Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.

The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs by glycans, expansion of appropriate naive B cells with immunogens, and selection of functional antibody mutations. Here, we demonstrate that immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAb bound to HIV-1 Env demonstrated binding angles and heavy-chain interactions characteristic of all known human CD4-mimicking bnAbs. Macaque nAb were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAb. This vaccine study initiated in primates the B cells from which CD4bs bnAbs can derive, accomplishing the key first step in the development of an effective HIV-1 vaccine.

Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.

A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.

The CH1 domain influences the expression and antigen sensing of the HIV-specific CH31 IgM-BCR and IgG-BCR.

How different classes of the B cell antigen receptor (BCR) sense viral antigens used in vaccination protocols is poorly understood. Here, we study antigen binding and sensing of human Ramos B cells expressing a BCR of either the IgM or IgG1 class with specificity for the CD4-binding-site of the envelope (Env) protein of the HIV-1. Both BCRs carry an identical antigen binding site derived from the broad neutralizing antibody (bnAb) CH31. We find a five times higher expression of the IgG1-BCR in comparison to the IgM-BCR on the surface of transfected Ramos B cells. The two BCR classes also differ from each other in their interaction with cognate HIV Env antigens in that the IgG1-BCR and IgM-BCR bind preferentially to polyvalent and monovalent antigens, respectively. By generating an IgM/IgG1 chimeric BCR, we found that the class-specific BCR expression and antigen-sensing behavior can be transferred with the CH1γ domain from the IgG1-BCR to the IgM-BCR. Thus, the class of CH1 domain has an impact on BCR assembly and expression as well as on antigen sensing.

Non-neutralizing SARS-CoV-2 N-terminal domain antibodies protect mice against severe disease using Fc-mediated effector functions.

Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing, yet it protected mice and cynomolgus macaques from severe disease. The mechanisms of NTD non-neutralizing antibody-mediated protection are unknown. Here we show that Fc effector functions mediate NTD non-neutralizing antibody (non-nAb) protection against SARS-CoV-2 MA10 viral challenge in mice. Though non-nAb prophylactic infusion did not suppress infectious viral titers in the lung as potently as neutralizing antibody (nAb) infusion, disease markers including gross lung discoloration were similar in nAb and non-nAb groups. Fc functional knockout substitutions abolished non-nAb protection and increased viral titers in the nAb group. Fc enhancement increased non-nAb protection relative to WT, supporting a positive association between Fc functionality and degree of protection from SARS-CoV-2 infection. For therapeutic administration of antibodies, non-nAb effector functions contributed to virus suppression and lessening of lung discoloration, but the presence of neutralization was required for optimal protection from disease. This study demonstrates that non-nAbs can utilize Fc-mediated mechanisms to lower viral load and prevent lung damage due to coronavirus infection.

Dynamics and Activation of Membrane-Bound B Cell Receptor Assembly.

B-cell receptor complexes (BCR) are expressed on the surface of a B-cell and are the critical regulators of adaptive immune response. Even though the relevance of antibodies has been known for almost a hundred years, the antigen-dependent activation of antibody-producing B-cells has remained elusive. Several models have been proposed for BCR activation, including cross-linking, conformation-induced oligomerization, and dissociation activation models. Recently, the first cryo-EM structure of the human B-cell antigen receptor of the IgM isotype was published. Given the new asymmetric BCR complex, we have carried out extensive molecular dynamics simulations to probe the conformational changes upon antigen binding and the influence of the membrane. We identified two critical dynamical events that could be associated with antigen-dependent activation of BCR. First, antigen binding caused increased flexibility in regions distal to the antigen binding site. Second, this increased flexibility led to the rearrangement of helices in transmembrane helices, including the relative interaction of Igα/Igß, which has been responsible for intracellular signaling. Further, these transmembrane rearrangements led to changes in localized lipid composition. Even though the simulations considered only a single BCR complex, our work indirectly supports the dissociation activation model.

Enhancing breast cancer classification via histopathological image analysis: Leveraging self-supervised contrastive learning and transfer learning.

Breast cancer, a significant threat to women's health, demands early detection. Automating histopathological image analysis offers a promising solution to enhance efficiency and accuracy in diagnosis. This study addresses the challenge of breast cancer histopathological image classification by leveraging the ResNet architecture, known for its depth and skip connections. In this work, two distinct approaches were pursued, each driven by unique motivations. The first approach aimed to improve the learning process through self-supervised contrastive learning. It utilizes a small subset of the training data for initial model training and progressively expands the training set by incorporating confidently labeled data from the unlabeled pool, ultimately achieving a reliable model with limited training data. The second approach focused on optimizing the architecture by combining ResNet50 and Inception module to get a lightweight and efficient classifier. The dataset utilized in this work comprises histopathological images categorized into benign and malignant classes at varying magnification levels (40X, 100X, 200X, 400X), all originating from the same source image. The results demonstrate state-of-the-art performance, achieving 98% accuracy for images magnified at 40X and 200X, and 94% for 100X and 400X. Notably, the proposed architecture boasts a substantially reduced parameter count of approximately 3.6 million, contrasting with existing leading architectures, which possess parameter sizes at least twice as large.

Identification and functional characterization of putative ligand binding domain(s) of JlpA protein of Campylobacter jejuni.

Among the major Surface Exposed Colonization Proteins (SECPs) of Campylobacter jejuni (C. jejuni), Jejuni lipoprotein A (JlpA) plays a crucial role in host cell adhesion specifically by binding to the N-terminal domain of the human heat shock protein 90α (Hsp90α-NTD). Although the JlpA binding to Hsp90α activates NF-κB and p38 MAP kinase pathways, the underlying mechanism of JlpA association with the cellular receptor remains unclear. To this end, we predicted two potential receptor binding sites within the C-terminal domain of JlpA: one spanning from amino acid residues Q332-A354 and the other from S258-T295; however, the latter exhibited weaker binding. To assess the functional attributes of these predicted sequences, we generated two JlpA mutants (JlpAΔ1: S258-T295; JlpAΔ2: Q332-A354) and assessed the Hsp90α-binding affinity-kinetics by in vitro and ex vivo experiments. Our findings confirmed that the residues Q332-A354 are of greater importance in host cell adhesion with a measurable impact on cellular responses. Further, thermal denaturation by circular dichroism (CD) confirmed that the reduced binding affinity of the JlpAΔ2 to Hsp90α is not associated with protein folding or stability. Together, this study provides a possible framework for determining the molecular function of designing rational inhibitors efficiently targeting JlpA.

Temporal evolution of electron cloud in a cylindrical Penning trap at room temperature.

The temporal evolution of the electron cloud at room temperature has been recorded through a resonance circuit by observing the axial oscillation frequency of its center of mass. The electron cloud undergoes radial expansion by interacting with the residual gas molecules, and it is finally lost upon hitting the Penning trap electrodes. It has been confirmed through detailed experimental investigations that the unique temporal pattern of frequency variation is a consequence of the cloud's radial expansion. Consequently, this approach offers a non-destructive means for single-shot detection, enabling continuous monitoring of the electron cloud's radial expansion during the confinement time. This technique offers a significant advantage over its destructive alternatives.

Status of Serum Calcium in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) remains a major public health problem with relatively high prevalence rates worldwide (5-13%). COPD is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The purpose of the study was to explore the alteration of serum calcium in patients with COPD. This cross-sectional study was carried out in the Department of Biochemistry, Mymensingh Medical College, Bangladesh from January 2021 to December 2021. Data was collected from Medicine Department of Mymensingh Medical College Hospital, Mymensingh. A total number of 120 subjects participated in this study. Out of them, 60 apparently normal healthy individuals were selected as Group I and another 60 diagnosed COPD patients were selected as Group II. Serum calcium was measured by colorimetric method using the test kit. The results were calculated and analyzed by using statistical package for social science (SPSS), windows package version 21.0. Data were expressed in mean ±SD and statistical significance was done by Student's unpaired 't' test. In this study, the mean ±SD values of serum calcium were 9.21±1.06mg/dl and 8.26±0.95mg/dl in Group I and Group II respectively. The results were highly significant (p<0.001). The result suggested that there was significant relation between COPD and alteration of serum calcium. So, by this study we recommended that routine evaluation of serum calcium is important for prevention of exacerbations, reduction of morbidity and mortality in patients with COPD.

Influence of membrane on the antigen presentation of the HIV-1 envelope membrane proximal external region (MPER).

The membrane proximal external region (MPER) of the HIV envelope glycoproteins has generated renewed interest after a recent phase I vaccine trial that presented MPER lipid-peptide epitopes demonstrated promise to elicit a broad neutralization response. The antigenicity of MPER is intimately associated with the membrane, and its presentation relies significantly on the lipid composition. This review brings together recent findings on the influence of membranes on the conformation of MPER and its recognition by broadly neutralizing antibodies. Specifically, the review highlights the importance of properly accounting for the balance between protein-protein and membrane-protein interactions in vaccine design.

Antimicrobial susceptibility pattern of aerobic bacteria responsible for post-surgical wound infection of the patients admitted into Khulna Medical College Hospital, Bangladesh.

Resistance against antimicrobial agents is dramatically increasing and gradually impacting treatment costs. Using existing drugs would have helped avoid bacterial infections in various circumstances. The primary objectives of this study were to determine the prevalence of pathogens responsible for postsurgical wound infections and their antimicrobial susceptibility and resistance pattern among the patients admitted to Khulna Medical College Hospital, Khulna Bangladesh. This cross-sectional study involved 250 patients suffering from postsurgical wound infection as respondents. The bacterial pathogens were isolated from pus samples obtained from those patients. The isolated bacterial pathogens were identified through several standard biochemical tests, and finally, the culture sensitivity tests of those bacterial isolates were performed. The study was conducted from August 2019 to June 2020. Data regarding the patient's age, gender, occupation, surgery performed, duration of hospital stay, and comorbidity were also documented using standard questionnaires. Five bacterial pathogens were identified with different frequencies, including Pseudomonas aeruginosa (36 %), Escherichia coli (21.2 %), Staphylococcus aureus (8.8 %), Klebsiella spp. (7.2 %) and Proteus spp. (4.8 %). These bacterial pathogens showed sensitivity to ciprofloxacin (75 %), piperacillin-tazobactam (56.7 %) and gentamicin (50 %). Besides, S. aureus showed sensitivity to linezolid and vancomycin and resistance to cefuroxime, ceftazidime and imipenem. Male patients (68.4 %) suffered more from postsurgical wound infection than female patients (31.6 %). Patients aged 31 to 40 years were more severely affected than patients from other age groups. Postsurgical wound infection was vigorously observed in the patients who underwent hand surgery. Intensive occurrence of this infection was found in the patients who stayed in the hospital from 31 to 40 days. Diabetic patients suffered more from postsurgical wound infection compared to the other patients. Throughout the study, ciprofloxacin has been the best performer against E. coli, Klebsiella spp., and Proteus spp., and gentamicin showed better performance against S. aureus. The antibiotic resistance pattern of these bacterial pathogens reflects the worldwide necessity of rational antibiotic management and proper steps to maintain hospital hygiene in Bangladesh.

Microsecond dynamics control the HIV-1 Envelope conformation.

The HIV-1 Envelope (Env) glycoprotein facilitates host cell fusion through a complex series of receptor-induced structural changes. Although remarkable progress has been made in understanding the structures of various Env conformations, microsecond timescale dynamics have not been studied experimentally. Here, we used time-resolved, temperature-jump small-angle x-ray scattering to monitor structural rearrangements in an HIV-1 Env SOSIP ectodomain construct with microsecond precision. In two distinct Env variants, we detected a transition that correlated with known Env structure rearrangements with a time constant in the hundreds of microseconds range. A previously unknown structural transition was also observed, which occurred with a time constant below 10 µs, and involved an order-to-disorder transition in the trimer apex. Using this information, we engineered an Env SOSIP construct that locks the trimer in the prefusion closed state by connecting adjacent protomers via disulfides. Our findings show that the microsecond timescale structural dynamics play an essential role in controlling the Env conformation with impacts on vaccine design.

Estimation of country-specific tuberculosis resistance antibiograms using pathogen genomics and machine learning.

BACKGROUND: Global tuberculosis (TB) drug resistance (DR) surveillance focuses on rifampicin. We examined the potential of public and surveillance Mycobacterium tuberculosis (Mtb) whole-genome sequencing (WGS) data, to generate expanded country-level resistance prevalence estimates (antibiograms) using in silico resistance prediction. METHODS: We curated and quality-controlled Mtb WGS data. We used a validated random forest model to predict phenotypic resistance to 12 drugs and bias-corrected for model performance, outbreak sampling and rifampicin resistance oversampling. Validation leveraged a national DR survey conducted in South Africa. RESULTS: Mtb isolates from 29 countries (n=19 149) met sequence quality criteria. Global marginal genotypic resistance among mono-resistant TB estimates overlapped with the South African DR survey, except for isoniazid, ethionamide and second-line injectables, which were underestimated (n=3134). Among multidrug resistant (MDR) TB (n=268), estimates overlapped for the fluoroquinolones but overestimated other drugs. Globally pooled mono-resistance to isoniazid was 10.9% (95% CI: 10.2-11.7%, n=14 012). Mono-levofloxacin resistance rates were highest in South Asia (Pakistan 3.4% (0.1-11%), n=111 and India 2.8% (0.08-9.4%), n=114). Given the recent interest in drugs enhancing ethionamide activity and their expected activity against isolates with resistance discordance between isoniazid and ethionamide, we measured this rate and found it to be high at 74.4% (IQR: 64.5-79.7%) of isoniazid-resistant isolates predicted to be ethionamide susceptible. The global susceptibility rate to pyrazinamide and levofloxacin among MDR was 15.1% (95% CI: 10.2-19.9%, n=3964). CONCLUSIONS: This is the first attempt at global Mtb antibiogram estimation. DR prevalence in Mtb can be reliably estimated using public WGS and phenotypic resistance prediction for key antibiotics, but public WGS data demonstrates oversampling of isolates with higher resistance levels than MDR. Nevertheless, our results raise concerns about the empiric use of short-course fluoroquinolone regimens for drug-susceptible TB in South Asia and indicate underutilisation of ethionamide in MDR treatment.

Study on the effect of different contact times on the migration of heavy metals into different foodstuffs served in plastic cups.

Heavy metal concentrations of Pb, Cd, Cr, and Cu leaching from single-use plastic cups were identified, and the risks associated with them were assessed in real time (up to 10 min). All samples (tea, carbonated beverage, and lassi) were placed in disposable plastic cups and held for less than 1 min, 5 min, and 10 min, respectively. Prior to digestion, the solids were ashed in a muffle furnace at 550 °C for 30 min. The filtrates were then tested for heavy metals. The samples were all confirmed to be contaminated with heavy metals. Heavy metals leached from the plastic cups in the following order: Cu > Pb > Cr > Cd. The samples' HI values were less than one, hence there was no evidence of a non-carcinogenic risk. The ILCR values for this heavy metal contamination in samples exceed 10-3, indicating a high carcinogenic risk. Lassi poses the highest possible carcinogenic risk. A rise in temperature and a drop in pH also resulted in heavy metal migration. Heavy metal leaching from plastic cups poses a serious health risk due to its toxicity. The proposed legislation should prohibit or restrict the serving of warm and hot beverages in plastic cups.

In Silico-Based Identification of Natural Inhibitors from Traditionally Used Medicinal Plants that can Inhibit Dengue Infection.

Dengue fever (DF) is an endemic disease that has become a public health concern around the globe. The NS3 protease-helicase enzyme is an important target for the development of antiviral drugs against DENV (dengue virus) due to its impact on viral replication. Inhibition of the activity of the NS3 protease-helicase enzyme complex significantly inhibits the infection associated with DENV. Unfortunately, there are no scientifically approved antiviral drugs for its prevention. However, this study has been developed to find natural bioactive molecules that can block the activity of the NS3 protease-helicase enzyme complex associated with DENV infection through molecular docking, MM-GBSA (molecular mechanics-generalized born surface area), and molecular dynamics (MD) simulations. Three hundred forty-two (342) compounds selected from twenty traditional medicinal plants were retrieved and screened against the NS3 protease-helicase protein by molecular docking and MM-GBSA studies, where the top six phytochemicals have been identified based on binding affinities. The six compounds were then subjected to pharmacokinetics and toxicity analysis, and we conducted molecular dynamics simulations on three protein-ligand complexes to validate their stability. Through computational analysis, this study revealed the potential of the two selected natural bioactive inhibitors (CID-440015 and CID-7424) as novel anti-dengue agents.

Comparative Study of Treatment Outcome with Tenofovir Alafenamide and Entecavir in Patients with HBV Related Acute on Chronic Liver Failure.

Major causes of acute insult in Hepatitis B virus related acute on chronic liver failure in the Asian region are reactivation of Hepatitis B virus and super infection with hepatitis A and E virus (ACLF). Anti viral therapy should be started as soon as possible in the ACLF patients at presentation while waiting for confirmation by HBV DNA level. This randomized controlled trial was carried out at the Department of Hepatology, BSMMU, Bangladesh from September 2019 to august 2020 with Hepatitis B virus related ACLF patient. This trial was conducted among twenty seven HBV acute on chronic liver failure patient to compare Child Turcotte pugh (CTP) score, Model for end stage liver disease (MELD) score, Asia Pacific Association for study of Liver (APASL) ACLF Research consortium (AARC) score, survival of the patients and HBV DNA level at 3 months with antiviral therapy between tenofovir alafenamide (25mg) and entecavir (0.5mg) group. CTP score, MELD score and AARC score were significantly (p<0.05) decline from baseline to all subsequent follow-up at 1st (at 7 days), 2nd (at 14 days), 3rd (at 30 days) and 4th (at 90 days) in each group but non significant (p>0.05) difference occurred between two group. All twenty seven patients had detectable HBV DNA level at pre-treatment and all survived patients became undectable at 4th, 90 days follow-up. Total 10 patients (37.07%) were survived at 90 days follow-up, out of them seven patients (70.0%) were in tenofovir alafenamide group and three patients (30.0%) were in entecavir group which was statistically significant (p<0.05) in between two group. Hepatic encephalopathy and hepatorenal syndrome were most common causes of death in both groups. Both drugs tenofovir alafenamide and entecavir significantly improves liver functions but the former one is superior regarding survival.

A HIV-1 Gp41 Peptide-Liposome Vaccine Elicits Neutralizing Epitope-Targeted Antibody Responses in Healthy Individuals.

Background: HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the HIV-1 gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand bnAb precursors in monkeys. Methods: The HVTN133 phase 1 clinical trial (NCT03934541) studied the MPER-peptide liposome immunogen in 24 HIV-1 seronegative individuals. Participants were recruited between 15 July 2019 and 18 October 2019 and were randomized in a dose-escalation design to either 500 mcg or 2000 mcg of the MPER-peptide liposome or placebo. Four intramuscular injections were planned at months 0, 2, 6, and 12. Results: The trial was stopped prematurely due to an anaphylaxis reaction in one participant ultimately attributed to vaccine-associated polyethylene glycol. The immunogen induced robust immune responses, including MPER+ serum and blood CD4+ T-cell responses in 95% and 100% of vaccinees, respectively, and 35% (7/20) of vaccine recipients had blood IgG memory B cells with MPER-bnAb binding phenotype. Affinity purification of plasma MPER+ IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations. Conclusions: MPER-peptide liposomes induced gp41 serum neutralizing epitope-targeted antibodies and memory B-cell responses in humans despite the early termination of the study. These results suggest that the MPER region is a promising target for a candidate HIV vaccine.

Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction.

A major goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs). Although success has been achieved in initiating bnAb B cell lineages, design of boosting immunogens that select for bnAb B cell receptors with improbable mutations required for bnAb affinity maturation remains difficult. Here, we demonstrate a process for designing boosting immunogens for a V3-glycan bnAb B cell lineage. The immunogens induced affinity-matured antibodies by selecting for functional improbable mutations in bnAb precursor knockin mice. Moreover, we show similar success in prime and boosting with nucleoside-modified mRNA-encoded HIV-1 envelope trimer immunogens, with improved selection by mRNA immunogens of improbable mutations required for bnAb binding to key envelope glycans. These results demonstrate the ability of both protein and mRNA prime-boost immunogens for selection of rare B cell lineage intermediates with neutralizing breadth after bnAb precursor expansion, a key proof of concept and milestone toward development of an HIV-1 vaccine.

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and, in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. To precisely engineer bnAb boosting immunogens, we used molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env). By mapping how bnAbs use encounter states to find their bound states, we identified Env mutations that were predicted to select for specific antibody mutations in two HIV-1 bnAb B cell lineages. The Env mutations encoded antibody affinity gains and selected for desired antibody mutations in vivo. These results demonstrate proof-of-concept that Env immunogens can be designed to directly select for specific antibody mutations at residue-level precision by vaccination, thus demonstrating the feasibility of sequential bnAb-inducing HIV-1 vaccine design.

Antioxidant potential and α-glucosidase inhibitory activity of onion (Allium cepa L. ) peel and bulb extracts / Atividade antioxidante e potencial inibidor de glucosidase de extratos de casca e bulbo de cebola (Allium cepa) preparados por etanol e água

Abstract Allium cepa L. is a commonly consumed vegetable that belongs to the Amaryllidaceae family and contains nutrients and antioxidants in ample amounts. In spite of the valuable food applications of onion bulb, its peel and outer fleshy layers are generally regarded as waste and exploration of their nutritional and therapeutic potential is still in progress with a very slow progression rate. The present study was designed with the purpose of doing a comparative analysis of the antioxidant potential of two parts of Allium cepa, i.g., bulb (edible part) and outer fleshy layers and dry peels (inedible part). Moreover, the inhibitory effect of the onion bulb and peel extracts on rat intestinal α-glucosidase and pancreatic α-amylase of porcine was also evaluated. The antioxidant potential of onion peel and bulb extracts were evaluated using 2,2-diphenyl- 1-picryl hydrazyl (DPPH), ferric-reducing antioxidant power assay (FRAP), 2,2'-azino-bis- 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay, H2O2 radical scavenging activity and Fe2+ chelating activity. Total flavonoids and phenolic content of ethanolic extract of onion peel were significantly greater as compared to that of onion bulb. Ethanolic extract of onion peel also presented better antioxidant and free-radical scavenging activity as compared to the ethanolic extract of bulb, while the aqueous extract of bulb presented weakest antioxidative potential. Onion peel extract's α-glucosidase inhibition potential was also correlated with their phenolic and flavonoid contents. The current findings presented onion peel as a possible source of antioxidative agents and phenolic compounds that might be beneficial against development of various common chronic diseases that might have an association with oxidative stress. Besides, outer dry layers and fleshy peels of onion exhibited higher phenolic content and antioxidant activities, compared to the inner bulb. The information obtained by the present study can be useful in promoting the use of vegetable parts other than the edible mesocarp for several future food applications, rather than these being wasted.

Resumo Allium cepa pertence à família Liliaceae e é rica em nutrientes e antioxidantes. Apesar das expressivas aplicações alimentares do bulbo da cebola, sua casca e outras camadas externas são geralmente consideradas resíduos, e seu potencial nutricional e terapêutico ainda é pouco explorado. O presente estudo foi delineado com o objetivo de investigar comparativamente o potencial antioxidante de duas partes de Allium cepa, por exemplo o bulbo (parte comestível) e camadas externas e cascas secas (parte não comestível). Além disso, o efeito inibitório dos extratos do bulbo de cebola e casca sobre a α-glucosidase intestinal de ratos e α-amilase pancreática suína também foi avaliado. O potencial antioxidante dos extratos da casca de cebola e bulbo foi avaliado utilizando-se 2,2-difenil-1-picrilhidrazil (DPPH), método de poder antioxidante de redução do ferro (FRAP), método 2,2'-azino-bis-3-etilbenzotiazolina-6-ácido sulfônico (ABTS) de eliminação de radicais, atividade de eliminação de radicais H2O2 e atividade quelante do Fe2+. Os flavonoides totais e os teores fenólicos do extrato de etanol da casca de cebola foram significativamente maiores quando comparados ao do bulbo. O extrato de etanol da casca de cebola também apresentou melhor atividade antioxidante e eliminação de radicais livres quando comparado ao extrato de etanol do bulbo, enquanto o extrato aquoso de bulbo apresentou menor potencial antioxidante. O potencial de inibição da α-glicosidase dos extratos de casca de cebola correlacionou-se com seus teores fenólicos e de flavonoides. Os resultados encontrados identificaram que a casca de cebola é uma possível fonte de agentes antioxidantes e compostos fenólicos que podem ser benéficos contra o desenvolvimento de várias doenças crônicas que estão associadas ao estresse oxidativo. Além disso, as camadas externas secas e as cascas da cebola exibiram maior conteúdo fenólico e atividades antioxidantes, em comparação com o bulbo interno. As informações obtidas pelo presente estudo podem promover o uso de outras partes vegetais além do mesocarpo comestível para futuras aplicações em alimentos, ao invés de serem desperdiçadas.