Miracle-dz/UniFAR-FTUs huggingface dataset:
N-acetyl Cysteine Coated Gallium Particles Demonstrate High Potency against Pseudomonas aeruginosa PAO1

Nosocomial infections pose serious health concerns with over 2 million reported annually in the United States. Many of these infections are associated with bacterial resistance to antibiotics and hence, alternative treatments are critically needed. The objective of this study was to assess the antimicrobial efficacy of a gallium (Ga)-based particle coated with N-Acetyl Cysteine (Ga-NAC) against Pseudomonas aeruginosa PAO1. Our studies showed the Minimum Inhibitory Concentration (MIC) of PAO1 treated with Ga-NAC was 1 µg/mL. Cytotoxicity of Ga-NAC against multiple cell lines was determined with no cytotoxicity observed up to concentrations of 2000 µg/mL (metal concentration), indicating a high therapeutic window. To elucidate potential antibacterial modes of action, Inductively Coupled Plasma—Mass Spectrometry (ICP-MS), infrared spectroscopy, and atomic force microscopy (AFM) were used. The results suggest improved Ga3+ interaction with PAO1 through Ga-NAC particles. No significant change in cell membrane chemistry or roughening was detected. As cell membrane integrity remained intact, the antimicrobial mode of action was linked to cellular internalization of Ga and subsequent iron metabolic disruption. Furthermore, Ga-NAC inhibited and disrupted biofilms seen with crystal violet assay and microscopy. Our findings suggest the Ga-NAC particle can potentially be used as an alternative to antibiotics for treatment of Pseudomonas aeruginosa infections.
Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan*

Bisecting GlcNAc, a branching sugar in N-glycan highly expressed in brain, is involved in Alzheimer's disease, but its physiological function is largely unclear. In this manuscript, the authors revealed that loss of bisecting GlcNAc in mice leads to upregulation of various types of terminal modifications of N-glycans. As a mechanism, many glycosyltransferases were found to commonly prefer glycans without bisecting GlcNAc as a substrate. These data indicate that bisecting GlcNAc generally suppresses terminal modifications of N-glycans. Graphical Abstract Highlights Loss of bisecting GlcNAc in N-glycan increases various terminal glycan modifications. Glycosyltransferases commonly do not act well on glycans with bisecting GlcNAc. Presence of bisecting GlcNAc alters overall conformation of N-glycan. Bisecting GlcNAc serves as a general suppressor for terminal modification. Glycoproteins are decorated with complex glycans for protein functions. However, regulation mechanisms of complex glycan biosynthesis are largely unclear. Here we found that bisecting GlcNAc, a branching sugar residue in N-glycan, suppresses the biosynthesis of various types of terminal epitopes in N-glycans, including fucose, sialic acid and human natural killer-1. Expression of these epitopes in N-glycan was elevated in mice lacking the biosynthetic enzyme of bisecting GlcNAc, GnT-III, and was conversely suppressed by GnT-III overexpression in cells. Many glycosyltransferases for N-glycan terminals were revealed to prefer a nonbisected N-glycan as a substrate to its bisected counterpart, whereas no up-regulation of their mRNAs was found. This indicates that the elevated expression of the terminal N-glycan epitopes in GnT-III-deficient mice is attributed to the substrate specificity of the biosynthetic enzymes. Molecular dynamics simulations further confirmed that nonbisected glycans were preferentially accepted by those glycosyltransferases. These findings unveil a new regulation mechanism of protein N-glycosylation.
Cumulative intake of artificially sweetened and sugar-sweetened beverages and risk of incident type 2 diabetes in young adults: the Coronary Artery Risk Development In Young Adults (CARDIA) Study.

BACKGROUND Epidemiological evidence has demonstrated a positive association between artificially sweetened beverage (ASB) and sugar-sweetened beverage (SSB) consumption and type 2 diabetes (T2D) risk. However, research informing this topic in young adults is limited. OBJECTIVE This study examined the association between ASB, SSB, and total sweetened beverage (TSB; combined ASB and SSB) consumption and T2D risk in young adults. METHODS A prospective analysis of 4719 Black and White men and women aged 18-30 y at baseline was conducted from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Each participant's beverage intake was assessed using the CARDIA Diet History at baseline and at study Years 7 and 20. Multivariable Cox proportional hazards regression models were used to examine cumulative average ASB, SSB, and TSB intakes and risk of T2D. RESULTS During the 30-y follow-up period, 680 participants developed T2D. ASB consumption was associated with a 12% greater risk of T2D per serving/day (HR 1.12, 95% CI 1.04-1.20) in a model adjusted for lifestyle factors, diet quality, and dieting behavior. Further adjustments for baseline BMI (HR 1.07, 95% CI 0.99-1.14) and weight change during follow-up (HR 1.04, 95% CI 0.97-1.12) attenuated the association. SSB and TSB consumption as continuous variables per 1 serving/day of intake were associated with 6% and 5% increased risks of T2D, respectively (HRSSB 1.06, 95% CI 1.01-1.10; HRTSB 1.05, 95% CI 1.01-1.09), in the model accounting for lifestyle factors, dieting behavior, baseline BMI, and weight change. Results were consistent when the exposures were modeled in categories of consumption and quintiles. CONCLUSIONS In young adults, long-term ASB, SSB, and TSB consumption were associated with increased risks of T2D. However, the estimates for ASB were attenuated when accounting for weight changes.
Repression of TGF-β Signaling in Breast Cancer Cells by miR-302/367 Cluster

Objective Epigenetic alterations of the malignantly transformed cells have increasingly been regarded as an important event in the carcinogenic development. Induction of some miRNAs such as miR-302/367 cluster has been shown to induce reprogramming of breast cancer cells and exert a tumor suppressive role by induction of mesenchymal to epithelial transition, apoptosis and a lower proliferation rate. Here, we aimed to investigate the impact of miR-302/367 overexpression on transforming growth factor-beta (TGF-β) signaling and how this may contribute to tumor suppressive effects of miR-302/367 cluster. Materials and Methods In this experimental study, MDA-MB-231 and SK-BR-3 breast cancer cells were cultured and transfected with miR-302/367 expressing lentivector. The impact of miR-302/367 overexpression on several mediators of TGF-β signaling and cell cycle was assessed by quantitative real-time polymerase chain reaction (qPCR) and flow cytometry. Results Ectopic expression of miR-302/367 cluster downregulated expression of some downstream elements of TGF-β pathway in MDA-MB-231 and SK-BR-3 breast cancer cell lines. Overexpression of miR-302/367 cluster inhibited proliferation of the breast cancer cells by suppressing the S-phase of cell cycle which was in accordance with inhibition of TGF-β pathway. Conclusion TGF-β signaling is one of the key pathways in tumor progression and a general suppression of TGF-β mediators by the pleiotropically acting miR-302/367 cluster may be one of the important reasons for its anti-tumor effects in breast cancer cells.
Interleukin‐1 alpha derived from ultraviolet B‐exposed keratinocytes is associated with a decrease of endocytic collagen receptor Endo180

Endo180 contributes to the remodeling of the collagen fibers that comprise the dermal matrix due to the internalization of extracellular collagen fragments. In the sun‐exposed elder skin, an accumulation of collagen fragments was observed in the dermal matrix which was associated with a reduction in Endo180 in the dermal fibroblasts. This suggests that the loss of Endo180 results in the accumulation of collagen fragments in the surrounding fibroblasts and causes interference with dermal matrix remodeling via collagen fibers. The purpose of the study was to identify a mechanism by which ultraviolet B (UVB) exposure induces a loss of Endo 180 with a specific focus on the crosstalk between keratinocytes and fibroblasts.
Blood-sparing removal technique of extracorporeal membrane oxygenation circuit in a Jehovah Witness patient

Abstract Rationale: Percutaneous cardiopulmonary support (PCPS) using extracorporeal membrane oxygenation (ECMO) is widely used in the critical patients with cardiopulmonary collapse. It is a representative blood-consuming procedure. In limited situations in which the option of blood transfusion is unavailable, there is no general agreement as to whether ECMO is contraindicated. Patient concerns: A 61-year-old male Jehovah Witness with acute respiratory collapse and loss of consciousness was rushed to our emergency room. Throughout his hospital course, the patient's family refused any type of blood transfusion even at the risk of death. Diagnosis: The clinical situations were secondary to a massive pulmonary thromboembolism Interventions: The patient underwent veno-venous ECMO via both femoral veins. The patient was recovered by intensive medical care although the level of hemoglobin (Hb) and hematocrit (Hct) was gradually decreased from 15.8 g/dl and 46.8% to 11.7 g/dl and 36.5%, respectively. Outcomes: On hospital day 3, ECMO was successfully removed using a blood-sparing ECMO removal technique involving the recycling of blood within the circuit by continuous saline infusion. There was no significant change in level of Hb/Hct and hemodynamic profile. At 2 days after ECMO removal, the level of Hb/Hct was elevated up to 9.2 g/dl and 30.0%, respectively without any transfusion. Lessons: Our blood-sparing removal technique of ECMO appears to be feasible and led to no significant adverse impact on hemodynamic status. The technique might be helpful for critical patients who cannot receive blood transfusion due to any cause.
Traditional Chinese medicine (Xiaoai Jiedu Decoction) as an adjuvant treatment for prevention new colorectal adenomatous polyp occurrence in post-polypectomy

Abstract Background: Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy. Methods/Design: A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years. Discussion: This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy. Trial registration: NCT03616444.
Suicidal Ideation and Severity of Distress among Refugees Residing in Asylum Accommodations in Sweden

Refugees worldwide suffer high levels of distress and are at increased risk for death by suicide. The Refugee Health Screener (RHS) was developed to screen for emotional distress among refugees and can be used to assess distress severity. This paper examines the association between distress severity and suicidal ideation in a sample of refugees residing in asylum accommodations. Data from the RHS and item 9 on the Patient Health Questionnaire-9 (PHQ-9) was analyzed. Results showed that individuals at moderate and severe levels of distress were much more likely to exhibit suicidal ideation than individuals with low levels of distress. Even though we cannot conclude that individuals with low levels of distress do not have thoughts of ending their lives, further suicide assessment is warranted in asylum seekers with moderate to severe distress on the RHS.
Down-Regulation of miR-200c and Up-Regulation of miR-30c Target both Stemness and Metastasis Genes in Breast Cancer

Objective microRNAs (miRNAs) play important role in progression of tumorigenesis. They can target self-renewal and epithelial-mesenchymal transition (EMT) abilities in tumor cells, especially in cancer stem cells (CSCs). The objective of this study was to implement data mining to identify important miRNAs for targeting both self-renewal and EMT. We also aimed to evaluate these factors in mammospheres as model of breast cancer stem cells (BCSCs) and metastatic tumor tissues. Materials and Methods In this experimental study, mammospheres were derived from MCF-7 cells and characterized for the CSCs properties. Then expression pattern of the selected miRNAs in spheroids were evaluated, using the breast tumor cells obtained from seven patients. Correlation of miRNAs with self-renewal and EMT candidate genes were assessed in mammospheres and metastatic tumors. Results The results showed that mammospheres represented more colonogenic and spheroid formation potential than MCF-7 cells (P<0.05). Additionally, they had enhanced migration and invasive capabilities. Our computational analyses determined that miR-200c and miR-30c could be candidates for targeting both stemness and EMT pathways. Expression level of miR-200c was reduced, while miR-30c expression level was enhanced in mammospheres, similar to the breast tumor tissues isolated from three patients with grade II/III who received neo-adjuvant treatment. Expression level of putative stem cell markers (OCT4, SOX2, c-MYC) and EMT-related genes (SNAIL1, CDH2, TWIST1/2) were also significantly increased in mammospheres and three indicated patients (P<0.05). Conclusion Simultaneous down-regulation and up-regulation of respectively miR-200c and miR-30c might be signature of BCSC enrichment in patients post neo-adjuvant therapy. Therefore, targeting both miR-200c and miR-30c could be useful for developing new therapeutic approaches, against BCSCs.
Nocturnal dipping status and the association of morning blood pressure surge with subclinical target organ damage in untreated hypertensives

The authors aimed to investigate the association between sleep‐through morning surge (MS) in blood pressure (BP) and subclinical target organ damage in untreated hypertensives with different nocturnal dipping status. This cross‐sectional study included 1252 individuals who underwent anthropometric measurements, serum biochemistry evaluation, 24‐hour ambulatory blood pressure monitoring, echocardiography, and carotid ultrasonography. Left ventricular mass index, left atrial dimension, and carotid intima‐media thickness were evaluated. Participants were grouped according to nocturnal systolic BP dipping rate (388 dippers, 10%‐20%; 674 non‐dippers, 0%‐10%; 190 reverse dippers, <0%). Twenty‐two extreme dippers were excluded. While reverse dippers exhibited the most severe signs of damage, only dippers showed significant and positive correlation between MS and hypertension‐mediated organ damage (all P < .05), with significant area under the receiver operating characteristic curve for discriminating left ventricular hypertrophy (0.662), left atrial enlargement (0.604), and carotid intima‐media thickening (left, 0.758; right, 0.726; all P < .05). MS showed significant association with subclinical organ damage on both logistic and multiple linear regression analysis adjusted for age, sex, body mass index, smoking status, and alcohol consumption status, as well as for the levels of fasting blood glucose, uric acid, serum creatinine, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol, even when 24‐hour, daytime, nocturnal, and morning systolic BP were included (odds ratio >1 and P < .01 for all types of damage). Besides race, nocturnal dipping status might affect the role of MS in subclinical target organ damage, with a significant association only in dippers, independent of other systolic BP parameters. Dipping status might account for the discrepancies across previous reports.
Ghrelin Derangements in Idiopathic Dilated Cardiomyopathy: Impact of Myocardial Disease Duration and Left Ventricular Ejection Fraction

Background: Ghrelin may exert positive effects on cardiac structure and function in heart failure (HF) patients. Methods: We assessed ghrelin levels in 266 dilated cardiomyopathy (DCM) patients and in 200 age, gender and body mass index (BMI) matched controls. Further, we evaluated the expression of ghrelin and growth hormone secretagogue-receptor (GHSR) in the myocardium of 41 DCM patients and in 11 controls. Results: DCM patients had significantly lower levels of total, acylated and unacylated ghrelin when compared to controls (p < 0.05 for all). In controls, we observed a negative correlation of ghrelin with age, male gender and BMI. These correlations were lost in the DCM group, except for male gender. Total ghrelin was higher in patients with more recent diagnosis when compared to patients with longer duration of the DCM (p = 0.033). Further, total ghrelin was higher in patients with lower left ventricular systolic function (<40% LVEF, vs. 40% ≤ LVEF < 49% vs. LVEF ≥ 50%: 480.8, vs. 429.7, vs. 329.5 pg/mL, respectively, p = 0.05). Ghrelin prepropeptide was expressed more in DCM patients than in controls (p = 0.0293) while GHSR was expressed less in DCM patients (p < 0.001). Furthermore, ghrelin showed an inverse correlation with its receptor (ρ = −0.406, p = 0.009), and this receptor showed a significant inverse correlation with Interleukin-1β (ρ = −0.422, p = 0.0103). Conclusion: DCM duration and severity are accompanied by alterations in the ghrelin–GHSR system.
Analytical and Computational Methods for the Estimation of Drug-Polymer Solubility and Miscibility in Solid Dispersions Development

The development of stable solid dispersion formulations that maintain desired improvement of drug dissolution rate during the entire shelf life requires the analysis of drug-polymer solubility and miscibility. Only if the drug concentration is below the solubility limit in the polymer, the physical stability of solid dispersions is guaranteed without risk for drug (re)crystallization. If the drug concentration is above the solubility, but below the miscibility limit, the system is stabilized through intimate drug-polymer mixing, with additional kinetic stabilization if stored sufficiently below the mixture glass transition temperature. Therefore, it is of particular importance to assess the drug-polymer solubility and miscibility, to select suitable formulation (a type of polymer and drug loading), manufacturing process, and storage conditions, with the aim to ensure physical stability during the product shelf life. Drug-polymer solubility and miscibility can be assessed using analytical methods, which can detect whether the system is single-phase or not. Thermodynamic modeling enables a mechanistic understanding of drug-polymer solubility and miscibility and identification of formulation compositions with the expected formation of the stable single-phase system. Advance molecular modeling and simulation techniques enable getting insight into interactions between the drug and polymer at the molecular level, which determine whether the single-phase system formation will occur or not.
Nutritional Aspects in Diabetic CKD Patients on Tertiary Care

Background and objectives: Diabetes is largely prevalent in the chronic kidney disease (CKD) population. Both conditions have metabolic and nutritional abnormalities that affect body composition and the presence of diabetes makes the dietary management of CKD patients more difficult. The aim of this study was to assess peculiar nutritional and functional aspects of diabetic patients in an adult/elderly CKD population, and their predictive significance. Materials and methods: This prospective cohort study included 144 out-patients aged >55 years, affected by stage 3b-4 CKD, on tertiary care clinic; 48 (40 males) were type 2 diabetics and 96 (80 males) were nondiabetics. The two groups have similar age, gender, and residual renal function (30 ± 9 vs. 31 ± 11 mL/min×1.73). All patients underwent a comprehensive nutritional and functional assessment and were followed for 31 ± 14 months. Results: Diabetic CKD patients showed higher waist circumference and fat body mass, lower muscle mass, and lower number of steps per day and average daily METs. Meanwhile, resting energy expenditure (REE), as assessed by indirect calorimetry, and dietary energy intake were similar as well as hand-grip and 6 min walking test. Diabetic patients did not show a greater risk for all-cause mortality and renal death with respect to nondiabetics. Middle arm muscle circumference, phase angle, serum cholesterol, and serum albumin were negatively related to the risk of mortality and renal death after adjustment for eGFR. Conclusions: CKD diabetic patients differed from nondiabetics for a greater fat mass, lower muscle mass, and lower physical activity levels. This occurred at the same REE and dietary energy intake. The outcome of diabetic or nondiabetic CKD patients on tertiary care management was similar in terms of risk for mortality or renal death. Given the same residual renal function, low levels of muscle mass, phase angle, serum albumin, and cholesterol were predictive of poor outcome. Overall, a malnutrition phenotype represents a major predictor of poor outcome in diabetic and nondiabetic CKD patients.