In vitro anti-diabetic effect of flavonoids and pheophytins from Allophylus cominia Sw. on the glucose uptake assays by HepG2, L6, 3T3-L1 and fat accumulation in 3T3-L1 adipocytes

BACKGROUND AND PURPOSE: Based on ethno-botanical information collected from diabetic patients in Cuba and firstly reported inhibition of PTP1B and DPPIV enzymes activities, Allophylus cominia (A. cominia) was identified as possible source of new drugs that could be used for the treatment of type 2 diabetes mellitus (T2-DM). EXPERIMENTAL APPROACH: in this study, the activity of the characterised extracts from A. cominia was tested on the glucose uptake using HepG2 and L6 cells, 3T3-L1 fibroblasts and adipocytes as well as their effect on the fat accumulation using 3T3-L1 adipocytes. KEY RESULTS: on 2-NBDG glucose uptake assay using HepG2 and L6 cells, extracts from A. cominia enhanced insulin activity by increasing glucose uptake. On HepG2 cells Insulin EC50 of 93 ± 21nM decreased to 13 ± 2nM in the presence of the flavonoids mixture from A.cominia. In L6 cells, insulin also produced a concentration-dependent increase with an EC50 of 28.6 ± 0.7nM; EC50 decreased to 0.08 ± 0.02nM and 5 ± 0.9nM in the presence of 100μg/ml of flavonoids and pheophytins mixtures, respectively. In 3T3-L1 fibroblasts, insulin had an EC50 of >1000nM that decreased to 38 ± 4nM in the presence of the flavonoids extract. However, in adipocytes, insulin produced a significant concentration-dependent increase and an EC50 of 30 ± 8nM was a further confirmation of the insulin responsiveness of the adipocytes to the insulin. At 100µg/ml, flavonoids and pheophytins extracts decreased fat accumulation in 3T3-L1 adipocytes by two folds in comparison to the control differentiated cells (p<0.05). The crude extract of A. cominia did not show any enhancement of 2-NBDG uptake by 3T3-L1 adipocytes in the presence or absence of 100nM insulin. In addition, in fully differentiated adipocytes, both extracts produced significant decrease in lipid droplets in the cells and no lipid accumulation were seen after withdrawal of the extracts from the cell growth medium. However, there was no effect of both extracts on total protein concentration in cells as well as on Glut-4 transporters. CONCLUSIONS AND IMPLICATIONS: the pharmacological effects of the extracts from A. cominia observed in experimental diabetic models were shown in this study. A. cominia is potentially a new candidate for the treatment and management of T2-DM

In vitro anti-diabetic activity of flavonoids and pheophytins from Allophylus cominia Sw . on PTP1B, DPPIV, alpha-glucosidase and alpha-amylase enzymes

BACKGROUND: Ethno-botanical information from diabetic patients in Cuba led to the identification of Allophylus cominia as a possible source of new drugs for the treatment of type 2 diabetes mellitus (T2-DM). EXPERIMENTAL: Chemical characterization of the extracts from A. cominia was carried out using chromatographic and spectroscopic methods. The extracts were tested for their activity on PTP1B, DPPIV, α-glucosidase enzymes and α-amylase. RESULTS: The flavonoid rich fractions from A. cominia inhibited DPPIV enzyme (75.3±2.33%) at 30µg/ml and produced a concentration-dependent inhibition against DPPIV with a Ki value of 2.6µg/ml. At 30µg/ml, flavonoids and pheophytins extracts significantly inhibited PTP1B enzyme (100±2.6% and 68±1% respectively). The flavonoids, pheophytin A and pheophytin B fractions showed significant concentration-dependent inhibition against PTP1B with Ki values of 3µg/ml, 0.64µg/ml and 0.88µg/ml respectively. At 30µg/ml, the flavonoid fraction significantly inhibited α-glucosidase enzyme (86±0.3%) in a concentration-dependent pattern with a Ki value of 2µg/ml. None of the fractions showed significant effects on α-amylase. Fatty acids, tannins, pheophytins A and B, and a mixture of flavonoids were detected in the methanolic extract from A. cominia. The identified flavonoids were mearnsitrin, quercitrin, quercetin-3-alloside, and naringenin-7-glucoside. CONCLUSION: The pharmacological effects of the extracts from A. cominia earlier observed in experimental diabetic models was confirmed in this study. Thus a new drug or formulation for the treatment of T2-DM could be developed from A. cominia

Coulomb Gauge QCD, Confinement, and the Constituent Representation

Quark confinement and the genesis of the constituent quark model are examined in nonperturbative QCD in Coulomb gauge. We employ a self-consistent method to construct a quasiparticle basis and to determine the quasiparticle interaction. The results agree remarkably well with lattice computations. They also illustrate the mechanism by which confinement and constituent quarks emerge, provide support for the Gribov-Zwanziger confinement scenario, clarify several perplexing issues in the constituent quark model, and permit the construction of an improved model of low energy QCD.Comment: 43 pages, 14 figures, revtex, uses psfig.st

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Searches for electroweak neutralino and chargino production in channels with Higgs, Z, and W bosons in pp collisions at 8 TeV

Searches for supersymmetry (SUSY) are presented based on the electroweak pair production of neutralinos and charginos, leading to decay channels with Higgs, Z, and W bosons and undetected lightest SUSY particles (LSPs). The data sample corresponds to an integrated luminosity of about 19.5 fb(-1) of proton-proton collisions at a center-of-mass energy of 8 TeV collected in 2012 with the CMS detector at the LHC. The main emphasis is neutralino pair production in which each neutralino decays either to a Higgs boson (h) and an LSP or to a Z boson and an LSP, leading to hh, hZ, and ZZ states with missing transverse energy (E-T(miss)). A second aspect is chargino-neutralino pair production, leading to hW states with E-T(miss). The decays of a Higgs boson to a bottom-quark pair, to a photon pair, and to final states with leptons are considered in conjunction with hadronic and leptonic decay modes of the Z and W bosons. No evidence is found for supersymmetric particles, and 95% confidence level upper limits are evaluated for the respective pair production cross sections and for neutralino and chargino mass values

A vicious cycle: employment challenges associated with diabetes foot ulcers in an economically marginalized Southwest US sample

Aim: To describe patients’ reported employment challenges associated with diabetic foot ulcers (DFUs). Methods: Fifteen patients from under-resourced communities in Southern Arizona, with a history of DFUs and/or amputations, were recruited from a tertiary referral center from June 2020 to February 2021. Participants consented to an audio-recorded semi-structured phone interview. Interviews were transcribed and thematically analyzed using the Dedoose data analysis platform. Results: Participants shared a common theme around the cyclic challenges of DFU prevention/management and employment. Those employed in manual labor-intensive jobs or jobs requiring them to be on their feet for long durations of time believed working conditions contributed to the development of their DFUs. Patients reported work incapacity due to declines in mobility and the need to offload for DFU management. Many expressed frustration and emotional distress related to these challenges noting that DFUs resulted in lower remuneration as medical expenses increased. Consequently, loss of income and/or medical insurance often hindered participants’ ability to manage DFUs and subsequent complications. Conclusion: These data illuminate the vicious cycle of DFU and employment challenges that must be addressed through patient-centered prevention strategies. Healthcare providers should consider a person’s contextual factors such as employment type to tailor treatment approaches. Employers should establish inclusive policies that support patients with DFUs returning to work through flexible working hours and adapted work tasks as needed. Policymakers can also mitigate employment challenges by implementing social programs that provide resources for employees who are unable to return to work in their former capacity. Copyright © 2023 Palmer, Crocker, Marrero and Tan.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Rates of Diabetes-Related Major Amputations among Racial and Ethnic Minority Adults Following Medicaid Expansion under the Patient Protection and Affordable Care Act

Importance: It is not known whether implementation of Medicaid expansion under the Patient Protection and Affordable Care Act (ACA) was associated with improvements in the outcomes among racial and ethnic minority adults at risk of diabetes-related major amputations. Objective: To explore the association of early Medicaid expansion with outcomes of diabetic foot ulcerations (DFUs). Design, Setting, and Participants: This cohort study included hospitalizations for DFUs among African American, Asian and Pacific Islander, American Indian or Alaska Native, and Hispanic adults as well as adults with another minority racial or ethnic identification aged 20 to 64 years. Data were collected from the State Inpatient Databases for 19 states and the District of Columbia for 2013 to the third quarter of 2015. The analysis was performed on December 4, 2019, and updated on November 9, 2021. Exposures: States were categorized into early-adopter states (expansion by January 2014) and nonadopter states. Main Outcomes and Measures: Poisson regression was performed to examine the associations of state type, time, and their combined association with the proportional changes of major amputation rate per year per 100000 population. Results: Among the 115071 hospitalizations among racial and ethnic minority adults with DFUs (64% of sample aged 50 to 64 years; 35%, female; 61%, African American; 25%, Hispanic; 14%, other racial and ethnic minority group), there were 36829 hospitalizations (32%) for Medicaid beneficiaries and 10500 hospitalizations (9%) for uninsured patients. Hospitalizations increased 3% (95% CI, 1% to 5%) in early-adopter states and increased 8% (95% CI, 6% to 10%) in nonadopter states after expansion, a significant difference (P for interaction <.001). Although there was no change in the amputation rate (0.08%; 95% CI, -6% to 7%) in early-adopter states after expansion, there was a 9% (95% CI, 3% to 16%) increase in nonadopter states, a significant change (P =.04). For uninsured adults, the amputation rate decreased 33% (95% CI, 10% to 50%) in early-adopter states and did not change (12%; 95% CI, -10% to 38%) in nonadopter states after expansion, a significant difference (P =.006). There was no difference in the change of amputation rate among Medicaid beneficiaries between state types after expansion. Conclusions and Relevance: This study found a relative improvement in the major amputation rate among African American, Hispanic, and other racial and ethnic minority adults in early-expansion states compared with nonexpansion states, which could be because of the recruitment of at-risk uninsured adults into the Medicaid program during the first 2 years of ACA implementation. Future study is required to evaluate the long-term association of Medicaid expansion and the rates of amputation.. © 2022 American Medical Association. All rights reserved.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Dataset on the kinetics of the inhibition of PTP1B by the flavonoids and pheophytin A from Allophylus cominia

The data presented in this article are related to the research article under the title “in vitro anti-diabetic activity of flavonoids and pheophytins from Allophylus cominia Sw. on PTP1B, DPPIV, alpha-glucosidase and alpha-amylase enzymes” (Semaan et al., 2017) [3]. This article defines the kinetics of inhibition of flavonoids and pheophytin A extracts from A. cominia which showed an inhibition of the PTP1B enzyme activity. The main reason to make these results public is to confirm that this study was followed up and no more experiments are needed, also to confirm that these compounds can be reported as PTP1B inhibitors. Keywords: Flavonoids, Pheophytin, Inhibition, Kinetics, PTP1B enzym