The pathogenesis of cryptoglandular anal fistula: New insight into the immunological profile

Litta, Francesco; Papait, Andrea; Lucchetti, Donatella; Farigu, Serafina; Parello, Angelo; Tenore, Claudio Ricciardi; Campennì, Paola; Silini, Antonietta; Giustiniani, Maria Cristina; Parolini, Ornella; Sgambato, Alessandro; Ratto, Carlo

doi:10.1111/codi.16290

Cited by 9 publications

(2 citation statements)

References 46 publications

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“…The expression of M1-associated cytokines (IL-6, IL-1β, and TNF-α) and chemokines (CXCL1, CXCL9-12, and CCL12) was also suppressed by ON101. Conversely, chemokines including CCL2, IL-4, and CCL3, which have been shown to display M2 macrophage-recruiting abilities [ 25 , 53 , 54 , 99 ], were up-regulated upon ON101 treatment, suggesting that M1 macrophage suppression leads to the alleviation of the chronic inflammatory cytokine profile and alters the microenvironment to favour M2 macrophage recruitment [ 97 ]. Furthermore, ON101 stimulated the expression of GCSF and CXCL3 from adipocyte progenitor cells (ADPCs), which are a type of skin-resident mesenchymal stem cell.…”

Section: Innovative Therapies For Diabetic Foot Ulcersmentioning

confidence: 99%

New Horizons of Macrophage Immunomodulation in the Healing of Diabetic Foot Ulcers

Lin

Hung²,

Chen³

et al. 2022

Pharmaceutics

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Diabetic foot ulcers (DFUs) are one of the most costly and troublesome complications of diabetes mellitus. The wound chronicity of DFUs remains the main challenge in the current and future treatment of this condition. Persistent inflammation results in chronic wounds characterized by dysregulation of immune cells, such as M1 macrophages, and impairs the polarization of M2 macrophages and the subsequent healing process of DFUs. The interactive regulation of M1 and M2 macrophages during DFU healing is critical and seems manageable. This review details how cytokines and signalling pathways are co-ordinately regulated to control the functions of M1 and M2 macrophages in normal wound repair. DFUs are defective in the M1-to-M2 transition, which halts the whole wound-healing machinery. Many pre-clinical and clinical innovative approaches, including the application of topical insulin, CCL chemokines, micro RNAs, stem cells, stem-cell-derived exosomes, skin substitutes, antioxidants, and the most recent Phase III-approved ON101 topical cream, have been shown to modulate the activity of M1 and M2 macrophages in DFUs. ON101, the newest clinically approved product in this setting, is designed specifically to down-regulate M1 macrophages and further modulate the wound microenvironment to favour M2 emergence and expansion. Finally, the recent evolution of macrophage modulation therapies and techniques will improve the effectiveness of the treatment of diverse DFUs.

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Section: Innovative Therapies For Diabetic Foot Ulcersmentioning

confidence: 99%

New Horizons of Macrophage Immunomodulation in the Healing of Diabetic Foot Ulcers

Lin

Hung²,

Chen³

et al. 2022

Pharmaceutics

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“…The role of visceral adipose tissue (VAT) in colonic inflammation has been reported, and its abnormal accumulation is often associated with a more severe disease phenotype as well as a poor prognosis in perianal patients [6][7][8][9]. The VAT plays a key role in the synthesis of adipokines, serving as signaling molecules or cytokines.…”

Section: Introductionmentioning

confidence: 99%

Role of Adipose Tissue Hormones in Pathogenesis of Cryptoglandular Anal Fistula

Włodarczyk,

Maryńczak

et al. 2024

IJMS

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The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly. Recently, adipose tissue hormones have been proposed to play a role in the genesis of cryptoglandular anal fistulas. The expression of adipose tissue hormones and epithelial-to-mesenchymal transition (EMT) factors were characterized based on 30 samples from simple fistulas and 30 samples from complex cryptoglandular perianal fistulas harvested during surgery. Tissue levels of leptin, resistin, MMP2, and MMP9 were significantly elevated in patients who underwent operations due to complex cryptoglandular perianal fistulas compared to patients with simple fistulas. Adiponectin and E-cadherin were significantly lowered in samples from complex perianal fistulas in comparison to simple fistulas. A negative correlation between leptin and E-cadherin levels was observed. Resistin and MMP2 levels, as well as adiponectin and E-cadherin levels, were positively correlated. Complex perianal cryptoglandular fistulas have a reduced level of the anti-inflammatory adipokine adiponectin and have an increase in the levels of proinflammatory resistin and leptin. Abnormal secretion of these adipokines may affect the integrity of the EMT in the fistula tract. E-cadherin, MMP2, and MMP9 expression levels were shifted in patients with more advanced and complex perianal fistulas. Our results supporting the idea of using mesenchymal stem cells in the treatment of cryptoglandular perianal fistulas seem reasonable, but further studies are warranted.

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Quaternized Molecular Brush‐Grafted Injectable Microgel with Anti‐Inflammatory and Drainage Properties for Efficient Therapy of Anal Fistula

Wang,

Ma,

et al. 2024

Advanced Science

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Anal fistula is a common disease with recurrent inflammation and accumulated exudate. Traditional treatments often fail to effectively eliminate inflammation and ensure adequate drainage, leading to prolonged healing time and a high recurrence rate. Herein, a new class of quaternized molecular brush‐grafted injectable microgel (denoted as GAA@CNT‐g‐PVBTMA) is developed through thermal polymerization and mechanical fragmentation to promote the healing process of anal fistula. Benefiting from the fragmented morphology with a porous structure, the microgel can effectively fill the fistula and facilitate the drainage of exudate. Owing to the electrostatic interactions between the positively charged quaternized carbon nanotube molecular brush (CNT‐g‐PVBTMA) and the negatively charged inflammatory cytokines, GAA@CNT‐g‐PVBTMA microgel exhibits excellent anti‐inflammatory properties with scavenging rates of 92.6% for tumor necrosis factor‐α (TNF‐α) and 92.5% for interleukin‐1β (IL‐1β). Rat inflammatory anal fistula model demonstrates that the microgel can effectively reduce inflammation and epithelialization of the fistula, thereby promoting the healing of the anal fistula. By integrating effective filling, adequate drainage, and excellent anti‐inflammatory properties, GAA@CNT‐g‐PVBTMA microgel provides a promising new direction for the treatment of anal fistula.

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The pathogenesis of cryptoglandular anal fistula: New insight into the immunological profile

Cited by 9 publications

References 46 publications

New Horizons of Macrophage Immunomodulation in the Healing of Diabetic Foot Ulcers

New Horizons of Macrophage Immunomodulation in the Healing of Diabetic Foot Ulcers

Role of Adipose Tissue Hormones in Pathogenesis of Cryptoglandular Anal Fistula

Quaternized Molecular Brush‐Grafted Injectable Microgel with Anti‐Inflammatory and Drainage Properties for Efficient Therapy of Anal Fistula

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