S100A14 Protein Expression in Prostate Cancer Cell Lines

https://digitalcommons.unmc.edu/surp2023/1000/thumbnail.jp

Delineating the role of FANCA in glucose-stimulated insulin secretion in β cells through its protein interactome

Hyperinsulinemia affects 72% of Fanconi anemia (FA) patients and an additional 25% experience lowered glucose tolerance or frank diabetes. The underlying molecular mechanisms contributing to the dysfunction of FA pancreas β cells is unknown. Therefore, we sought to evaluate the functional role of FANCA, the most commonly mutated gene in FA, in glucosestimulated insulin secretion (GSIS). This study reveals that FANCA or FANCB knockdown impairs GSIS in human pancreas β cell line EndoC-βH3. To identify potential pathways by which FANCA might regulate GSIS, we employed a proteomics approach to identify FANCA protein interactions in EndoC-βH3 differentially regulated in response to elevated glucose levels. Glucose-dependent changes in the FANCA interaction network were observed, including increased association with other FA family proteins, suggesting an activation of the DNA damage response in response to elevated glucose levels. Reactive oxygen species increase in response to glucose stimulation and are necessary for GSIS in EndoC-βH3 cells. Glucose-induced activation of the DNA damage response was also observed as an increase in the DNA damage foci marker γ-H2AX and dependent upon the presence of reactive oxygen species. These results illuminate the role of FANCA in GSIS and its protein interactions regulated by glucose stimulation that may explain the prevalence of β cell-specific endocrinopathies in FA patients

Association between diabetes at different diagnostic ages and risk of cancer incidence and mortality: a cohort study

BackgroundDifferent ages for diagnosis of diabetes have diverse effects on risks of cardiovascular disease, dementia, and mortality, but there is little evidence of cancer. This study investigated the relationship between diabetes at different diagnostic ages and risks of cancer incidence and mortality in people aged 37–73 years.MethodsParticipants with diabetes in the UK Biobank prospective cohort were divided into four groups: ≤40, 41–50, 51–60, and >60 years according to age at diagnosis. A total of 26,318 diabetics and 105,272 controls (1:4 randomly selected for each diabetic matched by the same baseline age) were included. We calculated the incidence density, standardized incidence, and mortality rates of cancer. Cox proportional hazard model was used to examine the associations of diabetes at different diagnostic ages with cancer incidence and mortality, followed by subgroup analyses.ResultsCompared to corresponding controls, standardized incidence and mortality rates of overall and digestive system cancers were higher in diabetes diagnosed at age 41–50, 51–60, and >60 years, especially at 51–60 years. Individuals diagnosed with diabetes at different ages were at higher risk to develop site-specific cancers, with a prominently increased risk of liver cancer since the diagnosis age of >40 years. Significantly, participants with diabetes diagnosed at 51–60 years were correlated with various site-specific cancer risks [hazard ratio (HR) for incidence: 1.088–2.416, HR for mortality: 1.276–3.269]. Moreover, for mortality of digestive system cancers, we observed an interaction effect between smoking and diabetes diagnosed at 51–60 years.ConclusionOur findings highlighted that the age at diagnosis of diabetes, especially 51–60 years, was critical risks of cancer incidence and mortality and may represent a potential preventative window for cancer

Up-Converting Nanoparticle-Based Immunochromatographic Strip for Multi-Residue Detection of Three Organophosphorus Pesticides in Food

Organophosphorus (OP) pesticides are widely used to control pests because of their high activity. This study described a rapid and sensitive lateral flow immunochromatographic (LFIC) assay based on up-converting nanoparticles (UCNPs) for multi-residue detection of three OP pesticides. The developed assay integrated novel fluorescent material UCNPs labeled with a broad-specific monoclonal antibody. Based on the competitive platform by immobilized antigen in the test zone, the optimized UCNPs-LFIC assay enabled sensitive detection for parathion, parathion-methyl, and fenitrothion with IC50 of 3.44, 3.98, and 12.49 ng/mL (R2 ≥ 0.9776) within 40 min. The detectable ability ranged from 0.98 to 250 ng/mL. There was no cross-reactivity with fenthion, phoxim, isocarbophos, chlorpyrifos, or triazophos, even at a high concentration of 500 ng/mL. Matrix interference from various agricultural products was also studied in food sample detection. In the spiked test, recoveries of the three OP pesticides ranged from 67 to 120% and relative standard deviations were below 19.54%. These results indicated that the proposed strip assay can be an alternative screening tool for rapid detection of the three OP pesticides in food samples

Profiling of mismatch discrimination in RNAi enabled rational design of allele-specific siRNAs

Silencing specificity is a critical issue in the therapeutic applications of siRNA, particularly in the treatment of single nucleotide polymorphism (SNP) diseases where discrimination against single nucleotide variation is demanded. However, no generally applicable guidelines are available for the design of such allele-specific siRNAs. In this paper, the issue was approached by using a reporter-based assay. With a panel of 20 siRNAs and 240 variously mismatched target reporters, we first demonstrated that the mismatches were discriminated in a position-dependent order, which was however independent of their sequence contexts using position 4th, 12th and 17th as examples. A general model was further built for mismatch discrimination at all positions using 230 additional reporter constructs specifically designed to contain mismatches distributed evenly along the target regions of different siRNAs. This model was successfully employed to design allele-specific siRNAs targeting disease-causing mutations of PIK3CA gene at two SNP sites. Furthermore, conformational distortion of siRNA-target duplex was observed to correlate with the compromise of gene silencing. In summary, these findings could dramatically simplify the design of allele-specific siRNAs and might also provide guide to increase the specificity of therapeutic siRNAs

The Effect of Hepatosteatosis on Response to Antiviral Treatment in Patients with Chronic Hepatitis B: A Meta-Analysis

Background. This study is to systematically analyze the effects of hepatosteatosis on the response to antiviral treatment in patients with chronic hepatitis B (CHB) and hepatosteatosis. Methods. Systematic search was performed in PubMed, Embase, Web of Science, Elsevier, and the Chinese BioMedical literature databases for relevant studies published until February 2016. Treatment outcomes were compared between patients with CHB plus concomitant hepatosteatosis and those without hepatosteatosis. Results. A total of 8 prospective cohort studies (399 patients with CHB plus hepatosteatosis and 688 patients with only CHB) were included. Biochemical and virological response at both 48 and 96 weeks were significantly lower in patients with CHB plus hepatosteatosis as compared to that in patients with only CHB. Subgroup analysis based on methods used for diagnosis of hepatosteatosis and treatment regimens showed that when hepatosteatosis was diagnosed on Doppler ultrasound and treated with nucleotide analogues, patients with CHB plus hepatosteatosis showed lower biochemical (62.7% versus 75.8%, P=0.002) and virological response (66.2% versus 72.3%, P=0.006) as compared to that in patients with CHB. Conclusion. Hepatosteatosis lowers the efficacy of antiviral treatment in patients with CHB, especially when hepatosteatosis was diagnosed on ultrasound findings and treated with nucleotide analogues

Delineating the role of FANCA in glucose-stimulated insulin secretion in β cells through its protein interactome

Hyperinsulinemia affects 72% of Fanconi anemia (FA) patients and an additional 25% experience lowered glucose tolerance or frank diabetes. The underlying molecular mechanisms contributing to the dysfunction of FA pancreas β cells is unknown. Therefore, we sought to evaluate the functional role of FANCA, the most commonly mutated gene in FA, in glucosestimulated insulin secretion (GSIS). This study reveals that FANCA or FANCB knockdown impairs GSIS in human pancreas β cell line EndoC-βH3. To identify potential pathways by which FANCA might regulate GSIS, we employed a proteomics approach to identify FANCA protein interactions in EndoC-βH3 differentially regulated in response to elevated glucose levels. Glucose-dependent changes in the FANCA interaction network were observed, including increased association with other FA family proteins, suggesting an activation of the DNA damage response in response to elevated glucose levels. Reactive oxygen species increase in response to glucose stimulation and are necessary for GSIS in EndoC-βH3 cells. Glucose-induced activation of the DNA damage response was also observed as an increase in the DNA damage foci marker γ-H2AX and dependent upon the presence of reactive oxygen species. These results illuminate the role of FANCA in GSIS and its protein interactions regulated by glucose stimulation that may explain the prevalence of β cell-specific endocrinopathies in FA patients

Low Molecular Weight Organic Acids Increase Cd Accumulation in Sunflowers through Increasing Cd Bioavailability and Reducing Cd Toxicity to Plants

The use of low molecular weight organic acids (LMWOAs) for the phytoremediation of heavy metals has become a promising technique. We chose five kinds of organic acids (oxalic acid (OA), acetic acid (AA), tartaric acid (TA), malic acid (MA), and citric acid (CA)) with six application rates (1, 2, 3, 4, 5, and 6 mmol/kg) and planted sunflowers (Helianthus annuus L.) in Cd-polluted soil to study the efficiency of the phytoremediation of Cd and the degree of Cd toxicity to plants. Treatment with no acid application served as the control (CK). We analyzed the plant height dry matter and the Cd and nonprotein sulfhydryl (NPT) contents in the soil and plant tissues. OA, AA, TA, MA, and CA increased plant heights by 17.6–47.40%, 21.25–39.17%, 12.5–35.52, 5.10–30.50%, and 16.15–49.17%, respectively; shoot biomass of the sunflowers was increased except with MA. NPT decreased under LMWOA application, which, in the roots, increased with the increase in root Cd under LMWOA treatment; however, there was no obvious relationship in the stems and leaves. The composition of Cd in the soil changed significantly under the LMWOA treatments compared to the CK, and the changes in carbonate Cd and Fe-Mn oxide Cd were the most prominent. The plant Cd accumulation of OA, AA, TA, MA, and CA increased by 43.31%, 55.25%, 48.69%, 0.52%, and 32.94%, respectively, and the increase in root Cd content and shoot dry matter quality promoted the increase in Cd accumulation. The LMWOAs were more likely to affect the phytoremediation of Cd by changing total P (TP) rather than total N (TN)

The electronic structure and elastic properties of Ca doped Ti

The lattice parameters, formation energy and electronic structure as well as elastic property and Debye temperature of Ca-doped Ti2Ni alloy have been calculated. The results show that the structural stability of Ca replacing the Ti atomic site is more stable than that of Ca replacing the Ni atom. This is consistent with the calculated energy band structure and electronic density of the state. The elastic properties approximated by Voigt–Reuss–Hill formulae show that the ratio of bulk modulus to shear modulus and Poisson’s ratio of Ca replacing Ni system are greater than that of Ca replacing Ti system, the interstitial doping system and the pure Ti2Ni alloy, implying that Ca replacing Ni is more malleable and the ductility of Ti2Ni alloy can be tailored by Ca doping. The hardness and Debye temperature also indicate that both ratios of Ca replacing Ti system are higher than that of Ca replacing Ni system