Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of CUEDC2 in colorectal cancer with different invasion and migration abilities

Objective To investigate CUE domain containing 2 (CUEDC2) expression in colorectal cancer with different invasion and migration abilities. Methods Fresh colon cancer tissues, obtained from patients with or without lymph node metastasis who were treated at the Department of General Surgery, Chinese People's Liberation Army General Hospital, and SW620 and HT29 colorectal cancer cell lines, were analysed for CUEDC2 expression. Results Real-time polymerase chain reaction showed significantly higher CUEDC2 mRNA levels in colon cancer tissue from patients with (n = 8) versus without (n = 8) lymph node metastasis, and in SW620 versus HT29 cells. Western blots revealed significantly higher CUEDC2 protein levels in colon cancer tissues from patients with versus without lymph node metastasis, and in SW620 versus HT29 cells. Colorectal cancer tissues from patients with lymph node metastasis showed more intense immunohistochemical staining and moderate staining of cell nuclei and cytoplasm versus less intense/weak staining in tissues from patients without lymph node metastasis. Conclusions CUEDC2 is highly expressed in colorectal cancer tissues and colorectal cancer cell lines with high invasion and migration ability. CUEDC2 may be involved in promoting invasion and metastasis in colorectal cancer.
Thyroid stimulating hormone (TSH) autoregulation reduces variation in the TSH response to thyroid hormones

ABSTRACT The physiological functions of Thyroid Stimulating Hormone (TSH) autoregulation, the ultra-short feedback loop inhibition of TSH by TSH itself, have not been determined. In this work we explored the role of TSH autoregulation in thyroid homeostasis. We synthesized the known physiology of autoregulation with theknown physiological relationships between thyroid hormones; in particular between free thyroxine and TSH. We analysed the implications of TSH autoregulation, on the generation of the TSH response to free thyroxine (the ‘TSH curve’), and on the variation inthis response, which might result from variations in hypothalamopituitary or thyroid gland function. Our analysis demonstrated that, in the circumstances of inter-individual and intra-individual variations to hypothalamo-pituitary function TSH autoregulation lessens variation in the TSH curve. This in turn enhances the probability of generating and maintaining a euthyroid free thyroxine value. This contribution of TSH autoregulation to the stabilisation of thyroid physiology offers a logical explanation for the evolutionary selection of this physiological process.
Drosophila Sister-of-Sex-lethal reinforces a male-specific gene expression pattern by controlling Sex-lethal alternative splicing

In Drosophila, female development is governed by a single RNA-binding protein, Sex-lethal (Sxl), that controls the expression of key factors involved in dosage compensation, germline homeostasis and the establishment of female morphology and behaviour. Sxl expression in female flies is maintained by an auto-regulatory, positive feedback loop with Sxl controlling splicing of its own mRNA. Until now, it remained unclear how males prevent accidental triggering of the Sxl expression cascade and protect themselves against runaway protein production. Here, we identify the protein Sister-of-Sex-lethal (Ssx) as an inhibitor of Sxl auto-regulatory splicing. Sxl and Ssx have a comparable RNA-binding specificity and compete for binding to RNA regulatory elements present in the Sxl transcript. In cultured Drosophila cells, Sxl-induced changes to alternative splicing can be reverted by the expression of Ssx. Moreover, in adult male flies ablation of the ssx gene results in a low level of productive Sxl mRNA splicing and Sxl protein production in isolated, clonal cell populations. In sum, this demonstrates that Ssx safeguards male animals against Sxl protein production to reinforce a stable, male-specific gene expression pattern.
A longitudinal study of parental anti-substance-use socialization for early adolescents’ substance-use behaviors

ABSTRACT The present study examines the role of communication in shaping norms and behaviors with significant personal and societal consequences. Based on primary socialization theory and the general theory of family communication, parental anti-substance-use socialization processes were hypothesized to influence early adolescents’ substance-use norms and behaviors. Using longitudinal data (N = 1059), the results revealed that parent-adolescent prevention communication about substance use in the media and parental anti-substance-use injunctive norms were positively associated with early adolescents’ personal anti-substance-use norms, which, in turn, led to decreases in recent alcohol, cigarette, and marijuana use. It was also found that family expressiveness and structural traditionalism positively related to the hypothesized association between parental socialization processes and early adolescents’ norms and behaviors.
Molecular Mechanisms Related to Hormone Inhibition Resistance in Prostate Cancer

Management of metastatic or advanced prostate cancer has acquired several therapeutic approaches that have drastically changed the course of the disease. In particular due to the high sensitivity of prostate cancer cells to hormone depletion, several agents able to inhibit hormone production or binding to nuclear receptor have been evaluated and adopted in clinical practice. However, despite several hormonal treatments being available nowadays for the management of advanced or metastatic prostate cancer, the natural history of the disease leads inexorably to the development of resistance to hormone inhibition. Findings regarding the mechanisms that drive this process are of particular and increasing interest as these are potentially related to the identification of new targetable pathways and to the development of new drugs able to improve our patients’ clinical outcomes.
Genetic control of the mouse HDL proteome defines HDL traits, function, and heterogeneity[S]

HDLs are nanoparticles with more than 80 associated proteins, phospholipids, cholesterol, and cholesteryl esters. The potential inverse relation of HDL to coronary artery disease (CAD) and the effects of HDL on myriad other inflammatory conditions warrant a better understanding of the genetic basis of the HDL proteome. We conducted a comprehensive genetic analysis of the regulation of the proteome of HDL isolated from a panel of 100 diverse inbred strains of mice (the hybrid mouse diversity panel) and examined protein composition and efflux capacity to identify novel factors that affect the HDL proteome. Genetic analysis revealed widely varied HDL protein levels across the strains. Some of this variation was explained by local cis-acting regulation, termed cis-protein quantitative trait loci (QTLs). Variations in apoA-II and apoC-3 affected the abundance of multiple HDL proteins, indicating a coordinated regulation. We identified modules of covarying proteins and defined a protein-protein interaction network that describes the protein composition of the naturally occurring subspecies of HDL in mice. Sterol efflux capacity varied up to 3-fold across the strains, and HDL proteins displayed distinct correlation patterns with macrophage and ABCA1-specific cholesterol efflux capacity and cholesterol exchange, suggesting that subspecies of HDL participate in discrete functions. The baseline and stimulated sterol efflux capacity phenotypes were associated with distinct QTLs with smaller effect size, suggesting a multigenetic regulation. Our results highlight the complexity of HDL particles by revealing the high degree of heterogeneity and intercorrelation, some of which is associated with functional variation, and support the concept that HDL-cholesterol alone is not an accurate measure of HDL’s properties, such as protection against CAD.
Influenza virus inoculum volume is critical to elucidate age‐dependent mortality in mice

The elderly exhibit increased mortality to influenza viral infection for unclear reasons. Mice are frequently used to model how aging impacts disease. Several studies have shown that aged mice exhibit an increased mortality to influenza virus, but two recent studies demonstrated the opposite. These two studies administered the virus intranasally in 20 µL, whereas the other studies used a viral inoculum in at least 30 µL. To determine whether the volume of the inoculum could explain the conflicting reports, we infected young and aged mice via intranasal instillation of 40 µL or 20 µL containing 1 x 104 plaque‐forming units (PFU) of H1N1 influenza virus. We found that intranasal administration of 40 µL but not 20 µL of inoculum resulted in age‐dependent mortality in mice. Compared to aged mice infected with 40 µL inoculum, those infected with 20 µL inoculum showed reduced levels of live virus and IFN‐β in the lung 3 days postinfection. Furthermore, aged mice administered 40 µL of Evans blue intranasally displayed increased dye retention in their bronchoalveolar lavage fluid compared to those administered 20 µL of Evans blue. Our data demonstrate that the inoculating volume of virus is critical for adequate delivery of influenza virus to the lung and thus for efficient infection of aged mice. These findings shed light on discrepant results in the literature regarding aged mice and influenza infection, and establish that mice can be used to examine how aging impacts the response to this biomedically important infection.
Marketing Strategy, Serving Size, and Nutrition Information of Popular Children’s Food Packages in Taiwan

A content analysis was used to investigate the marketing strategies, serving size, and nutrition quality in Taiwan popular children’s snacks and drinks. A total of 361 snacks and 246 drinks were collected. It was found that 38.6% of snacks and 25.3% of drinks were child-targeted (CT) foods, and 78.1% and 85.4% of the snacks and drinks had health and nutrition marketing (HNM). Serving size was significantly positively correlated to calories among different food categories in this study. Only the CT breads, ready-to-eat cereals, and fruit/vegetable juice had smaller serving sizes than did the corresponding non-CT products. These CT products had significantly fewer calories than did the corresponding non-CT products. Approximately 30% of snacks and 18% of drinks had both CT and HNM. Moreover, 82.7% of CT snacks and 100.0% of CT drinks with HNM were high in sugar. About 95% of foods with no added sugar claim were high sugar. CT foods are not necessarily healthier than non-CT foods, even the CT food with HNM. Health professionals should help parents assess the nutrition quality of the popular children’s foods. Further research was needed to investigate the effect of these marketing strategies and serving size on children’s food consumption.
VCAN Canonical Splice Site Mutation is Associated With Vitreoretinal Degeneration and Disrupts an MMP Proteolytic Site

Purpose To gain insight into the pathophysiology of vitreoretinal degeneration, the clinical course of three family members with Versican Vitreoretinopathy (VVR) is described, and a canonical splice site mutation in the gene encoding for versican (VCAN) protein was biochemically analyzed. Methods A retrospective chart review, human eye histopathology, Sanger DNA sequencing, protein structural modeling, and in vitro proteolysis assays were performed. Results The proband (II:1), mother (I:2), and younger sibling (II:2) suffered retinal degeneration with foveal sparing and retinal detachments with proliferative vitreoretinopathy, features that were confirmed on histopathologic analysis. All affected members carried a heterozygous adenine to guanine variant (c.4004-2A>G) predicted to result in exon 8 skipping or the deletion of 13 amino acids at the beginning of the GAGβ chain (VCAN p.1335-1347). This deleted region corresponded to a putative MMP cleavage site, validated using fluorescence resonance energy transfer (FRET)-based proteolysis assays. Proteomic network analysis identified 10 interacting partners in the human vitreous and retina linked to retinal detachment and degeneration. Conclusions VVR causes significant ocular disease, including retinal detachment and retinal dystrophy. The intronic VCAN mutation removes an MMP cleavage site, which alters versican structure and results in abnormal vitreous modeling. Disruption of a versican protein network may underlie clinicopathologic disease features and point to targeted therapies.
Association between asthma and risk of benign prostatic hyperplasia: a retrospective population-based study

Abstract Objective The association between asthma and benign prostatic hyperplasia (BPH) has rarely been explored. We investigated whether male asthmatic patients had an increased risk of BPH by conducting this retrospective nationwide population-based study. Methods We utilized data derived from the National Health Insurance Research Database (NHIRD) in Taiwan. A total of 9778 male patients aged >40 years who were newly diagnosed with asthma between 2000 and 2006 were included in the asthma group. Male enrollees without asthma were selected as the non-asthma group from the same database. Both the groups were followed up until the end of 2013. We performed Cox proportional hazard regression analysis to estimate the risk of BPH and transurethral resection of the prostate (TURP) in the male patients with asthma compared with that in those without asthma. Results The risk of BPH and TURP in the asthma group was 1.40-fold (95% confidence interval [CI] = 1.30–1.42) and 1.30-fold (95% CI= 1.31–1.50) higher than that in the non-asthma group, respectively, after adjusting for comorbidities, relevant medications and number of annual outpatient visits. Conclusions The male patients with asthma were found to have a higher risk of BPH than did those without asthma.
New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity

New analogs of nortopsentin, a natural 2,4-bis(3′-indolyl)imidazole alkaloid, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, and in which a 7-azaindole portion substituted the original indole moiety, were efficiently synthesized. Among all derivatives, prescreened against the HCT-116 colon rectal carcinoma cell line, the two most active compounds were selected and further investigated in different human tumor cells showing IC50 values in the micromolar and submicromolar range. Flow cytometric analysis of propidium iodide-stained MCF-7 cells demonstrated that both the active derivatives caused cell cycle arrest in the G0–G1 phase. The cell death mechanism induced by the compounds was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and observed morphological evaluation using acridine orange/ethidium bromide double staining. Moreover, further tested on intestinal normal-like differentiated Caco-2 cell line, they exhibited preferential toxicity towards cancer cells.
Complementary roles of photoperiod and temperature in environmental sex determination in Daphnia spp.

ABSTRACT Daphnia spp. , a keystone genus in freshwater lentic habitats, are subject to environmental sex determination wherein environmental conditions dictate offspring sex and whether they reproduce asexually or sexually. The introduction of males into a population denotes the first step in the switch from asexual parthenogenetic reproduction to sexual reproduction. We tested the hypothesis that photoperiod and temperature co-regulate male sex determination and that these environmental stimuli would activate elements of the male sex determination signaling cascade. The results revealed that photoperiod was a critical cue in creating permissive conditions for male production. Further, under photoperiod-induced permissive conditions, male sex determination was temperature dependent. The two daphnid species evaluated, Daphnia pulex and Daphnia magna, exhibited different temperature dependencies. Daphnia pulex produced fewer males with increasing temperatures between 16 and 22°C, and D. magna exhibited the opposite trend. We found consistent expression patterns of key genes along the male sex-determining signaling pathway in D. pulex independent of environmental stimuli. mRNA levels for the enzyme responsible for synthesis of the male sex-determining hormone, methyl farnesoate, were elevated early in the reproductive cycle, followed by increased mRNA levels of the methyl farnesoate receptor subunits Met and SRC. Environmental conditions that stimulated male offspring production significantly increased Met mRNA levels. The results indicate that male sex determination in daphnids is under the permissive control of photoperiod and the regulatory control of temperature. Further, these environmental cues may stimulate male sex determination by increasing levels of the Met subunit of the methyl farnesoate receptor. Summary: Male sex determination in daphnids is controlled by photoperiod and temperature, which may act by increasing levels of the Met subunit of the methyl farnesoate receptor.
A study on relationship between metabolic syndrome and colorectal cancer.

PURPOSE To investigate the effects of metabolic syndrome (MS) and its components on the pathological manifestations and metastasis of colorectal cancer (CRC). METHODS Clinical and pathological data of inpatients with CRC admitted to our hospital from January 1st 2010 to December 31st 2017 were collected, including the patients' general information, initial symptoms, previous history, family history, whether MS or related components were complicated, endoscopic description, imaging diagnosis, pathological diagnosis and metastasis. According to the diagnostic criteria of MS, the patients were divided into MS group and non-MS group, and then patients in non-MS group were further grouped based on whether they met MS single component. The clinical and pathological characteristics in each group were analyzed by SPSS 20.0 statistical software. RESULTS Among 1528 CRC patients, 76 (4.9%) were complicated with MS. CRC patients complicated with MS and those complicated with hypertension alone or diabetes alone were diagnosed at higher age, and most of them were elderly (p<0.05). CRC patients with body mass index (BMI) ≥25 kg/m2 were diagnosed at lower age (p<0.05). The infiltration depth of CRC patients with diabetes was higher than that in the non-diabetic group, and it was more likely to invade the whole layer (p<0.05). The locations of CRC lesions in different BMI subgroups, fatty liver and nonfatty liver subgroups had statistically significant differences (p<0.05). In BMI ≥25 kg/m2 group, CRC was mostly located in the left colon and rectum, while it was mostly located in the rectum in CRC patients with fatty liver. CONCLUSION Reducing the occurrence of MS and its components can reduce the incidence of CRC, and reduce its pathological manifestations and affect its metastasis at the same time.
Glucocerebrosidase mutations and synucleinopathies: Toward a model of precision medicine

Glucocerebrosidase is a lysosomal enzyme. The characterization of a direct link between mutations in the gene coding for glucocerebrosidase (GBA1) with the development of Parkinson's disease and dementia with Lewy bodies has heightened interest in this enzyme. Although the mechanisms through which glucocerebrosidase regulates the homeostasis of α‐synuclein remains poorly understood, the identification of reduced glucocerebrosidase activity in the brains of patients with PD and dementia with Lewy bodies has paved the way for the development of novel therapeutic strategies directed at enhancing glucocerebrosidase activity and reducing α‐synuclein burden, thereby slowing down or even preventing neuronal death. Here we reviewed the current literature relating to the mechanisms underlying the cross talk between glucocerebrosidase and α‐synuclein, the GBA1 mutation‐associated clinical phenotypes, and ongoing therapeutic approaches targeting glucocerebrosidase. © 2018 International Parkinson and Movement Disorder Society
Selenium Species: Current Status and Potentials in Cancer Prevention and Therapy

Selenium (Se) acts as an essential trace element in the human body due to its unique biological functions, particularly in the oxidation-reduction system. Although several clinical trials indicated no significant benefit of Se in preventing cancer, researchers reported that some Se species exhibit superior anticancer properties. Therefore, a reassessment of the status of Se and Se compounds is necessary in order to provide clearer insights into the potentiality of Se in cancer prevention and therapy. In this review, we organize relevant forms of Se species based on the three main categories of Se—inorganic, organic, and Se-containing nanoparticles (SeNPs)—and overview their potential functions and applications in oncology. Here, we specifically focus on the SeNPs as they have tremendous potential in oncology and other fields. In general, to make better use of Se compounds in cancer prevention and therapy, extensive further study is still required to understand the underlying mechanisms of the Se compounds.
Influence of Hemodialysis Treatment on Biochemical Markers of Bone Disease

Abstract Introduction. Bone disease is a chronic complication of chronic kidney disease and major clinical problem in hemodialysis (HD) patients. The aim of our study was to assess the influence of treatment longevity on biochemical parameters of mineral and bone metabolism in HD patients, and to identify the most important parameters. Methods. The research was observational and retrospective, involved 70 patients, mean age 58.69±12.54, divided into groups in respect to the duration of dialysis treatment (Group I-5 years, Group II-5-10 years and Group III-over 10 years). Results. Serum phosphorus was increased, but the values tend to increase along with dialysis duration - (Group I: 1.93±0.45; Group II: 1.97±0.50; Group III: 2.01±0.37; p>0,05). Calcium values were also not significantly increased based on the duration of treatment [Group I: 2.3 (2.2-2.41); Group II: 2.46 (2.15-2.6), Group III: 2.35 (2.10-2.52)]. Dialysis and PTH correlated positively in the first group of patients (Rho=0.470, p=0.013). The values of calcium and alkaline phosphatase correlated positively in all patients (Rho=0.351, p=0.003). PTH was significantly higher in the second and third compared to the first group (p=0.009 and p=0.038, respectively), and there was no significant difference between the second and the third group. Interestingly, parathyroidectomized patients had higher PTH values compared to those without parathyroidectomy (557 vs. 359 pg/ml). Conclusion. The most reliable marker for clinical monitoring of bone disease in dialysis patients is PTH. The values of calcium and phosphorus are highly variable and not reliable parameters for bone disease follow-up.
A Facile Electrochemical Sensor Labeled by Ferrocenoyl Cysteine Conjugate for the Detection of Nitrite in Pickle Juice

Simple and facile electrochemical sensors for nitrite detection were fabricated by directly depositing ferrocenoyl cysteine conjugates Fc[CO-Cys(Trt)-OMe]2 [Fc(Cys)2] or Fc[CO-Glu-Cys-Gly-OH] [Fc-ECG] on screen-printed electrodes (SPEs). The modified carbon electrodes were characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Results indicated that Fc-ECG/SPE sensor showed enhanced current response and a lower overpotential than Fc(Cys)2/SPE sensor for nitrite detection. Optimal operating conditions were estimated for nitrite detection by DPV. The concentration of nitrite showed a good linear relationship with the current response in the range of 1.0–50 μmol·L−1 and with 0.3 μmol·L−1 as the concentration for limit of detection. There were no interferences from most common ions. The development of this electrochemical sensor was used for nitrite detection in pickled juice with a R.S. D. lower than 2.1% and average recovery lower than 101.5%, which indicated that disposable electrochemical sensor system can be applied for rapid and precise nitrite detection in foods.