Mapping variants in HTLV-1 genome to analyze their impacts on the HAM/TSP development: A systematic review.

The reasons that lead some individuals living with the Human T Lymphotropic Virus 1 (HTLV-1) to develop HAM/TSP are still unclear. To better understand the viral genetic factors that may be associated with the development of HAM/TSP, this study aims to evaluate the impact of HTLV-1 genome mutations on the development of this disease through a systematic review. This review followed the PRISMA guidelines and was registered in the PROSPERO database. The search for articles was performed in PMC, PubMed, Lilacs, SciELO, and Embase databases using the following search descriptors: HTLV-1, HAM/TSP, mutation, polymorphism, genetic variation, and sequenc*. From the 1,929 articles found in the search, 20 were selected according to the pre-defined inclusion and exclusion criteria. A total of 619 HAM/TSP cases were compared with 555 AC controls. The mutations possibly related to the disease progression were detected in hbz (R119Q), tax (A7959V), ORF-I (R88K, P86S, S69G, P45L, L40F, C39R, CR9Y), and gp46 (V247I, N93D, S72G) genetic regions. The data collected and analyzed here indicate that mutations in the HTLV-1 genome could play an important role in the chronic inflammatory state and may be related to the development of HAM/TSP.

Combined expression of JHDM1D/KDM7A gene and long non-coding RNA RP11-363E7.4 as a biomarker for urothelial cancer prognosis.

Bladder cancer is the tenth most frequently diagnosed cancer globally. Classification of high- or low-grade tumors is based on cytological differentiation and is an important prognostic factor. LncRNAs regulate gene expression and play critical roles in the occurrence and development of cancer, however, there are few reports on their diagnostic value and co-expression levels with genes, which may be useful as specific biomarkers for prognosis and therapy in bladder cancer. Thus, we performed a marker lesion study to investigate whether gene/lncRNA expression in urothelial carcinoma tissues may be useful in differentiating low-grade and high-grade tumors. RT-qPCR was used to evaluate the expression of the JHDM1D gene and the lncRNAs CTD-2132N18.2, SBF2-AS1, RP11-977B10.2, CTD-2510F5.4, and RP11-363E7.4 in 20 histologically diagnosed high-grade and 10 low-grade tumors. A protein-to-protein interaction network between genes associated with JHDM1D gene was constructed using STRING website. The results showed a moderate (positive) correlation between CTD-2510F5.4 and CTD2132N18.2. ROC curve analyses showed that combined JHDM1D and RP11-363E7.4 predicted tumor grade with an AUC of 0.826, showing excellent accuracy. In conclusion, the results indicated that the combined expression of JHDM1D and RP11-363E7.4 may be a prognostic biomarker and a promising target for urothelial tumor therapy.

Sequential Separation of Essential Oil Components during Hydrodistillation of Fresh Foliage from Azorean Cryptomeria japonica (Cupressaceae): Effects on Antibacterial, Antifungal, and Free Radical Scavenging Activities.

Cryptomeria japonica wood industry generates large amounts of foliage biomass residues. Due to the increasing applications and markets for essential oils (EOs), fresh Azorean C. japonica foliage (Az-CJF) residues are used for local EO production. Hydrodistillation (HD), a common process for obtaining EOs, also provides the possibility to fractionate them. Thus, this study evaluated the in vitro antimicrobial and antioxidant activities of six Az-CJF EO fractions (Frs. 1-6), collected at sequential HD timeframes (HDTs: 0-2, 2-10, 10-30, 30-60, 60-120, and 120-240 min), in comparison to the crude EO, obtained from a non-fractionated HD (0-240 min HDT). Antimicrobial activities were assessed via disc diffusion method against seven bacteria (foodborne and/or human pathogens) and two Penicillium spp. (phytopathogenic fungi), and antioxidant activity was estimated using DPPH and ABTS assays. Concerning the antibacterial activity, all the EO samples were effective only toward Gram-positive bacteria. Fractions 1-3 (<30 min HDT) were the most active, with growth inhibition zones (GIZ) of 7.0-23.3 mm (1.4-2.2 times higher than those of the crude EO), being Bacillus spp. (B. licheniformis and B. subtilis) the most sensitive, followed by Staphylococcus aureus and Micrococcus luteus. Regarding the antifungal activity, Frs. 1-3 also displayed the best activities, but only against P. italicum (GIZ around 9.0 mm), while the crude EO showed no antifungal activity. Overall, the best antimicrobial properties of Frs. 1-3 could be attributed, at least in part, to their highest content in α-pinene and bornyl acetate. On the other hand, Frs. 4-6 (>30 min HDT) exhibited the strongest antioxidant activities (EC50 values: 1.5-2.3 and 1.0-1.7 mg mL-1 for DPPH and ABTS, respectively), being at least 1.3-fold higher than those of the crude EO. The presence of nezukol, elemol, and eudesmol isomers could strongly contribute to the best free radical scavenging properties of Frs. 4-6. In conclusion, HD was found to be an efficient process for obtaining new Az-CJF EO fractions with variable and enhanced bioactivities due to their differential composition, as assessed using GC-MS. Hence, these findings could contribute to increasing the commercial potential of the C. japonica EO industry, namely, the Fr2 and Fr6, which presented the most significant activities and can have potential applications in the food, medical, and agriculture sectors.

In silico and in vivo analysis reveal impact of c-Myc tag in FMC63 scFv-CD19 protein interface and CAR-T cell efficacy.

Anti-CD19 CAR-T cell therapy represents a breakthrough in the treatment of B-cell malignancies, and it is expected that this therapy modality will soon cover a range of solid tumors as well. Therefore, a universal cheap and sensitive method to detect CAR expression is of foremost importance. One possibility is the use of epitope tags such as c-Myc, HA or FLAG tags attached to the CAR extracellular domain, however, it is important to determine whether these tags can influence binding of the CAR with its target molecule. Here, we conducted in-silico structural modelling of an FMC63-based anti-CD19 single-chain variable fragment (scFv) with and without a c-Myc peptide tag added to the N-terminus portion and performed molecular dynamics simulation of the scFv with the CD19 target. We show that the c-Myc tag presence in the N-terminus portion does not affect the scFv's structural equilibrium and grants more stability to the scFv. However, intermolecular interaction potential (IIP) analysis reveals that the tag can approximate the complementarity-determining regions (CDRs) present in the scFv and cause steric impediment, potentially disturbing interaction with the CD19 protein. We then tested this possibility with CAR-T cells generated from human donors in a Nalm-6 leukemia model, showing that CAR-T cells with the c-Myc tag have overall worse antitumor activity, which was also observed when the tag was added to the C-terminus position. Ultimately, our results suggest that tag addition is an important aspect of CAR design and can influence CAR-T cell function, therefore its use should be carefully considered.

Analysis of epidemiological and clinical aspects in cases of fungal osteomyelitis caused by non-Candida species.

Osteomyelitis caused by non-Candida species is rare and often neglected, and current recommendations are based on primarily clinical experience and expert opinion. The objective of this study was to describe a case series of non-Candida fungal osteomyelitis. This retrospective study included 10 patients with non-Candida fungal osteomyelitis. Patients with osteomyelitis and microbiologically confirmed non-Candida species from bone fragment cultures were selected from the institution Infection Control Board database. Fusarium spp. were the most commonly isolated fungus from bone fragment cultures in five patients (50%). The majority did not present immunosuppression. The most common etiology was post-traumatic (n = 7, 70%), particularly open fractures. All patients were treated with antifungals associated with surgery. The antifungals used were itraconazole in five patients (50%), and voriconazole in another five patients (50%), with a median duration of antifungal therapy of four weeks (range: 3-25). There were no observed deaths within 30 days and one year. An antifungal approach combined with surgical treatment demonstrated favorable clinical outcomes, including low mortality rates and effective remission.

Adhesion of Acanthamoeba on Scleral Contact Lenses According to Lens Shape.

Purpose: To investigate the adhesion of Acanthamoeba to scleral contact lens (ScCL) surface according to lens shape. Methods: Two strains of A. polyphaga (CDC:V062 and ATCC 30461) and one clinical Acanthamoeba isolate, were inoculated onto five contact lens (CL): one first-generation silicone hydrogel (SHCL; lotrafilcon B; adhesion control) containing plasma surface treatment; two ScCL (fluorosilicone acrylate) one containing surface treatment composed of plasma and the other containing plasma with Hydra-PEG, and two CL designed with a flat shape having the same material and surface treatments of the ScCL. Trophozoites that adhered to the lens's surfaces were counted by inverted optical light microscopy. Possible alterations of the lens surface that could predispose amoeba adhesion and Acanthamoeba attached to these lens surfaces were evaluated by scanning electron microscopy (SEM). Results: All strains revealed greater adhesion to the ScCL when compared with the flat lenses (P < 0.001). The clinical isolate and the ATCC 30461 had a higher adhesion (P < 0.001) when compared with the CDC:V062. A rough texture was observed on the surface of the lenses that have been examined by SEM. Also, SEM revealed that the isolates had a rounded appearance on the surface of the ScCL in contrast with an elongated appearance on the surface of the silicone hydrogel. Conclusions: The findings revealed that the curved shape of the ScCL favors amoeba adhesion.

Bilateral testicular myxosarcoma in a cryptorchid dog.

Myxosarcoma is a rare malignant mesenchymal neoplasm of soft tissues originating from fibroblasts. This report describes a case of bilateral myxosarcoma in a three-year-old cryptorchid dog. The animal was referred to the veterinary clinic because of the absence of testicles in the scrotum. Ultrasonography revealed two masses in the abdominal cavity with testicular echotexture. Exploratory laparotomy revealed the presence of cryptorchid testicles, and orchiectomy was recommended to treat the animal. Testicles were gray and reddish in color and enlarged with firm consistency. For histopathological analysis, testis fragments were fixed in 10% formalin and stained with hematoxylin and eosin and Alcian blue. Immunohistochemistry was performed using the following primary antibodies:1A4, HHF35, desmin, glial fibrillary acidic protein, CD31, S-100, vimentin, and Ki-67. Histopathological evaluation revealed the proliferation of fusiform and round cells associated with extensive areas of myxoid matrix. Neoplasms featured multinucleated giant cells, pleomorphism, karyomegaly, nuclear hyperchromasia, anisokaryosis, mitoses, and necrosis, with coarse chromatin and prominent nucleoli. Immunohistochemical analysis of vimentin- and the Alcian blue-positive cells confirmed the diagnosis of myxosarcoma. A high mitotic count and Ki-67 proliferative index suggests this myxosarcoma had a high degree of malignancy. To the best of our knowledge, this is the first case report of bilateral testicular myxosarcoma in a cryptorchid animal.

Deflamin Attenuated Lung Tissue Damage in an Ozone-Induced COPD Murine Model by Regulating MMP-9 Catalytic Activity.

Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from Lupinus albus, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson's trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity.

Silymarin inhibits dermal gelatinolytic activity and reduces cutaneous inflammation.

Milk thistle (Silybum marianum) is well-known for its antioxidant activity due to the presence of silymarin. Albeit some studies show a potential for skin inflammation, its activity against dermal MMP-9 and MMP-2 remains to be studied. Silymarin isolated from an S. marianum herbal extract was tested for gelatinase inhibition in the presence of isolated MMP-9 and in dermal adenocarcinome HaCaT cells. Silymarin was then further tested in vivo, using a cutaneous inflammation mice model mediated by reactive oxygen species. Silymarin was able to significantly inhibit gelatinolytic activity in vitro without impairing cell growth and viability. Furthermore, inhibition was more pronounced in cells than with the isolated gelatinase, suggesting an additional effect upon metabolic pathways. In vivo, silymarin was able to reduce ear edema up to 74% and attenuated histological lesions. Results highlight silymarin potential for application in skin inflammatory disorders via gelatinase inhibition.

Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia.

Vincristine-induced peripheral neuropathy is a common side effect of vincristine treatment, which is accompanied by pain and can be dose-limiting. The molecular mechanisms that underlie vincristine-induced pain are not well understood. We have established an animal model to investigate pathophysiological mechanisms of vincristine-induced pain. Our previous studies have shown that the tetrodotoxin-sensitive voltage-gated sodium channel Nav1.6 in medium-diameter dorsal root ganglion (DRG) neurons contributes to the maintenance of vincristine-induced allodynia. In this study, we investigated the effects of vincristine administration on excitability in small-diameter DRG neurons and whether the tetrodotoxin-resistant (TTX-R) Nav1.8 channels contribute to mechanical allodynia. Current-clamp recordings demonstrated that small DRG neurons become hyper-excitable following vincristine treatment, with both reduced current threshold and increased firing frequency. Using voltage-clamp recordings in small DRG neurons, we now show an increase in TTX-R current density and a -7.3 mV hyperpolarizing shift in the half-maximal potential (V1/2) of activation of Nav1.8 channels in vincristine-treated animals, which likely contributes to the hyperexcitability that we observed in these neurons. Notably, vincristine treatment did not enhance excitability of small DRG neurons from Nav1.8 knockout mice, and the development of mechanical allodynia was delayed but not abrogated in these mice. Together, our data suggest that sodium channel Nav1.8 in small DRG neurons contributes to the development of vincristine-induced mechanical allodynia.

Effects of Particle Size on Physicochemical and Nutritional Properties and Antioxidant Activity of Apple and Carrot Pomaces.

The food processing industry is growing rapidly and producing large amounts of by-products, such as pomaces, which are considered as no-value waste and cause significant environmental pollution. The main by-products of fruit juice processing companies are apple and carrot pomaces, which can be used to create new functional food products. In the present study, the effects of particle size (PS) on the proximate composition, nutritional properties, and antioxidant activity of apple pomace flour (APF) and carrot pomace flour (CPF) were determined. Four different PS fractions, PS > 1 mm, 1 > PS > 0.71 mm, 0.71 > PS > 0.18 mm, and 0.18 > PS > 0.075 mm were used for the present study. Their vitamin, carotenoid, organic acid, and reducing sugar contents were determined using HPLC. The proximate compositions of each PS fraction of the AP and CP flours were determined using recommended international standard methods. DPPH, FRAP, and Folin-Ciocalteu methods were used to measure their antioxidant activity and total phenolic compounds, respectively. The moisture content (around 12.1 mg/100 g) was similar in all PS fractions and in both flours. The APF had lower protein (4.3-4.6 g/100 g dw) and ash (1.7-2.0 g/100 g dw) contents compared to the CPF, with protein contents ranging from 6.4-6.8 g/100 g dw and ash contents ranging from 5.8-6.1 g/100 g dw. Smaller particles, regardless of flour type, exhibited higher sugar and phenolic contents and antioxidant activity, while vitamins were more abundant in particles larger than 1 mm. In the APF, larger particles had a higher fiber content than smaller particles, while their fat content was the lowest. PS also had an impact on the results of the carotenoid contents. This study underscores the direct impact of PS on the distribution of sugars, crude fiber, fat, carotenoids, vitamins, total phenolic compounds, and antioxidant activity in pomaces.

Processo de trabalho das enfermeiras da atenção primária à saúde frente à pandemia por covid-19 / Nurses' work process of primary health care in the face of the covid-19 pandemic / Proceso de trabajo de las enfermeras de la atención primaria de salud ante la pandemia del covid-19

Objetivo: Analisar o processo de trabalho das enfermeiras da Atenção Primária à Saúde frente à pandemia de COVID-19. Métodos: Trata-se de uma pesquisa qualitativa, descritiva e exploratória. A coleta de dados ocorreu de abril a maio de 2021, por meio de entrevista semiestruturada com 09 enfermeiras. Os dados foram analisados por meio de análise temática, e interpretados à luz da literatura pertinente. Resultados: Evidenciou-se o medo de faltar Equipamentos de Proteção Individual e recusa de atendimentos na falta destes. Utilizou-se a teleconsulta como meio de assistência de enfermagem, que mostrou limitações, como: invasão de privacidade das enfermeiras, extensão da jornada de trabalho e sobrecarga. Priorizou-se o atendimento à saúde da mulher e da criança. E ainda, notou-se o esforço no acolhimento aos casos suspeitos e agudos de COVID-19. Verificou-se a sobrecarga de trabalho e acúmulo de funções. Entretanto, lições foram adquiridas como a valorização de medidas de proteção, como a higiene das mãos. Conclusão: Infere-se a necessidade de criação e validação de novos protocolos que fortaleçam a assistência de enfermagem, bem como a importância de estimular as políticas de saúde para controle das Infecções Relacionadas à Assistência à Saúde. (AU)

Objective: To analyze the work process of Primary Health Care nurses in the face of the COVID-19 pandemic. Methods: This is a qualitative, descriptive and exploratory research. Data were analyzed using thematic analysis and interpreted in light of the relevant literature. Results: The fear of lacking personal protective equipment was evidenced and the refusal of care in the absence of these. Teleconsultation was used as a means of nursing care, which showed limitations such as invasion of nurses' privacy, extension of the workday and overload. The health care of women and children was prioritized. Also, there was an effort to host suspected and acute cases of COVID-19. There was work overload and accumulation of functions. However, lessons were learned, such as valuing protective measures such as hand hygiene. Conclusion: The need to create and validate new protocols that strengthen nursing care is inferred, as well as the importance of stimulating health policies to control Health-Related Infections. (AU)

Objetivo: Analizar el proceso de trabajo de las enfermeras de Atención Primaria de Salud frente a la pandemia de COVID-19. Métodos: Se trata de una investigación cualitativa, descriptiva y exploratoria. Los datos se analizaron mediante un análisis temático y se interpretaron a la luz de la bibliografía pertinente. Resultados: Se evidenció el miedo a la falta de equipo de protección personal y la negativa de atención en ausencia de estos. La teleconsulta fue utilizada como medio de atención de enfermería, que mostró limitaciones como la invasión de la privacidad de los enfermeros, la duración de la jornada laboral y la sobrecarga. Se priorizó la atención de la salud de las mujeres y los niños. Además, hubo un esfuerzo para albergar casos sospechosos y agudos de COVID-19. Había sobrecarga de trabajo y acumulación de funciones. Sin embargo, se aprendieron lecciones, como la valoración de medidas de protección como la higiene de manos. Conclusión: Se infiere la necesidad de crear y validar nuevos protocolos que fortalezcan los cuidados de enfermería, así como la importancia de estimular políticas de salud para el control de las Infecciones Relacionadas con la Salud. (AU)

Reinventando a participação no SUS: o controle social em defesa da Democracia e do Direito à Saúde - 30 anos do Conselho Municipal de Saúde de Porto Alegre! / Reinventing participation in the SUS: social control in defense of Democracy and the Right to Health - 30 years of the Porto Alegre Municipal Health Council!

Este livro celebra os 30 anos do Conselho Municipal de Saúde de Porto Alegre e reúne um conjunto de textos que apresentam e discutem ações e lutas ocorridas a partir de 2017 relacionadas ao CMS-POA, buscando sistematizar e dar visibilidade aos temas emergentes e principais desafios enfrentados no período. O CMS-POA tem a tradição de compartilhar seu percurso e suas reflexões por meio de notas públicas, manifestos e, a cada quinquênio, um livro. Os livros comemorativos têm se consolidado ao longo dos 15, 20, 25 e agora 30 anos do Conselho. Os registros memoriais dessa trajetória constituem um movimento de resistência e refundação dos fazeres do Conselho, que tem enfrentado o desafio de monitorar e consolidar o SUS na cidade. Nesse livro, em especial, buscamos aprofundar o tema emergente do empresariamento da Saúde, mas também de ações e projetos desenvolvidos pelo CMS-POA e por seus parceiros, o que demanda reflexões sobre o atual cenário das políticas de saúde e dos interesses em disputa. Os textos foram escritos por parceiros históricos do Conselho que conosco acreditam que saúde é democracia e, portanto, se faz com participação social.

Health promotion and prevention actions in the Brazilian Unified Health System (SUS): evaluation of the temporal trend and impact of the COVID-19 pandemic / Ações de promoção e prevenção em saúde no Sistema Único de Saúde (SUS): avaliação da tendência temporal e do impacto da pandemia da COVID-19

Objective: To evaluate health promotion and prevention in the Brazilian Unified Health System (SUS) between 2008 and 2022. Method: An epidemiological study was conducted, with an ecological approach, as a time series. APPS-related data available in the Outpatient Information System of the SUS (SIA/SUS) over the last 15 years were used, normalized to every 100,000 Brazilian residents, characterizing the incidence. COVID-19 pre- and post-pandemic periods were outlined to verify its impact on productivity. The data were analyzed with a significance level of 5%. Result: Between 2008 and 2022, 6,933,081,931 APPS were carried out in the SUS. The most frequent modality was home visits (56.3%), and the most common health professionals were health and endemic agents (59.8%). For the entire study period, the incidence was 3,407,327 APPS per 100,000 Brazilian residents, with an annual median of 281,999. Furthermore, there was a significant decreasing trend over the last 15 years (p <0.001), whose annual percentage change was estimated at -6.7%. Disregarding COVID-19 pandemic years, the trend remained to decrease (p = 0.028). At last, when comparing it to the pre-pandemic period, the incidence of APPS were 32% lower in the first, 26% lower in the second, and 21% lower in the third year after the COVID-19 pandemic onset (p <0.001). Conclusion: It was possible to conclude that APPS in the SUS have reduced in the last 15 years

Objetivo: Avaliar as ações de promoção e prevenção em saúde (APPS) realizadas no Sistema Único de Saúde (SUS) entre 2008 e 2022. Método: Foi conduzido um estudo epidemiológico, com abordagem ecológica, do tipo série temporal. Foram utilizados os dados relativos às APPS no Sistema de Informações Ambulatoriais do SUS (SIA/SUS) nos últimos 15 anos, normalizada a cada 100.000 residentes brasileiros, caracterizando a incidência. Foram delineados períodos pré e pós-pandemia da COVID-19 para verificar o seu impacto na produtividade. Os dados foram analisados com nível de significância de 5%. Resultado: Entre 2008 e 2022, 6.933.081.931 APPS foram realizadas no SUS. A modalidade mais frequente foram as visitas domiciliares (56,3%) e os profissionais da saúde mais comuns foram os agentes de saúde e endemias (59,8%). Para todo o período, a incidência foi de 3.407.327 APPS a cada 100.000 residentes brasileiros, com mediana anual de 281.999. Ademais, houve uma tendência de redução ao longo dos últimos 15 anos (p <0,001), cuja variação percentual anual foi estimada em -6,7%. Desconsiderando o período da pandemia da COVID-19, a tendência permaneceu decrescente (p = 0,028). Por fim, ao compará-la com o período pré-pandemia, a incidência de APPS foi 32% menor no primeiro, 26% menor no segundo e 21% menor no terceiro ano após o início da pandemia da COVID-19 (p <0,001). Conclusão: Foi possível concluir que as APPS no SUS reduziram nos últimos 15 anos

Milk Antiviral Proteins and Derived Peptides against Zoonoses.

Milk is renowned for its nutritional richness but also serves as a remarkable reservoir of bioactive compounds, particularly milk proteins and their derived peptides. Recent studies have showcased several robust antiviral activities of these proteins, evidencing promising potential within zoonotic viral diseases. While several publications focus on milk's bioactivities, antiviral peptides remain largely neglected in reviews. This knowledge is critical for identifying novel research directions and analyzing potential nutraceuticals within the One Health context. Our review aims to gather the existing scientific information on milk-derived antiviral proteins and peptides against several zoonotic viral diseases, and their possible mechanisms. Overall, in-depth research has increasingly revealed them as a promising and novel strategy against viruses, principally for those constituting a plausible pandemic threat. The underlying mechanisms of the bioactivity of milk's proteins include inhibiting viral entry and attachment to the host cells, blocking replication, or even viral inactivation via peptide-membrane interactions. Their marked versatility and effectiveness stand out compared to other antiviral peptides and can support future research and development in the post-COVID-19 era. Overall, our review helps to emphasize the importance of potentially effective milk-derived peptides, and their significance for veterinary and human medicines, along with the pharmaceutical, nutraceutical, and dairy industry.

PI3K Signaling Pathways as a Molecular Target for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common type of cancer that affects the central nervous system (CNS). It currently accounts for about 2% of diagnosed malignant tumors worldwide, with 296,000 new cases reported per year. The first-choice treatment consists of surgical resection, radiotherapy, and adjuvant chemotherapy, which increases patients' survival by 15 months. New clinical and pre-clinical research aims to improve this prognosis by proposing the search for new drugs that effectively eliminate cancer cells, circumventing problems such as resistance to treatment. One of the promising therapeutic strategies in the treatment of GBM is the inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway, which is closely related to the process of tumor carcinogenesis. This review sought to address the main scientific studies of synthetic or natural drug prototypes that target specific therapy co-directed via the PI3K pathway, against human glioblastoma.

Recalculating the Route: Repositioning Antimicrobial Peptides for Cancer Treatment.

Resistance to antimicrobial drugs has been considered a public health problem. Likewise, the increasing resistance of cancer cells to drugs currently used in therapy has also become a problem. Therefore, the research and development of synthetic peptides bring a new perspective on the emergence of new drugs for treating this resistance since bioinformatics provides a means to optimize these molecules and save time and costs in research. Peptides have several mechanisms of action, such as forming pores on the cell membrane and inhibiting protein synthesis. Some studies report the use of antimicrobial peptides with the potential for action against cancer cells, suggesting a repositioning of antimicrobial peptides to fight back cancer resistance. There is an alteration in the microenvironment, making its net charge negative for the survival and growth of cancer cells. The changes in glycoproteins favor the membrane to have a more negative charge, favoring the interaction between the cells and the peptide, thus making possible the repositioning of these antimicrobial peptides against cancer. Here, we will discuss the mechanism of action, targets and effects of peptides, comparison between microbial and cancer cells, and proteomic changes caused by the interaction of peptides and cells.

Mutation of p53 increases the competitive ability of pluripotent stem cells.

During development, the rate of tissue growth is determined by the relative balance of cell division and cell death. Cell competition is a fitness quality-control mechanism that contributes to this balance by eliminating viable cells that are less fit than their neighbours. The mutations that confer cells with a competitive advantage and the dynamics of the interactions between winner and loser cells are not well understood. Here, we show that embryonic cells lacking the tumour suppressor p53 are 'super-competitors' that eliminate their wild-type neighbours through the direct induction of apoptosis. This elimination is context dependent, as it does not occur when cells are pluripotent and it is triggered by the onset of differentiation. Furthermore, by combining mathematical modelling and cell-based assays we show that the elimination of wild-type cells is not through competition for space or nutrients, but instead is mediated by short-range interactions that are dependent on the local cell neighbourhood. This highlights the importance of the local cell neighbourhood and the competitive interactions within this neighbourhood for the regulation of proliferation during early embryonic development.