine-derived bacterial strains, Bacillus siamensis 168CLC-66.1 and Tsukamurella pseudospumae IV19-045. The structures of 1-3 were determined by extensive analysis and comparison of their spectroscopic data with literature values. The absolute configurations of sugar moieties were determined by chemical derivatization followed by LC-MS analysis. Cytotoxicity of 1-3 against six cancer cell lines was evaluated by SRB assay, and 1 showed moderate activity against all the tested cell lines with GI50 values ranging from 8.0 to 10.9 µM.

Nitrogen-Containing Secondary Metabolites from a Deep-Sea Fungus Aspergillus unguis and Their Anti-Inflammatory Activity.

Aspergillus is well-known as the second-largest contributor of fungal natural products. Based on NMR guided isolation, three nitrogen-containing secondary metabolites, including two new compounds, variotin B (1) and coniosulfide E (2), together with a known compound, unguisin A (3), were isolated from the ethyl acetate (EtOAc) extract of the deep-sea fungus Aspergillus unguis IV17-109. The planar structures of 1 and 2 were elucidated by an extensive analysis of their spectroscopic data (HRESIMS, 1D and 2D NMR). The absolute configuration of 2 was determined by comparison of its optical rotation value with those of the synthesized analogs. Compound 2 is a rare, naturally occurring substance with an unusual cysteinol moiety. Furthermore, 1 showed moderate anti-inflammatory activity with an IC50 value of 20.0 µM. These results revealed that Aspergillus unguis could produce structurally diverse nitrogenous secondary metabolites, which can be used for further studies to find anti-inflammatory leads.

Isolation, Structure Determination, and Semisynthesis of Diphenazine Compounds from a Deep-Sea-Derived Strain of the Fungus Cystobasidium laryngis and Their Biological Activities.

Phenazostatins E-J (1-6), six new diphenazine derivatives, were isolated from the EtOAc extract of the culture broth of a strain of Cystobasidium laryngis derived from deep-sea sediments of the Indian Ocean Ridge. The structures of 1-6 were elucidated based on the HRESIMS and 1D and 2D NMR spectra. The absolute configurations of 1-6, except for 3 and 6, were determined by modified Mosher's method, ECD data analysis, and calculations of optical rotation values. The absolute configurations of 3 and 6 were identified by chemical derivatization and comparing the specific rotation values with those of semisynthetic 3 obtained by the oxidation of 1 and saphenic acid (7). Phenazostatin J (6) was semisynthesized using saphenic acid (7) to prepare additional material for biological testing. During the purification of semisynthetic 6, a side product 9 was obtained from the reaction mixture along with 6. Compounds 1-6, along with previously reported 7 and 8, were assessed for anti-neuroinflammatory activity in LPS-induced BV-2 microglia cells. Compound 6 exhibited the highest anti-neuroinflammatory effect with an IC50 value of 0.30 µM, but it showed cytotoxicity at higher concentrations than 1.0 µM. Accordingly, cytotoxicities of 1-9 were evaluated against six human cancer cell lines. Among tested compounds, 6 and 9 showed potent cytotoxicity (IC50 values: 7.7-72 nM). Especially, 6 exhibited the strongest cytotoxicity with an IC50 value of 7.7 nM against the NUGC-3 (stomach) cell line, displaying 19-fold stronger activity than the positive control, adriamycin.

Antibacterial and Cytotoxic Phenolic Polyketides from Two Marine-Derived Fungal Strains of Aspergillus unguis.

A chemical investigation on the EtOAc extracts from two marine-derived fungal strains of Aspergillus unguis resulted in the isolation of three previously undescribed phenolic polyketides including unguidepside C (1), aspersidone B (3), and agonodepside C (12), and their 14 known congeners. The structures of the new compounds were determined based on detailed analysis and comparison of their spectroscopic data with literature values, as well as Snatzke's method. The new compounds (1, 3, and 12) displayed a significant anti-Gram-positive bacterial activity, with MIC values ranging from 5.3 to 22.1 µM. Additionally, the isolated compounds (1-11 and 13-16) were evaluated for their cytotoxicity against a panel of tumor cell lines. Most of them (except for 9) displayed cytotoxicity against all the tested cell lines, with IC50 values ranging from 2.5 to 46.9 µM.

Anti-Mycoplasma Activity of Bacilotetrins C-E, Cyclic Lipodepsipeptides from the Marine-Derived Bacillus subtilis and Structure Revision of Bacilotetrins A and B.

Mycoplasma hyorhinis most commonly causes polyserositis and arthritis in swine and is a common contaminant during the cell culture in the laboratory. In our continuing research for diverse bioactive compounds from Bacillus subtilis 109GGC020, we discovered uncommon cyclic lipotetrapeptides showing inhibitory activities against M. hyorhinis with similar structures to previously reported bacilotetrins A and B. Bacilotetrins C-E (1-3), new cyclic lipodepsipeptides, were isolated from the EtOAc extract obtained from the fermentation of marine-derived Bacillus subtilis isolated from a marine sponge sample collected from the Gageo reef, Republic of Korea. The structures of 1-3, consisting of three leucine residues, one glutamic acid, and a ß-hydroxy fatty acid, were elucidated by detailed analysis of 1D, 2D NMR, and HR-ESIMS data. The absolute configurations of the amino acids and ß-hydroxy fatty acid were established by advanced Marfey's method and Mosher's method, respectively. The localization of L- and D-amino acids within the compounds was determined by retention time comparison of each purchased dipeptide standard to the partial hydrolysate products using LC-MS. Compounds 1-3 exhibited anti-mycoplasma activity, with an MIC value of 31 µg/mL, twofold stronger than that of the positive control, BioMycoX®. Detailed analysis and comparison of the spectroscopic data between bacilotetrins A (4) and B (5) and 1-3 led us to revise the structures of 4 and 5.

Polyketides and Meroterpenes from the Marine-Derived Fungi Aspergillus unguis 158SC-067 and A. flocculosus 01NT-1.1.5 and Their Cytotoxic and Antioxidant Activities.

Ten secondary metabolites, including a new grifolin analog, grifolin B (1); a new homovalencic acid derivative, 12-hydroxyhomovalencic acid (7); and a compound isolated from a natural source for the first time (9), along with seven known compounds, grifolin (2), averantin (3), 7-chloroaverantin (4), 1'-O-methylaverantin (5), 7-hydroxy-2-(2-hydroxypropyl)-5-pentylchromone (6), homovalencic acid (8), and bekeleylactone E (10), were isolated from two fungal strains. The structures of 1-10 were identified by detailed analysis and comparison of their spectroscopic data with literature values. Compounds 9 and 10 showed moderate cytotoxic activity against a panel of cancer cell lines (PC-3, HCT-15, MDA-MB-231, ACHN, NCI-H23, NUGC-3), with the GI50 values ranging from 1.1 µM to 3.6 µM, whereas 1 displayed a weak 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity without cytotoxicity against all tested cell lines.