Search Results (20)

Satellite DNAs (satDNAs) play a crucial role in understanding chromosomal evolution and the differentiation of sex chromosomes across diverse taxa, particularly when high karyotypic diversity occurs. The Physalaemus cuvieri–Physalaemus ephippifer species complex comprises at least seven divergent lineages, each exhibiting specific karyotypic signatures. The group composed of Ph. ephippifer, Lineage 1B of ‘Ph. cuvieri’ (L1B), and a lineage resulting from their secondary contact is especially intriguing due to varying degrees of sex chromosome heteromorphism. In this study, we characterized the satellitome of Ph. ephippifer in order to identify novel satDNAs that may provide insights into chromosomal evolution, particularly concerning sex chromosomes. We identified 62 satDNAs in Ph. ephippifer, collectively accounting for approximately 10% of the genome. Notably, nine satDNA families were shared with species from distantly related clades, raising questions about their potential roles in anurans genomes. Among the seven satDNAs mapped via fluorescent in situ hybridization, PepSat3 emerged as a strong candidate for the centromeric sequence in this group. Additionally, PepSat11 and PepSat24 provided evidence supporting a translocation involving both arms of the W chromosome in Ph. ephippifer. Furthermore, a syntenic block composed of PepSat3, PcP190, and PepSat11 suggested an inversion event during the divergence of Ph. ephippifer and L1B. The variation in signal patterns of satDNAs associated with nucleolar organizer regions (NORs) highlights the complexity of NOR evolution in this species complex, which exhibits substantial diversity in this genomic region. Additionally, our findings for PepSat30-350 emphasize the importance of validating the sex-biased abundance of satDNAs. Full article

Recent evidence has highlighted the critical role of lipids in tumor biology. In this study, we analyzed the plasma lipid profiles of 151 melanoma patients (University of Debrecen, Department of Dermatology, Hungary) to examine the associations between specific lipid species and commonly used LDL-C lipid parameters, as well as the Breslow thickness and ulceration of primary tumors. Our analysis included patients who underwent primary tumor resection, comprising 83 individuals without metastases and 68 with metastases at the time of blood sampling. Lipid profiling was performed using the Lipidyzer™ platform, which targets over 1100 lipid species. Following quality control filtering, 802 lipids were included in the subsequent analyses. Ten lipids were found to have decreased plasma levels, while one lipid exhibited elevated plasma levels, both associated with an increased risk of higher Breslow thickness. Additionally, patients with thicker tumors (≥2 mm) demonstrated significantly higher LDL-C levels after adjusting for age, sex, therapy, and tumor presence (p = 0.032). Using forward stepwise regression, we identified a combination of four lipids—(CE(20:5), LCER(24:1), PE(P18:1/18:1), and LPE(18:2))—that demonstrated the strongest correlation with Breslow depth (AUC = 0.779, as determined by ROC analysis). Additionally, we identified 11 lipids significantly associated with tumor ulceration. Stepwise regression analysis further revealed two lipids (FFA(16:0) and PC(15:0/18:1)) capable of predicting tumor ulceration with an AUC score of 0.740. These findings suggest that individual lipid metabolism may influence tumor thickness and ulceration during the development and progression of primary melanoma. Full article

Background/Objectives: The Prostate Cancer Patient Empowerment Program (PC-PEP) is a 6-month, home-based intervention aimed at enhancing mental health in men undergoing curative prostate cancer treatment. This exploratory secondary analysis evaluates PC-PEP’s impact on relationship satisfaction, quality of life, and support group attendance among partnered participants. Methods: In a crossover randomized clinical trial ClinicalTrials.gov identifier: NCT03660085) of 128 men aged 50–82 scheduled for curative prostate cancer surgery or radiotherapy, 119 participants in relationships were included. Of these, 59 received the 6-month PC-PEP intervention, while 60 were randomized to a waitlist-control arm, receiving standard care for 6 months before starting PC-PEP. The intervention included daily emails with video instructions on mental and physical health, diet, social support, fitness, stress reduction, and intimacy. Outcomes were assessed using the Dyadic Adjustment Scale (DAS) and the Functional Assessment of Cancer Therapy–Prostate (FACT-P). Results: While relationship satisfaction remained stable, a significant improvement in emotional well-being was observed at 12 months in participants undergoing radiation therapy (p = 0.045). The PC-PEP intervention also led to significantly higher support group attendance at both 6 months (p = 0.001) and 12 months (p = 0.003), emphasizing its role in fostering social support and community engagement. Conclusions: The PC-PEP program effectively maintains relationship satisfaction and enhances emotional well-being, particularly in patients with fewer physical side effects. Its design promotes comprehensive care by integrating physical, psychological, and social support, making it a valuable resource for improving the quality of life in prostate cancer patients and potentially applicable to other cancer types. Full article

Background/Objectives: Psychological distress is a significant concern among cancer patients, negatively affecting their quality of life and adherence to treatment. The Cancer Patient Empowerment Program (CancerPEP) was developed as a comprehensive, home-based intervention aimed at reducing psychological distress by incorporating physical activity, dietary guidance, and social support. This study aimed to evaluate the feasibility, accrual and attrition rates, safety, and effectiveness of the CancerPEP intervention, with and without the biofeedback device, on psychological distress from baseline to 6 months, specifically focusing on the effects of group randomization and the difference between pre- and post-intervention results. Methods: This single-site, crossover randomized clinical trial included 104 cancer patients who were randomized to receive the CancerPEP intervention, with or without a Heart Rate Variability (HRV) biofeedback monitor. At 6 months, participants who did not receive the device were allowed to use one until the end of the year, while those who did receive the device were followed up to 12 months. Randomization was stratified by the presence or absence of clinically significant psychological distress and metastatic status. Psychological distress was assessed using the Kessler Psychological Distress Scale (K10) at baseline, 6 months, and 12 months. The primary endpoint was the presence of nonspecific psychological distress, as measured by the K10 scale at 6 months from the trial start, based on group randomization. A secondary exploratory analysis assessed psychological distress at baseline, 6 months, and 12 months for both groups, while controlling for group randomization and prognostic covariates. Prognostic covariates included age; comorbidities; time between diagnosis and randomization; treatment modality; relationship status; and use of prescribed medications for anxiety, depression, or both. An exploratory sub-analysis was conducted for the breast cancer subgroup, based on the sample size available after recruitment. The trial is registered at ClinicalTrials.gov (NCT05508412). Results: The provision of the HRV biofeedback monitor in conjunction with the CancerPEP intervention did not significantly affect the primary outcome in either the full sample or the breast cancer subgroup, indicating that the HRV biofeedback provision was not beneficial in this trial. No self-reported or otherwise discovered adverse events at the 6-month mark were observed. About 10% of participants were lost to follow-up in both the early and late HRV monitor provision groups. Participation in the CancerPEP program led to a significant reduction in psychological distress over time. The odds of psychological distress were significantly higher at the start of the trial than at the end of the intervention (aOR = 2.64, 95% CI: 1.53–4.56) or 6 months after the intervention (aOR = 2.94, 95% CI: 1.62–5.30). Similarly, in the breast cancer subgroup, distress was higher at the trial’s start than at 6 months, i.e., after the intervention (aOR = 2.25, 95% CI: 1.24–4.08), or at the end of the trial at 12 months (aOR = 2.73, 95% CI: 1.35–5.52). Conclusions: CancerPEP significantly reduces psychological distress in cancer patients, with consistent improvements noted across various cancer types and stages, including benefits specifically for breast cancer patients. These findings build upon the success of the Prostate Cancer Patient Empowerment Program (PC-PEP), indicating that a similar comprehensive intervention can be advantageous for all cancer patients and may be further tailored to address specific needs. With its holistic approach—encompassing physical, dietary, and psychosocial support—CancerPEP shows promise as a vital component of survivorship care. Ongoing 24-month evaluations will yield critical data on its long-term benefits. Additionally, a randomized trial with a control group (usual care without intervention) for breast cancer patients is currently under way and could potentially guide the integration of CancerPEP into standard oncology care to enhance patient outcomes and quality of life. Full article

Understanding how interventions reduce psychological distress in patients with prostate cancer is crucial for improving patient care. This study examined the roles of self-efficacy, illness perceptions, and heart rhythm coherence in mediating the effects of the Prostate Cancer Patient Empowerment Program (PC-PEP) on psychological distress compared to standard care. In a randomized controlled trial, 128 patients were assigned to either the PC-PEP intervention or standard care. The PC-PEP, a six-month program emphasizing daily healthy living habits, included relaxation and stress management, diet, exercise, pelvic floor muscle exercises, and strategies to improve relationships and intimacy, with daily activities supported by online resources and live sessions. Participants in the intervention group showed significant improvements in self-efficacy and specific illness perceptions, such as personal control and emotional response, compared to the control group. These factors mediated the relationship between the intervention and its psychological benefits, with self-efficacy accounting for 52% of the reduction in psychological distress. No significant differences in heart rhythm coherence were observed. This study highlights the critical role of self-efficacy and illness perceptions in enhancing psychological health in prostate cancer patients through the PC-PEP. The results underscore this program’s effectiveness and the key mechanisms through which it operates. Given the high rates of distress among men undergoing prostate cancer treatments, these findings emphasize the importance of integrating the PC-PEP into clinical practice. The implementation of the PC-PEP in clinical settings can provide a structured approach to reducing psychological distress and improving overall patient well-being. Full article

(1) Autophagy plays a significant role in development and cell proliferation. This process is mainly accomplished by the LC3 protein, which, after maturation, builds the nascent autophagosomes. The inhibition of LC3 maturation results in the interference of autophagy activation. (2) In this study, starting from the structure of a known LC3B binder (LIR2-RavZ peptide), we identified new LC3B ligands by applying an in silico drug design strategy. The most promising peptides were synthesized, biophysically assayed, and biologically evaluated to ascertain their potential antiproliferative activity on five humans cell lines. (3) A cyclic peptide (named Pep6), endowed with high conformational stability (due to the presence of a disulfide bridge), displayed a K_d value on LC3B in the nanomolar range. Assays accomplished on PC3, MCF-7, and A549 cancer cell lines proved that Pep6 exhibited cytotoxic effects comparable to those of the peptide LIR2-RavZ, a reference LC3B ligand. Furthermore, it was ineffective on both normal prostatic epithelium PNT2 and autophagy-defective prostate cancer DU145 cells. (4) Pep6 can be considered a new autophagy inhibitor that can be employed as a pharmacological tool or even as a template for the rational design of new small molecules endowed with autophagy inhibitory activity. Full article

Background: The Prostate Cancer—Patient Empowerment Program (PC-PEP) is a six-month daily home-based program shown to improve mental health and urinary function. This secondary analysis explores weight loss in male PC-PEP participants. Methods: In a randomized clinical trial with 128 men undergoing curative prostate cancer (PC) treatment, 66 received ‘early’ PC-PEP, while 62 were assigned to the ‘late’ waitlist-control group, receiving 6 months of standard-of-care treatment followed by 6 months of PC-PEP. PC-PEP comprised 182 daily emails with video-based exercise and dietary (predominantly plant-based) education, live online events, and 30 min strength training routines (using body weight and elastic bands). Weight and height data were collected via online surveys (baseline, 6 months, and 12 months) including medical chart reviews. Adherence was tracked weekly. Results: No attrition or adverse events were reported. At 6 months, the early PC-PEP group experienced significant weight loss, averaging 2.7 kg (p < 0.001) compared to the waitlist-control group. Weight loss was noted in the late intervention group of PC-PEP, albeit less pronounced than in the early group. Early PC-PEP surgery patients lost on average 1.4 kg (SE = 0.65) from the trial’s start to surgery day. High adherence to exercise and dietary recommendations was noted. Conclusions: PC-PEP led to significant weight loss in men undergoing curative prostate cancer treatment compared to standard-of-care. Full article

Purpose: This is a secondary analysis examining a six-month home-based Prostate Cancer-Patient Empowerment Program (PC-PEP) on patient-reported urinary, bowel, sexual, and hormonal function in men with curative prostate cancer (PC) against standard of care. Methods: In a crossover clinical trial, 128 men scheduled for PC surgery (n = 62) or radiotherapy with/without hormones (n = 66) were randomized to PC-PEP (n = 66) or waitlist-control and received the standard of care for 6 months, and then PC-PEP to the end of the year. PC-PEP included daily emails with video instructions, aerobic and strength training, dietary guidance, stress management, and social support, with an initial PFMT nurse consultation. Over 6 months, participants in the PC-PEP received optional text alerts (up to three times daily) reminding them to follow the PFMT video program, encompassing relaxation, quick-twitch, and endurance exercises; compliance was assessed weekly. Participants completed baseline, 6, and 12-month International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC) questionnaires. Results: At 6 months, men in the PC-PEP reported improved urinary bother (IPSS, p = 0.004), continence (EPIC, p < 0.001), and irritation/obstruction function (p = 0.008) compared to controls, with sustained urinary continence benefits at 12 months (p = 0.002). Surgery patients in the waitlist-control group had 3.5 (95% CI: 1.2, 10, p = 0.024) times and 2.3 (95% CI: 0.82, 6.7, p = 0.11) times higher odds of moderate to severe urinary problems compared to PC-PEP at 6 and 12 months, respectively. Conclusions: PC-PEP significantly improves lower urinary tract symptoms, affirming its suitability for clinical integration alongside established mental health benefits in men with curative prostate cancer. Full article

A 28-day Prostate Cancer-Patient Empowerment Program (PC-PEP) developed through patient engagement was successful at promoting mental and physical health. Thirty prostate cancer patients from Halifax, Canada participated in the 28-day PC-PEP intervention in early 2019. PC-PEP encompassed daily patient education and empowerment videos, prescribed physical activities (including pelvic floor exercises), a mostly plant-based diet, stress reduction techniques, intimacy education, social connection, and support. Quantitative exit surveys and semi-structured interviews (conducted in focus groups of ten) were used to assess perceived factors that facilitated or impeded adherence to the program. The program received high praise from the patients and was deemed extremely useful by the participating men, who rated it 9 out of 10. Patients expressed that the multifaceted, online, home-based nature of the program helped them adhere to it better than they would have had to a single or less comprehensive intervention. Feedback from the participants indicated that the program, when viewed as a whole, was perceived as greater than the sum of its individual parts. Furthermore, the program addressed various issues, including emotional vulnerability and distress, physical fitness, urinary incontinence, challenges in expressing emotions, perceived lack of control over healthcare decisions, emotional fragility, and hesitancy to discuss prostate cancer-related matters in social settings. Patients highly (9.6/10) endorsed integrating the program into the standard care regimen from the very beginning of diagnosis. However, challenges such as work commitments were noted. Patients’ high endorsement of PC-PEP suggests that its implementation into the standard of care from day one of diagnosis may be warranted. Full article

Prostate cancer (PCa) survivors often experience post-treatment challenges that impact their well-being and mental health. The Prostate Cancer Patient Empowerment Program (PC-PEP) aims to address these issues through a comprehensive intervention, involving daily meditation/breathing exercises, physical activity, pelvic floor exercises, emotional connection strategies, and peer support. This study presents a secondary analysis of a Phase 2 feasibility study that evaluated the effects of a 28-day PC-PEP intervention on stress reduction. Thirty patients with PCa from the Maritimes, Canada, underwent pre- and post-intervention assessments to measure brainwave activity (delta, theta, alpha, beta, and gamma) using the Muse™ headband, and heart rate variability (HRV) using the HeartMath^® Inner Balance™ as indicators of stress reduction. A statistically significant Time × Sensor Scalp Assessment Time interaction emerged for all brain waves. Amplitudes were generally higher during the first half of the meditation assessment time but became comparable afterward. A statistically significant Time × Sensor Scalp Location × Sensor Scalp Assessment Time interaction also emerged for alpha waves, indicating higher prefrontal lobe amplitudes than temporal lobe amplitudes from pre- to post-assessment. There were no statistically significant differences in HRV metrics from pre- to post-intervention, except for a marginally significant achievement score, indicating increased HRV coherence post-intervention. The findings suggest that the stress reduction component of PC-PEP successfully improved outcomes related to decreased stress. These results have implications for the development of future iterations of PC-PEP interventions, aiming to optimize participant benefits. Full article

Necrotic enteritis (NE) is an intestinal disease that results in poor performance, inefficient nutrient absorption, and has a devastating economic impact on poultry production. This study evaluated the effects of a saponin-based product (Clarity Q, CQ) during an NE challenge. A total of 1200 male chicks were randomly assigned to four dietary treatments (10 pens/treatment; 30 birds/pen): treatment 1 (NC), a non-medicated corn–soybean basal diet; treatment 2 (PC), NC + 50 g/metric ton (MT) of bacitracin methylene disalicylate (BMD); and treatments 3 (CQ15) and 4 (CQ30), NC + 15 and 30 g/MT, respectively. On the day (d) of placement, birds were challenged by a coccidia vaccine to induce NE. On d 8, 14, 28, and 42, performance parameters were measured. On d 8, three birds/pen were necropsied for NE lesions. On d 8 and d 14, jejunum samples from one bird/pen were collected for mRNA abundance of tight junction proteins and nutrient transporter genes. Data were analyzed in JMP (JMP Pro, 16), and significance (p ≤ 0.05) between treatments was identified by Fisher’s least significant difference (LSD) test. Compared to PC and NC, CQ15 had higher average daily gain (ADG), while CQ30 had lower average daily feed intake (ADFI) and feed conversion ratio (FCR). NE lesions in the duodenum were lower in CQ15 compared to all other treatments. On d 8, mRNA abundance of CLDN1, CLDN5, AMPK, PepT2, GLUT2, and EAAT3 were significantly greater in CQ30 (p < 0.05) compared to both PC and NC. On d 14, mRNA abundance of ZO2 and PepT2 was significantly lower in PC when compared to all treatments, while that of ANXA1, JAM3, and GLUT5 was comparable to CQ15. In summary, adding Clarity Q to broiler diets has the potential to alleviate adverse effects caused by this enteric disease by improving performance, reducing intestinal lesions, and positively modulating the mRNA abundance of various tight junction proteins and key nutrient transporters during peak NE infection. Full article

Melanoma is difficult to treat with chemotherapy, prompting the need for new treatments. Protease inhibitors have emerged as promising candidates as tumor cell proteases promote metastasis. Researchers have developed a chimeric form of the Bauhinia bauhinioides kallikrein inhibitor, rBbKIm, which has shown negative effects on prostate tumor cell lines DU145 and PC3. Crataeva tapia bark lectin, CrataBL, targets sulfated oligosaccharides in glycosylated proteins and has also demonstrated deleterious effects on prostate and glioblastoma tumor cells. However, neither rBbKIm nor its derived peptides affected the viability of SK-MEL-28, a melanoma cell line, while CrataBL decreased viability by over 60%. Two peptides, Pep. 26 (Ac-Q-N-S-S-L-K-V-V-P-L-NH2) and Pep. 27 (Ac-L-P-V-V-K-L-S-S-N-Q-NH2), were also tested. Pep. 27 suppressed cell migration and induced apoptosis when combined with vemurafenib, while Pep. 26 inhibited cell migration and reduced nitric oxide and the number of viable cells. Vemurafenib, a chemotherapy drug used to treat melanoma, was found to decrease the release of interleukin 8 and PDGF-AB/BB cytokines and potentiated the effects of proteins and peptides in reducing these cytokines. These findings suggest that protease inhibitors may be effective in blocking melanoma cells and highlight the potential of CrataBL and its derived peptides. Full article

Maternal hyperglycemia is associated with disrupted transplacental arachidonic acid (AA) supply and eicosanoid synthesis, which contribute to adverse pregnancy outcomes. Since placental inositol is lowered with increasing glycemia, and since myo-inositol appears a promising intervention for gestational diabetes, we hypothesized that myo-inositol might rectify glucose-induced perturbations in placental AA metabolism. Term placental explants (n = 19) from women who underwent a mid-gestation oral glucose-tolerance-test were cultured with ¹³C-AA for 48 h in media containing glucose (5, 10 or 17 mM) and myo-inositol (0.3 or 60 µM). Newly synthesized ¹³C-AA-lipids were quantified by liquid-chromatography-mass-spectrometry. Increasing maternal fasting glycemia was associated with decreased proportions of ¹³C-AA-phosphatidyl-ethanolamines (PE, PE-P), but increased proportions of ¹³C-AA-triacylglycerides (TGs) relative to total placental ¹³C-AA lipids. This suggests altered placental AA compartmentalization towards storage and away from pools utilized for eicosanoid production and fetal AA supply. Compared to controls (5 mM glucose), 10 mM glucose treatment decreased the amount of four ¹³C-AA-phospholipids and eleven ¹³C-AA-TGs, whilst 17 mM glucose increased ¹³C-AA-PC-40:8 and ¹³C-AA-LPC. Glucose-induced alterations in all ¹³C-AA lipids (except PE-P-38:4) were attenuated by concurrent 60 µM myo-inositol treatment. Myo-inositol therefore rectifies some glucose-induced effects, but further studies are required to determine if maternal myo-inositol supplementation could reduce AA-associated pregnancy complications. Full article

Most in vivo ³¹P MR studies are realized on 3T MR systems that provide sufficient signal intensity for prominent phosphorus metabolites. The identification of these metabolites in the in vivo spectra is performed by comparing their chemical shifts with the chemical shifts measured in vitro on high-field NMR spectrometers. To approach in vivo conditions at 3T, a set of phantoms with defined metabolite solutions were measured in a 3T whole-body MR system at 7.0 and 7.5 pH, at 37 °C. A free induction decay (FID) sequence with and without ¹H decoupling was used. Chemical shifts were obtained of phosphoenolpyruvate (PEP), phosphatidylcholine (PtdC), phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), glycerophosphoetanolamine (GPE), uridine diphosphoglucose (UDPG), glucose-6-phosphate (G6P), glucose-1-phosphate (G1P), 2,3-diphosphoglycerate (2,3-DPG), nicotinamide adenine dinucleotide (NADH and NAD⁺), phosphocreatine (PCr), adenosine triphosphate (ATP), adenosine diphosphate (ADP), and inorganic phosphate (Pi). The measured chemical shifts were used to construct a basis set of ³¹P MR spectra for the evaluation of ³¹P in vivo spectra of muscle and the liver using LCModel software (linear combination model). Prior knowledge was successfully employed in the analysis of previously acquired in vivo data. Full article

Background: We tested the antitumor effects of a modified E2F peptide substituting D-Arg for L-Arg, conjugated to penetratin (PEP) against solid tumor cell lines and the CCRF-leukemia cell line, alone and in combination with pemetrexed or with cisplatin. For in-vivo studies, the peptide was encapsulated in PEGylated liposomes (PL-PEP) to increase half-life and stability. Methods: Prostate cancer (DU145 and PC3), breast cancer (MCF7, MDA-MB-468, and 4T1), lymphoma (CCRF-CEM), and non-small cell lung cancer (NSCLC) cell lines (H2009, H441, H1975, and H2228) were treated with D-Arg PEP in combination with cisplatin or pemetrexed. Western blot analysis was performed on the NSCLC for E2F-1, pRb, thymidylate synthase, and thymidine kinase. The H2009 cell line was selected for an in-vivo study. Results: When the PEP was combined with cisplatin and tested against solid tumor cell lines and the CCRF-CEM leukemia cell line, there was a modest synergistic effect. A marked synergistic effect was seen when the combination of pemetrexed and the PEP was tested against the adenocarcinoma lung cancer cell lines. The addition of the PEP to pemetrexed enhanced the antitumor effects of pemetrexed in a xenograft of the H2009 in mice. Conclusions: The D-Arg PEP in combination with cisplatin caused synergistic cell kill against prostate, breast, lung cancers, and the CCRF-CEM cell line. Marked synergy resulted when the D-Arg PEP was used in combination with pemetrexed against the lung adenocarcinoma cell lines. A xenograft study using the PL-PEP in combination with pemetrexed showed enhanced anti-tumor effects compared to each drug alone. Full article