Antioxidant and Antibacterial Activity of Mexican Oregano Essential Oil, Extracted from Plants Occurring Naturally in Semiarid Areas and Cultivated in the Field and Greenhouse in Northern Mexico.

In recent years, the determination of the antioxidant and antibacterial activity of essential oils in wild plants, such as Mexican oregano (Lippia graveolens Kunth), has become increasingly important. The objective was to compare the antioxidant and antibacterial activity of Mexican oregano essential oil obtained from plants occurring naturally in semiarid areas (Wild1 and Wild2), and those cultivated in the field (CField) and greenhouse (CGreenhouse) in northern Mexico. The Mexican oregano essential oil extraction was performed using the hydrodistillation method, the antioxidant activity was determined using the ABTS method, and the antibacterial activity was assessed through bioassays under the microwell method at nine different concentrations. The aim was to determine the diameter of the inhibition zone and, consequently, understand the sensitivity level for four bacterial species. The results revealed an antioxidant activity ranging from 90% to 94% at the sampling sites, with Wild1 standing out for having the highest average antioxidant activity values. Likewise, six out of the nine concentrations analyzed showed some degree of sensitivity for all the sampling sites. In this regard, the 25 µL mL-1 concentration showed the highest diameter of inhibition zone values, highlighting the Wild2 site, which showed an average diameter greater than 30 mm for the four bacteria tested. Only in the case of S. typhi did the CGreenhouse site surpass the Wild2, with an average diameter of the inhibition zone of 36.7 mm. These findings contribute to the search for new antioxidant and antibacterial options, addressing the challenges that humanity faces in the quest for opportunities to increase life expectancy.

Molecular and long-term behavioral consequences of neonatal opioid exposure and withdrawal in mice.

Introduction: Infants exposed to opioids in utero are at high risk of exhibiting Neonatal Opioid Withdrawal Syndrome (NOWS), a combination of somatic withdrawal symptoms including high pitched crying, sleeplessness, irritability, gastrointestinal distress, and in the worst cases, seizures. The heterogeneity of in utero opioid exposure, particularly exposure to polypharmacy, makes it difficult to investigate the underlying molecular mechanisms that could inform early diagnosis and treatment of NOWS, and challenging to investigate consequences later in life. Methods: To address these issues, we developed a mouse model of NOWS that includes gestational and post-natal morphine exposure that encompasses the developmental equivalent of all three human trimesters and assessed both behavior and transcriptome alterations. Results: Opioid exposure throughout all three human equivalent trimesters delayed developmental milestones and produced acute withdrawal phenotypes in mice reminiscent of those observed in infants. We also uncovered different patterns of gene expression depending on the duration and timing of opioid exposure (3-trimesters, in utero only, or the last trimester equivalent only). Opioid exposure and subsequent withdrawal affected social behavior and sleep in adulthood in a sex-dependent manner but did not affect adult behaviors related to anxiety, depression, or opioid response. Discussion: Despite marked withdrawal and delays in development, long-term deficits in behaviors typically associated with substance use disorders were modest. Remarkably, transcriptomic analysis revealed an enrichment for genes with altered expression in published datasets for Autism Spectrum Disorders, which correlate well with the deficits in social affiliation seen in our model. The number of differentially expressed genes between the NOWS and saline groups varied markedly based on exposure protocol and sex, but common pathways included synapse development, the GABAergic and myelin systems, and mitochondrial function.

Dodonaea viscosa Jacq. induces cytotoxicity, antiproliferative activity, and cell death in colorectal cancer cells via regulation of caspase 3 and p53.

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and is the second leading cause of cancer-related death due to an insufficiency prognosis and is generally diagnosed in the last step of development. The Peruvian flora has a wide variety of medicinal plants with therapeutic potential in several diseases. Dodonaea viscosa Jacq. is a plant used to treat inflammatory process as well as gastrointestinal diseases. The aim of this study was to examine the cytotoxic, antiproliferative, and cell death-inducing effects of D. viscosa on colorectal cancer cells (SW480 and SW620). The hydroethanolic extract was obtained by maceration at 70% ethanol, the phytochemical constituents were identified by LC-ESI-MS. D. viscosa revealed 57 compounds some of them are: isorhamnetin, kaempferol, quercetin, methyl dodovisate B, hardwickiic acid, viscosol, and dodonic acid. Regarding the antitumoral activity, D. viscosa induced cytotoxic and antiproliferative activity in both SW480 and SW620 cancer cells, accompanied with, important changes in mitochondrial membrane potential, formation of the Sub G0/G1 population and increasing levels of apoptotic biomarkers (caspase 3 and the tumor suppressor protein p53) in the metastatic derivative cell line (SW620), suggesting an intrinsic apoptotic process after the treatment with the hydroethanolic extract of D. viscosa.

New Hybrid Scaffolds Based on 5-FU/Curcumin: Synthesis, Cytotoxic, Antiproliferative and Pro-Apoptotic Effect.

A series of 5-FU-Curcumin hybrids were synthesized, and their structures were elucidated by spectroscopic analysis. The synthesized hybrid compounds were evaluated in different colorectal cancer cell lines (SW480 and SW620) and in non-malignant cells (HaCaT and CHO-K1), to determine their chemopreventive potential. Hybrids 6a and 6d presented the best IC50 value against the SW480 cell line with results of 17.37 ± 1.16 µM and 2.43 ± 0.33 µM, respectively. Similarly, compounds 6d and 6e presented IC50 results of 7.51 ± 1.47 µM and 14.52 ± 1.31 µM, respectively, against the SW620 cell line. These compounds were more cytotoxic and selective than curcumin alone, the reference drug 5-fluorouracil (5-FU), and the equimolar mixture of curcumin and 5-FU. In addition, hybrids 6a and 6d (in SW480) and compounds 6d and 6e (in SW620) induced cell cycle arrest in S-phase, and, compounds 6d and 6e caused a significant increase in the sub-G0/G1 phase population in both cell lines. Hybrid 6e was also observed to induce apoptosis of SW620 cells with a respective increase in executioner caspases 3 and 7. Taken together, these results suggest that the hybrids could actively act on a colorectal cancer model, making them a privileged scaffold that could be used in future research.

Resveratrol/Hydrazone Hybrids: Synthesis and Chemopreventive Activity against Colorectal Cancer Cells.

A series of resveratrol/hydrazone hybrids were obtained and elucidated by spectroscopic analysis. All compounds were evaluated against colorectal cancer cells (SW480 and Sw620) and nonmalignant cell lines (HaCaT and CHO-K1) to establish the selectivity index. Among the hybrids evaluated, compounds 6e and 7 displayed the highest cytotoxic activity with IC50 values of = 6.5 ± 1.9 µM and 19.0 ± 1.4 µM, respectively, on SW480 cells. In addition, hybrid 7 also exhibited activity on SW620 cells with an IC50 value of 38.41 ± 3.3 µM. Both compounds were even more toxic against these malignant cells in comparison to the nonmalignant ones, as evidenced by higher selectivity indices 48 h after treatment. These compounds displayed better activity and selectivity than parental compounds (PIH and Resveratrol) and the reference drug (5-FU). In addition, it was observed that both compounds caused antiproliferative activity probably exerted by cell cycle arrest at the G2/M or G0/G1 phases, with the formation of cells in the subG0/G1 phase. Furthermore, it was noticed that compound 7 induced mitochondrial depolarization in SW480 cells and positive staining for propidium iodide in both cancer cell lines, suggesting cell membrane damage involving either apoptosis or other processes of death.

Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells.

A series of 5-FU-Genistein hybrids were synthesized and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated in human colon adenocarcinoma cells (SW480 and SW620) and non-malignant cell lines (HaCaT and CHO-K1). Hybrid 4a displayed cytotoxicity against SW480 and SW620 cells with IC50 values of 62.73 ± 7.26 µM and 50.58 ± 1.33 µM, respectively; compound 4g induced cytotoxicity in SW620 cells with an IC50 value of 36.84 ± 0.71 µM. These compounds were even more selective than genistein alone, the reference drug (5-FU) and the equimolar mixture of genistein plus 5-FU. In addition, hybrids 4a and 4g induced time- and concentration-dependent antiproliferative activity and cell cycle arrest at the S-phase and G2/M. It was also observed that hybrid 4a induced apoptosis in SW620 cells probably triggered by the extrinsic pathway in response to the activation of p53, as evidenced by the increase in the levels of caspases 3/8 and the tumor suppressor protein (Tp53). Molecular docking studies suggest that the most active compound 4a would bind efficiently to proapoptotic human caspases 3/8 and human Tp53, which in turn could provide valuable information on the biochemical mechanism for the in vitro cytotoxic response of this compound in SW620 colon carcinoma cell lines. On the other hand, molecular dynamics (MD) studies provided strong evidence of the conformational stability of the complex between caspase-3 and hybrid 4a obtained throughout 100 ns all-atom MD simulation. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analyses of the complex with caspase-3 showed that the interaction between the ligand and the target protein is stable. Altogether, the results suggest that the active hybrids, mainly compound 4a, might act by modulating caspase-3 activity in a colorectal cancer model, making it a privileged scaffold that could be used in future investigations.

Inverted urethral flap reconstruction after partial penectomy: Long-term oncological and functional outcomes.

INTRODUCTION: Penile aesthetics after partial penectomy (PP) for penile cancer (PC), significantly affect a patient's health-related quality of life (HRQoL), self-esteem, and sexual function. Satisfactory reconstruction has become a major milestone in the treatment of these patients. METHODS: Clinical charts of all patients that underwent PP and reconstruction with an inverted urethral flap (IUF) were reviewed. The primary endpoints were recurrence-free survival (RFS), overall survival (OS), and progression-free survival (PFS) which were graphically represented by Kaplan-Meier estimates. The key secondary endpoints were Health-related quality of life (HRQoL), erectile function, and lower urinary tract symptoms. RESULTS: Between May 2007 and December 2019, 74 patients with PC underwent PP and IUF reconstruction. The median age was 62 years (IQR 52-76), median follow-up was 72 months (IQR 38-121). Twenty-nine patients (39.2%) underwent inguinal lymph node dissection, 62 (83.8%) underwent dynamic sentinel lymph node biopsy. Kaplan-Meier estimates of OS, RFS, and PFS showed a 6-year OS of 86.5%, 6-year RFS of 90.5%, and a 6-year PFS of 85.1%. Regarding functional outcomes, we found a mean global health score of 84.6% ± 10.4 at the EQ-5D-3L-VAS. The mean Voiding score of the ICIQ-MLUTS was 1.7 ± 3.2 and a mean IIEF-5 score of 17.3 ± 7. CONCLUSIONS: To the best of our knowledge, we report the largest cohort in the literature of PP with IUF reconstruction. These results are important since early-stage PC is the most common stage at diagnosis. In carefully selected patients' preservation of a longer urethral stump to allow for the inverted flap is safe and does not compromise oncological outcomes while preserving HRQoL.

Real World Data of Penile Cancer Treatment at a High-Volume Center in South America: Insights and Survival Trends.

OBJECTIVE: To report survival trends and oncological outcomes of penile cancer surgically treated patients, at a high-volume center, treating more than 25 patients each year, in a high incidence country. METHODS: Clinical charts of all patients that underwent surgical management for penile cancer were reviewed. The primary end points were cancer specific survival (CSS), progression-free survival, and local recurrence free survival. Kaplan-Meier plots were used for survival analyses. Multivariate analysis was performed using cox proportional hazard age-adjusted models to determine the effect of pN, pT, lymphovascular invasion for CSS. RESULTS: A total of 209 patients were identified, with a median follow up of 96 months (IQR 49-133). Organ-sparing surgerywas performed in 72.7%, 56.9% underwent dynamic sentinel lymph node biopsy, 110 patients underwent inguinal lymph node dissection, and 45 (21.5%) pelvic lymph node dissection. A total of 75 (35.8%) of patients relapsed, median time to relapse of 12 months (IQR 6-25). Overall estimates of CSS showed an 8-year CSS of 68.9%. Eight-year CSS was 90.5% for N0, and 32.8% in pN3 (P <.001). The Cox proportional hazard model showed that pN1-3, pT2-4, lymphovascular invasion and positive dynamic sentinel lymph node biopsy were the variables associated with worse 8-year CSS. CONCLUSION: To the best of our knowledge, we report one of the largest cohorts on the survival outcomes of penile cancer surgical treatment, in a single institution, over a long period of time, were most patients are referred with high-risk, locally advanced or nodal disease.

Prognostic Factors for Inguinal Lymph Node Involvement and Tumor Recurrence in Squamous Cell Carcinoma of the Penis / Factores pronósticos de compromiso ganglionar inguinal y recaída tumoral en carcinoma escamocelular de pene

Zoom Image Abstract Introduction Penile carcinoma is an aggressive disease with catastrophic consequences that frequently lead to death. Therefore, further knowledge on the prognostic factors that can help identify patients in need of more aggressive treatments becomes essential. Objective To identify the prognostic factors for lymph node (LN) involvement and tumor recurrence in patients diagnosed with squamous cell carcinoma of the penis (SCCP). Methods A retrospective cohort study was conducted. Patients diagnosed and treated for SCCP at Instituto Nacional de Cancerología between 2008 and 2015 were included in the sample. Cases in which no information on recurrence was available for the follow-up were excluded, as well as patients with no initial pathology and those getting penile reconstructions after cancer. Relevant data was retrieved from the medical records of each patient, and a descriptive analysis was performed. Subsequently, this data was used to apply a logistic regression model to determine the potential clinical and histopathological prognostic factors. Results A total of 104 patients were included in the present study. The average age of the sample was 59 years, while the follow-up averaged 24 months per patient. Inguinal lymphadenectomy was performed on 61 patients (59%) during the follow-up. The logistic regression model showed that lymphovascular invasion (odds ratio [OR]: 6.7; 95% confidence interval [95%CI]: 1.2­35) and poor tumor differentiation (OR: 17; 95%CI: 3.2­92) were associated with tumor recurrence. Likewise, the lymphadenectomy procedures showed that lymphovascular invasion was associated with LN involvement (OR: 3.3; 95%CI: 1.1­10). Conclusion Lymphovascular invasion was the strongest prognostic factor observed in our sample, aiding in the prediction of inguinal LN involvement and tumor recurrence in SCCP patients

Introduccion El cáncer de pene es una enfermedad agresiva con consecuencias catastróficas que frecuentemente llevan a la muerte. Por lo tanto, es esencial un mayor conocimiento sobre los factores pronósticos que pueden ayudar a identificar a los pacientes que necesitan tratamientos más agresivos. Objetivo Identificar los factores pronósticos patológicos de compromiso ganglionar inguinal y recaída tumoral en pacientes con carcinoma escamocelular de pene. Métodos Se realizó un estudio de cohorte retrospectivo. Se incluyeron en la muestra pacientes diagnosticados y tratados por carcinoma escamocelular de pene (SCCP) en el Instituto Nacional de Cancerología entre 2008 y 2015. Los casos en los que no había información sobre la recurrencia en el seguimiento fueron excluidos, así como los pacientes sin patología inicial y aquellos que reciben reconstrucciones del pene después del cáncer. Se recuperaron los datos relevantes de los registros médicos de cada paciente, y una descripción fue realizada. Posteriormente, estos datos se utilizaron para aplicar un modelo de regresión logística para determinar los posibles factores pronósticos clínicos e histopatológicos. Resultados Un total de 104 pacientes fueron incluidos en el estudio. La edad promedio de la muestra fue de 59 años, mientras que el seguimiento promedió fue de 24 meses por paciente. La linfadenectomía inguinal se realizó en 61 pacientes (59%) durante el seguimiento. El modelo de regresión logística mostró que la invasión linfovascular (odds ratio [OR]: 6,7; intervalo de confianza del 95% [IC 95%]: 1,2­35) y la pobre diferenciación tumoral (OR: 17; IC 95%: 3,2­92) se asociaron con recurrencia tumoral. Así mismo, los procedimientos de linfadenectomía mostraron que la invasión linfovascular se asoció con afectación de LN. (OR: 3,3; IC 95%: 1,1-10). Conclusión La invasión linfovascular es el factor pronóstico independiente más importante que se asocia de manera independiente con compromiso ganglionar inguinal positivo y recaída tumoral.

Clinical and Histopathological Characteristics of Prostate Cancer Patients Taken to Palliative Transurethral Prostate Resection.

Introduction In prostate cancer (PCa) patients who have been treated with radiotherapy and/or androgen deprivation therapy (ADT), palliative transurethral resection of the prostate (TURP) is a management option in the presence of lower urinary tract symptoms (LUTS). The present work seeks to describe the clinical and histopathological characteristics of patients with PCa taken to palliative TURP. Methods An observational, descriptive and retrospective study of patients with PCa who underwent palliative TURP for the relief of obstructive urinary symptoms at an oncology reference center between January 2006 and June 2014 was performed. Among the included patients were those with localized PCa treated with radiotherapy and those with advanced PCa with or without metastasis who had previously received ADT. Results Sixty-six patients with a diagnosis of PCa taken to palliative RTUP were identified. Fifty patients (78.4%) were received some type of ADT, seven patients (10.7%) received curative radiotherapy along with adjuvant ADT, five patients (7.8%) were previously treated with only radiotherapy, and two patients (3.1 %) had received no prior management and thus were taken to bilateral orchiectomy along with palliative TURP in a single surgical act. With regard to the pathology reports, tumor tissue was found in 50 patients (76%), and no tumor was observed in the remaining 16 patients (24%). In one case (1.5%), the Gleason score (GS) could not be determined due to the effects of orchiectomy. Under-staging in the grade group was evidenced in 23 patients (46.9%), over-staging in three patients (6.3%), and no difference in 23 patients (46.9%), when compared to the initial GS at biopsy. The mortality rate and the incidence of TURP syndrome were low (3.1% and 1.5%, respectively). A 46% reduction in the mean serum prostate-specific antigen (PSA) value was documented when the preoperative and postoperative values were compared. Conclusion A decrease in the serum PSA levels was observed after palliative TURP, and despite having received ADT, it was possible to determine tumor pathology in the resected tissue, being able to identify a greater grade group compared the GS at the time of diagnosis. The palliative TURP proved to be a safe procedure to relieve LUTS in patients with advanced PCa, with a low morbidity and mortality rate.

Eficacia y seguridad del dietiletilbestrol, en el tratamiento del cáncer de próstata resistente a la castración / Effectiveness and Safety of Diethylstilbestrol in the Treatment of Castration Resistant Prostate Cancer

Introducción y objetivos Existen múltiples opciones de tratamiento en pacientes con cáncer de próstata resistente a la castración, entre ellas el Dietilestilbestrol (DES) sin embargo, su uso es controversial. Este estudio tiene como objetivo determinar la eficacia y seguridad del DES, en el tratamiento de pacientes con cáncer de próstata resistente a la castración en nuestra población. Métodos y Materiales Se realizó un estudio de corte transversal, incluyendo los pacientes con cáncer de próstata resistente a la castración que recibieron tratamiento con DES. Se realizó un análisis demográfico, bivariado, tomando como desenlace la respuesta del PSA (Ausente, Completa o Parcial), el tiempo medio de progresión del PSA y la presencia de eventos adversos asociados al medicamento. Resultados Noventa y un pacientes incluidos al final del estudio. La distribución de respuesta del PSA fue así: Respuesta en 57 (63,7%) pacientes, (Completa 28% - 31,1% y parcial 29% - 32,2%). Ausente en 33 (36,7%) pacientes. El análisis bivariado no evidenció asociación entre las variables y los desenlaces propuestos. El tiempo medio de progresión del PSA fue de 10,43 meses (Log-rank p = 0.001), no se encontraron diferencias estadísticamente significativas para el tiempo medio a progresión en asociación con la respuesta al PSA (respuesta o ausente y la presencia de enfermedad metastásica), Log-rank p = 0,789, Log-rank p = 0,218, Log-rank p = 0,780 respectivamente. La tasa de complicaciones asociadas a DES fue del 4,4% y correspondió en todos los casos a trombosis venosa profunda. Conclusiones El DES en pacientes con cáncer de próstata resistente a la castración continúa siendo una herramienta de tratamiento eficaz y con baja tasa de eventos adversos en nuestra población.

Introduction and Objectives There are multiple treatment options in patients with castration-resistant prostate cancer, including diethylstilbestrol (DES), but its use is controversial. This study aims to determine the efficacy and safety of DES in the treatment of patients with castration resistant prostate cancer in our population. Methods and Materials A cross-sectional study was performed, including patients with castration resistant prostate cancer who were treated with DES. A demographic analysis was performed, bivariate analysis, taking as outcome PSA response (Complete or partial), the median time to PSA progression and the presence of adverse events associated with the drug. Results 91 patients included at the end of the study. The distribution of PSA response was so; Response in 57 (63.7%) patients (Full 28 to 31.1% and partial 29 to 32.2%). Absent in 33 (36.7%) patients. Bivariate analysis evidenced no association between the variables and proposed outcomes. The median time to PSA progression was 10.43 months (log-rank p = 0.001), no statistically significant differences in the average time to progression was found in association with PSA response (response or absent and the presence of disease metastatic), Log-rank p = 0.789, log-rank p = 0.218, log-rank p = 0.780 respectively. The rate of complications associated with DES was 4.4% and corresponded in all cases to deep vein thrombosis. Conclusions DES in patients with resistant prostate cancer castration continued to be an effective choice of tool of treatment with a low rate of adverse events in our population.

Reporte de caso: Carcinoma escamocelular de próstata tratado con radioterapia externa técnica IMRT / Case report: Prostate squamous cell carcinoma managed with an external intensity-modulated radiotherapy technique

Resumen La incidencia de carcinoma escamocelular de próstata es del 0,5 al 1% de todas las lesiones neoplásicas de esta glándula. Por su rareza, no existen recomendaciones protocolizadas sobre el manejo de estos pacientes. Se reporta el caso de un paciente tratado en el Instituto con este diagnóstico, así como su desenlace a dos años de seguimiento y la revisión del tema. Reporte de caso: Paciente masculino de 79 anos de edad, con diagnóstico de carcinoma escamocelular infiltrante de próstata estadificado como T4NxMx. PSA de 2,64 y Gleason no determinable. Se descartó posible primario de órgano aledaño a la próstata y los estudios de extensión fueron negativos. Fue tratado con radioterapia externa como monoterapia y se utilizó técnica IMRT. Recibió una dosis en pelvis de 46 Gy en fracciones de 2 Gy día (PTV 1), posteriormente refuerzo en próstata y vesículas hasta 56 Gy (PTV 1,1) y en próstata hasta 76 Gy (PTV 1,1,1). A los dos años de seguimiento se documentaron lesiones pulmonares a las cuales se les practicó biopsia y el estudio anatomopatológico fue compatible con carcinoma escamocelular invasivo.

Abstract The incidence of squamous cell carcinoma of prostate is between 0.5-1% of all neoplastic lesions of this gland. Due to their rarity, there are no protocolised recommendations on the management of these patients. A report is presented on a patient with this diagnosis treated at our institution, its outcome at two years of follow-up, and a review of the subject. Case report: Male patient, 79 years old, diagnosed with invasive squamous cell carcinoma of the prostate. Staged as T4NxMx/IPSA 2.64/Gleason undeterminable. Work up studies were negative, and primaries from nearby organs were ruled out. He was treated with radiotherapy as monotherapy and was scheduled for an intensity-modulated radiotherapy (IMRT) technique, initially to the pelvis at a radiotherapy dose of 46 Gy 2Gy daily (PTV 1), further reinforcing prostate and vesicles up to 56 Gy (1.1 PTV), and finally to 76 Gy to prostate (PTV 1,1,1). With a follow-up of two years, lung lesions were found, which were biopsied and positive for squamous cell carcinoma.

Metastasectomy of Abdominal Wall Lesions due to Prostate Cancer Detected Through PET/CT Gallium 68-PMSA: First Case Report.

Introducing the topic of abdominal wall metastasis secondary to prostate cancer with a reminder of the disease's rarity, being the first published case. This article is about a 66 year old patient diagnosed with prostate cancer [cT2aNxMx iPSA: 5,6 ng/ml Gleason 3+3, (Grade 1 Group)], treated with radical prostatectomy as well as accompanied with amplified pelvic lymphadenectomy, who subsequently presented metastatic lesions to the abdominal wall diagnosed with PET/CT Gallium 68-PMSA technique and treated with abdominal metastasectomy with adequate short term results.