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Cell Reports Oct 2018Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory...
Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1CCD301A myeloid dendritic cell population in psoriatic epidermis, and IL1βCCL3CD14 monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation.
Topics: Amphiregulin; Biomarkers; Cell Aggregation; Cell Communication; Cell Differentiation; Cell Proliferation; Epidermis; Foreskin; Hair Follicle; Humans; Inflammation; Keratinocytes; Kinetics; Male; Psoriasis; S100 Proteins; Single-Cell Analysis; Time Factors; Transcription, Genetic; Transcriptome; Wnt Proteins
PubMed: 30355494
DOI: 10.1016/j.celrep.2018.09.006 -
International Journal of Impotence... May 2022Preputioplasty denotes various surgical techniques directed at resolving phimosis without the need for radical or partial circumcision. This narrative review summarizes... (Review)
Review
Preputioplasty denotes various surgical techniques directed at resolving phimosis without the need for radical or partial circumcision. This narrative review summarizes the best-known surgical techniques of preputioplasty. A MEDLINE and EMBASE-based literature search of original manuscripts and case reports published in English has been carried out using the following key words: "circumcision", "partial circumcision", "phimosis", "paraphimosis", and "preputioplasty". Six different procedures are explored in more detail and illustrated. The complication rates of all surgical procedures presented here are reported to be low. In cases of medical (rather than cultural and religious) indications, foreskin-preserving procedures present useful alternatives to circumcision in the routine clinical practice of urologists and pediatric surgeons.
Topics: Child; Circumcision, Male; Foreskin; Humans; Male; Phimosis
PubMed: 34853437
DOI: 10.1038/s41443-021-00505-9 -
Current HIV/AIDS Reports Dec 2022Voluntary medical male circumcision (VMMC) is a surgical procedure that reduces HIV acquisition risk by almost two-thirds. However, global implementation is lagging, in... (Review)
Review
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.
Topics: Male; Humans; Circumcision, Male; HIV Infections; Foreskin; Penis; Sexually Transmitted Diseases
PubMed: 36308579
DOI: 10.1007/s11904-022-00634-w -
Urology May 2023
Topics: Humans; Male; Foreskin; Penis; Circumcision, Male
PubMed: 36868413
DOI: 10.1016/j.urology.2023.02.018 -
Journal of Family Medicine and Primary... May 2020Understanding the Indian perspective, effectiveness, and acceptability of prepuce conservation in children with phimosis. Circumcision is performed and recommended far...
AIM
Understanding the Indian perspective, effectiveness, and acceptability of prepuce conservation in children with phimosis. Circumcision is performed and recommended far too often for nonphysiological phimosis. Will a less radical approach be acceptable in the subcontinent?
METHOD
A two-arm study with the first arm as KAP (knowledge, attitude, and practice) study ( = 502). The second arm recruited deserving boys ( = 47) with symptomatic phimosis (see inclusion criteria). Betamethasone ointment was applied twice daily over the foreskin and gently massaged to stretch the phimotic band. Those who failed were offered lateral preputioplasty or circumcision. Religious beliefs influence attitude and practice and these were looked at with subgroup analysis.
RESULTS
Most (85%) knew that circumcision was not the only treatment for phimosis. Though many parents (93%) knew the importance of foreskin cleanliness, few practiced it. The success of the steroid application was 81% ( = 38/47). Eight underwent preputioplasty. Minor discomfort as morbidity was noted. All parents were able to completely retract the foreskin of their children by the end of one month and were happy about the cosmetic result.
CONCLUSIONS
KAP data on foreskin health is not available in the subcontinent, and this is a landmark study. Religious belief and community identity play a strong role in decisions related to foreskin preservation. Prepuce hygiene and knowledge about the usefulness of the foreskin is poor. The combination of medical and surgical methods of conserving the prepuce was effective. A high rate of success and the non-mutilating cosmetic result of prepuce preservation were acceptable to these parents.
PubMed: 32754491
DOI: 10.4103/jfmpc.jfmpc_49_20 -
Canadian Family Physician Medecin de... Mar 2017
Review
Topics: Catheterization; Circumcision, Male; Foreskin; Humans; Male
PubMed: 28292801
DOI: No ID Found -
Aging Sep 2022Feeder cells provide an optimal microenvironment for the propagation of human embryonic stem cells (hESCs) by supplying currently known or unknown factors. However, the...
Feeder cells provide an optimal microenvironment for the propagation of human embryonic stem cells (hESCs) by supplying currently known or unknown factors. However, the hESCs grown on feeder cells are not suitable for the purpose of clinical application because of the risk of contamination. In recent years, the feeder-free culture method has been developed to eliminate contamination, but some studies show that hESCs exhibit poor growth patterns in a feeder-free culture system. Regarding this phenomenon, we speculate that some genes related to hESC propagation were differently expressed in hESCs grown on feeder cells. To test this hypothesis, 3 hESC lines (NF4, NF5 and P096) were efficiently expanded in a feeder-free culture system or on human foreskin fibroblast (HFF) cells. The different gene expression patterns of hESCs in these 2 conditions were analyzed through microarrays. The results revealed that the hESCs cultured in both conditions maintained the expression of stemness markers and the ability to spontaneously differentiate into the 3 germ layers. The analysis of gene expression profiles revealed that 23 lncRNA and 15 genes were significantly differentially expressed in these two culture conditions. Furthermore, GO analyses showed that these genes were involved in such biological processes as growth factor stimuli, cell growth, and stem cell maintenance. To summarize, our study demonstrated that the hESCs grown on the HFF showed different gene expression patterns compared to those grown in a feeder-free culture system, suggesting that these differently expressed lncRNAs and genes played important roles in maintaining hESC propagation.
Topics: Cell Differentiation; Feeder Cells; Fibroblasts; Foreskin; Human Embryonic Stem Cells; Humans; Male; RNA, Long Noncoding
PubMed: 36103219
DOI: 10.18632/aging.204282 -
Canadian Family Physician Medecin de... Mar 2007To review the differences between physiologic and pathologic phimosis, review proper foreskin care, and discuss when it is appropriate to seek consultation regarding a... (Review)
Review
OBJECTIVE
To review the differences between physiologic and pathologic phimosis, review proper foreskin care, and discuss when it is appropriate to seek consultation regarding a phimotic foreskin.
SOURCES OF INFORMATION
This paper is based on selected findings from a MEDLINE search for literature on phimosis and circumcision referrals and on our experience at the Children's Hospital of Eastern Ontario Urology Clinic. MeSH headings used in our MEDLINE search included "phimosis," "referral and consultation," and "circumcision." Most of the available articles about phimosis and foreskin referrals were retrospective reviews and cohort studies (levels II and III evidence).
MAIN MESSAGE
Phimosis is defined as the inability to retract the foreskin. Differentiating between physiologic and pathologic phimosis is important, as the former is managed conservatively and the latter requires surgical intervention. Great anxiety exists among patients and parents regarding non-retractile foreskins. Most phimosis referrals seen in pediatric urology clinics are normal physiologically phimotic foreskins. Referrals of patients with physiologic phimosis to urology clinics can create anxiety about the need for surgery among patients and parents, while unnecessarily expanding the waiting list for specialty assessment. Uncircumcised penises require no special care. With normal washing, using soap and water, and gentle retraction during urination and bathing, most foreskins will become retractile over time.
CONCLUSION
Physiologic phimosis is often seen by family physicians. These patients and their parents require reassurance of normalcy and reinforcement of proper preputial hygiene. Consultation should be sought when evidence of pathologic phimosis is present, as this requires surgical management.
Topics: Adolescent; Adrenal Cortex Hormones; Anti-Bacterial Agents; Balanitis; Child; Child, Preschool; Circumcision, Male; Family Practice; Follow-Up Studies; Foreskin; Humans; Hygiene; Male; Phimosis; Remission, Spontaneous; Severity of Illness Index
PubMed: 17872680
DOI: No ID Found -
Canadian Family Physician Medecin de... Oct 2010
Topics: Circumcision, Male; Foreskin; Genital Diseases, Male; Humans; Male; Practice Patterns, Physicians'; Urology
PubMed: 20944035
DOI: No ID Found -
International Journal of Molecular... Aug 2022Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and...
PURPOSE
Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA-damaging insults, such as ionizing radiation (IR). Using ex vivo irradiated cultured foreskin, H2A.J was analyzed as a biomarker of radiation-induced senescence, potentially initiating the inflammatory cascade of radiation-induced skin injury.
METHODS
Human foreskin explants were collected from young donors, irradiated ex vivo with 10 Gy, and cultured in air-liquid interphase for up to 72 h. At different time-points after ex vivo IR exposure, the foreskin epidermis was analyzed for proliferation and senescence markers by immunofluorescence and immunohistochemical staining of sectioned tissue. Secretion of cytokines was measured in supernatants by ELISA. Using our mouse model with fractionated in vivo irradiation, H2A.J expression was analyzed in epidermal stem/progenitor cell populations localized in different regions of murine hair follicles (HF).
RESULTS
Non-vascularized foreskin explants preserved their tissue homeostasis up to 72 h (even after IR exposure), but already non-irradiated foreskin epithelium expressed high levels of H2A.J in all epidermal layers and secreted high amounts of cytokines. Unexpectedly, no further increase in H2A.J expression and no obvious upregulation of cytokine secretion was observed in the foreskin epidermis after ex vivo IR. Undifferentiated keratinocytes in murine HF regions, by contrast, revealed low H2A.J expression in non-irradiated skin and significant radiation-induced H2A.J upregulations at different time-points after IR exposure. Based on its staining characteristics, we presume that H2A.J may have previously underestimated the importance of the epigenetic regulation of keratinocyte maturation.
CONCLUSIONS
Cultured foreskin characterized by highly keratinized epithelium and specific immunological features is not an appropriate model for studying H2A.J-associated tissue reactions during radiation-induced dermatitis.
Topics: Animals; Cells, Cultured; Cellular Senescence; Cytokines; Epigenesis, Genetic; Foreskin; Histones; Humans; Male; Mice; Radiation, Ionizing; Radiodermatitis
PubMed: 36077226
DOI: 10.3390/ijms23179830