RESUMEN
HSV infects keratinocytes in the epidermis of skin via nectin-1. We established a human foreskin explant infection model to investigate HSV entry and spread. HSV1 entry could only be achieved by the topical application of virus via high density microarray projections (HD-MAPs) to the epidermis, which penetrated beyond one third of its thickness, simulating in vivo microtrauma. Rapid lateral spread of HSV1 to a mean of 13 keratinocytes wide occurred after 24 hours and free virus particles were observed between keratinocytes, consistent with an intercellular route of spread. Nectin-1 staining was markedly decreased in foci of infection in the epidermis and in the human keratinocyte HaCaT cell line. Nectin-1 was redistributed, at the protein level, in adjacent uninfected cells surrounding infection, inducible by CCL3, IL-8 (or CXCL8), and possibly CXCL10 and IL-6, thus facilitating spread. These findings provide the first insights into HSV1 entry and spread in human inner foreskin in situ.
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Quimiocinas , Prepucio , Herpes Simple , Herpesvirus Humano 1 , Queratinocitos , Nectinas , Humanos , Masculino , Queratinocitos/virología , Queratinocitos/metabolismo , Prepucio/virología , Prepucio/citología , Nectinas/metabolismo , Herpes Simple/virología , Herpes Simple/metabolismo , Quimiocinas/metabolismo , Herpesvirus Humano 1/fisiología , Moléculas de Adhesión Celular/metabolismo , Internalización del VirusRESUMEN
The protozoan parasite Toxoplasma gondii lives inside a vacuole in the host cytosol where it is protected from host cytoplasmic innate immune responses. However, IFNγ-dependent cell-autonomous immunity can destroy the vacuole and the parasite inside. Toxoplasma strain differences in susceptibility to human IFNγ exist, but the Toxoplasma effector(s) that determine these differences are unknown. We show that in human primary fibroblasts, the polymorphic Toxoplasma-secreted effector GRA15 mediates the recruitment of ubiquitin ligases, including TRAF2 and TRAF6, to the vacuole membrane, which enhances recruitment of ubiquitin receptors (p62/NDP52) and ubiquitin-like molecules (LC3B, GABARAP). This ultimately leads to lysosomal degradation of the vacuole. In murine fibroblasts, GRA15-mediated TRAF6 recruitment mediates the recruitment of immunity-related GTPases and destruction of the vacuole. Thus, we have identified how the Toxoplasma effector GRA15 affects cell-autonomous immunity in human and murine cells.
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Prepucio/parasitología , Interferón gamma/farmacología , Proteínas Protozoarias/metabolismo , Toxoplasma/crecimiento & desarrollo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Células Cultivadas , Fibroblastos/citología , Fibroblastos/metabolismo , Fibroblastos/parasitología , Prepucio/citología , Prepucio/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interferón gamma/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Ratones , Transducción de Señal , Toxoplasma/metabolismo , Vacuolas/metabolismoRESUMEN
OBJECTIVES: To compare the efficiency and safety of a novel flexible ureteral access sheath (f-UAS) and traditional ureteral access sheath (UAS) during retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS: Between January 2022 and September 2022, a total of 152 consecutive cases with renal stones underwent RIRS with the f-UAS. Their outcomes were compared with those of another 152 consecutive cases undergoing RIRS with traditional UAS using a 1:1 scenario matched-pair analysis, with matching parameters including age and stone size. The f-UAS is a novel UAS with a 10-cm-long tube at the tip that can follow the bends of flexible ureteroscope (f-URS). RESULTS: Baseline characteristics were found to be similar between the two groups. The f-UAS group demonstrated significantly higher SFR (76.3% vs. 7.2%; P < 0.001) at 1 day postoperatively and a higher clearance rate of stone volume (98.11% vs. 91.78%; P < 0.001). The f-UAS group also had lower total complications rate (9.9% vs. 22.4%; P = 0.003), lower incidence of fever (5.9% vs 11.9%; P = 0.001), shorter operative times (56.5 min vs. 59.9 min; P = 0.047), and lower usage rate of baskets (17.1% vs. 100%; P < 0.001). There was no significant difference in SFR at 1 month postoperatively (P = 0.627) and in the length of postoperative hospital stay between the two groups (P = 0.225). CONCLUSION: Compared to the traditional UAS during RIRS, the f-UAS showed several advantages, including higher SFR at 1 day postoperatively, shorter operative times, lower incidence of complications, and less use of basket.
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Cálculos Renales , Uréter , Humanos , Masculino , Uréter/cirugía , Fiebre , Prepucio , Cálculos Renales/cirugía , Tiempo de InternaciónRESUMEN
BACKGROUND: Wound healing is one of the important processes in the body. Attempts to create new drugs are of interest due to the side effects of natural and chemical wound healing compounds. To overcome this obstacle, stem cells have been used as healing agents. However, both difficulties in collection and risks such as rejection and teratoma in the recipient body have limited the use of stem cells, directly. Since the potential content of the stem cells can be transferred to the recipient cells by vesicles, small extracellular vesicles have recently become prominent agents. METHODS AND RESULTS: The wound-healing effect of extracellular vesicles derived from foreskin cells was investigated in both keratinocyte and endothelial cells. Migration assay, RT-PCR, Col1a1 ELISA and Western Blot experiments were utilized to reveal healing effect of EVs and its possible molecular pathways. EV-treated groups exhibited more proliferative, invasive, and migrative characteristics. When comparing to the control group, new vessel formation was induced in EV groups. An increase in gene levels of growth factors related to wound healing and change in the mitogen-activated protein kinase (MAPK) signaling pathway proteins in EV-treated groups were determined. Possible molecular mechanisms underlying cell movements were associated with the MAPK pathway. It was found that human foreskin cell EVs (hFS-Exo) may have a potential to heal wounds in a short period of time by triggering the MAPK pathway. CONCLUSIONS: hFS-Exo could be a new promising wound healing agent in the future.
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Vesículas Extracelulares , Proteínas Quinasas Activadas por Mitógenos , Masculino , Humanos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Células Endoteliales , Prepucio , Angiogénesis , Vesículas Extracelulares/metabolismo , Movimiento CelularRESUMEN
BACKGROUND: Bioscaffolds and cells are two main components in the regeneration of damaged tissues via cell therapy. Umbilical cord stem cells are among the most well-known cell types for this purpose. The main objective of the present study was to evaluate the effect of the pretreatment of the foreskin acellular matrix (FAM) by monophosphoryl lipid A (MPLA) and Lactobacillus casei supernatant (LCS) on the attraction of human umbilical cord mesenchymal stem cells (hucMSC). METHODS AND RESULTS: The expression of certain cell migration genes was studied using qRT-PCR. In addition to cell migration, transdifferentiation of these cells to the epidermal-like cells was evaluated via immunohistochemistry (IHC) and immunocytochemistry (ICC) of cytokeratin 19 (CK19). The hucMSC showed more tissue tropism in the presence of MPLA and LCS pretreated FAM compared to the untreated control group. We confirmed this result by scanning electron microscopy (SEM) analysis, glycosaminoglycan (GAG), collagen, and DNA content. Furthermore, IHC and ICC data demonstrated that both treatments increase the protein expression level of CK19. CONCLUSION: Pretreatment of acellular bioscaffolds by MPLA or LCS can increase the migration rate of cells and also transdifferentiation of hucMSC to epidermal-like cells without growth factors. This strategy suggests a new approach in regenerative medicine.
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Lacticaseibacillus casei , Lípido A , Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/metabolismo , Lacticaseibacillus casei/metabolismo , Lípido A/metabolismo , Lípido A/análogos & derivados , Movimiento Celular/efectos de los fármacos , Piel/metabolismo , Andamios del Tejido/química , Masculino , Cordón Umbilical/citología , Cordón Umbilical/metabolismo , Prepucio/citología , Transdiferenciación Celular/efectos de los fármacos , Ingeniería de Tejidos/métodos , Matriz Extracelular/metabolismo , Queratina-19/metabolismo , Queratina-19/genéticaRESUMEN
PURPOSE: To report the 12-month results of a novel urethroplasty technique relying on a spiral preputial graft for panurethral stricture disease. MATERIALS AND METHODS: Twenty consecutive patients were treated between May and October 2021 at our center. A spiral preputial mucocutaneous graft is a foreskin-based graft, developed from a 5-cm-wide preputial skin, which is harvested using a helicoidal shape and can reach up to 20 cm in length. Stricture characteristics were assessed through preoperative retrograde and voiding cystourethrogram and maximum uroflowmetry data (Qmax). Complications were collected up to 30 days after surgery and graded using the Clavien-Dindo (C-D) classification. The patients were followed up to 12 months. RESULTS: Preoperative median Qmax was 6.5 ml/s [interquartile range (IQR): 4.0-8.7]. After a median follow-up of 12 months (IQR 12-13), six patients experienced at least one complication. Of them, two patients had grade 2 C-D complications, while only one developed a grade 3a C-D complication. The median postoperative Qmax was 16 ml/s (IQR: 13-18). Only one patient had early urethral stricture recurrence treated with dilatation after catheter removal. At one-year follow-up, no other patients had urethral stricture recurrence with an overall median Qmax of 15.1 ml/s (IQR 13.5-16.4). CONCLUSIONS: Our novel single-stage spiral preputial graft urethroplasty for panurethral stricture treatment appears to be safe and could be used as a valid alternative to two-stage procedures or even to single-stage buccal mucosa graft augmentation.
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Cistografía , Prepucio , Pene , Trasplante de Piel , Humanos , Prepucio/cirugía , Estrechez Uretral/cirugía , Complicaciones Posoperatorias , Resultado del Tratamiento , Masculino , Pene/diagnóstico por imagen , Pene/cirugíaRESUMEN
BACKGROUND: Dysregulated apoptosis of penile mesenchymal cells during male urethragenesis has been previously demonstrated to underly hypospadiac urethral closure failure, and androgen receptor (AR) has been shown to play a central role in regulating penile mesenchyme cell proliferation and survival. However, the regulatory mechanisms upstream and downstream of AR remain poorly understood. Our clinical data and bioinformatics analysis previously indicated that hsa_circ_0000417, a circRNA significantly downregulated in hypospadias preputial specimens, may act as a ceRNA for AR via sequestering hsa_miR-6756-5p, and that the biological functions of hsa_circ_0000417 may significantly involve the PI3K/AKT pathway. In this study, we employed human foreskin fibroblasts (HFF-1) to experimentally validate this putative hsa_circ_0000417/miR-6756-5p/AR axis and its impact on penile mesenchymal cell proliferation and apoptosis. METHOD AND RESULTS: We showed that hsa_circ_0000417 knockdown significantly promoted proliferation and suppressed apoptosis of HFF-1 cells. Mechanistically, hsa_circ_0000417 functioned as a molecular sponge for miR-6756-5p in HFF-1 cells and relieved the latter's translational repression on AR mRNA, leading to decreased AKT activation and increased expression of pro-apoptotic proteins BAX and cleaved-caspase 9. Conversely, elevated levels of miR-6756-5p resulted in diminished AR expression concomitant with enhanced AKT activation and HFF-1 cell proliferation. CONCLUSIONS: Collectively, our data describe for the first time a circRNA-mediated post-transcriptional regulatory mechanism of AR and its functional consequences in penile mesenchymal cells in the context of hypospadias. These findings may contribute to advancing our current understanding of the roles of AR and mesenchymal cell fate decisions during penile morphogenesis.
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Hipospadias , MicroARNs , Humanos , Masculino , Receptores Androgénicos/genética , Andrógenos , Prepucio , Regulación hacia Abajo/genética , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt/genética , ARN Circular/genética , MicroARNs/genética , Proliferación Celular/genética , Línea Celular TumoralRESUMEN
Individual mammalian cells exhibit large variability in cellular volume, even with the same absolute DNA content, and so must compensate for differences in DNA concentration in order to maintain constant concentration of gene expression products. Using single-molecule counting and computational image analysis, we show that transcript abundance correlates with cellular volume at the single-cell level due to increased global transcription in larger cells. Cell fusion experiments establish that increased cellular content itself can directly increase transcription. Quantitative analysis shows that this mechanism measures the ratio of cellular volume to DNA content, most likely through sequestration of a transcriptional factor to DNA. Analysis of transcriptional bursts reveals a separate mechanism for gene dosage compensation after DNA replication that enables proper transcriptional output during early and late S phase. Our results provide a framework for quantitatively understanding the relationships among DNA content, cell size, and gene expression variability in single cells.
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Dosificación de Gen , Hibridación Fluorescente in Situ/métodos , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Transcripción Genética , Animales , Caenorhabditis elegans/genética , Células Cultivadas , Fibroblastos/citología , Prepucio/citología , Expresión Génica , Humanos , Masculino , Datos de Secuencia Molecular , Fase SRESUMEN
Despite significant advancements in tissue engineering and regenerative medicine during the last two decades, the fabrication of proper scaffolds with appropriate cells can still be considered a critical achievement in this field. Hypoxia is a major stumbling block to chronic wound healing, which restrains tissue engineering plans because a lack of oxygen may cause cell death. This study evaluated the cocultured human keratinocytes and human adipose-derived mesenchymal stem cells (AMSCs) on a multilayer oxygen-releasing electrospun scaffold based on PU/PCL.Sodium percarbonate (SPC)-gelatin/PU. The scaffold was characterized using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) methods. Flow cytometry confirmed mesenchymal stem cells, and then the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and DAPI staining were used to assess the in vitro biocompatibility of the scaffold. The experimental results showed that the multilayer electrospun scaffold containing 2.5% SPC could efficiently produce oxygen. Furthermore, according to cell viability results, this structure makes a suitable substrate for the coculture of keratinocytes and AMSCs. Gene expression analysis of various markers such as Involucrin, Cytokeratin 10, and Cytokeratin 14 after 14 days confirmed that keratinocytes and AMSCs coculture on PU/PCL.SPC-gelatin/PU electrospun scaffold promotes dermal differentiation and epithelial proliferation compared to keratinocytes single-cell culture. Therefore, our study supports using oxygen-releasing scaffolds as a potential strategy to hasten skin tissue regeneration. Based on the results, this structure is suggested as a promising candidate for cell-based skin tissue engineering. Given that the developed oxygen-generating polymeric electrospun scaffolds could be used as part of a future strategy for skin tissue engineering, the PU/PCL.SPC-gelatin/PU hybrid electrospun multilayer scaffold in combination with keratinocyte/AMSC coculture is proposed as an effective substrate for skin tissue engineering and regenerative medicine platforms.
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Células Madre Mesenquimatosas , Andamios del Tejido , Masculino , Humanos , Técnicas de Cocultivo , Andamios del Tejido/química , Gelatina/metabolismo , Prepucio , Oxígeno/farmacología , Oxígeno/metabolismo , Queratinocitos/metabolismo , Células Madre Mesenquimatosas/metabolismoRESUMEN
OBJECTIVE: To define and classify megameatus anomalies, the parameters of a considerable number of cases were investigated and compared with those of normal children. METHODS: A total of 1150 normal babies were examined during routine nonmedical circumcision, and another 750 boys referred with hypospadias were examined during the previous 3 years. All patients were evaluated and assessed for the size, location, and configuration of the urinary meatus, and penile length and girth were measured. Children with normal size and location of the meatus were considered control group A, and 42 cases of different forms of megameatus were considered group B. Other penoscrotal, urinary, and general anomalies were examined and investigated accordingly. All data were analyzed by the SPSS 9.0.1 statistical package and compared by paired t tests. RESULTS: Forty-two uncircumcised patients aged from 1 month to 4 years (mean 18 months) were diagnosed with a urinary meatus that engrossed the whole ventral or dorsal aspects of the glans, exceeding half the width of the glans or penile girth with the complete vanishing of the glans closure in most cases. Megameatus is usually associated with the abnormal meatal position as hypospadiac, orthotopic, or epispadic. Additionally, megameatus may be associated with a normally intact or deficient prepuce. Consequently, we had four categories of megameatus, and the intact prepuce orthotopic megameatus subcategory has not been described before. Megameatus was also detected with deficient prepuce, and this was considered a hypospadiac variant. CONCLUSION: Megameatus is diagnosed precisely with penile biometry and is classified into 4 groups: hypospadiac, epispadic, and orthotopic or central, either with or without intact prepuce. This classification is applicable for expansion to other centers.
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Circuncisión Masculina , Epispadias , Hipospadias , Masculino , Lactante , Niño , Humanos , Pene/anomalías , Hipospadias/cirugía , Prepucio , Uretra/anomalíasRESUMEN
This short communication describes a case of a 30-year-old stallion with a mass on the base of the penis causing paraphimosis. The patient was submitted to anti-inflammatory and diuretic therapy with no signs of improvement, so 16 days after the lesion was detected, the animal was euthanized. Necropsy was performed, and histopathological assessment of the lesion was conducted. The mass was composed primarily of channels and cavernous structures, lined by elongated cells of vascular origin, located in the preputium. The lesion was diagnosed as a preputial lymphangioma. To the authors' best knowledge, the anatomical location of this neoplasm (which is rare in veterinary medicine) has not been previously reported.
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Enfermedades de los Caballos , Linfangioma , Masculino , Animales , Caballos , Linfangioma/cirugía , Linfangioma/veterinaria , Linfangioma/diagnóstico , Prepucio , Pene/patología , Enfermedades de los Caballos/cirugíaRESUMEN
Leontopodium alpinum is a source of raw material for food additives and skin health. The purpose of this study was to investigate the application of Leontopodium alpinum callus culture extract (LACCE) to prevent blue light damage to the skin. We screened and identified the blue light-damage-protecting activities and mechanisms of ten components of LACCE, including chlorogenic acid (A), isoquercitrin (B), isochlorogenic acid A (C), cynaroside (D), syringin (E), isochlorogenic acid (F), cynarin (G), rutin (H), leontopodic acid A (I), and leontopodic acid B (J), using a novel blue light-induced human foreskin fibroblast (HFF-1) cell injury model. The study examined the cytotoxicity of ten ingredients using the cell counting kit-8 (CCK-8) assay, and selecting concentrations of 5, 10, and 20 µM for experiments with a cell viability above 65%. We explored the effects and mechanisms of action of these LACCE components in response to blue light injury using Western blotting and an enzyme-linked immunosorbent assay. We also measured ROS secretion and Ca2+ influx. Our study revealed that leontopodic acid A effectively boosted COI-1 expression, hindered MMP-1 expression, curbed ROS and Ca2+ endocytosis, and reduced OPN3 expression. These results provide theoretical support for the development of new raw materials for the pharmaceutical and skincare industries.
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Prepucio , Luz , Humanos , Masculino , Especies Reactivas de Oxígeno , Extractos Vegetales/farmacología , Fibroblastos , Opsinas de BastonesRESUMEN
Leontopodium alpinum is an important source of raw material for food, medicine, and modern cosmetics. The purpose of this study was to develop a new application for protection against blue light damage. To investigate the effects and mechanism of action of Leontopodium alpinum callus culture extract (LACCE) on blue light damage, a blue-light-induced human foreskin fibroblast damage model was established. The contents of collagen (COL-I), matrix metalloproteinase 1 (MMP-1), and opsin 3 (OPN3) were detected using enzyme-linked immunosorbent assays and Western blotting. The calcium influx and reactive oxygen species (ROS) levels were measured via flow cytometry and the results showed that the LACCE (10-15 mg/mL) promoted the production of COL-I, inhibited the secretion of MMP-1, OPN3, ROS and calcium influx, and may play a role in inhibiting the activation of blue light on the OPN3-calcium pathway. Thereafter, high-performance liquid chromatography and ultra-performance liquid chromatography-tandem mass spectrometry were used to quantitatively analyze the contents of nine active ingredients in the LACCE. The results indicated that LACCE has an anti-blue-light-damage effect and provides theoretical support for the development of new raw materials in the natural food, medicine, and skin care industries.
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Prepucio , Metaloproteinasa 1 de la Matriz , Humanos , Masculino , Especies Reactivas de Oxígeno/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Prepucio/metabolismo , Calcio/farmacología , Extractos Vegetales/química , Fibroblastos , Opsinas de Bastones/farmacologíaRESUMEN
PURPOSE: Considerable controversy exists regarding the surgery for concealed penis. We describe a new technique for repairing concealed penis by symmetrical pterygoid flap surgery. METHODS: From January 2016 to July 2022, we evaluated 181 cases of concealed penis that were surgically treated using the symmetrical pterygoid flap surgery. We measured the penile size preoperative and 2, 4, 12 weeks, and 1 year postoperative to confirm the improvement. A questionnaire was administered to the patients and parents to assess satisfaction regarding penile size, morphology, and hygiene. RESULT: The perpendicular penile length was1.59±0.32cm preoperative and 3.82±1.02 cm after the procedure (p < 0.05), and 4.21±1.91cm after one year of postoperative (p < 0.05). The overall satisfaction of patients was 97.89%, while the overall satisfaction of older children patients (age>7) was 75.24%. Parents focus more on the penile exposure size, while patients focus more on the penile morphology. Almost every patient had postoperative penile foreskin edema. However, this symptom had spontaneously resolved by 4-6 weeks. The complications such as skin necrosis, tissue contracture, or wound infection were 4.42%. CONCLUSION: The symmetrical pterygoid flap surgery is an effective surgical technique for the management of concealed penis in children producing predictable results and excellent satisfaction of the parents and patients.
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Enfermedades del Pene , Procedimientos de Cirugía Plástica , Niño , Masculino , Humanos , Adolescente , Procedimientos Quirúrgicos Urológicos Masculinos/métodos , Colgajos Quirúrgicos , Pene/cirugía , Prepucio/cirugía , Enfermedades del Pene/cirugíaRESUMEN
Circumcision is the simplest, most commonly used and most effective treatment for male prepuce overlength, phimosis and other diseases. There has also been a shift from traditional circumcision to simpler, faster, less invasive, instrument-based methods. This paper reviews the surgical methods of circumcision(Traditional circumcisionãElectrosurgical circumcisionãLaser circumcisionãSleeve circumcision, Dermotomy at the base of penis, Shangring, Gomco, Mogen, PlastiBell, PrePex, Alisklamp and Disposable circumcision suture apparatus), hoping to provide reference for clinicians to choose the appropriate circumcision methods for patients.
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Circuncisión Masculina , Fimosis , Humanos , Masculino , Pene , Prepucio , Pelvis , Fimosis/cirugíaRESUMEN
OBJECTIVE: To explore the safety, feasibility, and technical points of the improved circumcision procedure assisted by a precise marking method circumcision device. METHOD: A retrospective analysis was conducted on 41 cases of modified foreskin circumcision using precise marking method in the urology department of our hospital from February 2021 to January 2023 as the observation group, and 60 cases of traditional foreskin circumcision assisted by traditional foreskin circumcision during the same period as the control group. Compare and analyze indicators such as the distance from the anastomotic margin to the coronal sulcus, postoperative erectile tension, edema, hematoma, postoperative infection, and the presence of sexual intercourse pain between two groups of patients. The number of patients in the observation group who experienced erectile tension at 3 months after surgery was lower than that in the control group (P<0.05), and the number of patients with sexual pain was lower than that in the control group (P<0.05). The distance from the incision edge to the coronal sulcus was closer to 0.5 cm in the observation group (P<0.05). CONCLUSION: Compared with traditional circumcision, the precise marking method assisted by a modified circumcision device can more accurately control the position of the cutting edge, reduce the incidence of postoperative erectile tension and sexual pain, and is a feasible and safe surgical method.
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Circuncisión Masculina , Fimosis , Masculino , Humanos , Prepucio/cirugía , Estudios Retrospectivos , Fimosis/cirugía , DolorRESUMEN
Even though its development starts early in utero, neonatal skin is still immature at birth relative to adult and undergoes a maturation process extending to the first years of life. It is now established that the stratum corneum is thinner and dryer and that skin contains less natural moisturizing factors and lipids in newborns compared to children and adults. Moreover, it has been shown that skin surface area expansion is not linear throughout life and is peaking perinatally, suggesting that baby skin has a higher epidermal cellular turnover. Despite growing resources showing differences between adult and infant skin physiology, molecular and metabolic specificities of baby skin are still poorly understood. To address this critical knowledge gap, we performed an integrative transcriptomic and metabolomic study comparing human primary foreskin and abdominal keratinocytes from male babies and female adults, respectively. Based on state-of-the-art integrative frameworks, our analyses revealed a major shift in the global energetic metabolism in baby foreskin keratinocytes compared to adult abdominal keratinocytes, highlighting increased amino acid metabolism and mitochondrial oxidative phosphorylation in baby cells to fuel the citric acid cycle, while showing glycolysis as the major cell energy source in adult cells.
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Prepucio , Queratinocitos , Adulto , Células Cultivadas , Niño , Células Epidérmicas , Epidermis/metabolismo , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Piel/metabolismoRESUMEN
Toxoplasma gondii infects virtually any nucleated cell and resides inside a non-phagocytic vacuole surrounded by a parasitophorous vacuolar membrane (PVM). Pivotal to the restriction of T. gondii dissemination upon infection in murine cells is the recruitment of immunity regulated GTPases (IRGs) and guanylate binding proteins (GBPs) to the PVM that leads to pathogen elimination. The virulent T. gondii type I RH strain secretes a handful of effectors including the dense granule protein GRA7, the serine-threonine kinases ROP17 and ROP18, and a pseudo-kinase ROP5, that synergistically inhibit the recruitment of IRGs to the PVM. Here, we characterise GRA60, a novel dense granule effector, which localises to the vacuolar space and PVM and contributes to virulence of RH in mice, suggesting a role in the subversion of host cell defence mechanisms. Members of the host cell IRG defence system Irgb10 and Irga6 are recruited to the PVM of RH parasites lacking GRA60 as observed previously for the avirulent RHΔrop5 mutant, with RH preventing such recruitment. Deletion of GRA60 in RHΔrop5 leads to a recruitment of IRGs comparable to the single knockouts. GRA60 therefore represents a novel parasite effector conferring resistance to IRGs in type I parasites, and found associated to ROP18, a member of the virulence complex.
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Proteínas Protozoarias/inmunología , Proteínas Protozoarias/metabolismo , Toxoplasma/inmunología , Toxoplasma/metabolismo , Toxoplasmosis/inmunología , Toxoplasmosis/metabolismo , Animales , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/metabolismo , ADN Protozoario , Fibroblastos/parasitología , Prepucio/parasitología , GTP Fosfohidrolasas/inmunología , GTP Fosfohidrolasas/metabolismo , Técnicas de Inactivación de Genes , Interacciones Huésped-Parásitos , Humanos , Inmunidad , Interferón gamma/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Mutación , Proteínas Serina-Treonina Quinasas/metabolismo , Toxoplasma/genética , Vacuolas/metabolismo , VirulenciaRESUMEN
PURPOSE OF REVIEW: Voluntary medical male circumcision (VMMC) is a surgical procedure that reduces HIV acquisition risk by almost two-thirds. However, global implementation is lagging, in part due to VMMC hesitancy. A better understanding of the mechanism(s) by which this procedure protects against HIV may increase acceptance of VMMC as an HIV risk reduction approach among health care providers and their clients. RECENT FINDINGS: HIV acquisition in the uncircumcised penis occurs preferentially across the inner foreskin tissues, due to increased susceptibility that is linked to elevated inflammatory cytokine levels in the sub-preputial space and an increased tissue density of HIV-susceptible CD4 + T cells. Inflammation can be caused by sexually transmitted infections, but is more commonly induced by specific anaerobic components of the penile microbiome. Circumcision protects by both directly removing the susceptible tissues of the inner foreskin, and by inducing a less inflammatory residual penile microbiome. VMMC reduces HIV susceptibility by removing susceptible penile tissues, and also through impacts on the penile immune and microbial milieu. Understanding these mechanisms may not only increase VMMC acceptability and reinvigorate global VMMC programs, but may also lead to non-surgical HIV prevention approaches focused on penile immunology and/or microbiota.
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Circuncisión Masculina , Infecciones por VIH , Enfermedades de Transmisión Sexual , Masculino , Humanos , Infecciones por VIH/prevención & control , Prepucio , PeneRESUMEN
OBJECTIVE: This study summarizes the short-term efficacy of the one-stage tubularized urethroplasty using the free inner in proximal hypospadias. METHODS: A retrospective analysis was conducted on 42 patients with proximal hypospadias. All cases were treated with one-stage tubularized urethroplasty from January 2020 to June 2021. The postoperative complications like urethral fistula, urethral stricture, diverticulum, and split penis head were recorded. RESULTS: Patients were followed up for 3 to 15 months (an average of 8.5 months). A total of 26 cases (62%) were repaired without any complication. Five patients (11.9%) developed urinary fistulas and underwent secondary repair: three cases with anastomotic fistulas and two cases of coronal fistulas. Nine patients (21.4%) had stenosis of the head segment of the penis, six (14.3%) had stenosis that was relieved by urethral dilatation combined with topical mometasone furoate 1 month after urethral catheter removal. Two patients (4.8%) had severe stenosis with secondary surgical stenosis incision, and one (2.4%) had combined urethral diverticulum in which urethral stenosis incision and diverticulectomy were performed. CONCLUSIONS: Tubularized urethroplasty using the free inner bears the advantages of easy access, reduced short-term complications, low incidence of diverticula.