Structural and functional properties of a high moisture extruded mixture of pea proteins (Pisum sativum), amaranth flour (Amaranthus hypochondriacus), and oat flour (Avena sativa).

Textured vegetable proteins (TVP) are an alternative to meet the increasing demand for non-animal food. This study aimed to develop a TVP from mixtures with 45 % pea protein isolate (PPI) enriched with amaranth (AF) and oat (OF) flours using high-moisture extrusion technology (HME) varying the moisture (50-70 %) and the temperature in the second heating zone of the extruder (110-140 °C). After extrusion, all samples demonstrated higher values of water absorption capacity (WAC) than non-extruded mixtures. Mixture of AF:OF:PPI (40:15:45 %) extruded at 60 % moisture and 135 °C showed promising functional properties with WAC and WSI values of 3.2 ± 0.2 g H2O/g and 24.89 ± 2.31 %, respectively, and oil absorption capacity (OAC) of 1.3 g oil/g. The extrusion process altered the thermal and structural properties of proteins promoting a desirable fibrous structure. This confirms the feasibility of using HME to develop TVP based on PPI, AF, and OF.

Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Nanoformulated CHO-rPb27 vaccine enhances immunity and controls infection, mitigating lung inflammation and dysfunction during experimental Paracoccidioidomycosis in mice.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the dimorphic fungus within the genus Paracoccidioides, particularly Paracoccidioides brasiliensis. The traditional approach to treating this pulmonary infection involves prolonged therapy periods, ranging from weeks to years, often resulting in a notable frequency of disease relapse. Nanotechnology has emerged as a promising avenue for developing novel antifungal therapies and effective vaccines. This is attributed to its capability to facilitate targeted drug and antigen delivery, thereby mitigating toxicity and treatment expenses. This study investigates the synergistic properties of the CHO-rPb27 vaccine nanoformulation against experimental PCM. The therapeutic efficacy of CHO-rPb27 treatment is juxtaposed with the prophylactic protocol. Our findings demonstrate that both protocols effectively control P. brasiliensis pulmonary infection by eliciting a robust cellular and humoral immune response. This response attenuates chronic tissue damage and mitigates pulmonary mechanical dysfunction in mice.

Unveiling the Complexity of cis-Regulation Mechanisms in Kinases: A Comprehensive Analysis.

Protein cis-regulatory elements (CREs) are regions that modulate the activity of a protein through intramolecular interactions. Kinases, pivotal enzymes in numerous biological processes, often undergo regulatory control via inhibitory interactions in cis. This study delves into the mechanisms of cis regulation in kinases mediated by CREs, employing a combined structural and sequence analysis. To accomplish this, we curated an extensive dataset of kinases featuring annotated CREs, organized into homolog families through multiple sequence alignments. Key molecular attributes, including disorder and secondary structure content, active and ATP-binding sites, post-translational modifications, and disease-associated mutations, were systematically mapped onto all sequences. Additionally, we explored the potential for conformational changes between active and inactive states. Finally, we explored the presence of these kinases within membraneless organelles and elucidated their functional roles therein. CREs display a continuum of structures, ranging from short disordered stretches to fully folded domains. The adaptability demonstrated by CREs in achieving the common goal of kinase inhibition spans from direct autoinhibitory interaction with the active site within the kinase domain, to CREs binding to an alternative site, inducing allosteric regulation revealing distinct types of inhibitory mechanisms, which we exemplify by archetypical representative systems. While this study provides a systematic approach to comprehend kinase CREs, further experimental investigations are imperative to unravel the complexity within distinct kinase families. The insights gleaned from this research lay the foundation for future studies aiming to decipher the molecular basis of kinase dysregulation, and explore potential therapeutic interventions.

Immunohistochemical evaluation of cyclin D1 and p63 in odontogenic keratocyst and unicystic ameloblastoma.

INTRODUCTION: Odontogenic keratocyst (OKC) and unicystic ameloblastoma (UA) are lesions of odontogenic origin. Both lesions are morphologically cysts. However, they are classified as developmental cysts and epithelial odontogenic tumours, respectively. Cyclin D1 (CCD1) dysregulation is associated with oncogenic activity and malignancies, while tumour protein p63 (p63) alterations are associated with tumourigenesis. AIM: To evaluate and compare the protein expression of CCD1 and p63 in sporadic OKC (OKC-sp), syndromic OKC (OKC-sy), and UA. MATERIAL AND METHODS: 45 cases from the Anatomical Pathology Department, Faculty of Dentistry, University of Chile were analysed and divided into groups: OKC-sp (n=15), OKC-sy (n=15) and UA (n=15), the latter categorised into intraluminal and/or luminal (n=7) and mural (n=8). Immunohistochemical staining for CCD1 and p63 proteins was performed from paraffin-embedded sections. Statistical analysis included the Shapiro-Wilk test, one-way ANOVA with Tukey's multiple comparisons, and Spearman's correlation coefficient (p<0.05). RESULTS: There was an involvement mainly in women in the mandibular area, and a high frequency of jaw expansion, especially in the mural UA. P63 protein expression was higher than CCD1 in all cystic lesions, particularly in mural UA (p<0.001). No correlation was found between CCD1 and p63 expression. CONCLUSION: P63 may serve as a valuable marker for evaluating cell proliferative activity in odontogenic cystic lesions, providing insights into the aggressive behaviour of mural UA.

Assessing the effect of deep eutectic solvents on α-chymotrypsin thermal stability and activity.

Optimizing the liquid reaction phase holds significant potential for enhancing the efficiency of biocatalytic pro- cesses since it determines reaction equilibrium and kinetics. This study investigates the influence of the addition of deep eutectic solvents on the stability and activity of α-chymotrypsin, a proteolytic enzyme with industrial rele- vance. Deep eutectic solvents, composed of choline chloride or betaine mixed with glycerol or sorbitol, were added in the reaction phase at various concentrations. Experimental techniques, including kinetic and fluorometry, were employed to assess the α-chymotrypsin activity, thermal stability, and unfolding reversibility. Atomistic molecular dynamics simulations were also conducted to assess the interactions and provide molecular-level insights between α-chymotrypsin and the solvent. The results showed that among all studied mixtures, adding choline chloride + sorbitol improved thermal stability up to 18 °C and reaction kinetic efficiency up to two-fold upon adding choline chloride + glycerol. Notably, the choline chloride + sorbitol system exhibited the most substantial stabilization effect, attributed to the surface preferential accumulation of sorbitol, as corroborated by the computational anal- yses. This work highlights the potential of tailoring liquid reaction phase of α-chymotrypsin catalyzed reaction using neoteric solvents to enhance α-chymotrypsin performance and stability in industrial applications.

Structural and biochemical insights of xylose MFS and SWEET transporters in microbial cell factories: challenges to lignocellulosic hydrolysates fermentation.

The production of bioethanol from lignocellulosic biomass requires the efficient conversion of glucose and xylose to ethanol, a process that depends on the ability of microorganisms to internalize these sugars. Although glucose transporters exist in several species, xylose transporters are less common. Several types of transporters have been identified in diverse microorganisms, including members of the Major Facilitator Superfamily (MFS) and Sugars Will Eventually be Exported Transporter (SWEET) families. Considering that Saccharomyces cerevisiae lacks an effective xylose transport system, engineered yeast strains capable of efficiently consuming this sugar are critical for obtaining high ethanol yields. This article reviews the structure-function relationship of sugar transporters from the MFS and SWEET families. It provides information on several tools and approaches used to identify and characterize them to optimize xylose consumption and, consequently, second-generation ethanol production.

Nutritional strategies for improving sarcopenia outcomes in older adults: A narrative review.

Sarcopenia is characterized by a decline in muscle strength, generalized loss of skeletal muscle mass, and impaired physical performance, which are common outcomes used to screen, diagnose, and determine severity of sarcopenia in older adults. These outcomes are associated with poor quality of life, increased risk of falls, hospitalization, and mortality in this population. The development of sarcopenia is underpinned by aging, but other factors can lead to sarcopenia, such as chronic diseases, physical inactivity, inadequate dietary energy intake, and reduced protein intake (nutrition-related sarcopenia), leading to an imbalance between muscle protein synthesis and muscle protein breakdown. Protein digestion and absorption are also modified with age, as well as the reduced capacity of metabolizing protein, hindering older adults from achieving ideal protein consumption (i.e., 1-1.5 g/kg/day). Nutritional supplement strategies, like animal (i.e., whey protein) and plant-based protein, leucine, and creatine have been shown to play a significant role in improving outcomes related to sarcopenia. However, the impact of other supplements (e.g., branched-chain amino acids, isolated amino acids, and omega-3) on sarcopenia and related outcomes remain unclear. This narrative review will discuss the evidence of the impact of these nutritional strategies on sarcopenia outcomes in older adults.

Unraveling the Role of JMJD1B in Genome Stability and the Malignancy of Melanomas.

Genome instability relies on preserving the chromatin structure, with any histone imbalances threating DNA integrity. Histone synthesis occurs in the cytoplasm, followed by a maturation process before their nuclear translocation. This maturation involves protein folding and the establishment of post-translational modifications. Disruptions in this pathway hinder chromatin assembly and contribute to genome instability. JMJD1B, a histone demethylase, not only regulates gene expression but also ensures a proper supply of histones H3 and H4 for the chromatin assembly. Reduced JMJD1B levels lead to the cytoplasmic accumulation of histones, causing defects in the chromatin assembly and resulting in DNA damage. To investigate the role of JMJD1B in regulating genome stability and the malignancy of melanoma tumors, we used a JMJD1B/KDM3B knockout in B16F10 mouse melanoma cells to perform tumorigenic and genome instability assays. Additionally, we analyzed the transcriptomic data of human cutaneous melanoma tumors. Our results show the enhanced tumorigenic properties of JMJD1B knockout melanoma cells both in vitro and in vivo. The γH2AX staining, Micrococcal Nuclease sensitivity, and comet assays demonstrated increased DNA damage and genome instability. The JMJD1B expression in human melanoma tumors correlates with a lower mutational burden and fewer oncogenic driver mutations. Our findings highlight JMJD1B's role in maintaining genome integrity by ensuring a proper histone supply to the nucleus, expanding its function beyond gene expression regulation. JMJD1B emerges as a crucial player in preserving genome stability and the development of melanoma, with a potential role as a safeguard against oncogenic mutations.

Extraction and Concentration of Spirulina Water-Soluble Metabolites by Ultrafiltration.

Spirulina (Arthospira platensis) is known for its rich content of natural compounds like phycocyanin, chlorophylls, carotenoids, and high protein levels, making it a nutrient-dense food. Over the past decade, research has aimed to optimize the extraction, separation, and purification of these valuable metabolites, focusing on technologies such as high-pressure processing, ultrasound-assisted extraction, and microwave-assisted extraction as well as enzymatic treatments, chromatographic precipitation, and membrane separation. In this study, various extraction methods (conventional vs. ultrasound-assisted), solvents (water vs. phosphate buffer), solvent-to-biomass ratios (1:5 vs. 1:10), and ultrafiltration (PES membrane of MWCO 3 kDa, 2 bar) were evaluated. The quantities of total protein, phycocyanin (PC), chlorophyll a (Cla), and total carotenoids (TCC) were measured. The results showed that ultrasound-assisted extraction (UAE) with phosphate buffer at a 1:10 ratio yielded a metabolite-rich retentate (MRR) with 37.0 ± 1.9 mg/g of PC, 617 ± 15 mg/g of protein, 0.4 ± 0.2 mg/g of Cla, and 0.15 ± 0.14 mg/g of TCC. Water extraction in the concentration process achieved the highest concentrations in MRR, with approximately 76% PC, 92% total protein, 62% Cla, and 41% TCC. These findings highlight the effective extraction and concentration processes to obtain a metabolite-rich retentate from Spirulina biomass, reducing the volume tenfold and showing potential as a functional ingredient for the food, cosmetic, and pharmaceutical industries.

An Assessment of the Impact of Insect Meal in Dry Food on a Dog with a Food Allergy: A Case Report.

Food allergy triggers an immune response to dietary proteins, resulting in food rejection and dermatological and gastrointestinal manifestations. The preferred therapies include diets with hydrolyzed proteins or unusual single-source proteins, with insect protein emerging as a promising option, with no reported allergic reactions in dogs with a food allergy. In this case study, the effects of including black soldier fly larva (BSFL) meal were observed in a 5-year-old spayed beagle previously diagnosed with a food allergy. The objective was to assess the potential of BSFL meal as an adjunct in treating a food allergy. As part of the protocol, two nutritionally very similar diets were used, differing only in the protein source: the control diet, with poultry by-product meal; and the BSFL diet, which completely replaced the poultry by-product meal. After a 12-day adaptation period to the BSFL diet, the dog showed no gastrointestinal changes, maintaining an adequate fecal score and no clinical signs of the disease. A challenge test with the control diet resulted in episodic gastrointestinal symptoms, which were reversed within two days by reintroducing the BSFL diet. The BSFL protein-based diet was effective in controlling the dog's clinical signs.

Carbohydrate-Binding Mechanism of the Coagulant Lectin from Moringa oleifera Seeds (cMoL) Is Related to the Dimeric Protein Structure.

This study characterized the binding mechanisms of the lectin cMoL (from Moringa oleifera seeds) to carbohydrates using spectroscopy and molecular dynamics (MD). The interaction with carbohydrates was studied by evaluating lectin fluorescence emission after titration with glucose or galactose (2.0-11 mM). The Stern-Volmer constant (Ksv), binding constant (Ka), Gibbs free energy (∆G), and Hill coefficient were calculated. After the urea-induced denaturation of cMoL, evaluations were performed using fluorescence spectroscopy, circular dichroism (CD), and hemagglutinating activity (HA) evaluations. The MD simulations were performed using the Amber 20 package. The decrease in Ksv revealed that cMoL interacts with carbohydrates via a static mechanism. The cMoL bound carbohydrates spontaneously (ΔG < 0) and presented a Ka on the order of 102, with high selectivity for glucose. Protein-ligand complexes were stabilized by hydrogen bonds and hydrophobic interactions. The Hill parameter (h~2) indicated that the binding occurs through the cMoL dimer. The loss of HA at urea concentrations at which the fluorescence and CD spectra indicated protein monomerization confirmed these results. The MD simulations revealed that glucose bound to the large cavity formed between the monomers. In conclusion, the biotechnological application of cMoL lectin requires specific methods or media to improve its dimeric protein structure.

ATR-FTIR spectroscopy to evaluate serum protein expression in a murine cerebral ischemia model.

Stroke is a prevalent vascular disease that causes disability and death worldwide. Molecular techniques have been developed to assess serum concentrations of biomarkers associated with this disease, such as some proteins. ATR-FTIR was proposed as an alternative technique to determine protein expression during the early stages of stroke. Serum samples from sham, ischemic, and ischemic treated with estradiol benzoate (EB; as a neuroprotective agent) male rats were evaluated at 0, 2-, 4-, 6-, 12-, and 24-hours post-ischemia. The analysis was developed in the mid-infrared region but mainly focused on the protein region (1500-1700 cm-1), where it was possible to observe the modulation in the absorbance intensity. The peaks at 1545, 1645, 1635, and 1650 cm-1 associated with amide II, amide I, ß-sheets, and α-helixes, respectively, were prominent peaks where protein modulation was observed. The results demonstrate that infrared spectroscopy could be a good alternative technique to determine the modulation of protein expression during stroke events.

Pneumococcal surface protein A (PspA) prevents killing of Streptococcus pneumoniae by indolicidin.

Pneumococcal surface protein A (PspA) is an important virulence factor in Streptococcus pneumoniae that binds to lactoferrin and protects the bacterium from the bactericidal action of lactoferricins-cationic peptides released upon lactoferrin proteolysis. The present study investigated if PspA can prevent killing by another cationic peptide, indolicidin. PspA-negative pneumococci were more sensitive to indolicidin-induced killing than bacteria expressing PspA, suggesting that PspA prevents the bactericidal action of indolicidin. Similarly, chemical removal of choline-binding proteins increased sensitivity to indolicidin. The absence of capsule and PspA had an additive effect on pneumococcal killing by the AMP. Furthermore, anti-PspA antibodies enhanced the bactericidal effect of indolicidin on pneumococci, while addition of soluble PspA fragments competitively inhibited indolicidin action. Previous in silico analysis suggests a possible interaction between PspA and indolicidin. Thus, we hypothesize that PspA acts by sequestering indolicidin and preventing it from reaching the bacterial membrane. A specific interaction between PspA and indolicidin was demonstrated by mass spectrometry, confirming that PspA can actively bind to the AMP. These results reinforce the vaccine potential of PspA and suggest a possible mechanism of innate immune evasion employed by pneumococci, which involves binding to cationic peptides and hindering their ability to damage the bacterial membranes.

Genus-targeted markers for the taxonomic identification and monitoring of coagulase-positive and coagulase-negative Staphylococcus species.

The Staphylococcus genus comprises multiple pathogenic and opportunistic species that represent a risk to public health. Epidemiological studies require accurate taxonomic classification of isolates with enough resolution to distinguish clonal complexes. Unfortunately, 16 S rRNA molecular analysis and phenotypic characterization cannot distinguish all species and do not offer enough resolution to assess intraspecific diversity. Other approaches, such as Multilocus Sequence Tagging, provide higher resolution; however, they have been developed for Staphylococcus aureus and a few other species. Here, we developed a set of genus-targeted primers using five orthologous genes (pta, tuf, tpi, groEs, and sarA) to identify all Staphylococcus species within the genus. The primers were initially evaluated using 20 strains from the Collection of Microorganisms of Interest in Animal Health from AGROSAVIA (CMISA), and their amplified sequences were compared to a set of 33 Staphylococcus species. This allowed the taxonomic identification of the strains even on close species and the establishment of intraspecies diversity. To enhance the scope and cost-effectiveness of the proposed strategy, we customized the primer sets for an Illumina paired-end amplicon protocol, enabling gene multiplexing. We assessed five genes across 177 strains, generating 880 paired-end libraries from the CMISA. This approach significantly reduced sequencing costs, as all libraries can be efficiently sequenced in a single MiSeq run at a fraction (one-fourth or less) of the cost associated with Sanger sequencing. In summary, this method can be used for precise identification and diversity analysis of Staphylococcus species, offering an advancement over traditional techniques in both resolution and cost-effectiveness.

Distinguishing Protein Corona from Nanoparticle Aggregate Formation in Complex Biological Media Using X-ray Photon Correlation Spectroscopy.

In biological systems, nanoparticles interact with biomolecules, which may undergo protein corona formation that can result in noncontrolled aggregation. Therefore, comprehending the behavior and evolution of nanoparticles in the presence of biological fluids is paramount in nanomedicine. However, traditional lab-based colloid methods characterize diluted suspensions in low-complexity media, which hinders in-depth studies in complex biological environments. Here, we apply X-ray photon correlation spectroscopy (XPCS) to investigate silica nanoparticles (SiO2) in various environments, ranging from low to high complex biological media. Interestingly, SiO2 revealed Brownian motion behavior, irrespective of the complexity of the chosen media. Moreover, the SiO2 surface and media composition were tailored to underline the differences between a corona-free system from protein corona and aggregates formation. Our results highlighted XPCS potential for real-time nanoparticle analysis in biological media, surpassing the limitations of conventional techniques and offering deeper insights into colloidal behavior in complex environments.

Backbone 1H, 15N, and 13C resonance assignments of the FF1 domain from P190A RhoGAP in 5 and 8 M urea.

The Rho GTPase (Ras homolog GTPases) system is a crucial signal transducer that regulates various cellular processes, including cell cycle and migration, genetic transcription, and apoptosis. In this study, we investigated the unfolded state of the first FF domain (FF1) of P190A RhoGAP, which features four tandem FF domains. For signal transduction, FF1 is phosphorylated at tyrosine 308 (Y308), which is buried in the hydrophobic core and is inaccessible to kinases in the folded domain. It was proposed, therefore, that the phosphorylation occurs in a transiently populated unfolded state of FF1. To probe the folding pathway of the RhoGAP FF1 domain, here we have performed a nearly complete backbone resonance assignments of a putative partially unfolded state of FF1 in 5 M urea and its fully unfolded state in 8 M urea.

Combined additive effects of neuronal membrane glycoprotein GPM6a and the intercellular cell adhesion molecule ICAM5 on neuronal morphogenesis.

The mechanisms underlying neuronal development and synaptic formation in the brain depend on intricate cellular and molecular processes. The neuronal membrane glycoprotein GPM6a promotes neurite elongation, filopodia/spine formation, and synapse development, yet its molecular mechanisms remain unknown. Since the extracellular domains of GPM6a (ECs) command its function, we investigated the interaction between ICAM5, the neuronal member of the intercellular adhesion molecule (ICAM) family, and GPM6a's ECs. Our study aimed to explore the functional relationship between GPM6a and ICAM5 in hippocampal culture neurons and cell lines. Immunostaining of 15 days in vitro (DIV) neurons revealed significant co-localization between endogenous GPM6a clusters and ICAM5 clusters in the dendritic shaft. These results were further corroborated by overexpressing GPM6a and ICAM5 in N2a cells and hippocampal neurons at 5 DIV. Moreover, results from the co-immunoprecipitations and cell aggregation assays prove the cis and trans interaction between both proteins in GPM6a/ICAM5 overexpressing HEK293 cells. Additionally, GPM6a and ICAM5 overexpression additively enhanced neurite length, the number of neurites in N2a cells, and filopodia formation in 5 DIV neurons, indicating their cooperative role. These findings highlight the dynamic association between GPM6a and ICAM5 during neuronal development, offering insights into their contributions to neurite outgrowth, filopodia formation, and cell-cell interactions.

Potential uses of silkworm pupae (Bombyx mori L.) in food, feed, and other industries: a systematic review.

The increasing pressures imposed on ecosystems by the growing needs of the human population are stimulus for research into innovative and unconventional sources of raw materials for different industries. This systematic review was carried out to investigate the available literature on the possible industrial uses of silkworm (Bombyx mori L.) pupae, a residue of silk production. The review was conducted using an adapted version of PRISMA. After a screening process, 105 articles were obtained and subjected to a detailed quantitative and qualitative analysis. It was found that in the last decade there has been a significant increase in the number of papers devoted to the study of the potential use of silkworm pupae in different applications, with a significantly higher number in the last three years of the scope of this review, indicating a growing interest in the subject. From the analysis of the information collected, promising uses in human and animal food, such as fish, mammalian, poultry, swine and companion animals, as well as potential uses for the pharmaceutical industry, were identified. The evaluated research identified compounds with antioxidant activity and important contents of unsaturated fatty acids, which are related to beneficial effects on cardiovascular health, diabetes control, reduction of the risk of developing certain types of cancer and inflammatory activity, among other benefits. One of the most relevant findings is that many studies report a significant concentration of α-linolenic acid in silkworm pupae oil, which is attributed with anticancer, anti-inflammatory, antioxidant, anti-obesity and neuroprotective properties, among others.

STAT3 and the STAT3­regulated inhibitor of apoptosis protein survivin as potential therapeutic targets in colorectal cancer (Review).

Colorectal cancer (CRC) is one of the leading types of cancer worldwide. CRC development has been associated with the constitutive activation of signal transducer and activator of transcription 3 (STAT3). STAT3 is a master regulator of inflammation during cancer-associated colitis, and becomes upregulated in CRC. In CRC, STAT3 is activated by IL-6, among other pro-inflammatory cytokines, inducing the expression of target genes that stimulate proliferation, angiogenesis and the inhibition of apoptosis. One of the main STAT3-regulated inhibitors of apoptosis is survivin, which is a bifunctional protein that regulates apoptosis and participates in cell mitosis. Survivin expression is normally limited to foetal tissue; however, survivin is also upregulated in tumours. In silico and experimental analyses have shown that the STAT3 interactome is relevant during CRC progression, and the constitutive STAT3-survivin axis participates in development of the tumour microenvironment and response to therapy. The presence of a STAT3-survivin axis has been documented in CRC cohorts, and the expression of these molecules is associated with poor prognosis and a higher mortality rate in patients with CRC. Thus, STAT3, survivin, and the upstream activators IL-6 and IL-6 receptor, are considered therapeutic targets for CRC. Efforts to develop drugs targeting the STAT3-survivin axis include the evaluation of phytochemical compounds, small molecules and monoclonal antibodies. In the present review, the expression, function and participation of the STAT3-survivin axis in the progression of CRC were investigated. In addition, an update on the pre-clinical and clinical trials evaluating potential treatments targeting the STAT3-survivin axis is presented.