IgG4-related disease: Case report and 6-year follow-up of an elusive diagnosis mimicking malignancy.

Key Clinical Message: IgG4-related disease is a rare and emerging pathology, characterized by the appearance of pseudotumors. Due to the ability to mimic other pathologies, it is essential to consider it as a differential diagnosis in multisystemic processes. The diagnosis is challenging, requiring a multidisciplinary approach, to minimize the associated morbidity and mortality. Abstract: IgG4-related disease (IgG4-RD) is a rare, emerging, systemic and chronic pathology, characterized by the appearance of pseudotumors resulting from tissue infiltration by IgG4-positive plasma cells that promote eosinophilic inflammation of the tissue with subsequent fibrosis. We present the case of a male, 45-year-old patient, with marked weight loss and skin pallor detected by his family doctor during a child health consultation of his daughter. When questioned, the patient referred complaints of postprandial discomfort in the left hypochondrium with a feeling of fullness, weight loss, chronic fatigue and hyperhidrosis that had lasted for a month. On physical examination, he was pale, and had pain at palpation of the left hypochondrium. Laboratory data showed increased inflammation markers, abdominal ultrasound and CT demonstrated numerous enlarged lymph nodes in the upper quadrants, raising concern for a malignant lymphoproliferative process. Serological, imaging, clinical and laparoscopic excisional biopsy revealed features of IgG4-related disease and excluded malignant lymphoproliferative disease. The immediate response to treatment with oral prednisolone 30 mg/day also contributed for diagnosis confirmation. Due to refractory disease after gradual prednisolone reduction, second-line therapy with rituximab was initiated. Over the 6 years of follow-up, the patient presented multiple exacerbations characterized by the emergence of systemic symptoms, being maintained under close clinical and imaging follow-up by reumathology, infectious diseases, and family medicine specialists.

Humulus lupulus aqueous extract and hydrolate as a potential ingredient for cosmetics: chemical characterization and in vitro antimicrobial, cytotoxicity, antioxidant and anti-inflammatory assessment.

Humulus lupulus extracts have in their composition different molecules, such as polyphenols, α-acids, ß-acids, and hydrocarbons, which contribute to the plant's medicinal properties. These molecules are associated with antimicrobial, antioxidant and anti-inflammatory activities. OBJECTIVE: This work focuses on the evaluation of H. lupulus biological activities, with the aim of evaluating its potential for inclusion in cosmetic formulations. METHODS: Two distinct aqueous extracts and two hydrolates obtained via hydrodistillation were evaluated. These include the flower parts (FE, FH) and the mix of aboveground parts (ME, MH). The chemical profiles for both aqueous extracts and hydrolates were identified by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Antimicrobial, antioxidant, cytotoxicity, and anti-inflammatory activity were tested in vitro using standard methods. RESULTS: Rutin was the major compound found in FE (40.041 µg mg-1 of extract) and ME (2.909 µg mg-1 of extract), while humulenol II was the most abundant compound in hydrolates (FH: 20.83%; MH: 46.80%). Furthermore, FE was able to inhibit the growth of Staphylococcus aureus and Staphylococcus epidermis with MIC values of 50% and 25% (v/v), respectively. FH showed the same effect in Staphylococcus aureus (50% v/v). FH evidenced poor antioxidant potential in DPPH scavenging test and demonstrated significant antioxidant and anti-inflammatory effects by reducing (***p < 0.001) intracellular reactive oxygen species (ROS), NO (nitric oxide) levels (***p < 0.001) and cyclooxygenase-2 (COX-2) protein expression (***p < 0.001) in lipopolysaccharide (LPS)-stimulated macrophages. Nevertheless, it is important to note that FH exhibited cytotoxicity at high concentrations in 3T3 fibroblasts and RAW 264.7 macrophages. CONCLUSION: The studied H. lupulus aqueous extracts and hydrolates revealed that FH stands out as the most promising bioactive source for cosmetic formulations. However, future research addressing antimicrobial activity is necessary to confirm its potential incorporation into dermatological and cosmetic formulations.

Use of Various Sugarcane Byproducts to Produce Lipid Extracts with Bioactive Properties: Physicochemical and Biological Characterization.

Sugarcane, a globally cultivated crop constituting nearly 80% of total sugar production, yields residues from harvesting and sugar production known for their renewable bioactive compounds with health-promoting properties. Despite previous studies, the intricate interplay of extracts from diverse sugarcane byproducts and their biological attributes remains underexplored. This study focused on extracting the lipid fraction from a blend of selected sugarcane byproducts (straw, bagasse, and filter cake) using ethanol. The resulting extract underwent comprehensive characterization, including physicochemical analysis (FT-IR, DSC, particle size distribution, and color) and chemical composition assessment (GC-MS). The biological properties were evaluated through antihypertensive (ACE), anticholesterolemic (HMG-CoA reductase), and antidiabetic (alpha-glucosidase and Dipeptidyl Peptidase-IV) assays, alongside in vitro biocompatibility assessments in Caco-2 and Hep G2 cells. The phytochemicals identified, such as ß-sitosterol and 1-octacosanol, likely contribute to the extract's antidiabetic, anticholesterolemic, and antihypertensive potential, given their association with various beneficial bioactivities. The extract exhibited substantial antidiabetic effects, inhibiting α-glucosidase (5-60%) and DPP-IV activity (25-100%), anticholesterolemic potential with HMG-CoA reductase inhibition (11.4-63.2%), and antihypertensive properties through ACE inhibition (24.0-27.3%). These findings lay the groundwork for incorporating these ingredients into the development of food supplements or nutraceuticals, offering potential for preventing and managing metabolic syndrome-associated conditions.

Hijacking of internal calcium dynamics by intracellularly residing viral rhodopsins.

Rhodopsins are ubiquitous light-driven membrane proteins with diverse functions, including ion transport. Widely distributed, they are also coded in the genomes of giant viruses infecting phytoplankton where their function is not settled. Here, we examine the properties of OLPVR1 (Organic Lake Phycodnavirus Rhodopsin) and two other type 1 viral channelrhodopsins (VCR1s), and demonstrate that VCR1s accumulate exclusively intracellularly, and, upon illumination, induce calcium release from intracellular IP3-dependent stores. In vivo, this light-induced calcium release is sufficient to remote control muscle contraction in VCR1-expressing tadpoles. VCR1s natively confer light-induced Ca2+ release, suggesting a distinct mechanism for reshaping the response to light of virus-infected algae. The ability of VCR1s to photorelease calcium without altering plasma membrane electrical properties marks them as potential precursors for optogenetics tools, with potential applications in basic research and medicine.

Vaginal prevention of Candida albicans: synergistic effect of lactobacilli and mannan oligosaccharides (MOS).

Vulvovaginal candidiasis (VVC) affects approximately 30-50% of women at least once during their lifetime, causing uncomfortable symptoms and limitations in their daily quality of life. Antifungal therapy is not very effective, does not prevent recurrencies and usually causes side effects. Therefore, alternative therapies are urgently needed. The goal of this work was to investigate the potential benefits of using mannan oligosaccharides (MOS) extracts together with a Lactobacillus sp. pool, composed by the most significant species present in the vaginal environment, to prevent infections by Candida albicans. Microbial growth of isolated strains of the main vaginal lactobacilli and Candida strains was assessed in the presence of MOS, to screen their impact upon growth. A pool of the lactobacilli was then tested against C. albicans in competition and prophylaxis studies; bacterial and yeast cell numbers were quantified in specific time points, and the above-mentioned studies were assessed in simulated vaginal fluid (SVF). Finally, adhesion to vaginal epithelial cells (HeLa) was also evaluated, once again resorting to simultaneous exposure (competition) or prophylaxis assays, aiming to measure the effect of MOS presence in pathogen adherence. Results demonstrated that MOS extracts have potential to prevent vaginal candidiasis in synergy with vaginal lactobacilli, with improved results than those obtained when using lactobacilli alone. KEY POINTS: Potential benefits of MOS extracts with vaginal lactobacilli to prevent C. albicans infections. MOS impacts on growth of vaginal lactobacilli pool and C. albicans in SVF. MOS extracts in synergy with L. crispatus inhibit C. albicans adhesion in HeLa cells.

European value-based healthcare benchmarking: moving from theory to practice.

BACKGROUND: Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. METHODS: In the VOICE community-a European healthcare centre cluster intending to address VBHC from theory to practice-information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. RESULTS: Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. CONCLUSIONS: To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions.

Study of Ecological Relationship of Yeast Species with Candida albicans in the Context of Vulvovaginal Infections.

The role of the fungal community, the mycobiota, in the health of the vagina is currently an important area of research. The emergence of new sequencing technologies and advances in bioinformatics made possible the discovery of novel fungi inhabiting this niche. Candida spp. constitutes the most important group of opportunistic pathogenic fungi, being the most prevalent fungal species in vulvovaginal infections. However, fungi such as Rhodotorula spp., Naganishia spp. and Malassezia spp. have emerged as potential pathogens in this niche, and therefore it is clinically relevant to understand their ecological interaction with Candida spp. The main aim of this study was to evaluate the impact of yeasts on Candida albicans' pathogenicity, focusing on in-vitro growth, and biofilm formation at different times of co-culture and germ tube formation. The assays were performed with isolated species or with co-cultures of C. albicans (ATCC10231) with one other yeast species: Rhodotorula mucilaginosa (DSM13621), Malassezia furfur (DSM6170) or Naganishia albida (DSM70215). The results showed that M. furfur creates a symbiotic relationship with C. albicans, enhancing the growth rate of the co-culture (149.69%), and of germ tube formation of C. albicans (119.8%) and inducing a higher amount of biofilm biomass of the co-culture, both when mixed (154.1%) and preformed (166.8%). As for the yeasts R. mucilaginosa and N. albida, the relationship is antagonistic (with a significant decrease in all assays), thus possibly repressing the mixture's pathogenicity. These results shed light on the complex interactions between yeasts in the vaginal mycobiome.

A loss-of-function NCSTN mutation associated with familial Dowling Degos disease and hidradenitis suppurativa.

Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in KRT5, POGLUT-1 and POFUT-1 genes have been associated with DDD, and loss-of-function mutations in PSENEN, a subunit of the gamma-secretase complex, were found in patients presenting with DDD or DDD comorbid with hidradenitis suppurativa (HS). A nonsense mutation in NCSTN, another subunit of the gamma-secretase, was already described in a patient suffering from HS and DDD but whether NCSTN could be considered a novel gene for DDD is still debated. Here, we enrolled a four-generation family with HS and DDD. Through Whole Exome Sequencing (WES) we identified a novel nonsense mutation in the NCSTN gene in all the affected family members. To study the impact of this variant, we isolated outer root sheath cells from patients' hair follicles. We showed that this variant leads to a premature stop codon, activates a nonsense-mediated mRNA decay, and causes NCSTN haploinsufficiency in affected individuals. In fact, cells treated with gentamicin, a readthrough agent, had the NCSTN levels corrected. Moreover, we observed that this haploinsufficiency also affects other subunits of the gamma-secretase complex, possibly causing DDD. Our findings clearly support NCSTN as a novel DDD gene and suggest carefully investigating this co-occurrence in HS patients carrying a mutation in the NCSTN gene.

The chloroplast protein HCF164 is predicted to be associated with Coffea SH9 resistance factor against Hemileia vastatrix.

To explore the connection between chloroplast and coffee resistance factors, designated as SH1 to SH9, whole genomic DNA of 42 coffee genotypes was sequenced, and entire chloroplast genomes were de novo assembled. The chloroplast phylogenetic haplotype network clustered individuals per species instead of SH factors. However, for the first time, it allowed the molecular validation of Coffea arabica as the maternal parent of the spontaneous hybrid "Híbrido de Timor". Individual reads were also aligned on the C. arabica reference genome to relate SH factors with chloroplast metabolism, and an in-silico analysis of selected nuclear-encoded chloroplast proteins (132 proteins) was performed. The nuclear-encoded thioredoxin-like membrane protein HCF164 enabled the discrimination of individuals with and without the SH9 factor, due to specific DNA variants linked to chromosome 7c (from C. canephora-derived sub-genome). The absence of both the thioredoxin domain and redox-active disulphide center in the HCF164 protein, observed in SH9 individuals, raises the possibility of potential implications on redox regulation. For the first time, the identification of specific DNA variants of chloroplast proteins allows discriminating individuals according to the SH profile. This study introduces an unexplored strategy for identifying protein/genes associated with SH factors and candidate targets of H. vastatrix effectors, thereby creating new perspectives for coffee breeding programs.

Effect of Mannan Oligosaccharides Extracts in Uropathogenic Escherichia coli Adhesion in Human Bladder Cells.

Urinary tract infections (UTIs) are a common public health problem, mainly caused by uropathogenic Escherichia coli (UPEC). Patients with chronic UTIs are usually treated with long-acting prophylactic antibiotics, which promotes the development of antibiotic-resistant UPEC strains and may complicate their long-term management. D-mannose and extracts rich in D-mannose such as mannan oligosaccharides (MOS; D-mannose oligomers) are promising alternatives to antibiotic prophylaxis due to their ability to inhibit bacterial adhesion to urothelial cells and, therefore, infection. This highlights the therapeutic potential and commercial value of using them as health supplements. Studies on the effect of MOS in UTIs are, however, scarce. Aiming to evaluate the potential benefits of using MOS extracts in UTIs prophylaxis, their ability to inhibit the adhesion of UPEC to urothelial cells and its mechanism of action were assessed. Additionally, the expression levels of the pro-inflammatory marker interleukin 6 (IL-6) were also evaluated. After characterizing their cytotoxic profiles, the preliminary results indicated that MOS extracts have potential to be used for the handling of UTIs and demonstrated that the mechanism through which they inhibit bacterial adhesion is through the competitive inhibition of FimH adhesins through the action of mannose, validated by a bacterial growth impact assessment.

Zika virus: Critical crosstalk between pathogenesis, cytopathic effects, and macroautophagy.

Zika virus (ZIKV) is a re-emerging positive-sense RNA arbovirus. Its genome encodes a polyprotein that is cleaved by proteases into three structural proteins (Envelope, pre-Membrane, and Capsid) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). These proteins have essential functions in viral replication cycle, cytopathic effects, and host cellular response. When infected by ZIKV, host cells promote macroautophagy, which is believed to favor virus entry. Although several authors have attempted to understand this link between macroautophagy and viral infection, little is known. Herein, we performed a narrative review of the molecular connection between macroautophagy and ZIKV infection while focusing on the roles of the structural and nonstructural proteins. We concluded that ZIKV proteins are major virulence factors that modulate host-cell machinery to its advantage by disrupting and/or blocking specific cellular systems and organelles' function, such as endoplasmic reticulum stress and mitochondrial dysfunction.

Peptide extract from spent yeast improves resistance of Saccharomyces cerevisiae to oxidative stress.

Yeast cells face various stress factors during industrial fermentations, since they are exposed to harsh environmental conditions, which may impair biomolecules productivity and yield. In this work, the use of an antioxidant peptide extract obtained from industrial spent yeast was explored as supplement for Saccharomyces cerevisiae fermentation to prevent a common bottleneck: oxidative stress. For that, a recombinant yeast strain, producer of ß-farnesene, was firstly incubated with 0.5 and 0.7 g/L peptide extract, in the presence and absence of hydrogen peroxide (an oxidative stress inducer), for 1-5 h, and then assayed for intracellular reactive oxygen species, and growth ability in agar spot assays. Results showed that under 2 mM H2O2, the peptide extract could improve cells growth and reduce reactive oxygen species production. Therefore, this antioxidant effect was further evaluated in shake-flasks and 2-L bioreactor batch fermentations. Peptide extract (0.7 g/L) was able to increase yeast resistance to the oxidative stress promoted by 2 mM H2O2, by reducing reactive oxygen species levels between 1.2- and 1.7-fold in bioreactor and between 1.2- and 3-fold in shake-flask fermentations. Moreover, improvements on yeast cell density of up to 1.5-fold and 2-fold, and on biomolecule concentration of up to 1.6-fold and 2.8-fold, in bioreactor and shake-flasks, respectively, were obtained. Thus, culture medium supplementation with antioxidant peptide extracted from industrial spent yeast is a promising strategy to improve fermentation performance while valuing biomass waste. This valorization can promote a sustainable and eco-friendly solution for the biotechnology industry by the implementation of a circular economy model. KEY POINTS: • Peptide extract from spent yeast applied for the first time on yeast fermentation. • Antioxidant peptide extract enhanced S. cerevisiae oxidative stress resistance. • Fermentation performance under stress improved by peptide extract supplementation.

Uncovering the Yeast Diversity in the Female Genital Tract: An Exploration of Spatial Distribution and Antifungal Resistance.

Candida albicans is the leading cause of vulvovaginal yeast infections; however, other species are becoming relevant in this niche. The spatial distribution of these fungi in the female genital tract remains poorly understood. In this study, swab samples were collected from 33 patients, first from the anterior vulva and then from the upper third and right lateral wall of the vagina: 16 were with symptoms of vulvovaginal candidiasis and 17 were without characteristic symptoms; furthermore, the genus and species of each isolate were identified. In vitro susceptibility testing for fluconazole and clotrimazole was performed for all isolates. Candida albicans was the most common species (63.6%), followed by Rhodotorula spp. (51.5%), and then Candida parapsilosis (15.2%). Rhodotorula spp. and C. parapsilosis were more commonly associated with colonization, and C. albicans with infection. Rhodotorula spp. isolates presented a low susceptibility to fluconazole, with the MIC ranging from 32 to >64 µg/mL. Differences in susceptibility to fluconazole and clotrimazole between the pairs of vaginal and vulvar isolates were found for Candida albicans, Rhodotorula spp., and Nakaseomyces glabratus. The results suggest that different niches may impact the susceptibility profiles of the isolates, as well as their different clinical behaviors.

Vaginal Sheets with Thymbra capitata Essential Oil for the Treatment of Bacterial Vaginosis: Design, Characterization and In Vitro Evaluation of Efficacy and Safety.

We aimed to incorporate Thymbra capitata essential oil (TCEO), a potent antimicrobial natural product against bacterial vaginosis (BV)-related bacteria, in a suitable drug delivery system. We used vaginal sheets as dosage form to promote immediate relief of the typical abundant vaginal discharge with unpleasant odour. Excipients were selected to promote the healthy vaginal environment reestablishment and bioadhesion of formulations, while the TCEO acts directly on BV pathogens. We characterized vaginal sheets with TCEO in regard to technological characterization, predictable in vivo performance, in vitro efficacy and safety. Vaginal sheet D.O (acid lactic buffer, gelatine, glycerine, chitosan coated with TCEO 1% w/w) presented a higher buffer capacity and ability to absorb vaginal fluid simulant (VFS) among all vaginal sheets with EO, showing one of the most promising bioadhesive profiles, an excellent flexibility and structure that allow it to be easily rolled for application. Vaginal sheet D.O with 0.32 µL/mL TCEO was able to significantly reduce the bacterial load of all in vitro tested Gardnerella species. Although vaginal sheet D.O presented toxicity at some concentrations, this product was developed for a short time period of treatment, so this toxicity can probably be limited or even reversed when the treatment ends.

Spent Yeast Waste Streams as a Sustainable Source of Bioactive Peptides for Skin Applications.

Spent yeast waste streams are a byproduct obtained from fermentation process and have been shown to be a rich secondary source of bioactive compounds such as phenolic compounds and peptides. The latter are of particular interest for skin care and cosmetics as they have been shown to be safe and hypoallergenic while simultaneously being able to exert various effects upon the epidermis modulating immune response and targeting skin metabolites, such as collagen production. As the potential of spent yeast's peptides has been mainly explored for food-related applications, this work sought to understand if peptide fractions previously extracted from fermentation engineered spent yeast (Saccharomyces cerevisiae) waste streams possess biological potential for skin-related applications. To that end, cytotoxic effects on HaCat and HDFa cells and whether they were capable of exerting a positive effect upon the production of skin metabolites relevant for skin health, such as collagen, hyaluronic acid, fibronectin and elastin, were evaluated. The results showed that the peptide fractions assayed were not cytotoxic up to the highest concentration tested (500 µg/mL) for both cell lines tested. Furthermore, all peptide fractions showed a capacity to modulate the various target metabolites production with an overall positive effect being observed for the four fractions over the six selected targets (pro-collagen IαI, hyaluronic acid, fibronectin, cytokeratin-14, elastin, and aquaporin-9). Concerning the evaluated fractions, the overall best performance (Gpep > 1 kDa) was of an average promotion of 41.25% over the six metabolites and two cell lines assessed at a concentration of 100 µg/mL. These results showed that the peptide fractions assayed in this work have potential for future applications in skin-related products at relatively low concentrations, thus providing an alternative solution for one of the fermentation industry's waste streams and creating a novel and highly valuable bioactive ingredient with encompassing activity to be applied in future skin care formulations.

Effect of drying technology in Saccharomyces cerevisiae mannans: Structural, physicochemical, and functional properties.

Mannans are polysaccharides whose physicochemical and biological properties render them commercialization in several products. Since these properties are strongly dependent on production conditions, the present study aims to assess the impact of different drying technologies - freeze (FDM) and spray drying (SDM) - on the structural, physicochemical, and biological properties of mannans from Saccharomyces cerevisiae. Structural analysis was assessed by FT-IR, PXRD and SEM, whereas physicochemical properties were evaluated based on sugars, protein, ash and water contents, solubility, and molecular weight distribution. Thermal behaviour was analysed by DSC, and antioxidant activity by DPPH and ABTS assays. The parameters which revealed major differences, in terms of structural and physicochemical properties regarded morphology (SEM), physical appearance (colour), moisture (3.6 ± 0.1 % and 11.9 ± 0.6 % for FDM and SDM, respectively) and solubility (1 mg/mL for FDM and 25 mg/mL for SDM). Nevertheless, these differences were not translated into the antioxidant capacity.

Comparative Analysis of Mannans Extraction Processes from Spent Yeast Saccharomyces cerevisiae.

Mannans are outstanding polysaccharides that have gained exponential interest over the years. These polysaccharides may be extracted from the cell wall of Saccharomyces cerevisiae, and recovered from the brewing or synthetic biology industries, among others. In this work, several extraction processes-physical, chemical and enzymatic-were studied, all aiming to obtain mannans from spent yeast S. cerevisiae. Their performance was evaluated in terms of yield, mannose content and cost. The resultant extracts were characterized in terms of their structure (FT-IR, PXRD and SEM), physicochemical properties (color, molecular weight distribution, sugars, protein, ash and water content) and thermal stability (DSC). The biological properties were assessed through the screening of prebiotic activity in Lactobacillus plantarum and Bifidobacterium animalis. The highest yield (58.82%) was achieved by using an alkaline thermal process, though the correspondent mannose content was low. The extract obtained by autolysis followed by a hydrothermal step resulted in the highest mannose content (59.19%). On the other hand, the extract obtained through the enzymatic hydrolysis displayed the highest prebiotic activity. This comparative study is expected to lay the scientific foundation for the obtention of well-characterized mannans from yeast, which will pave the way for their application in various fields.

Spent Yeast Valorization for Food Applications: Effect of Different Extraction Methodologies.

Over the years, synthetic biology has been growing with the use of engineered yeast strains for the production of sustainable ingredients to meet global healthcare, agriculture, manufacturing and environmental challenges. However, as seen from the brewing industry perspective, these processes generate a substantial amount of spent yeast that contains high nutritional value related to its high protein content, showing its potential to be used as an alternative protein source. Taking into account the rising demand for protein because of the growth in the global population, the present study aims to produce peptide-rich extracts by different potentially scalable and sustainable methodologies in a circular economy approach for the food and nutraceutical industries. The results demonstrated that extraction from genetically modified strains allowed the production of extracts with an excellent nutritional profile and low molecular weight peptides. Furthermore, autolysis was shown to be a potential sustainable approach for this production, though other green metrics need to be explored in order to establish this process at an industrial level.