-
Cellular and Molecular Life Sciences :... May 2024RNA modifications are essential for the establishment of cellular identity. Although increasing evidence indicates that RNA modifications regulate the innate immune...
RNA modifications are essential for the establishment of cellular identity. Although increasing evidence indicates that RNA modifications regulate the innate immune response, their role in monocyte-to-macrophage differentiation and polarisation is unclear. While mA has been widely studied, other RNA modifications, including 5 hmC, remain poorly characterised. We profiled mA and 5 hmC epitranscriptomes, transcriptomes, translatomes and proteomes of monocytes and macrophages at rest and pro- and anti-inflammatory states. Transcriptome-wide mapping of mA and 5 hmC reveals enrichment of mA and/or 5 hmC on specific categories of transcripts essential for macrophage differentiation. Our analyses indicate that mA and 5 hmC modifications are present in transcripts with critical functions in pro- and anti-inflammatory macrophages. Notably, we also discover the co-occurrence of mA and 5 hmC on alternatively-spliced isoforms and/or opposing ends of the untranslated regions (UTR) of mRNAs with key roles in macrophage biology. In specific examples, RNA 5 hmC controls the decay of transcripts independently of mA. This study provides (i) a comprehensive dataset to interrogate the role of RNA modifications in a plastic system (ii) a resource for exploring different layers of gene expression regulation in the context of human monocyte-to-macrophage differentiation and polarisation, (iii) new insights into RNA modifications as central regulators of effector cells in innate immunity.
Topics: Macrophages; Cell Differentiation; Humans; Monocytes; Transcriptome; Gene Expression Regulation; RNA Processing, Post-Transcriptional; RNA, Messenger; Cell Polarity; RNA; Adenosine
PubMed: 38780787
DOI: 10.1007/s00018-024-05261-9 -
Frontiers in Immunology 2024Skin tissue-resident memory T (Trm) cells are produced by antigenic stimulation and remain in the skin for a long time without entering the peripheral circulation. In... (Review)
Review
Skin tissue-resident memory T (Trm) cells are produced by antigenic stimulation and remain in the skin for a long time without entering the peripheral circulation. In the healthy state Trm cells can play a patrolling and surveillance role, but in the disease state Trm cells differentiate into various phenotypes associated with different diseases, exhibit different localizations, and consequently have local protective or pathogenic roles, such as disease recurrence in vitiligo and maintenance of immune homeostasis in melanoma. The most common surface marker of Trm cells is CD69/CD103. However, the plasticity of tissue-resident memory T cells after colonization remains somewhat uncertain. This ambiguity is largely due to the variation in the functionality and ultimate destination of Trm cells produced from memory cells differentiated from diverse precursors. Notably, the presence of Trm cells is not stationary across numerous non-lymphoid tissues, most notably in the skin. These cells may reenter the blood and distant tissue sites during the recall response, revealing the recycling and migration potential of the Trm cell progeny. This review focuses on the origin and function of skin Trm cells, and provides new insights into the role of skin Trm cells in the treatment of autoimmune skin diseases, infectious skin diseases, and tumors.
Topics: Humans; Homeostasis; Memory T Cells; Immunologic Memory; Skin; Cell Plasticity; Animals; Skin Diseases; Antigens, CD
PubMed: 38779662
DOI: 10.3389/fimmu.2024.1378359 -
Blood Science (Baltimore, Md.) Jul 2024Engraftment syndrome (ES) is one of the most common complications in the early phase after autologous hematopoietic stem cell transplantation (ASCT), and we aimed to...
Engraftment syndrome (ES) is one of the most common complications in the early phase after autologous hematopoietic stem cell transplantation (ASCT), and we aimed to evaluate the incidence and risk factors for ES patients receiving ASCT in the era of plerixafor-based mobilization. A total of 294 were enrolled, and 16.0% (n = 47) experienced ES after ASCT. The main clinical manifestations were fever (100%), diarrhea (78.7%), skin rash (23.4%), and hypoxemia/pulmonary edema (12.8%). Plerixafor-based mobilization was associated with higher counts of CD3 cells, CD4 cells, and CD8 cells in grafts. In univariate analysis of the total cohort, age ≥60 years, receiving ASCT at complete remission (CR), higher number of mononuclear cell (MNC), CD3 cell counts, CD4 cells as well as CD8 cells transfused and plerixafor-based mobilization were associated with ES after ASCT. Multivariate analysis showed that age ≥60 years ( = .0014), receiving ASCT at CR ( = .002), and higher number of MNC transfused ( = .026) were associated with ES in total cohort. In plasma cell disease subgroup, age ≥60 years ( = .013), plerixafor-based mobilization ( = .036), and receiving ASCT at CR ( = .002) were associated with ES. Patients with more risk factors had a higher risk of ES. The 1-year probabilities of relapse, non-relapse mortality, and survival were comparable between patients with and without ES. Thus, plerixafor-based mobilization may influence the composition of T lymphocytes in grafts and increase the risk of ES, particularly in patients with plasma cell disease.
PubMed: 38779304
DOI: 10.1097/BS9.0000000000000190 -
World Journal of Urology May 2024To describe outcomes of staged-urethroplasty in complex anterior urethral strictures using full-thickness-skin-graft (FTSG) harvested from the hairless groin area, and...
PURPOSE
To describe outcomes of staged-urethroplasty in complex anterior urethral strictures using full-thickness-skin-graft (FTSG) harvested from the hairless groin area, and to identify factors influencing successful outcomes.
METHODS
Through retrospective chart review, we identified a total of 67 men who underwent the first-stage operation (grafting) using groin-FTSG for staged-urethroplasty to treat complex anterior urethral strictures unsuitable for one-stage urethroplasty. Among these, 59 underwent the second-stage operation (tubularization) at a median duration of 5.1-months after grafting. Patients were assessed for outcomes as scheduled after tubularization outcomes were analyzed only for 48 patients for whom ≥ 1-year follow-up data after tubularization were available. Their mean follow-up duration was 27.1 months. Success was defined as achieving physiologic voiding without requiring further procedures.
RESULTS
Median stricture-length was 5.5 cm in all 67 patients. After grafting, neourethral-opening-narrowing occurred in 18. Partial graft-loss occurred in 8, of whom only 3 underwent re-grafting. The percentage of patients who achieved successful outcomes was 81.3%. Improvements in maximum-urine-flow-rate and post-void-residual-urine-volume were maintained until the last follow-up visit. A urethrocutaneous-fistula occurred in one patient, while meatal-stenosis occurred in two. On multivariate-regression-analysis, the presence of neourethral-opening-narrowing was the only predictor of non-success after tubularization. Furthermore, the presence of hypertension, longer stricture-length, and a history of prior direct-vision-internal-urethrotomy were predictors of the occurrence of neourethral-opening-narrowing.
CONCLUSION
Staged-urethroplasty using groin-FTSG is well worth considering as a useful therapeutic option for complex anterior urethral strictures, with an acceptable success rate and low morbidity. The absence of neourethral-opening-narrowing after the first-stage operation leads to success.
Topics: Humans; Urethral Stricture; Male; Retrospective Studies; Skin Transplantation; Urologic Surgical Procedures, Male; Middle Aged; Urethra; Adult; Treatment Outcome; Groin; Aged; Young Adult
PubMed: 38775814
DOI: 10.1007/s00345-024-05049-3 -
JCI Insight May 2024Alloreactive memory, unlike naïve, CD8+ T cells resist transplantation tolerance protocols and are a critical barrier to long-term graft acceptance in the clinic. We...
Alloreactive memory, unlike naïve, CD8+ T cells resist transplantation tolerance protocols and are a critical barrier to long-term graft acceptance in the clinic. We here show that semi-allogeneic pregnancy successfully reprogrammed memory fetus/graft-specific CD8+ T cells (TFGS) towards hypofunction. Female C57BL/6 mice harboring memory CD8+ T cells generated by the rejection of BALB/c skin grafts and then mated with BALB/c males achieved rates of pregnancy comparable to naive controls. Post-partum fetus/graft-specific CD8+ T cells (TFGS) from skin-sensitized dams upregulated expression of T cell exhaustion (TEX) markers (Tox, Eomes, PD-1, TIGIT, and Lag3). Transcriptional analysis corroborated an enrichment of canonical T exhaustion (TEX) genes in post-partum memory TFGS and additionally, revealed a downregulation of a subset of memory-associated transcripts. Strikingly, pregnancy induced extensive epigenetic modifications of exhaustion- and memory-associated genes in memory TFGS, whereas minimal epigenetic modifications were observed in naive TFGS cells. Finally, post-partum memory TFGS durably expressed the exhaustion-enriched phenotype, and their susceptibility to transplantation tolerance was significantly restored compared to memory TFGS. These findings advance the concept of pregnancy as an epigenetic modulator inducing hypofunction in memory CD8+ T cells that has relevance not only for pregnancy and transplantation tolerance, but also for tumor immunity and chronic infections.
PubMed: 38771643
DOI: 10.1172/jci.insight.176381 -
Journal of Plastic Surgery and Hand... May 2024The purpose of this article is to introduce a method that combines limited debridement and ReCell® autologous cell regeneration techniques for the treatment of deep...
BACKGROUND
The purpose of this article is to introduce a method that combines limited debridement and ReCell® autologous cell regeneration techniques for the treatment of deep second-degree burn wounds.
METHOD
A total of 20 patients suffered with deep second-degree burns less than 10% of total body surface area (TBSA) who were admitted to our department, from June 2019 to June 2021, participated in this study. These patients first underwent limited debridement with an electric/pneumatic dermatome, followed by the ReCell® technique for secondary wounds. Routine treatment was applied to prevent scarring after the wound healed. Clinical outcomes were scored using the Vancouver Scar Scale (VSS).
RESULTS
All wounds of the patients healed completely. One patient developed an infection in the skin graft area and finally recovered by routine dressing changes. The average healing time was 12 days (range: 10-15 days). The new skin in the treated area was soft and matched the colour of the surrounding normal skin and the VSS score ranged from 3~5 for each patient. Of the 20 patients, 19 were very satisfied and 1 was satisfied.
CONCLUSIONS
This article reports a useful treatment method that combines electric dermatome-dependent limited debridement and the ReCell® technique for the treatment of deep second-degree burn wounds. It is a feasible and effective strategy that is easy to implement and minimally invasive, and it is associated with a short healing time, mild scar formation and little damage to the donor skin area.
Topics: Humans; Burns; Debridement; Male; Adult; Female; Skin Transplantation; Middle Aged; Young Adult; Wound Healing; Cicatrix; Adolescent; Polyesters
PubMed: 38769787
DOI: 10.2340/jphs.v59.24557 -
International Journal of Burns and... 2024In this experimental study, we aimed to determine whether platelet-rich plasma (PRP) is a suitable preservative for dermo-epidermal grafts. An additional objective was...
OBJECTIVE
In this experimental study, we aimed to determine whether platelet-rich plasma (PRP) is a suitable preservative for dermo-epidermal grafts. An additional objective was to investigate how long grafts can be stored without biological degradation.
METHODS
We compared pig skin graft preservation using PRP versus saline solution and crystalloid Custodiol, which is used for hypothermic preservation of organs for transplantation. Grafts (10 × 10 mm) were placed on gauze impregnated with one of the tested solutions, and stored for 3, 7, 11, and 15 days at a constant temperature of 4°C. We evaluated a total of 240 pig skin samples: 120 by histopathology and 120 by fluorescence optical microscopy.
RESULTS
Overall, Custodiol solution appeared to be the best medium for preservation of dermo-epidermal grafts, with beneficial properties manifested on days 7 and 11. Although we expected PRP to be a better preservative than saline, this was not confirmed by our results, as we found no significant difference between these two media. In fact, by day 3, the histopathological results were better with standard saline solution than with PRP. On day 15, with each tested solution, some samples showed histological changes that are incompatible with graft viability.
CONCLUSION
Overall, Custodiol appears to be the best medium for dermo-epidermal graft preservation. Moreover, the present findings suggest a maximum graft storage time of 11 days in all of the tested solutions. We do not recommend using grafts stored for 15 days, due to isolated signs of graft biodegradation with all solutions.
PubMed: 38764893
DOI: 10.62347/MLIW4300 -
CEN Case Reports May 2024Kidney transplantation is the encouraged kidney replacement therapy due to providing more prolonged survival with a better quality of life. Unfortunately, kidney...
Kidney transplantation is the encouraged kidney replacement therapy due to providing more prolonged survival with a better quality of life. Unfortunately, kidney transplant recipients are susceptible to infections because of long-term utilization of immunosuppression. Despite dermatophyte infections are generally not life-threatening, the clinical significance has been recently enhanced by an increasing number of immunocompromised patients. We have presented a rare dermatophytosis course, Majocchi's granuloma, that spreads to all extremities during the early post-transplant period. A young kidney transplant recipient was exposed to intensive immunosuppression therapy due to acute rejection in the early period of post-transplantation. After four months, numerous nodular skin lesions were raised on various body parts. An invasive fungal infection was identified in the skin biopsy. Also, Trichophyton rubrum was isolated in the tissue cultures. Consequently, the patient was diagnosed with Majocchi's granuloma. An effectual treatment was attained with an oral terbinafine tablet. Majocchi's granuloma is a distinct form of dermatophytosis characterized by the spreading of infection into the dermis. In this unexpected case, we alerted physicians to opportunistic infections in the kidney transplant recipient.
PubMed: 38763967
DOI: 10.1007/s13730-024-00883-1 -
Journal of Vascular Surgery. Venous and... May 2024Gynecological cancer-related lower extremity lymphedema (GC-LEL), a chronic, progressive condition, lacks a standardized treatment. Currently, supraclavicular...
Synchronous supraclavicular vascularized lymph node transfer and liposuction for gynecological cancer-related lower extremity lymphedema: a clinical comparative analysis of three different procedures.
OBJECTIVE
Gynecological cancer-related lower extremity lymphedema (GC-LEL), a chronic, progressive condition, lacks a standardized treatment. Currently, supraclavicular vascularized lymph node transfer (SC-VLNT) is a favored approach in the treatment of lymphedema, and there is a trend toward combination technology. This study conducts a comparative analysis of three techniques for treating GC-LEL with simultaneous SC-VLNT and liposuction.
METHODS
A cohort of 35 patients with GC-LEL was examined, comprising 13 patients who underwent single lymph nodes flap with a skin paddle (SLNF+P), 12 who received single lymph nodes flap without a skin paddle (SLNF), and 10 who accepted dual lymph nodes flap without a skin paddle (DLNF). Patient demographics and outcomes were meticulously documented, covering intra- and postoperative variables.
RESULTS
The median limb volume reduction were 56.4% (SLNF+P), 60.8% (SLNF), and 50.5% (DLNF) in stage II, and 54.0% (SLNF+P), 59.8% (SLNF), and 54.4% (DLNF) in stage III. DLNF group procedures entailed longer flap harvesting and transplantation times. The SLNF+P group, on average, had an 8-day postoperative hospitalization, longer than others. All patients noted subjective improvements in Lymphedema Quality of Life scores, with lymphoscintigraphy revealing enhanced lymphatic flow in 29 of the 35 cases. A notable decrease in cellulitis incidence was observed. Additionally, the occurrence of cellulitis decreased significantly, except for DLNF (Stage Ⅱ). The median follow-up time was 16 months (range, 12-36 months), with no reported severe postoperative complications.
CONCLUSIONS
For advanced GC-LEL, SLNF combined with liposuction is a preferred treatment, offering fewer complications, shorter operative time, and hospitalization.
PubMed: 38761979
DOI: 10.1016/j.jvsv.2024.101905 -
Cell Transplantation 2024Pressure injuries, or pressure ulcers, are a common problem that may lead to infections and major complications, besides being a social and economic burden due to the...
Pressure injuries, or pressure ulcers, are a common problem that may lead to infections and major complications, besides being a social and economic burden due to the costs of treatment and hospitalization. While surgery is sometimes necessary, this also has complications such as recurrence or wound dehiscence. Among the newer methods of pressure injury treatment, advanced therapies are an interesting option. This study examines the healing properties of bone marrow mononuclear cells (BM-MNCs) embedded in a plasma-based scaffold in a mouse model. Pressure ulcers were created on the backs of mice (2 per mouse) using magnets and assigned to a group of ulcers that were left untreated (Control, n = 15), treated with plasma scaffold (Plasma, n = 15), or treated with plasma scaffold containing BM-MNC (Plasma + BM-MNC, n = 15). Each group was examined at three time points (3, 7, and 14 days) after the onset of treatment. At each time point, animals were subjected to biometric assessment, bioluminescence imaging, and tomography. Once treatment had finished, skin biopsies were processed for histological and wound healing reverse transcription polymerase chain reaction (RT-PCR) array studies. While wound closure percentages were higher in the Plasma and Plasma + BM-MNC groups, differences were not significant, and thus descriptive data are provided. In all individuals, the presence of donor cells was revealed by immunohistochemistry on posttreatment onset Days 3, 7, and 14. In the Plasma + BM-MNC group, less inflammation was observed by positron emission tomography-computed tomography (PET/CT) imaging of the mice at 7 days, and a complete morphometabolic response was produced at 14 days, in accordance with histological results. A much more pronounced inflammatory process was observed in controls than in the other two groups, and this persisted until Day 14 after treatment onset. RT-PCR array gene expression patterns were also found to vary significantly, with the greatest difference noted between both treatments at 14 days when 11 genes were differentially expressed.
Topics: Animals; Wound Healing; Pressure Ulcer; Mice; Disease Models, Animal; Bone Marrow Cells; Male; Tissue Scaffolds; Mice, Inbred C57BL; Bone Marrow Transplantation; Leukocytes, Mononuclear
PubMed: 38761062
DOI: 10.1177/09636897241251619