Miracle-dz/UniFAR-FTUs huggingface dataset:
NMR evidence of charge‐dependent interaction between various PND V3 and CCR5 N‐terminal peptides

The third variable (V3) loop is an important region of glycoprotein 120 (gp120) for many biological processes, as it contains the highly conserved GPGR sequence and it represents the binding site for human immunodeficiency virus 1 (HIV‐1) antibodies and for CCR5 and CXCR4 host cell coreceptors. The interaction of the principal neutralizing determinant (PND) V3 with the chemokine receptor CCR5 N‐terminal region has been reported to be crucial for HIV‐1 infection. The goal of this study is to characterize the solution structures of three HIV‐1 gp120 V3 subtype B peptides and their interaction with a nonsulfated N‐terminal CCR5 peptide. NMR titration experiments revealed that the CCR5Nt‐PND V3 interaction is dependent on the number of the positively charged V3 residues, which is in agreement with the observation that increase in positive charge in the V3 sequence correlates with the augmentation of the interaction. As expected for free peptides in solution, the peptides representing the PND V3 region of gp120 exhibit conformational flexibility, but they also exhibit a large number of NOEs which allowed convergence to a dominant conformation. The PND V3 peptides retain the U‐turn conformation observed in the crystal structures of gp120 complexes independently of CCR5 presence. The interaction of different regions of the CCR5Nt peptide is gradually increasing proportionally to the positive charge increase in the V3 peptides. The data demonstrate that the PND V3 and CCR5Nt peptide sequences have propensities for interaction even in the absence of sulfated tyrosines and that their binding and selectivity is determined by simple electrostatic attraction mechanisms. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 94–109, 2009.
Caspase inhibitors protect against NMDA‐mediated retinal ganglion cell death

Background: Apoptosis is a major mechanism of cell death in glutamate‐induced excitotoxicity and caspases as the executors of apoptosis play an important role in the development of various central nervous system and eye diseases. We studied the involvement of certain caspases in excitotoxic retinal ganglion cell death, which was experimentally induced in Brown Norway Rats by application of the glutamate receptor agonist N‐methyl‐D‐aspartate (NMDA).
Prevention of Oxidative DNA Damage by Bioactive Berry Components

The hormone 17ß-estradiol (E2) causes oxidative DNA damage via redox cycling of its metabolites such as 4-hydroxy estradiol (4E2). In this study, ACI rats (8 wk old) were fed either AIN-93M diet or diets supplemented with 0.5% each of mixed berries (strawberry, blueberry, blackberry, and red and black raspberry), blueberry alone (BB; 2.5%), or ellagic acid (EA; 400 ppm) from 2 wk prior to and up to 12 wk of E2 treatment. The liver DNA was analyzed for the presence of 8-oxo-7,8-dihydroguanine (8-oxodG) and other polar adducts by 32P-postlabeling. Compared to sham treatment, E2 significantly increased the levels of both 8-oxodG and P-1 subgroup (259% and 214%, respectively; P< 0.05). EA diet significantly reduced E2-induced levels of 8-oxodG, P-1, P-2, and PL-1 by 79, 63, 44, and 67%, respectively (P< 0.001). BB diet also significantly reduced the levels of P-1, P-2, and PL-1 subgroups by 77, 43, and 68%, respectively (P< 0.001). Mixed berries were, however, ineffective. In addition, aqueous extracts of berries (2%) and EA (100 μM) were tested for their efficacy in diminishing oxidative DNA adducts induced by redox cycling of 4E2 catalyzed by copper chloride in vitro. EA was the most efficacious (90%), followed by extracts of red raspberry (70%), blueberry, and strawberry (50% each; P< 0.001).
Oxidative folding of hepcidin at acidic pH

Hepcidin is a four disulfide 25‐residue peptide hormone which has a central role in the regulation of iron homeostasis. To support studies on hepcidin we have sought to establish reliable and robust synthetic methods for the preparation of correctly folded materials. While correctly‐folded hepcidin has good aqueous solubility, we have found that its direct synthetic precursor, linear (reduced) hepcidin peptide, is resistant to solubilization, prone to precipitation at pH ≥ 6, and thus difficult to fold efficiently. Attempts to directly fold either the crude or purified linear hepcidin peptide by air or DMSO oxidation methods under basic conditions were ineffective. However, addition of a glutathione redox pair system improved folding of purified linear hepcidin at mild basic pH (pH 7.5). Under acidic conditions, it was possible to oxidatively fold both crude and purified hepcidin using a polymer‐supported oxidizing strategy. Peptide precipitation was also avoided under acidic conditions. Isolated folding yields of human hepcidin under acidic polymer‐assisted conditions were superior to yields under basic folding conditions. These studies enabled identification of a reliable synthetic route for correctly‐folded hepcidin. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 257–264, 2010.
Soy Consumption and Histopathologic Markers in Breast Tissue Using Tissue Microarrays

This study examined the relation of soy intake with hormonal and proliferation markers in benign and malignant breast tissue using tissue microarrays (TMAs). TMAs with up to 4 malignant and 4 benign tissue samples for 268 breast cancer cases were constructed. Soy intake in early life and in adulthood was assessed by questionnaire. The TMAs were stained for estrogen receptor (ER) α, ERβ, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), proliferating cell nuclear antigen (PCNA), and Ki-67 using standard immunohistochemical methods. Logistic regression was applied for statistical analysis. A higher percentage of women showed positive marker expression in malignant than in benign tissue. With one exception, HER2/neu, no significant associations between soy intake and pathologic markers were observed. Early life soy intake was associated with lower HER2/neu and PCNA staining of malignant tissue. In benign tissue, early life soy intake showed higher ER and PR expression, but no difference in proliferation markers. The results of this investigation provide some assurance that soy intake does not adversely affect markers of proliferation. TMAs were shown to be a useful tool for epidemiologic research.
Flavonoids, Proanthocyanidins, and Cancer Risk: A Network of Case-Control Studies From Italy

We considered flavonoids and proanthocyanidins in a network of multicentric Italian case-control studies including about 10,000 incident, histologically confirmed cases of selected cancers and over 16,000 controls. Odds ratios (ORs) for the highest vs. the lowest quintile of 6 classes of flavonoids and proanthocyanidins were estimated by multiple logistic regression models. Total flavonoids, flavanones, and flavonols were inversely related to oral and laryngeal cancers (ORs, respectively 0.56 and 0.60 for total flavonoids; 0.51 and 0.60 for flavanones; and 0.62 and 0.32 for flavonols). Flavanols were also inversely related to laryngeal cancer (OR = 0.64), whereas flavanones were inversely related to esophageal cancer (OR = 0.38). A reduced risk of colorectal cancer was found for high intake of anthocyanidins (OR = 0.67), flavonols (OR = 0.64), flavones (OR = 0.78), and isoflavones (OR = 0.76). Inverse relations with breast cancer were found for flavones (OR = 0.81) and flavonols (OR = 0.80). Flavonols (OR = 0.63) and isoflavones (OR = 0.51) were inversely associated to ovarian cancer, whereas flavonols (OR = 0.69) and flavones (OR = 0.68) were inversely associated to renal cancer. No association between flavonoids and prostate cancer emerged. We found inverse associations between proanthocyanidins and colorectal cancer. These associations appeared stronger for proanthocyanidins with a higher degree of polymerization (OR = 0.69 for ≥ 10 mers).
Bilateral severe anterior uveitis after unilateral selective laser trabeculoplasty

ing to malignancy was not convincing, and the likely cause for bone growth would be inflammation related to ISOI. In cases of chronic refractory sinusitis, lytic and blastic forms of osteitis occur, and can result in hyperostosis of the nasal and paranasal bones, which was seen in 64% of patients with recurrent rhinosinusitis. The chronic inflammation of ISOI likely caused a corresponding osteitis, an osteoblastic type in this case, producing hyperostosis and the bony changes seen in this case. Diagnosing ISOI is difficult and can further be complicated by the unusual finding of hyperostosis. Treatment of ISOI is controversial as studies using steroids, azathioprine, cyclosporine and radiation have been used with limited success. With our patient’s age and the systemic complications associated with his mesothelioma, treatment was deferred. This case highlights ISOI associated with hyperostosis, and it is important with this presentation that a concomitant work-up for occult malignancy is considered.
Functional classification of membrane transporters and channels based on filtered TM/non‐TM amino acid composition

Membrane transporters catalyze the transport of small solute molecules across biological barriers such as lipid bilayer membranes. As the experimental annotation of which proteins transport which substrates is incomplete it is highly desirable to develop computational methods that can assist in the classification and substrate annotation of putative membrane transport proteins. Here, we determined the similarity of membrane transporter sequences annotated in the Transport Classification Database (Saier et al., Nucleic Acids Res 2006, 34, D181‐D186) and Arabidopsis thaliana membrane transporters annotated in the database Aramemnon (Schwacke et al., Plant Physiol 2003, 131, 16‐26). The similarity measure was based on the amino acid composition either considering the full sequences or separately in the transmembrane (TM) and external parts of the sequences. We considered four different substrate sets and three different subfamilies and tried to classify the given proteins into these classes. Family or substrate prediction based on the simple amino acid frequency had an average accuracy of 76%. The differentiation between TM and non‐TM regions led to an improved accuracy of 80% on average. © 2012 Wiley Periodicals, Inc. Biopolymers 97:558–567, 2012.
Baseline Plasma Levels of Interleukin-8 in Stage IV Non-Small-Cell Lung Cancer Patients: Relationship With Nutritional Status and Prognosis

Interleukin (IL)-8 promotes cellular proliferation and angiogenesis in patients with non-small-cell lung cancer (NSCLC) and may be related to cachexia. Our aim was to investigate the relationship of IL-8 levels with nutritional status, and clinical outcome of patients with NSCLC. Patients with metastatic NSCLC referred for first-line therapy were eligible. Baseline IL-8 levels were measured in plasma. The Mini Nutritional Assessment (MNA) was used for the evaluation of the nutritional status, and patients were classified into 3 groups: A (score 24–30) “well nourished,” B (score 17–23.5) “risk of malnutrition,” and C (0–16.5) “malnourishment. ” Response to first-line chemotherapy, time-to-tumor progression (TTP), and overall survival (OS) were also recorded. In total, 114 patients (101 males, 88.5%; mean age = 67.5 yr) were evaluated. Performance status was 0–1 in 62% of the patients. According to the MNA, the majority of patients (71%) was either at nutritional risk or malnourished. IL-8 levels were significantly different between MNA groups (P = 0.023) and correlated with TTP (P = 0.013) and OS (P = 0.001) in univariate analysis. Baseline IL-8 levels correlate with the nutritional status of patients with metastatic NSCLC, suggesting that this cytokine may be related with cachexia.
ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED DRAINAGE FOR TUBERCULOUS LIVER ABSCESS DRAINAGE

Traditionally, either surgical or percutaneous drainage is recommended for liver abscess. Recently, several endoscopists have reported the endoscopic ultrasound (EUS)‐guided liver abscess drainage. Herein, we report a case of tuberculous liver abscess in which endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) was useful for the diagnosis and therapy. A 78‐year‐old woman suffered from continuous epigastric pain and fever up. Computed tomography (CT) showed a 70 mm multilocular and multiseptate cystic lesion around the head of pancreas and caudate lobe of the liver. After confirming liver abscess by EUS‐FNA, EUS‐guided liver abscess drainage was carried out. Finally, a 7 Fr straight stent and a 5 Fr nasocystic catheter were inserted into the cyst. Four weeks later, we found that cultured microorganism obtained using drainage catheter was Mycobacterium tuberculosis. Although he was doing well during 5 days after the procedure, CT showed the size of another abscess increased. Then, additional EUS‐guided abscess drainage was carried out at the body of the stomach into the abscess of the left lobe. Two weeks later, CT showed disappearance of abscesses. Then, she discharged with the internal stent still in place.
Deleterious Effects of High Concentrations of (-)-Epigallocatechin-3-Gallate and Atorvastatin in Mice With Colon Inflammation

Epigallocatechin-3-gallate (EGCG), atorvastatin (ATST), and their combination have been previously shown to inhibit colon carcinogenesis in animal models. We further investigated their inhibitory activities in azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated Balb/cJ mice and CD-1 mice in 2 slightly different models. The mice were maintained on the AIN93M diet, or a similar diet containing 0.03%, 0.1%, or 0.3% EGCG; 60-ppm ATST; or a combination of 0.1% EGCG and 60-ppm ATST. Unexpectedly, no significant inhibitory activity was observed, and some of the treatment groups resulted in higher tumor multiplicity. To study the effects of EGCG on colon inflammation, CD-1 or C57BL/6 mice were treated with 1.5% DSS for 7 days and sacrificed 3 days later. DSS induced rectal bleeding and colon shortening; treatment with 0.5% EGCG exacerbated the bleeding and decreased mouse body weight. Dietary 0.5% EGCG also increased serum levels of leukotriene B4 and prostaglandin E2. These results suggest that, in mice bearing colon inflammation, high concentrations of EGCG and ATST enhance colon bleeding and may promote colon carcinogenesis.
The Regulation of Immunological Processes by Peripheral Neurons

The nervous system and the immune system are the primary sensory interfaces between the internal and external environment. They are responsible for recognizing, integrating, and responding to stimuli with the appropriate valence and magnitude to optimize host fitness. Furthermore, an alluring parallel concept is that both systems have the capacity to form memories of these encounters leading to optimized and adaptive future responses. Recent work in the fields of neuroscience and immunology has led to a high-resolution map of cell subsets within both systems. Here, we start to leverage these advances to explore the relationship between these two sensory systems at the level of discrete cell subsets in immunological disease and homeostasis with a focus on interactions at barrier tissues. This work stems from the initial hypothesis that sensory neurons for noxious stimuli, nociceptors, regulate inflammation by controlling production of key instructive and effector cytokines derived from tissue-resident immune cells. In our first investigation focused on the skin, we identified that NaV1.8+ TRPV1+ nociceptors, via interactions with dDCs, are essential in vivo regulators of interleukin-(IL)-23/IL-17 pathway cutaneous immune responses. This set of studies raised several intriguing questions including determining what the inputs and outputs of nociceptors are that regulate IL-23 production from dDCs and whether nociceptors play a role in distinct inflammatory contexts. In further experiments we determined that while TRPV1 itself is dispensable, nociceptor activity is essential to promote disease and local cytokine production. As we found that nociceptors are critical for cutaneous IL-23
The closed wedge counter shift osteotomy for the correction of post-traumatic cubitus varus

A variety of osteotomies have been proposed to correct post-traumatic cubitus varus deformity. Each one of them has advantages and disadvantages or limitations. A new technique for correcting post-traumatic cubitus varus with closed wedge counter shift osteotomy of the distal humerus is described and the preliminary results in six cases are reported. Five patients showed excellent results and one patient showed good result. We believe that the described technique is an alternative to the other procedures for the treatment of post-traumatic cubitus varus with minimal internal rotation and hyperextension deformities. It has the advantages of being a simple, safe, inherently stable, technically sound procedure, and yields an excellent cosmetic outcome.
Solution structures and model membrane interactions of Ctriporin, an anti‐methicillin‐resistant Staphylococcus aureus Peptide from Scorpion Venom

Ctriporin peptide (Ctr), a novel antimicrobial peptide isolated from the venom of the scorpion Chaerilus tricostatus, shows a broad‐spectrum of antimicrobial activity and is able to inhibit antibiotic resistant pathogens, including Methicillin resistant Staphylococcus aureus, Methicillin Resistant Coagulase‐negative Staphylococcus, and Penicillin Resistant Staphylococcus epidermidis strains. To understand the active conformation of the Ctr peptide in membranes, we have investigated the interaction of Ctr with the negatively charged and zwitterionic membrane‐mimetic micelles such as sodium dodecyl sulphate (SDS) and n‐dodecylphosphocholine (DPC), respectively. The interactions were studied using fluorescence and circular dichroism (CD) spectroscopy. Fluorescence experiments revealed that the N‐terminus tryptophan residue of Ctr interacted with the hydrophobic core of the membrane mimicking micelles. The CD results suggest that interactions with membrane‐mimetic micelles induce an α‐helix conformation in Ctr. Moreover, we have determined the solution structures of Ctr in SDS and DPC micelles using nuclear magnetic resonance (NMR) spectroscopy. The structural comparison of Ctr in the presence of SDS and DPC micelles showed significant conformational changes. The observed structural differences of Ctr in anionic versus zwitterionic membrane‐mimetic micelles suggest that the mode of interaction of this peptide may be different in two environments which may account for its ability to differentiate bacterial and eukaryotic cell membrane. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 1143–1153, 2014.
Evaluation of Genotoxicity and Antigenotoxicity of Artepillin C in V79 Cells by the Comet and Micronucleus Assays

Artepillin C (3,5-diprenyl-p-coumaric acid) is one of the major phenolic compounds found in Brazilian green propolis, as well as in its botanical source, Baccharis dracunculifolia DC (Asteraceae). The present study evaluated the possible genotoxic and protective activities of artepillin C, in vitro, using methyl methanesulfonate (MMS) as a positive control, by comet and micronucleus assays. The cultures of Chinese hamster lung fibroblasts (V79 cells) were treated with different concentrations of artepillin C (2.5, 5.0, 10.0, and 20 μM). In antigenotoxicity assessment, the 3 concentrations of artepillin C (2.5, 5.0, and 10.0 μM) were associated with MMS (200 μM-comet assay and 400 μM-micronucleus assay). A statistically significant increase in the DNA damage and micronucleus frequencies was observed in the culture treated with the highest concentration of the artepillin C in comparison to the control group. All concentrations of artepillin C showed protective activity in relation to MMS-induced genotoxicity, which may be due to its antioxidant properties.
Investigating the Association of Lactation History and Postmenopausal Breast Cancer Risk in the Women's Health Initiative

Prolonged lactation (≥24 mo) has been associated with reduced breast cancer risk. This research examined this association in postmenopausal women in the Women's Health Initiative (WHI) Hormone Trial (HT) and Observational Study (OS). This retrospective cohort analysis included 69,358 predominantly overweight (65.4%), white (83.2%) postmenopausal women without breast cancer. Women in the HT were randomized to 0.625 mg conjugated equine estrogen (CEE), 0.625 CEE + 2.5 mg medroxyprogesterone acetate (CEE/MPA), or placebo. OS participants had no restrictions on hormone use. Lactation history was assessed via WHI Reproductive History Questionnaire. Most women breastfed at least 1 mo (58.0%); 35.4% breastfed 1–2 children; and 6.5% stated having breastfed ≥24mo. Women in the HT–CEE who breastfed their first child between 20–24 yr of age demonstrated a nonsignificant decreased risk of breast cancer (HR: 0.62; 95% CI: 0.38, 1.01). OS participants who reported CEE/MPA hormone use and age of first breastfeeding ≥30 yr showed a significant increased risk of breast cancer (HR: 1.66; 95% CI: 1.14, 2.41). Risk was increased if age of last breastfeeding was ≥35yr (HR: 1.50; 95% CI: 1.05, 2.14). This research did not demonstrate a significantly decreased risk of postmenopausal breast cancer in women who breastfed for ≥24 mo during their lifetime.
Solid‐phase synthesis, characterization, and cellular activities of collagen‐model Nanodiamond‐peptide conjugates

Nanodiamonds (NDs) have received considerable attention as potential drug delivery vehicles. NDs are small (∼5 nm diameter), can be surface modified in a controllable fashion with a variety of functional groups, and have little observed toxicity in vitro and in vivo. However, most biomedical applications of NDs utilize surface adsorption of biomolecules, as opposed to covalent attachment. Covalent modification provides reliable and reproducible ND–biomolecule ratios, and alleviates concerns over biomolecule desorption prior to delivery. The present study has outlined methods for the efficient solid‐phase conjugation of ND to peptides and characterization of ND–peptide conjugates. Utilizing collagen‐derived peptides, the ND was found to support or even enhance the cell adhesion and viability activities of the conjugated sequence. Thus, NDs can be incorporated into peptides and proteins in a selective manner, where the presence of the ND could potentially enhance the in vivo activities of the biomolecule it is attached to. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 186–195, 2015.
A Pilot Case-Cohort Study of Brain Cancer in Poultry and Control Workers

We conducted an exploratory study to investigate which exposures (including poultry oncogenic viruses) are associated with brain cancer in poultry workers. A total of 46,819 workers in poultry and nonpoultry plants from the same union were initially followed for mortality. Brain cancer was observed to be in excess among poultry workers. Here we report on a pilot case-cohort study with cases consisting of 26 (55%) of the 47 brain cancer deaths recorded in the cohort, and controls consisting of a random sample of the cohort (n = 124). Exposure information was obtained from telephone interviews, and brain cancer mortality risk estimated by odds ratios. Increased risk of brain cancer was associated with killing chickens, odds ratio (OR) = 5.8 (95% confidence interval, 1.2–28.3); working in a shell-fish farm, OR = 13.0 (95% CI, 1.9–84.2); and eating uncooked fish, OR = 8.2 (95% CI, 1.8–37.0). Decreased risks were observed for chicken pox illness, OR = 0.2 (95% CI, 0.1–0.6), and measles vaccination, OR = 0.2 (95% CI, 0.1–0.6). Killing chickens, an activity associated with the highest occupational exposure to poultry oncogenic viruses, was associated with brain cancer mortality, as were occupational and dietary shellfish exposures. These findings are novel.