Depression currently affects about 280 million people worldwide and its prevalence has been increasing dramatically, especially among the young and people of reproductive age, which consequently leads to an increase in antidepressant consumption. Antidepressants are associated with sexual dysfunction in both men and women; however, their role in male fertility has been scarcely studied. Fluoxetine and sertraline, two serotonin reuptake inhibitors (SSRIs), are among the most prescribed antidepressants worldwide. To determine their possible effects, human sperm cells were exposed to either sertraline or fluoxetine at concentrations previously found in blood and seminal fluid of patients undergoing treatment. Spermatozoa were incubated for up to 24 h at 37°C and 5% CO 2 , and important functional parameters such as sperm motility, viability, mitochondrial membrane potential, cellular reactive oxygen species (ROS) production, chromatin/DNA integrity, acrosome status, and tyrosine phosphorylation were assessed. At low levels, fluoxetine consistently decreased progressive motility throughout time while promoting fluctuations in ROS levels and sperm capacitation. Nevertheless, it did not affect viability, mitochondrial membrane potential, acrosome reaction nor chromatin/DNA integrity. Sertraline, on the other hand, had little to nonsignificant impact at low doses, but affected almost all tested parameters at supratherapeutic concentrations. Altogether, our results suggest that both antidepressants may impair sperm function, possibly through different mechanisms of action, but fluoxetine is the only exhibiting mild negative effects at doses found in vivo .
Humans ; Male ; Spermatozoa/drug effects* ; Fluoxetine/pharmacology* ; Sperm Motility/drug effects* ; Sertraline/pharmacology* ; Reactive Oxygen Species/metabolism* ; Antidepressive Agents/pharmacology* ; Membrane Potential, Mitochondrial/drug effects* ; Sperm Capacitation/drug effects* ; Selective Serotonin Reuptake Inhibitors/pharmacology* ; Cell Survival/drug effects* ; Acrosome Reaction/drug effects*

Background: Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes. Objective: This study investigates the effectiveness ­of 18F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of 18F-FDG. Methods: Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis wasperformed using the maximum standardized uptake value ­(SUVmax ) and volumetric SUV ­(SUV2SD ). Tissue expressionanalysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA. Results: Warty SCC showed the highest SUV value and significant differences in ­SUVmax (p=0.015). Higher ­SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative,GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value significantly differed for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant. Conclusions The study highlights correlations between the uptake of 18F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.

BACKGROUND: The main challenge in new drug development is accurately predicting the human response in preclinical models. METHODS: In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane. RESULTS: All models successfully replicated the structural and functional aspects of the intestinal barrier. The 3D bioprinted intestinal model, however, demonstrated superior epithelial barrier integrity enhanced tight junction formation, microvilli development, and increased mucus production. When subjected to Ibuprofen, the 3D bioprinted model provided a more predictive response, underscoring its potential as a reliable in vitro tool for drug toxicity testing. CONCLUSION Our 3D bioprinted intestinal model presents a robust and predictive platform for drug toxicity assessments, significantly reducing the need for animal testing. This model not only aligns with ethical testing protocols but also offers enhanced accuracy in predicting human responses, thereby advancing the field of drug development.

Background: Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes. Objective: This study investigates the effectiveness ­of 18F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of 18F-FDG. Methods: Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis wasperformed using the maximum standardized uptake value ­(SUVmax ) and volumetric SUV ­(SUV2SD ). Tissue expressionanalysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA. Results: Warty SCC showed the highest SUV value and significant differences in ­SUVmax (p=0.015). Higher ­SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative,GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value significantly differed for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant. Conclusions The study highlights correlations between the uptake of 18F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.

BACKGROUND: The main challenge in new drug development is accurately predicting the human response in preclinical models. METHODS: In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane. RESULTS: All models successfully replicated the structural and functional aspects of the intestinal barrier. The 3D bioprinted intestinal model, however, demonstrated superior epithelial barrier integrity enhanced tight junction formation, microvilli development, and increased mucus production. When subjected to Ibuprofen, the 3D bioprinted model provided a more predictive response, underscoring its potential as a reliable in vitro tool for drug toxicity testing. CONCLUSION Our 3D bioprinted intestinal model presents a robust and predictive platform for drug toxicity assessments, significantly reducing the need for animal testing. This model not only aligns with ethical testing protocols but also offers enhanced accuracy in predicting human responses, thereby advancing the field of drug development.

Background: Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes. Objective: This study investigates the effectiveness ­of 18F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of 18F-FDG. Methods: Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis wasperformed using the maximum standardized uptake value ­(SUVmax ) and volumetric SUV ­(SUV2SD ). Tissue expressionanalysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA. Results: Warty SCC showed the highest SUV value and significant differences in ­SUVmax (p=0.015). Higher ­SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative,GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value significantly differed for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant. Conclusions The study highlights correlations between the uptake of 18F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.

Background: Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes. Objective: This study investigates the effectiveness ­of 18F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of 18F-FDG. Methods: Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis wasperformed using the maximum standardized uptake value ­(SUVmax ) and volumetric SUV ­(SUV2SD ). Tissue expressionanalysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA. Results: Warty SCC showed the highest SUV value and significant differences in ­SUVmax (p=0.015). Higher ­SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative,GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value significantly differed for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant. Conclusions The study highlights correlations between the uptake of 18F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.

BACKGROUND: The main challenge in new drug development is accurately predicting the human response in preclinical models. METHODS: In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane. RESULTS: All models successfully replicated the structural and functional aspects of the intestinal barrier. The 3D bioprinted intestinal model, however, demonstrated superior epithelial barrier integrity enhanced tight junction formation, microvilli development, and increased mucus production. When subjected to Ibuprofen, the 3D bioprinted model provided a more predictive response, underscoring its potential as a reliable in vitro tool for drug toxicity testing. CONCLUSION Our 3D bioprinted intestinal model presents a robust and predictive platform for drug toxicity assessments, significantly reducing the need for animal testing. This model not only aligns with ethical testing protocols but also offers enhanced accuracy in predicting human responses, thereby advancing the field of drug development.

BACKGROUND: The main challenge in new drug development is accurately predicting the human response in preclinical models. METHODS: In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane. RESULTS: All models successfully replicated the structural and functional aspects of the intestinal barrier. The 3D bioprinted intestinal model, however, demonstrated superior epithelial barrier integrity enhanced tight junction formation, microvilli development, and increased mucus production. When subjected to Ibuprofen, the 3D bioprinted model provided a more predictive response, underscoring its potential as a reliable in vitro tool for drug toxicity testing. CONCLUSION Our 3D bioprinted intestinal model presents a robust and predictive platform for drug toxicity assessments, significantly reducing the need for animal testing. This model not only aligns with ethical testing protocols but also offers enhanced accuracy in predicting human responses, thereby advancing the field of drug development.

Background: Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes. Objective: This study investigates the effectiveness ­of 18F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of 18F-FDG. Methods: Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis wasperformed using the maximum standardized uptake value ­(SUVmax ) and volumetric SUV ­(SUV2SD ). Tissue expressionanalysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA. Results: Warty SCC showed the highest SUV value and significant differences in ­SUVmax (p=0.015). Higher ­SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative,GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value significantly differed for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant. Conclusions The study highlights correlations between the uptake of 18F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.