The therapeutic mechanism of baritinib in idiopathic granulomatous mastitis treatment elucidated by single-cell RNA sequencing
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE274011 | GEO | 2025/04/15
REPOSITORIES: GEO
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Project description:Background and Objective Non-puerperal mastitis (NPM) is a breast disease with poor clinical manifestations, which seriously affects women’s health and quality of life. Due to the low incidence rate of the disease and the paucity of related research, there is much misdiagnosis and mis-management of periductal mastitis (PDM) and granulomatous lobular mastitis (GLM). Therefore, understanding the differences between PDM and GLM, in terms of etiology and clinical manifestations, is crucial for patient treatment and prognosis. At the same time, choosing different treatment methods may not achieve the best treatment effect, so the appropriate treatment method can often reduce the patient’s pain and reduce the recurrence of the patient’s disease. Methods The PubMed database was searched for articles published from 1 January 1990 to 16 June 2022 using the following search terms: “non-puerperal mastitis”, “periductal mastitis”, “granulomatous lobular mastitis”, “mammary duct ectasia”, “idiopathic granulomatous mastitis”, “plasma cell mastitis”, and “identification”. The key findings of the related literatures were analyzed and summarized. Key Content and Findings We systematically described the key points in the differential diagnosis, treatment, and prognosis of PDM and GLM. The use of different animal models for research and novel drugs to treat the disease were also described in this paper. Conclusions The key points in the differentiation of the two diseases are clearly explained, and the respective treatment options and prognosis are summarized.
| S-EPMC9951018 | biostudies-literature
Project description:Granulomatous mastitis (GM) is a rare benign inflammatory breast disease that affects mostly women of childbearing age with a history of breastfeeding. The etiopathogenesis is still unknown; however, inflammation as the result of a reaction to trauma, metabolic or hormonal processes, autoimmunity, and an infection with Corynebacterium kroppenstedtii have all been implicated. Clinical findings are pain, mass, hyperemia, and inflammation. Because the clinical presentation can mimic infectious mastitis or inflammatory carcinoma, the disease course is often protracted. The diagnosis is made by histopathology. Biopsies show a granulomatous formation in combination with a localized infiltration of multi-nucleated giant cells, epithelioid histiocytes, and plasma cells. Ultrasound, mammography, and magnetic resonance imaging are not specific; however, ultrasound and mammography should be done to exclude other pathologies. Due to the lack of data including randomized controlled studies, the management of GM is controversial. In Western industrialized countries, most authors use a therapy regimen starting with antibiotics and corticosteroids, followed by continuous steroid therapy and surgery in patients with persisting symptoms. More data are needed to define the best therapy. The role of immunotherapy has not yet been ascertained. The implementation of a registry to collect more information on this rare disease is highly recommended.
| S-EPMC6381909 | biostudies-literature
Project description:Idiopathic granulomatous mastitis (IGM) is a rare and benign inflammatory breast disease with ambiguous aetiology. Contrastingly, lactational mastitis (LM) is commonly diagnosed in breastfeeding women. To investigate IGM aetiology, we profiled the microbial flora of pus and skin in patients with IGM and LM. A total of 26 patients with IGM and 6 patients with LM were included in the study. The 16S rRNA sequencing libraries were constructed from 16S rRNA gene amplified from total DNA extracted from pus and skin swabs in patients with IGM and LM controls. Constructed libraries were multiplexed and paired-end sequenced on HiSeq4000. Metagenomic analysis was conducted using modified microbiome abundance analysis suite customised R-resource for paired pus and skin samples. Microbiome multivariable association analyses were performed using linear models. A total of 21 IGM and 3 LM paired pus and skin samples underwent metagenomic analysis. Bray-Curtis ecological dissimilarity distance showed dissimilarity across four sample types (IGM pus, IGM skin, LM pus, and LM skin; PERMANOVA, p < 0.001). No characteristic dominant genus was observed across the IGM samples. The IGM pus samples were more diverse than corresponding IGM skin samples (Shannon and Simpson index; Wilcoxon paired signed-rank tests, p = 0.022 and p = 0.07). Corynebacterium kroppenstedtii, reportedly associated with IGM in the literature, was higher in IGM pus samples than paired skin samples (Wilcoxon, p = 0.022). Three other species and nineteen genera were statistically significant in paired IGM pus-skin comparison after antibiotic treatment adjustment and multiple comparisons correction. Microbial profiles are unique between patients with IGM and LM. Inter-patient variability and polymicrobial IGM pus samples cannot implicate specific genus or species as an infectious cause for IGM.
| S-EPMC9863225 | biostudies-literature
Project description:Background:The etiology and pathogenesis of granulomatous lobular mastitis (GLM) remain unknown, with no unified evaluation criteria or standard treatments. This study aimed to assess the etiology and features of GLM, as well as the effects of surgery (lesion excision + stage I breast reconstruction; LE + BR) for GLM. Methods:This study evaluated 178 female GLM patients retrospectively in 2006-2015. The surgery and non-surgery groups included 164 and 14 patients, respectively. All patients received conservative therapy (traditional Chinese medicine combined with regional wet compress and pus drainage). In addition, the surgery group (n=164) underwent LE + BR. Clinical data, including disease course, causes, lesion size, marital status, and treatment approaches, were assessed. Results:Follow-up was 13-117 months. Seventy-five of the 178 patients had no overt causes (42.1%); meanwhile, 63 (35.4%) and 16 (9.0%) had congenital nipple retraction and a history of psychotropic drugs for >1 year, respectively. The surgery group showed lesions significantly shrunk (?1 quadrant) with acute inflammation fully controlled; 8 showed recurrence, indicating a cure rate of 95.1% (156/164). In the non-surgery group, 4 cases showed relapse after 6-14 months (cure rate =71.4%; 10/14). Therefore, surgical treatment was significantly more efficient than non-surgical treatment (P=0.001). Kaplan-Meier survival curves for the two treatment types showed a significant difference in recurrence (log rank =11.84, P<0.001). Conclusions:In GLM patients, LE + BR is safe and effective with respect to cosmetic results, recovery time, and recurrence. Successful surgery should be performed for patients whose lesions ?1 quadrant, aim to achieve optimal GLM treatment.
| S-EPMC6989911 | biostudies-literature
Project description:Solid organ transplant represents a potentially lifesaving procedure for patients suffering from end-stage heart, lung, liver, and kidney failure. However, rejection remains a significant source of morbidity and immunosuppressive medications have significant toxicities. Janus kinase (JAK) inhibitors are effective immunosuppressants in autoimmune diseases and graft versus host disease after allogeneic hematopoietic cell transplantation. Here we examine the role of JAK inhibition in preclinical fully major histocompatibility mismatched skin and heart allograft models. Baricitinib combined with cyclosporine A (CsA) preserved fully major histocompatibility mismatched skin grafts for the entirety of a 111-day experimental period. In baricitinib plus CsA treated mice, circulating CD4+T-bet+ T cells, CD8+T-bet+ T cells, and CD4+FOXP3+ regulatory T cells were reduced. Single cell RNA sequencing revealed a unique expression profile in immune cells in the skin of baricitinib plus CsA treated mice, including decreased inflammatory neutrophils and increased CCR2- macrophages. In a fully major histocompatibility mismatched mismatched heart allograft model, baricitinib plus CsA prevented graft rejection for the entire 28-day treatment period compared with 9 days in controls. Our findings establish that the combination of baricitinib and CsA prevents rejection in allogeneic skin and heart graft models and supports the study of JAK inhibitors in human solid organ transplantation.
2024-06-13 | GSE269828 | GEO
Project description:Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast condition that is characterized by granulomatous inflammation. GLM remains a refractory disease due to its failure to respond to routine anti-inflammatory therapies and its high recurrence rate. Thus, the present study aimed to investigate the application of local heat therapy in GLM as a potential therapeutic strategy. The results revealed that the application of local heat therapy was associated with a shortened remission time for GLM, while the remission and recurrence rates were similar to those of existing therapies. The median first remission time following local heat therapy was significantly decreased compared with that following corticosteroid therapy (5.30 months vs. 11.27 months; P<0.05). The remission rates were not significantly different between the local heat therapy (76.9%), extensive excision (90.4%) and the corticosteroid therapy (85.7%) groups (P>0.05). In addition, the recurrence rates were not statistically different between the groups (local heat therapy, 8.3%; extensive excision, 10%; and corticosteroid therapy, 10%; P>0.05). The local heat therapy showed mild adverse effects and shortened healing times compared to the other therapies; however, further confirmation is required.
| S-EPMC8393844 | biostudies-literature
Project description: Not available
| S-EPMC10915423 | biostudies-literature
Project description:BackgroundGranulomatous mastitis (GM) is a rare chronic inflammatory disease of the breast. The current therapeutic effects of the antibiotic therapy and surgical or immunomodulatory (steroid) treatment are normally poor due to the unclear etiology.MethodThis study aimed to identify the differentially expressed mRNAs in GM tissues using RNA sequencing and further explored the functions of differentially expressed mRNAs resulting in GM. Moreover, we revealed the relationship between GM and breast cancer by shared highly expressed genes in GM tissues and breast cancer tissues.ResultsA total of 12,115 mRNAs were analyzed in the whole expression profile, and 207 mRNAs (136 upregulated and 71 downregulated mRNAs) were differently expressed between the GM tissues and normal tissues. The enrichment analysis showed that the differentially expressed mRNAs were enriched in the biological processes and played a significant role in the immune system. Besides, the genes expressed significantly highly in breast cancer tissues are found to be enriched with GM genes, which may explain the similar clinical features between breast cancer and GM. We also found that the HSD11B1 gene which was differentially expressed in GM was used as drug target of prednisone, which is a common treatment for GM.ConclusionThis study is the first to use sequencing technology to elucidate the genetic mechanisms of GM. The finding of this study may have potential value in GM diagnosis and also provides potential drug targets for GM treatment.
| S-EPMC8436716 | biostudies-literature
Project description:Background Idiopathic granulomatous mastitis (IGM) is a rare, benign, but locally aggressive breast disease. Steroids are widely used as a breast-conserving option, however, the response rate of steroids varies in reported studies, as well as its different reported usage. This prospective observational cohort study aimed to report the outcomes of methylprednisolone for IGM treatment. Methods From Aug 2019 to Dec 2021, the clinicopathological information of 156 IGM patients who sought treatment at West China Hospital was prospectively collected. A total of 88 patients treated with methylprednisolone were included in the study. The clinical features, treatment response, and follow-up data were analyzed. Results The median age at diagnosis was 32 years, and 90.9% of patients were multipara. The predominant symptom at presentation was painful breast mass, with a median size of 4.7 cm. For steroid usage, an initial 20 mg methylprednisolone daily was given until disease stable. The median duration of 20 mg methylprednisolone treatment was 45 (range, 14–376) days. The median duration of whole steroid therapy was 105 (range, 28–381) days. A total of 80.7% of patients (71/88) responded well to steroid treatment. In 63 patients, steroid treatment was successfully withdrawn, and treatment was completed. With an average of 283 days follow-up (range, 0–770 days), relapse was observed in 21 (33.33%) patients. Compared with patients with residual disease as shown by physical examination (PE), those with complete clinical remission (CCR) at the end of treatment had longer relapse-free intervals. Conclusions Steroids are the preferable breast-conserving option for IGM. Treatment with 20 mg methylprednisolone for an average of 1.5 months is usually required, and full steroid treatment might last for 3 months.
| S-EPMC9547707 | biostudies-literature
Project description:Purpose:analysing the differential expression of miRNAs in tissue between GLM patients and healthy controls, provide a comprehensive differential expression profile of miRNAs, screen out possible biomarkers, and elucidate post-transcriptional regulation from the whole level.Methods: The expression profile of miRNAs was measured here by high-throughput sequencing in tissue of GLM patients and healthy controls. Significantly differentially expressed miRNAs were screened by threshold setting and cluster analysis, and their target genes were analysed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment.Results: a total of 31,077 miRNAs were predicted by high-throughput sequencing.Under the condition of threshold ∣log2 fold change (log2FC)|>2.5, qvalue<0.001, 13 miRNAs that were expected to be GLM biomarkers were sreened out. The expression of 13 miRNAs in the GLM group were higher than in the control group, as follows: hsa-miR-106a-5p, hsa-miR-155-5p, hsa-miR-20b-5p, hsa-miR-223-5p, hsa-miR-3916, hsa-miR-4433a-3p, hsa-miR-4433b-5p, hsa-miR-451a, hsa-miR-4659a-3p, hsa-miR-4802-3p, hsa-miR-5571-3p, hsa-miR-624-5p, and hsa-miR-942-3p. Cell and biological process were the most significantly enriched GO term and KEGG pathway.Conclusions: This is the first report detailing genome-wide miRNA profiling of GLM, and the possible targets and pathways of GLM were analysed from bioinformatic analysis. This study finds that 13 significantly differential expressed miRNAs may have important theoretical significance and potential application value and need subsequent large-sample clinical trials for further validation.
2025-02-19 | GSE197083 | GEO