Predictors of mastectomy in breast cancer patients with complete remission of primary tumor after neoadjuvant therapy: A retrospective study.

INTRODUCTION: Neoadjuvant therapy (NAT) should increase the rate of breast-conserving surgery (BCS) in non-metastatic breast cancer (BC) patients, especially in those achieving tumor shrinkage. Still, the conversion from a pre-planned mastectomy to BCS in patients responding to NAT is not a widespread standard. We aimed to identify factors influencing surgical choices in this setting. MATERIALS AND METHODS: We retrospectively collected data of BC patients with complete remission of primitive tumor (ypT0) after NAT, treated with BCS or mastectomy in two Italian breast units. Predictors of mastectomy were explored using logistic regression. Distant recurrence and event-free survival were assessed in the BCS and mastectomy cohort. RESULTS: 243 patients were included, 147 (60.5 %) treated with BCS and 96 (39.5 %) treated with mastectomy. In the mastectomy group, there were more centrally-located, multiple and larger tumors. At univariate regression analysis, central location, baseline tumor extension on ultrasound (US) and magnetic resonance imaging (MRI), multiple foci and clinical stage were significantly associated with the chance of receiving mastectomy. At multivariate analysis, only baseline focality on US and extension on MRI retained significance as predictors of mastectomy. Distant recurrence and event-free survival were significantly longer in patients undergoing BCS. CONCLUSION: Baseline tumor extension and focality were the main predictors of mastectomy in patients with ypT0 after NAT. However, BCS did not negatively affect survival outcomes in our cohort. An effort should be made to avoid potentially unnecessary mastectomy in this population, aiming at minimizing surgery-associated toxicities and improving patients' quality of life.

Antioxidant Scavenging of the Superoxide Radical by Yerba Mate (Ilex paraguariensis) and Black Tea (Camellia sinensis) Plus Caffeic and Chlorogenic Acids, as Shown via DFT and Hydrodynamic Voltammetry.

We describe the antioxidant capability of scavenging the superoxide radical of several tea and yerba mate samples using rotating ring-disk electrochemistry (RRDE). We directly measured superoxide concentrations and detected their decrease upon the addition of an antioxidant to the electrochemical cell. We studied two varieties of yerba mate, two varieties of black tea from Bangladesh, a sample of Pu-erh tea from China, and two components, caffeic acid and chlorogenic acid. All of these plant infusions and components showed strong antioxidant activities, virtually annihilating the available superoxide concentration. Using density functional theory (DFT) calculations, we describe a mechanism of superoxide scavenging via caffeic and chlorogenic acids. Superoxide can initially interact at two sites in these acids: the H4 catechol hydrogen (a) or the acidic proton of the acid (b). For (a), caffeic acid needs an additional π-π superoxide radical, which transfers electron density to the ring and forms a HO2- anion. A second caffeic acid proton and HO2- anion forms H2O2. Chlorogenic acid acts differently, as the initial approach of superoxide to the catechol moiety (a) is enough to form the HO2- anion. After an additional acidic proton of chlorogenic acid is given to HO2-, three well-separated compounds arise: (1) a carboxylate moiety, (2) H2O2, and a (3) chlorogenic acid semiquinone. The latter can capture a second superoxide in a π-π manner, which remains trapped due to the aromatic ring, as for caffeic acid. With enough of both acids and superoxide radicals, the final products are equivalent: H2O2 plus a complex of the type [X-acid-η-O2], X = caffeic, chlorogenic. Chlorogenic acid (b) is described by the following reaction: 2 O2•- + 2 chlorogenic acid → 2 chlorogenic carboxylate + O2 + H2O2, and so, it acts as a non-enzymatic superoxide dismutase (SOD) mimic, as shown via the product formation of O2 plus H2O2, which is limited due to chlorogenic acid consumption. Caffeic acid (b) differs from chlorogenic acid, as there is no acidic proton capture via superoxide. In this case, approaching a second superoxide to the H4 polyphenol moiety forms a HO2- anion and, later, an H2O2 molecule upon the transfer of a second caffeic acid proton.

Parp-inhibitors in the therapeutic landscape of breast cancer patients with BRCA1 and BRCA2 pathogenic germline variants: An Italian consensus paper and critical review.

The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved medications and those with proven efficacy. This study utilized the Delphi method to present the first Italian consensus regarding genetic testing, the use of PARP inhibitors in both early and metastatic settings, and strategies for managing the potential toxicity of these novel drugs. The Panel unanimously agreed on various issues, including the timing, techniques, and patient characteristics for BRCA1/2 genetic testing, andthe appropriate placement of PARP inhibitors in the treatment algorithm for both early and advanced breast cancer. Nevertheless, some areas of divergence became evident, particularly regarding the use of axillary surgery for therapeutic purposes and the application of hormone replacement therapy in cases of bilateral mastectomy and risk-reducing salpingo-oophorectomy for patients treated for triple negative breast cancer. Additional research is needed in these particular domains to improve the care of patients with breast cancer who bear an increased genetic risk.

BRCA Testing for Patients Treated in Italy: A National Survey of Breast Centers Associated with Senonetwork.

BACKGROUND: Breast units (BUs) provide breast cancer (BC) care, including prevention, treatment, and genetic assessment. Genetic research has highlighted BRCA1/2 mutations as key hereditary BC risk factors. BRCA testing is crucial for personalized treatment and prevention strategies. However, the integration of BRCA testing in Italian BUs faces multiple challenges. This study, by Senonetwork Italia, aimed to evaluate genetic testing practices and identify obstacles within Italian BUs. METHODS: Senonetwork Italia conducted a 16-question web-based survey involving 153 BUs. The survey assessed aspects of BRCA testing, including timing, urgency, counseling, patient selection, and multi-gene panels. RESULTS: Of the 153 BUs, 109 (71.2%) responded. Testing before surgery was performed by 70.6% of centers, with urgent cases acknowledged by 87.2%. Most centers (56.0%) arranged urgent pre-test counseling within a week. BRCA mutation status influenced treatment decisions in 99.1% of cases. Multi-gene panels were used by 33.0% of centers for all genetic counseling cases, while 56.0% followed standard referral criteria. The main challenges included cost, reimbursement, and reporting timelines. CONCLUSIONS: This survey highlights significant variations in BRCA testing practices across Italian BUs and identifies key logistical and financial challenges. There is a need for standardized practices of genetic testing to ensure personalized and effective BC management in Italy.

Molecular Interactions and Mechanisms of COVID-19 Inhibition 2.0.

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Breakthrough Acute HIV Infections among Pre-Exposure Prophylaxis Users with High Adherence: A Narrative Review.

Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular focus on users with high adherence to PrEP. We searched the main databases (PubMed, Embase, and Scopus) with the keywords "PrEP" or "Pre-Exposure Prophylaxis" and "HIV" or "PLWH" and "breakthrough" or "acute infection" or "primary infection". We included all randomized clinical trials and non-experimental studies (both case reports and observational studies) ever published. In the present narrative review, we revise the diagnostic challenges related to HIV diagnosis in the setting of PrEP and the clinical characteristics and symptoms of breakthrough infections. We discuss the management of acute HIV infection during PrEP and the new challenges that arise from the use of long-acting drugs for PrEP. Our review underlines that although extremely rare, HIV seroconversions are still possible during PrEP, even in a context of high adherence. Efforts to promptly identify these events must be included in the PrEP follow-up in order to minimize the chance of overlooked HIV breakthrough infections and thus exposure to suboptimal concentrations of antiretrovirals.

Third national surgical consensus conference of the Italian Association of Breast Surgeons (ANISC) on management after neoadjuvant chemotherapy: The difficulty in reaching a consensus.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) has a profound impact on surgical management of breast cancer. For this reason, the Italian Association of Breast Surgeons (ANISC) promoted the third national Consensus Conference on this subject, open to multidisciplinary specialists. MATERIALS AND METHODS: The Consensus Conference was held on-line in November 2022, and after an introductory session with five core-team experts, participants were asked to vote on eleven controversial issues, while results were collected in real-time with a polling system. RESULTS: A total of 164 dedicated specialists from 74 Breast Centers participated. Consensus was reached for only three of the eleven issues, including: 1) the indication to assess the response with Magnetic Resonance Imaging (79 %); 2) the need to re-assess the biological factors of the residual tumor if present (96 %); 3) the possibility of omitting a formal axillary node dissection for cN1 patients if a pathologic Complete Response (pCR) was confirmed with analysis of one or more sentinel lymph nodes (82 %). The majority voted in favor of mapping both the breast and nodal lesions pre-NAC (59 %), and against the omission of sentinel lymph node biopsy in cN0 patients in the case of pathologic or clinical Complete Response (69 %). In cases of cT3/cN1+ tumors with pCR, only 8 % of participants considered appropriate the omission of Post-Mastectomy Radiation Therapy. CONCLUSION: There is still a wide variability in surgical approaches after NAC in the "real world". As NAC is increasingly used, multidisciplinary teams should be attuned to conforming their procedures to the rapid advances in this field.

Easy Anthropometric Measurements Are Representative of Baseline Values of Breast Q Values in Asymptomatic Women.

BACKGROUND: Measurements of breast morphology are a determinant of the assessment of any surgical procedure, either reconstructive or cosmetic. This study aims to investigate the association between easy anthropometric measurements and values of quality of life assessed in a sample of asymptomatic women. METHODOLOGY: Healthy asymptomatic women were admitted for this study. The following measurements were assessed: height, weight, nipple to sternal notch distance, areola to infra-mammary fold distance (right vs. left), right-left nipple distance. The Breast Q questionnaire (Italian translation V.1, pre-op breast conservation surgery) in the following domains: satisfaction with breasts; psycho-social satisfaction; physical satisfaction; sexual satisfaction, which was used to assess breast-related quality of life. RESULTS: One hundred and forty-five women responded to the breast Q questionnaire. The mean age of the sample was 44.3 years; the medium BMI was 24.1; Spearman correlation coefficients revealed that all the investigated values were negatively correlated to the "satisfaction with breasts" domain. Psychosexual satisfaction was associated with age; BMI; nipple to sternal notch distance. After normalization for age values, we observed that "satisfaction with breast" was, once again, highly correlated to BMI; nipple to sternal notch distance; areola to IMF distance. In all cases, the higher the values, the lower the scores. CONCLUSIONS: Distances between easy relevant anatomical landmarks are representative of patients' breast-related quality of life in a population of asymptomatic women. These findings allow us to identify an ideal anthropometric framework that can be used as a validated surgical endpoint for cosmetic and oncological procedures.

Is routine axillary lymph node dissection needed to tailor systemic treatments for breast cancer patients in the era of molecular oncology? A position paper of the Italian National Association of Breast Surgeons (ANISC).

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) management began when sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as standard of care in patients with node-negative BC. The second step consolidated ALND omission in selected subgroups of BC patients with up to two macrometastases and recognized BC molecular and genomic implication in predicting prognosis and planning adjuvant treatment. Outcomes from the recent RxPONDER and monarchE trials have come to challenge the previous cut-off of two SLN in order to inform decisions on systemic therapies for hormone receptor-positive (HR+), human epidermal growth factor receptor type-2 (HER2) negative BC, as the criteria included a cut-off of respectively three and four SLNs. In view of the controversy that this may lift in surgical practice, the Italian National Association of Breast Surgeons (Associazione Nazionale Italiana Senologi Chirurghi, ANISC) reviewed data regarding the latest trials on this topic and proposes an implementation in clinical practice. MATERIAL AND METHODS: We reviewed the available literature offering data on the pathological nodal status of cN0 breast cancer patients. RESULTS: The rates of pN2 status in cN0 patients ranges from 3.5 % to 16 %; pre-surgical diagnostic definition of axillary lymph node status in cN0 patients by ultrasound could be useful to inform about a possible involvement of ≥4 lymph nodes in this specific sub-groups of women. CONCLUSIONS: The Italian National Association of Breast Surgeons (ANISC) considers that for HR + HER2-/cN0-pN1(sn) BC patients undergoing breast conserving treatment the preoperative workup should be optimized for a more detailed assessment of the axilla and the technique of SLNB should be optimized, if considered appropriate by the surgeon, not considering routine ALND always indicated to determine treatment recommendations according to criteria of eligibility to RxPONDER and monarch-E trials.

One-Stage Implant-Based Breast Reconstruction With Polyurethane-Coated Device: Standardized Assessment of Outcomes.

BACKGROUND: Nipple-sparing mastectomies (NSMs) and implant-based breast reconstructions have evolved from 2-stage reconstructions with tissue expansion and implant exchange to direct-to-implant procedures. In this study, we tested safety and efficacy of polyurethane-based implants according to standard assessment tools. OBJECTIVES: This study aimed to test safety and feasibility of polyurethane-coated implants with standardized assessment employing internationally acknowledged evaluation criteria. METHODS: Cases of NSMs followed by breast reconstruction in 1 stage with immediate prepectoral polyurethane-coated implant placement were retrospectively reviewed. Preoperative characteristics of the population have been collected. Adherence to quality assurance criteria of the Association of Breast Surgery-British Association of Plastic Reconstructive and Aesthetic Surgeons was verified. Complications were assessed with the Clavien Dindo classification, modified for the breast. Rippling, implant rotation, and malposition were also evaluated. RESULTS: Sixty-three consecutive patients underwent 74 NSMs and immediate breast reconstruction with micro polyurethane foam-coated anatomic implants. In 5 cases we had unplanned readmissions with return to the operating room under general anesthesia (6.7%) and implant loss within 3 months from breast reconstruction (5 implants, 6.7%). Postoperative complications according to Clavien Dindo were grade 1 in 6 cases (8.1%), grade 2 in 3 cases (4%), and 3b in 5 cases (6.7%). CONCLUSIONS: Polyurethane-coated implants may prevent rotation and malposition and capsular contracture in the short term. Unplanned readmission rates and implant loss rates in the short term may be slightly higher.See the abstract translated into Hindi, Portuguese, Korean, German, Italian, Arabic, Chinese, and Taiwanese online here: https://doi.org/10.1093/asj/sjad301.

Ruthenium(II)-Arene Curcuminoid Complexes as Photosensitizer Agents for Antineoplastic and Antimicrobial Photodynamic Therapy: In Vitro and In Vivo Insights.

Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical-physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising.

Azadiradione, a Component of Neem Oil, Behaves as a Superoxide Dismutase Mimic When Scavenging the Superoxide Radical, as Shown Using DFT and Hydrodynamic Voltammetry.

The neem tree, Azadirachta indica, belongs to the Meliaceae family, and its use in the treatment of medical disorders from ancient times to the present in the traditional medical practices of Asia, Africa and the Middle East is well-documented. Neem oil, extracted from the seeds of the fruit, is widely used, with promising medicinal benefits. Azadiradione, a principal antioxidant component of the seeds of A. indica, is known to reduce oxidative stress and has anti-inflammatory effects. To directly measure the antioxidant ability of neem oil, we used Rotating Ring Disk Electrode (RRDE) hydrodynamic voltammetry to quantify how it can scavenge superoxide radical anions. The results of these experiments show that neem oil is approximately 26 times stronger than other natural products, such as olive oil, propolis and black seed oil, which were previously measured using this method. Next, computational Density Functional Theory (DFT) methods were used to arrive at a mechanism for the scavenging of superoxide radical anions with azadiradione. Our work indicates that azadiradione is an effective antioxidant and, according to our DFT study, its scavenging of the superoxide radical anion occurs through a reaction mechanism in which azadiradione mimics the antioxidant action of superoxide dismutase (SOD). In this mechanism, analogous to the SOD enzymatic reaction, azadiradione is regenerated, along with the production of two products: hydrogen peroxide and molecular oxygen. This antioxidant process provides an explanation for azadiradione's more general and protective biochemical effects.

Natural Language Processing to Extract Meaningful Information from a Corpus of Written Knowledge in Breast Cancer: Transforming Books into Data.

Introduction: Books and papers are the most relevant source of theoretical knowledge for medical education. New technologies of artificial intelligence can be designed to assist in selected educational tasks, such as reading a corpus made up of multiple documents and extracting relevant information in a quantitative way. Methods: Thirty experts were selected transparently using an online public call on the website of the sponsor organization and on its social media. Six books edited or co-edited by members of this panel containing a general knowledge of breast cancer or specific surgical knowledge have been acquired. This collection was used by a team of computer scientists to train an artificial neural network based on a technique called Word2Vec. Results: The corpus of six books contained about 2.2 billion words for 300d vectors. A few tests were performed. We evaluated cosine similarity between different words. Discussion: This work represents an initial attempt to derive formal information from textual corpus. It can be used to perform an augmented reading of the corpus of knowledge available in books and papers as part of a discipline. This can generate new hypothesis and provide an actual estimate of their association within the expert opinions. Word embedding can also be a good tool when used in accruing narrative information from clinical notes, reports, etc., and produce prediction about outcomes. More work is expected in this promising field to generate "real-world evidence."

Maytenus octogona Superoxide Scavenging and Anti-Inflammatory Caspase-1 Inhibition Study Using Cyclic Voltammetry and Computational Docking Techniques.

The relationship between oxidative stress and inflammation is well known, and exogenous antioxidants, primarily phytochemical natural products, may assist the body's endogenous defense systems in preventing diseases due to excessive inflammation. In this study, we evaluated the antioxidant properties of ethnomedicines from Peru that exhibit anti-inflammatory activity by measuring the superoxide scavenging activity of ethanol extracts of Maytenus octogona aerial parts using hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). The chemical compositions of these extracts are known and the interactions of three methide-quinone compounds found in Maytenus octogona with caspase-1 were analyzed using computational docking studies. Caspase-1 is a critical enzyme triggered during the activation of the inflammasome and its actions are associated with excessive release of cytokines. The most important amino acid involved in active site caspase-1 inhibition is Arg341 and, through docking calculations, we see that this amino acid is stabilized by interactions with the three potential methide-quinone Maytenus octogona inhibitors, hydroxytingenone, tingenone, and pristimerin. These findings were also confirmed after more rigorous molecular dynamics calculations. It is worth noting that, in these three compounds, the methide-quinone carbonyl oxygen is the preferred hydrogen bond acceptor site, although tingenone's other carbonyl group also shows a similar binding energy preference. The results of these calculations and cyclovoltammetry studies support the effectiveness and use of anti-inflammatory ethnopharmacological ethanol extract of Maytenus octogona (L'Héritier) DC.

Thoraco-dorsal artery perforator flap for totally autologous primary breast reconstruction. Assessment of feasibility with standard reporting scales.

This study reports on feasibility and applicability of totally autologous primary breast reconstructions based on TDAP flaps using a standard set of internationally approved reporting scales. We reviewed 15 cases in patients with a good donor area in the back not suitable for implant or free flaps reconstructions. Complications according to Clavien Dindo were: 1 Grade 1 (seroma in the back). The ABS-BAPRAS quality assurance indicators 10, 11, and 12 were entirely fulfilled. No pedicled flap loss occurred; no unplanned return to theatre and no unplanned readmission within 3 months. Breast-related quality of life values are reported at 3 months and one year in four domains of the BREAST Q v. 2.0 (breast reconstruction post-op questionnaire). At 1 year the mean Q-score for satisfaction with breast was 70.5, for psychosocial well-being was 72.3; for sexual well-being was 58.8; for physical well-being (chest wall) was 70.60. The TDAP based totally autologous breast reconstruction reported to be a feasible and safe alternative to implant based or free flaps reconstructions according to consolidate international outcome reporting measures.

Antioxidant Properties of Thymoquinone, Thymohydroquinone and Black Cumin (Nigella sativa L.) Seed Oil: Scavenging of Superoxide Radical Studied Using Cyclic Voltammetry, DFT and Single Crystal X-ray Diffraction.

Black cumin seeds and seed oil have long been used in traditional foods and medicine in South Asian, Middle Eastern and Mediterranean countries and are valuable flavor ingredients. An important ingredient of black cumin is the small molecule thymoquinone (TQ), which manifests low toxicity and potential therapeutic activity against a wide number of diseases including diabetes, cancer and neurodegenerative disorders. In this study, the antioxidant activities of black seed oil, TQ and a related molecule found in black cumin, thymohydroquinone (THQ), were measured using a direct electrochemical method to experimentally evaluate their superoxide scavenging action. TQ and the black seed oil showed good superoxide scavenging ability, while THQ did not. Density Functional Theory (DFT) computational methods were applied to arrive at a chemical mechanism describing these results, and confirmed the experimental Rotating Ring Disk Electrode (RRDE) findings that superoxide oxidation to O2 by TQ is feasible, in contrast with THQ, which does not scavenge superoxide. Additionally, a thorough inquiry into the unusual cyclic voltammetry pattern exhibited by TQ was studied and was associated with formation of a 1:1 TQ-superoxide radical species, [TQ-O2]-•. DFT calculations reveal this radical species to be involved in the π-π mechanism describing TQ reactivity with superoxide. The crystal structures of TQ and THQ were analyzed, and the experimental data reveal the presence of stacking intermolecular interactions that can be associated with formation of the radical species, [TQ-O2]-•. All three of these methods were essential for us to arrive at a chemical mechanism that explains TQ antioxidant activity, that incorporates intermolecular features found in the crystal structure and which correlates with the measured superoxide scavenging activity.

Echolocation clicks of free-ranging Indo-Pacific finless porpoises (Neophocaena phocaenoides) in Hainan waters.

The echolocation clicks of free-ranging Indo-Pacific finless porpoises (IPFPs, Neophocaena phocaenoides) have been rarely studied in the wild. This paper aims at describing the echolocation-click characteristics of IPFPs and examining whether IPFPs adapt their sonar system to the habitats in Hainan waters, China. The echolocation clicks were recorded using a 13 elements star-shaped array of hydrophones. A total of 65 on-axis clicks were identified and analyzed. IPFPs use echolocation clicks with a source level (SL) of 158 ± 9 dB re: 1 µPa peak-peak, mean peak, and centroid frequency of 134 ± 3 kHz, -3 dB bandwidth of 14 ± 2 kHz and produce at inter-click intervals of 104 ± 51 ms. The results relative to other porpoises show that finless porpoises in Hainan waters produce clicks with moderate SLs and high peak frequency. These results could be useful in detecting the presence and estimating the density of IPFPs during passive acoustic monitoring in the study area and serve to shed light on the interpopulation variation of click characteristics of finless porpoises as well.

Scavenging of Superoxide in Aprotic Solvents of Four Isoflavones That Mimic Superoxide Dismutase.

Isoflavones are plant-derived natural products commonly found in legumes that show a large spectrum of biomedical activities. A common antidiabetic remedy in traditional Chinese medicine, Astragalus trimestris L. contains the isoflavone formononetin (FMNT). Literature reports show that FMNT can increase insulin sensitivity and potentially target the peroxisome proliferator-activated receptor gamma, PPARγ, as a partial agonist. PPARγ is highly relevant for diabetes control and plays a major role in Type 2 diabetes mellitus development. In this study, we evaluate the biological role of FMNT, and three related isoflavones, genistein, daidzein and biochanin A, using several computational and experimental procedures. Our results reveal the FMNT X-ray crystal structure has strong intermolecular hydrogen bonding and stacking interactions which are useful for antioxidant action. Cyclovoltammetry rotating ring disk electrode (RRDE) measurements show that all four isoflavones behave in a similar manner when scavenging the superoxide radical. DFT calculations conclude that antioxidant activity is based on the familiar superoxide σ-scavenging mode involving hydrogen capture of ring-A H7(hydroxyl) as well as the π-π (polyphenol-superoxide) scavenging activity. These results suggest the possibility of their mimicking superoxide dismutase (SOD) action and help explain the ability of natural polyphenols to assist in lowering superoxide concentrations. The SOD metalloenzymes all dismutate O2•- to H2O2 plus O2 through metal ion redox chemistry whereas these polyphenolic compounds do so through suitable hydrogen bonding and stacking intermolecular interactions. Additionally, docking calculations suggest FMNT can be a partial agonist of the PPARγ domain. Overall, our work confirms the efficacy in combining multidisciplinary approaches to provide insight into the mechanism of action of small molecule polyphenol antioxidants. Our findings promote the further exploration of other natural products, including those known to be effective in traditional Chinese medicine for potential drug design in diabetes research.