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1.
Food Chem ; 398: 133923, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35987005

RESUMO

This study aimed to characterize a novel antimicrobial peptide (AMP) obtained from Moringa oleifera seed protein hydrolysates. Cell membrane chromatography and live bacteria adsorption were combined into a single step to efficiently isolate the active fraction of the AMP. Five peptides were identified by LC-MS/MS, among which the MCNDCGA peptide (termed MOp3) showed the greatest inhibitory effect against Staphylococcus aureus [minimum inhibitory concentration (MIC): 2 mg/mL]. MOp3 was identified as a hydrophobic anionic AMP rich in ß-sheet structures with negligible hemolytic activity at 2.0 × MIC. MOp3 had good tolerance to salt solutions at 5 % and pH range 6.0-8.0, but was sensitive to high temperatures (>100 °C) and acid protease. Microscopic observation further revealed that MOp3 induced irreversible damage onto the cell membrane of S. aureus and interacted with dihydrofolate reductase and DNA gyrase by hydrogen bonding and hydrophobic interaction. These findings highlight the potential application of a new antimicrobial agent against S. aureus in the food industry.


Assuntos
Moringa oleifera , Monofosfato de Adenosina/análise , Adsorção , Peptídeos Antimicrobianos , Cromatografia Líquida , Moringa oleifera/química , Extratos Vegetais/química , Sementes/química , Staphylococcus aureus , Espectrometria de Massas em Tandem
2.
Food Chem ; 400: 134001, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36084586

RESUMO

Flavonoids are associated with health benefits, but most of them have poor oral bioavailability due to their extremely low aqueous solubility. Flavonoid O-phosphorylation suggests a potent modification to solve the problems. Here, we isolated, identified and characterized an unprecedented phosphotransferase, flavonoid phosphate synthetase (BsFPS), from B. subtilis. The enzyme catalyzes the ATP-dependent phosphorylation of flavonoid to generate flavonoid monophosphates, AMP and orthophosphate. BsFPS is a promiscuous phosphotransferase that efficiently catalyzes structurally-diverse flavonoids, including isoflavones, flavones, flavonols, flavanones and flavonolignans. Based on MS and NMR analysis, the phosphorylation mainly occurs on the hydroxyl group at C-7 of A-ring or C-4' of B-ring in flavonoid skeleton. Notably, BsFPS is regioselective for the ortho-3',4'-dihydroxy moiety of catechol-containing structures, such as luteolin and quercetin, to produce phosphate conjugates at C-4' or C-3' of B-ring. Our findings highlight the potential for developing biosynthetic platform to obtain new phosphorylated flavonoids for pharmaceutical and nutraceutical applications.


Assuntos
Flavanonas , Flavonas , Flavonolignanos , Isoflavonas , Monofosfato de Adenosina , Trifosfato de Adenosina , Bacillus subtilis , Catecóis , Flavonoides/química , Ligases , Luteolina , Preparações Farmacêuticas , Fosfatos , Fosfotransferases , Quercetina
3.
Cell Rep ; 40(12): 111344, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36130485

RESUMO

Telomerase activation counteracts senescence and telomere erosion caused by uncontrolled proliferation. Epidermal growth factor receptor (EGFR) amplification drives proliferation while telomerase reverse transcriptase promoter (TERTp) mutations underlie telomerase reactivation through recruitment of GA-binding protein (GABP). EGFR amplification and TERTp mutations typically co-occur in glioblastoma, the most common and aggressive primary brain tumor. To determine if these two frequent alterations driving proliferation and immortality are functionally connected, we combine analyses of copy number, mRNA, and protein data from tumor tissue with pharmacologic and genetic perturbations. We demonstrate that proliferation arrest decreases TERT expression in a GABP-dependent manner and elucidate a critical proliferation-to-immortality pathway from EGFR to TERT expression selectively from the mutant TERTp through activation of AMP-mediated kinase (AMPK) and GABP upregulation. EGFR-AMPK signaling promotes telomerase activity and maintains telomere length. These results define how the tumor cell immortality mechanism keeps pace with persistent oncogene signaling and cell cycling.


Assuntos
Glioblastoma , Telomerase , Proteínas Quinases Ativadas por AMP/metabolismo , Monofosfato de Adenosina , Receptores ErbB/genética , Receptores ErbB/metabolismo , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Glioblastoma/genética , Humanos , Mutação/genética , Oncogenes , RNA Mensageiro , Telomerase/genética , Telomerase/metabolismo , Telômero/genética , Telômero/metabolismo
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 1753-1756, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36085854

RESUMO

Traumatic Brain Injury (TBI) patients present high levels of physical stress, which in some situations can manifest as Plateau Wave (PW) episodes. This intense stress phenomenon can be evidenced by Heart Rate Variability (HRV). Thus, the multivariate and simultaneous analysis of cardio-cerebrovascular oscillations, involving the RR intervals, mean arterial pressure (MAP) and the amplitude of intracranial pressure (AMP), will be useful to understand the interconnections between body signals, allowing the interpretation of the combined activity of pathophysiological mechanisms. In this work, the multiscale representation of the Transfer Entropy (TE) and of its decomposition in the network of these three interacting processes is obtained, based on a Vector AutoRegressive Fractionally Integrated (VARFI) framework for Gaussian processes. This method allows to assess directed interactions and to quantify the information flow accounting for the simultaneous presence of short-term dynamics and long-range correlations. The results show that the baseline RR, but not MAP can provide information about the possibility of a PW arising. During PW, the long-term correlations highlight synergistic interactions between MAP and AMP processes on RR. The multiscale decomposition of the information along with the incorporation of the long term correlations allowed a better description of HRV during PW, highlighting the fact that the HRV mirrors this cerebrovascular phenomena.


Assuntos
Lesões Encefálicas Traumáticas , Pressão Intracraniana , Monofosfato de Adenosina , Frequência Cardíaca , Humanos , Memória
5.
Oxid Med Cell Longev ; 2022: 3737137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092159

RESUMO

Acute renal ischemia/reperfusion (I/R) injury often occurs during kidney transplantation and other kidney surgeries, and the molecular mechanism involves oxidative stress. We hypothesized that ginsenoside Rg1 (Rg1), a saponin derived from ginseng, would protect the renal tissue against acute renal I/R injury by upregulating 5' adenosine monophosphate-activated protein kinase α1 (AMPKα1) expression and inhibiting oxidative stress. The models of acute anoxia/reoxygenation (A/R) damage in normal rat kidney epithelial cell lines (NRK-52E) and acute renal I/R injury in mice were constructed. The results revealed that pretreatment with 25 µM Rg1 significantly increased NRK-52E viability, decreased lactate dehydrogenase (LDH) activity and apoptosis, suppressed reactive oxygen species generation and oxidative stress, stabilized mitochondrial membrane potential and reduced mitochondria permeability transition pore openness, decreased adenosine monophosphate/adenosine triphosphate ratio, and upregulated the expression of AMPKα1, cytochrome b-c1 complex subunit 2, NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8, and B-cell lymphoma 2, while downregulating BCL2-associated X protein expression. The effects of Rg1 pretreatment were similar to those of pAD/Flag-AMPKα1. After acute renal I/R injury, serum creatinine, blood urea nitrogen, LDH activity, and oxidative stress in renal tissue significantly increased. Rg1 pretreatment upregulated AMPKα1 expression, which protects against acute renal I/R injury by maintaining renal function homeostasis, inhibiting oxidative stress, and reducing apoptosis. Compound C, a specific inhibitor of AMPK, reversed the effects of Rg1. In summary, Rg1 pretreatment upregulated AMPKα1 expression, inhibited oxidative stress, maintained mitochondrial function, improved energy metabolism, reduced apoptosis, and ultimately protected renal tissue against acute renal I/R injury.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Injúria Renal Aguda/tratamento farmacológico , Monofosfato de Adenosina , Animais , Ginsenosídeos , Isquemia , Rim/patologia , Rim/fisiologia , Camundongos , Ratos , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia
6.
Front Immunol ; 13: 943667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081510

RESUMO

Bacillus Calmette-Guérin (BCG) is a licensed prophylactic vaccine against tuberculosis (TB). Current TB vaccine efforts focus on improving BCG effects through recombination or genetic attenuation and/or boost with different vaccines. Recent years, it was revealed that BCG could elicit non-specific heterogeneous protection against other pathogens such as viruses through a process termed trained immunity. Previously, we constructed a recombinant BCG (rBCG-DisA) with elevated c-di-AMP as endogenous adjuvant by overexpressing di-adenylate cyclase of Mycobacterium tuberculosis DisA, and found that rBCG-DisA induced enhanced immune responses by subcutaneous route in mice after M. tuberculosis infection. In this study, splenocytes from rBCG-DisA immunized mice by intravenous route (i.v) elicited greater proinflammatory cytokine responses to homologous and heterologous re-stimulations than BCG. After M. tuberculosis infection, rBCG-DisA immunized mice showed hallmark responses of trained immunity including potent proinflammatory cytokine responses, enhanced epigenetic changes, altered lncRNA expressions and metabolic rewiring in bone marrow cells and other tissues. Moreover, rBCG-DisA immunization induced higher levels of antibodies and T cells responses in the lung and spleen of mice after M. tuberculosis infection. It was found that rBCG-DisA resided longer than BCG in the lung of M. tuberculosis infected mice implying prolonged duration of vaccine efficacy. Then, we found that rBCG-DisA boosting could prolong survival of BCG-primed mice over 90 weeks against M. tuberculosis infection. Our findings provided in vivo experimental evidence that rBCG-DisA with c-di-AMP as endogenous adjuvant induced enhanced trained immunity and adaptive immunity. What's more, rBCG-DisA showed promising potential in prime-boost strategy against M. tuberculosis infection in adults.


Assuntos
Mycobacterium bovis , Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Aciltransferases/genética , Monofosfato de Adenosina , Adjuvantes Imunológicos , Adjuvantes Farmacêuticos , Animais , Antígenos de Bactérias , Vacina BCG , AMP Cíclico , Citocinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Vacinas Sintéticas
7.
Oncol Nurs Forum ; 49(5): 471-479, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067239

RESUMO

OBJECTIVES: To determine the feasibility and acceptability of using a decision aid (DA) in a breast surgery clinic. SAMPLE & SETTING: 42 patients with minimally suspicious mammograms and two physicians participated in this study at an outpatient breast specialty clinic in Virginia. METHODS & VARIABLES: A quasiexperimental single group pilot study was conducted to determine the feasibility of DecisionKEYS, a theory-based, interactive DA intervention. Patients with minimally suspicious mammogram results chose between breast biopsy or close imaging follow-up. The Decisional Conflict Scale was used to measure decisional conflict. The Decision-Making Quality Scale was used to evaluate the overall decision process. Postintervention physician and patient feedback evaluated feasibility and acceptability. RESULTS: Participants and physicians rated the DA as helpful. Decisional Conflict Scale scores were low before and after the intervention. Physicians reported the DA was feasible for workflow, and the majority reported using the DA in making final recommendations. Management recommendation (breast biopsy, close imaging follow-up) changed in 26 of 42 cases from pre- to postintervention. The majority of participants underwent breast biopsy. IMPLICATIONS FOR NURSING: The feasibility and acceptability of the DA were beneficial to patients and clinic workflow.


Assuntos
Técnicas de Apoio para a Decisão , Detecção Precoce de Câncer , Monofosfato de Adenosina , Tomada de Decisões , Humanos , Mamografia , Projetos Piloto
8.
Oncol Nurs Forum ; 49(5): 395-408, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067240

RESUMO

OBJECTIVES: To examine associations of coping resources for psychological distress among newly diagnosed Spanish-speaking Latina women with breast cancer (LWBC). SAMPLE & SETTING: Analyses used baseline data from a randomized controlled trial of a stress management intervention among 151 LWBC. METHODS & VARIABLES: Dependent variables were health distress and anxiety. Coping resources at the intrapersonal, interpersonal, and organizational/community levels were included. RESULTS: At the intrapersonal level, self-efficacy for coping with breast cancer treatment was associated inversely with health distress and anxiety, and coping confidence with general problems was associated inversely with health distress. At the interpersonal level, having a sense of neighborhood cohesion was associated inversely with health distress. No organizational/community level resources were associated with health distress or anxiety. IMPLICATIONS FOR NURSING: Interventions that enhance self-efficacy in coping and foster skills to identify sources of neighborhood support may decrease psychological distress for Spanish-speaking LWBC.


Assuntos
Neoplasias da Mama , Angústia Psicológica , Adaptação Psicológica , Monofosfato de Adenosina , Neoplasias da Mama/psicologia , Feminino , Hispânico ou Latino , Humanos , Estresse Psicológico/terapia
9.
Oncol Nurs Forum ; 49(5): 409-420, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067241

RESUMO

OBJECTIVES: To evaluate the effect of a symptom management mobile application on quality of life and symptom severity in women with breast cancer undergoing chemotherapy. SAMPLE & SETTING: This parallel randomized pilot study consisted of women with breast cancer admitted to oncology outpatient clinics between November 2019 and January 2021 in Turkey. METHODS & VARIABLES: Participants (N = 40) were randomly assigned to the intervention (n = 20) or control group (n = 20). The intervention group used the mobile application in conjunction with usual care. The control group received usual care. Participants were assessed during the first, third, and last chemotherapy cycles. Data were collected using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 and the Edmonton Symptom Assessment System. RESULTS: During the study, the decrease in general health and physical functioning and the increase in the severity of depression/sadness in the intervention group were statistically lower than in the control group. IMPLICATIONS FOR NURSING: The use of a mobile application for symptom management may promote general well-being and physical function and may alleviate symptoms of depression/sadness in women with breast cancer undergoing chemotherapy. Further studies are needed to evaluate the application in clinical settings with larger groups.


Assuntos
Neoplasias da Mama , Aplicativos Móveis , Monofosfato de Adenosina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Projetos Piloto , Qualidade de Vida
10.
Oncol Nurs Forum ; 49(5): 421-431, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067242

RESUMO

OBJECTIVES: To examine colorectal cancer (CRC) survivors' symptom characteristics (occurrence, frequency, and severity) during acute cancer survivorship. PARTICIPANTS & SETTING: A cross-sectional study of 117 CRC survivors was conducted at a National Cancer Institute-designated cancer center in South Florida. METHODS & VARIABLES: Symptom characteristics were assessed by the Therapy-Related Symptom Checklist. Participants completed a 25-item demographic questionnaire. Mann-Whitney U and Kruskal-Wallis H tests assessed between-group differences based on sex, age, education, and months since diagnosis. Exploratory factor analysis was performed to identify preliminary symptom clusters. RESULTS: 117 CRC survivors completed the study (age range = 21-88 years, 56% male, and 79% stage IV). Common symptoms included peripheral neuropathy, fatigue/feeling sluggish, and skin changes. Significance was found between months since diagnosis and number of symptoms (p = 0.03), suggesting that symptoms accumulate with time. Chemotherapy (85%) was the most common treatment type, and exploratory factor analysis identified two chemotherapy-related symptom clusters. IMPLICATIONS FOR NURSING: Nurses are poised to identify, prevent, and promote self-management skills to reduce symptoms.


Assuntos
Sobreviventes de Câncer , Neoplasias Colorretais , Monofosfato de Adenosina , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/terapia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Síndrome , Adulto Jovem
11.
Oncol Nurs Forum ; 49(5): 445-453, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067244

RESUMO

OBJECTIVES: Hematologic malignancies (HMs) are life-threatening cancers that frequently entail aggressive, long, inpatient treatment protocols. This can result in numerous concurrent symptoms and decreased quality of life for patients and can affect family caregivers (FCs). This study examined the impact of an HM diagnosis on patients and on their FCs. SAMPLE & SETTING: A descriptive design was used to explore the experiences of 28 newly diagnosed patients and their FCs. All patients were receiving treatment on an inpatient acute oncology unit at a National Cancer Institute-designated cancer center. METHODS & VARIABLES: Semistructured, separate interviews with patients and FCs were recorded and transcribed verbatim. Textual and content analyses were conducted to generate common themes. RESULTS: Patients and FCs reported how diagnosis and treatment affected them physically, emotionally, logistically, and financially. They described the effects of their experiences with the health system and providers in areas such as diagnostic process, trust in the medical team, support needs, and hospitalization. IMPLICATIONS FOR NURSING: Understanding the parallel experiences of patients with HMs and their designated FCs allows researchers to develop targeted interventions and enables clinicians to provide personalized patient- and family-centered care.


Assuntos
Neoplasias Hematológicas , Neoplasias , Monofosfato de Adenosina , Cuidadores/psicologia , Família/psicologia , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Humanos , Neoplasias/psicologia , Cuidados Paliativos/psicologia , Qualidade de Vida/psicologia
12.
Oncol Nurs Forum ; 49(5): 433-443, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067243

RESUMO

OBJECTIVES: Patients with advanced cancer and minor children experience high rates of depression and anxiety. However, associations between parental status and other aspects of the patient experience are not well understood. This study compared patient-reported outcomes of patients with and without minor children. SAMPLE & SETTING: This was a retrospective analysis of 448 adults with stage III or IV solid tumors from a public research registry. METHODS & VARIABLES: Multiple linear regression models or modified Poisson regression models were fitted to evaluate differences in health-related quality of life, global health, and patient satisfaction scores between patients living with and without minors. RESULTS: One in five patients lived with minor children. They reported significantly worse health-related quality of life, global physical health, and global mental health. They also expressed lower satisfaction with time spent with their provider, communication, and financial aspects. IMPLICATIONS FOR NURSING: Patients with minor children may benefit from earlier identification and support for their psychosocial needs and concerns.


Assuntos
Neoplasias , Qualidade de Vida , Monofosfato de Adenosina , Adulto , Criança , Humanos , Neoplasias/psicologia , Satisfação do Paciente , Satisfação Pessoal , Qualidade de Vida/psicologia , Estudos Retrospectivos
13.
Oncol Nurs Forum ; 49(5): 455-460, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067245

RESUMO

OBJECTIVES: To evaluate preliminary efficacy, fidelity, and integrity of data collection of a nurse-led, telemedicine-delivered video visit intervention aimed at improving management of rural survivors' cancer-related distress symptoms. SAMPLE & SETTING: 21 rural survivors participated in a nurse-led telemedicine intervention delivered six weeks after the end of active cancer treatment. METHODS & VARIABLES: Participants' symptom management was measured with the Short Form Survivor Unmet Needs Survey, a four-factor, 30-item instrument that measures the unmet needs of adult survivors. Data were collected preintervention and six weeks postintervention. RESULTS: The mean difference between pre- and postintervention survey scores was -0.24, representing an overall improvement in management of unmet needs. The unmet emotional needs domain had the highest mean preintervention score and the largest mean reduction. All effect sizes were small. IMPLICATIONS FOR NURSING: A nurse-led, telemedicine-delivered video visit intervention may improve rural survivors' symptom management during early survivorship. Comparison with a control group using a sample size powered to detect clinically meaningful differences is an important next step to fully evaluate the impact of this model of care.


Assuntos
Neoplasias , Telemedicina , Monofosfato de Adenosina , Adulto , Humanos , Neoplasias/terapia , Qualidade de Vida/psicologia , População Rural , Sobreviventes/psicologia , Telemedicina/métodos
14.
Oncol Nurs Forum ; 49(5): 461-470, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36067246

RESUMO

OBJECTIVES: To examine the relationship between levels of anxiety about COVID-19 and attitudes toward colorectal cancer screening in adult men in Turkey. SAMPLE & SETTING: The participants in this study were 188 adult men, aged 50-70 years, who were not diagnosed with cancer, and who could use social media. The researchers shared the link to the study forms through social media, and data were collected between February 2021 and May 2021. METHODS & VARIABLES: A personal information form, the Coronavirus Anxiety Scale, and the Attitude Scale for Cancer Screening were used to collect descriptive research data. RESULTS: Participants had mean scores of 1.04 (SD = 2.12) for the Coronavirus Anxiety Scale and 95.28 (SD = 16.91) for the Attitude Scale for Cancer Screening. There was no significant correlation between the scores (p > 0.05). Family structure and the reasons for applying for colorectal cancer screening were significantly related to participation in colorectal cancer screening programs (p < 0.05). IMPLICATIONS FOR NURSING: Individualized screening models can be used to prevent the deferral of cancer screenings. To ensure early diagnosis of colorectal cancer, nurses should be encouraged to use telehealth applications and help individuals perform immunochemical tests at home.


Assuntos
COVID-19 , Neoplasias Colorretais , Monofosfato de Adenosina , Adulto , Ansiedade/diagnóstico , COVID-19/diagnóstico , COVID-19/epidemiologia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Humanos , Masculino , Turquia
15.
Sci Rep ; 12(1): 15515, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109548

RESUMO

Anorexia nervosa (AN), a psychiatric condition defined by low body weight for age and height, is associated with numerous dermatological conditions. Yet, clinical observations report that patients with AN do not suffer from infectious skin diseases like those associated with primary malnutrition. Cell-mediated immunity appears to be amplified in AN; however, this proinflammatory state does not sufficiently explain the lower incidence of infections. Antimicrobial peptides (AMPs) are important components of the innate immune system protecting from pathogens and shaping the microbiota. In Drosophila melanogaster starvation precedes increased AMP gene expression. Here, we analyzed skin microbiota in patients with AN and age-matched, healthy-weight controls and investigated the influence of weight gain on microbial community structure. We then correlated features of the skin microbial community with psoriasin and RNase 7, two highly abundant AMPs in human skin, to clarify whether an association between AMPs and skin microbiota exists and whether such a relationship might contribute to the resistance to cutaneous infections observed in AN. We find significant statistical correlations between Shannon diversity and the highly abundant skin AMP psoriasin and bacterial load, respectively. Moreover, we reveal psoriasin significantly associates with Abiotrophia, an indicator for the healthy-weight control group. Additionally, we observe a significant correlation between an individual's body mass index and Lactobacillus, a microbial indicator of health. Future investigation may help clarify physiological mechanisms that link nutritional intake with skin physiology.


Assuntos
Anorexia Nervosa , Microbiota , Monofosfato de Adenosina , Animais , Peptídeos Antimicrobianos , Drosophila melanogaster , Humanos , Proteína A7 Ligante de Cálcio S100
16.
Sci Rep ; 12(1): 15493, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109567

RESUMO

The main effectors in the innate immune system of Bombyx mori L. are antimicrobial peptides (AMPs). Here, we infected B. mori with varied inoculum sizes of Pseudomonas aeruginosa ATCC 25668 cells to investigate changes in morpho-anatomical responses, physiological processes and AMP production. Ultraviolet-visible spectra revealed a sharp change in λmax from 278 to 285 nm (bathochromic shift) in the hemolymph of infected B. mori incubated for 24 h. Further, Fourier Transform InfraRed studies on the hemolymph extracted from the infected B. mori showed a peak at 1550 cm-1, indicating the presence of α-helical peptides. The peptide fraction was obtained through methanol, acetic acid and water mixture (90:1:9) extraction, followed by peptide purification using Reverse Phase High Performance Liquid Chromatography. The fraction exhibiting antibacterial properties was collected and characterized by Matrix-Assisted Laser Desorption/Ionization-Time of Flight. A linear α-helical peptide with flexible termini (LLKELWTKMKGAGKAVLGKIKGLL) was found, corresponding to a previously described peptide from ant venom and here denominated as Bm-ponericin-L1. The antibacterial activity of Bm-ponericin-L1 was determined against ESKAPE pathogens. Scanning electron microscopy confirmed the membrane disruption potential of Bm-ponericin-L1. Moreover, this peptide also showed promising antibiofilm activity. Finally, cell viability and hemolytic assays revealed that Bm-ponericin-L1 is non-toxic toward primary fibroblasts cell lines and red blood cells, respectively. This study opens up new perspectives toward an alternative approach to overcoming multiple-antibiotic-resistance by means of AMPs through invertebrates' infection with human pathogenic bacteria.


Assuntos
Venenos de Formiga , Anti-Infecciosos , Bombyx , Infecções por Pseudomonas , Monofosfato de Adenosina , Animais , Antibacterianos/farmacologia , Hemolinfa , Humanos , Metanol , Peptídeos/química , Infecções por Pseudomonas/tratamento farmacológico , Água
17.
J Biomed Sci ; 29(1): 70, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109724

RESUMO

BACKGROUND: Seaweed polysaccharides have been recommended as anticancer supplements and for boosting human health; however, their benefits in the treatment of triple-negative breast cancers (TNBCs) and improving immune surveillance remain unclear. Olaparib is a first-in-class poly (ADP-ribose) polymerase inhibitor. Oligo-Fucoidan, a low-molecular-weight sulfated polysaccharide purified from brown seaweed (Laminaria japonica), exhibits significant bioactivities that may aid in disease management. METHODS: Macrophage polarity, clonogenic assays, cancer stemness properties, cancer cell trajectory, glucose metabolism, the TNBC 4T1 cells and a 4T1 syngeneic mouse model were used to inspect the therapeutic effects of olaparib and Oligo-Fucoidan supplementation on TNBC aggressiveness and microenvironment. RESULTS: Olaparib treatment increased sub-G1 cell death and G2/M arrest in TNBC cells, and these effects were enhanced when Oligo-Fucoidan was added to treat the TNBC cells. The levels of Rad51 and programmed death-ligand 1 (PD-L1) and the activation of epidermal growth factor receptor (EGFR) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) facilitate drug resistance and TNBC metastasis. However, the combination of olaparib and Oligo-Fucoidan synergistically reduced Rad51 and PD-L1 levels, as well as the activity of EGFR and AMPK; consistently, TNBC cytotoxicity and stemness were inhibited. Oligo-Fucoidan plus olaparib better inhibited the formation of TNBC stem cell mammospheroids with decreased subpopulations of CD44high/CD24low and EpCAMhigh cells than monotherapy. Importantly, Oligo-Fucoidan plus olaparib repressed the oncogenic interleukin-6 (IL-6)/p-EGFR/PD-L1 pathway, glucose uptake and lactate production. Oligo-Fucoidan induced immunoactive and antitumoral M1 macrophages and attenuated the side effects of olaparib, such as the promotion on immunosuppressive and protumoral M2 macrophages. Furthermore, olaparib plus Oligo-Fucoidan dramatically suppressed M2 macrophage invasiveness and repolarized M2 to the M0-like (F4/80high) and M1-like (CD80high and CD86high) phenotypes. In addition, olaparib- and Oligo-Fucoidan-pretreated TNBC cells resulted in the polarization of M0 macrophages into CD80(+) M1 but not CD163(+) M2 macrophages. Importantly, olaparib supplemented with oral administration of Oligo-Fucoidan in mice inhibited postsurgical TNBC recurrence and metastasis with increased cytotoxic T cells in the lymphatic system and decreased regulatory T cells and M2 macrophages in tumors. CONCLUSION: Olaparib supplemented with natural compound Oligo-Fucoidan is a novel therapeutic strategy for reprogramming cancer stemness, metabolism and the microenvironment to prevent local postsurgical recurrence and distant metastasis. The combination therapy may advance therapeutic efficacy that prevent metastasis, chemoresistance and mortality in TNBC patients.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Proteínas Quinases Ativadas por AMP , Adenosina/farmacologia , Difosfato de Adenosina/farmacologia , Difosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Antígeno B7-H1 , Linhagem Celular Tumoral , Suplementos Nutricionais , Molécula de Adesão da Célula Epitelial , Receptores ErbB , Pontos de Checagem da Fase G2 do Ciclo Celular , Glucose , Humanos , Interleucina-6 , Lactatos/farmacologia , Lactatos/uso terapêutico , Camundongos , Ftalazinas , Piperazinas , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Polissacarídeos/uso terapêutico , Ribose/farmacologia , Ribose/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
18.
Eur J Pharmacol ; 932: 175241, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36058291

RESUMO

Organ fibrosis is accompanied by pathological angiogenesis. Discovering new ways to ameliorate pathological angiogenesis may bypass organ fibrosis. The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been implicated in organ injuries and its activation inhibits endothelial proliferation. Currently, a controversy exists as to whether cGAS/STING activation exacerbates inflammation and tissue injury or mitigates damage, and whether one of these effects predominates under specific context. This study unveiled a new antifibrotic cGAS/STING signaling pathway that suppresses pathological angiogenesis in liver and kidney fibrosis. We showed that cGAS expression was induced in fibrotic liver and kidney, but suppressed in endothelial cells. cGAS genetic deletion promoted liver and kidney fibrosis and pathological angiogenesis, including occurrence of endothelial-to-mesenchymal transition. Meanwhile, cGAS deletion upregulated profibrotic Yes-associated protein (YAP) signaling in endothelial cells, which was evidenced by the attenuation of organ fibrosis in mice specifically lacking endothelial YAP. Pharmacological targeting of cGAS/STING-YAP signaling by both a small-molecule STING agonist, SR-717, and a G protein-coupled receptor (GPCR)-based antagonist that blocks the profibrotic activity of endothelial YAP, attenuated liver and kidney fibrosis. Together, our data support that activation of cGAS/STING signaling mitigates organ fibrosis and suppresses pathological angiogenesis. Further, pharmacological targeting of cGAS/STING-YAP axis exhibits the potential to alleviate liver and kidney fibrosis.


Assuntos
Células Endoteliais , Proteínas de Sinalização YAP , Monofosfato de Adenosina , Animais , Células Endoteliais/metabolismo , Fibrose , Guanosina Monofosfato , Interferons , Proteínas de Membrana/metabolismo , Camundongos , Neovascularização Patológica , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo
19.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36077500

RESUMO

Antimicrobial peptides (AMPs) are essential components of the mucosal barrier of the female reproductive tract (FRT) and are involved in many important physiological processes, including shaping the microbiota and maintaining normal reproduction and pregnancy. Gynecological cancers seriously threaten women's health and bring a heavy burden to society so that new strategies are needed to deal with these diseases. Recent studies have suggested that AMPs also have a complex yet intriguing relationship with gynecological cancers. The expression level of AMPs changes during tumor progression and they may act as promising biomarkers in cancer detection and prognosis prediction. Although AMPs have long been considered as host protective, they actually play a "double-edged sword" role in gynecological cancers, either tumorigenic or antitumor, depending on factors such as AMP and cancer types, as well as AMP concentrations. Moreover, AMPs are associated with chemoresistance and regulation of AMPs' expression may alter sensitivity of cancer cells to chemotherapy. However, more work is needed, especially on the identification of molecular mechanisms of AMPs in the FRT, as well as the clinical application of these AMPs in detection, diagnosis and treatment of gynecological malignancies.


Assuntos
Peptídeos Antimicrobianos , Neoplasias dos Genitais Femininos , Microbiota , Monofosfato de Adenosina , Feminino , Humanos
20.
Plant Physiol Biochem ; 189: 115-125, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36084527

RESUMO

Epidermal waxes are part of the outermost hydrophobic structures of apples and play a significant role in enhancing apple resistance and improving fruit quality. The biosynthetic precursors of epidermal waxes are very long-chain fatty acids (VLCFAs), which are made into different wax components through various wax synthesis pathways. In Arabidopsis thaliana, the AtLACS1 protein can activate the alkane synthesis pathway to produce very long-chain acyl CoAs (VLC-acyl-CoAs), which provide substrates for wax synthesis, from VLCFAs. The apple protein MdLACS1, encoded by the MdLACS1 gene, belongs to the AMP-binding superfamily and has long-chain acyl coenzyme A synthase activity, but its function in apple remains unclear. Here, we identified MdLACS1 in apple (Malus × domestica) and analyzed its function. Our results suggest that MdLACS1 promotes wax synthesis and improves biotic and abiotic stress tolerance, which were directly or indirectly dependent on wax. Our study further refines the molecular mechanism of wax biosynthesis in apples and elucidates the physiological function of wax in resistance to external stresses. These findings provide candidate genes for the synergistic enhancement of apple fruit quality and stress tolerance.


Assuntos
Arabidopsis , Malus , Acil Coenzima A/metabolismo , Monofosfato de Adenosina/metabolismo , Alcanos/metabolismo , Arabidopsis/metabolismo , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica de Plantas , Malus/genética , Malus/metabolismo , Epiderme Vegetal/metabolismo , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Ceras/metabolismo
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