{"title":"Elevated expression of REV7 correlates with poor prognosis in lung adenocarcinoma and its inactivation in carcinoma cells enhances chemosensitivity","authors":"Shoko Hayashi , Masaaki Ichinoe , Yasutaka Sakurai , Yurika Kesen , Takuya Kato , Itaru Sanoyama , Akiyoshi Hoshino , Kazu Shiomi , Masashi Mikubo , Yukitoshi Satoh , Yoshiki Murakumo","doi":"10.1016/j.prp.2024.155779","DOIUrl":"10.1016/j.prp.2024.155779","url":null,"abstract":"<div><div>REV7 is a multifunctional protein involved in the DNA damage response, cell cycle regulation, gene expression, or primordial germ cell maintenance. REV7 expression in tumor cells is associated with clinical aggressive features and chemoresistance in several human malignancies, however, the clinicopathological significance of REV7 in lung adenocarcinoma (LUAD) has not been studied yet. In this study, we investigated the significance of REV7 expression in LUAD using clinical materials and cell lines. REV7 expression in 142 invasive LUADs were determined using immunohistochemistry, and the relationship between REV7 expression and clinicopathological features was analyzed. High levels of REV7 expression in tumor tissues were positively associated with progressive tumor behavior as assessed by Ki-67 labeling indexes (<em>p</em> < 0.001), maximum standardized uptake values on positron emission tomography (<em>p</em> = 0.005), pathological stage (<em>p</em> = 0.031), N factor (<em>p</em> = 0.048), recurrence (<em>p</em> = 0.038), and disease-specific death (<em>p</em> = 0.020). The REV7-high-expression group showed poorer relapse-free survival (RFS) (<em>p</em> = 0.025) and overall survival (OS) (<em>p</em> = 0.019) compared to the REV7-low-expression group, and REV7 was a significant prognostic factor for RFS and OS. CRISPR/Cas9-mediated <em>REV7</em>-knockout and siRNA-mediated <em>REV7</em> knockdown were carried out using the LUAD cell lines A549 and H1975, respectively, and it was demonstrated that REV7 inactivation led to slower cell growth, attenuated activation of AKT signaling, and enhanced chemosensitivity compared with control cells. These results suggest that REV7 is a potential predictive biomarker for poor prognosis in invasive LUAD and a possible molecular target for LUAD management.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155779"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunodeficiency-related high-grade B-cell lymphoma with 11q aberration: Further evidence for a lymphoma entity from a patient with simultaneous papillary renal cell carcinoma following pediatric kidney transplant","authors":"Raffaella Guazzo , Anja Fischer , Margherita Vannucchi , Alberto Fabbri , Guido Garosi , Massimo Granai , Sergio Antonio Tripodi , Kathrin Oehl-Huber , Susanne Bens , Abubakar Moawia , Emanuele Cencini , Stefano Lazzi , Reiner Siebert , Lorenzo Leoncini","doi":"10.1016/j.prp.2024.155777","DOIUrl":"10.1016/j.prp.2024.155777","url":null,"abstract":"<div><div>Various aggressive lymphomas entities have been associated with immunodeficiency. To provide further evidence that also <em>MYC</em>-negative high-grade B-cell (formerly Burkitt-like) lymphoma with 11q aberrations comprises an immunodeficiency-related subtype, we here conducted a comprehensive pathological and genetic workup of a 25-year-old patient with this type of lymphoma and simultaneous papillary renal cell carcinoma. The patient developed both malignancies following extensive childhood immunosuppression and a kidney transplant. Germline and somatic genetic analyses included interphase cytogenetics, imbalance mapping, and exome sequencing. We identified potential germline-predisposition to inborn errors of immunity, kidney disease, and cancer, along with a germline region of homozygosity in 20q. Each tumor showed imbalances and single nucleotide variants typical for the respective diagnosis, with shared gains in the name-giving region in 11q, gain of the <em>MYC</em> gene in 8q24 and trisomy 12. While we can show that the imbalances in 8q and 11q arise from different mechanisms in both tumors, trisomy 12 involved gain of the same parental chromosome. Our findings corroborate the existence of a subtype of immunodeficiency-related high-grade B-cell lymphomas with 11q aberrations, provide further insights into its molecular pathogenesis, and reveal potential pitfalls in the molecular diagnosis of simultaneous tumors based on the technology applied.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155777"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fang Liu , Hui Fang , Weigang Zhang , Yuan Yuan , Zhe Yang , Lei Wang , Gang Wang
{"title":"C4d immunostaining facilitates differentiation of pemphigoid nodularis from prurigo nodularis","authors":"Fang Liu , Hui Fang , Weigang Zhang , Yuan Yuan , Zhe Yang , Lei Wang , Gang Wang","doi":"10.1016/j.prp.2024.155762","DOIUrl":"10.1016/j.prp.2024.155762","url":null,"abstract":"<div><div>Pemphigoid nodularis and prurigo nodularis have similar clinicopathological features and are difficult to distinguish. Enzyme-linked immunosorbent assays (ELISA) and direct/indirect immunofluorescence can support the diagnosis of pemphigoid nodularis, but sometimes show contradictory results or are unavailable. We aimed to develop a practical method for differentiating between pemphigoid nodularis and prurigo nodularis. We analyzed the results of ELISA, direct immunofluorescence (DIF), and C3d and C4d immunohistochemistry (IHC) in 15 and 25 cases of pemphigoid nodularis and prurigo nodularis, respectively. C3d and C4d IHC results were positive in 8/15 (53.3 %) and 13/15 (86.7 %) patients with pemphigoid nodularis, respectively, and negative in all 25 patients with prurigo nodularis. The highest sensitivity (86.7 %) and negative predictive values (92.6 %) were observed in both C4d IHC and anti-BP180 ELISA, whereas C3d IHC exhibited the lowest sensitivity (53.3 %) and negative predictive values (78.1 %). Therefore, anti-BP180 ELISA and C4d IHC were the most sensitive markers to diagnose pemphigoid nodularis. The combination of DIF, ELISA, and C4d IHC is a relatively accurate panel of investigations for distinguishing pemphigoid nodularis from prurigo nodularis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155762"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Relation of squamous differentiation in endometrioid carcinoma with MELF pattern to a high ratio of lymph node metastasis","authors":"Shinichiro Tahara , Kazuaki Sato , Kansuke Kido , Eiichi Morii","doi":"10.1016/j.prp.2024.155804","DOIUrl":"10.1016/j.prp.2024.155804","url":null,"abstract":"<div><div>One of the known histological patterns of endometrioid carcinoma (EC) in uterine corpus cancer is MELF (microcystic, elongated, and fragmented). MELF is associated with lymphovascular invasion and lymph node metastasis. Besides MELF, it is also known that squamous differentiation (SD) often occurs in EC. SD is known to be no significant difference in the frequency of lymph node metastasis in EC. However, there have been no previous reports on the association between MELF and SD. In this research, we investigated the presence of SD in MELF using an antibody to CK5. We examined 28 cases of EC with MELF pattern, in which 15 cases showed SD. Moreover, the relation of lymph node metastasis to SD was examined. Lymph node dissection was performed in 27 out of 28 cases. Among them, 12 cases showed lymph node metastasis. The ratio of lymph node metastasis was significantly higher in EC with SD (64.3 %, 9 in 14 cases) than EC without SD (23.1 %, 3 in 13 cases). In this study, we first showed the association between SD and MELF and that MELF with SD is associated with a high ratio of lymph node metastasis. It is clinically relevant to recognize that MELF with SD is aggressive with a high ratio of lymph node metastasis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155804"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinicopathological features and molecular genetic changes of primary renal hemangioblastoma, a TSC-associated tumor","authors":"Wanwan Gao , Ming Li","doi":"10.1016/j.prp.2025.155817","DOIUrl":"10.1016/j.prp.2025.155817","url":null,"abstract":"<div><h3>Background</h3><div>Renal hemangioblastoma (HB) is a rare extra-central nervous system (CNS) tumor, typically not linked to Von Hippel-Lindau (VHL) Syndrome, and its underlying genetic drivers and molecular mechanisms remain elusive. The objective of this study is to investigate the clinicopathological features and molecular genetic changes of primary renal hemangioblastomas.</div></div><div><h3>Methods</h3><div>Herein, the clinical, imaging, clinicopathological features, and immunophenotype in 3 cases of renal HB were retrospectively analyzed. Next generation sequencing (NGS) was employed to detect 116 gene loci, including VHL gene.</div></div><div><h3>Results</h3><div>Three patients (two males and one female) aged between 39 and 61 presented with renal masses detected by physical examination or imaging. Macroscopically, the tumors were well-demarcated, with a fibrous capsule and a grayish-yellow to brown, solid, medium-texture cut surface. Microscopically, the tumor cells were polygonal to oval and were separated by thin-walled branching capillaries into sheets and nests. The cells exhibited abundant, translucent, or pale pink cytoplas. Immunohistochemical (IHC) staining showed diffuse positivity for S-100 protein (3/3), Vimentin (3/3), α-Inhibin (3/3), and NSE (3/3) in all cases, with focal positivity for AE1/AE3, EMA, CD10, and PAX-8. Staining for SMA, CgA, Syn, HMB-45, and Melan-A was negative. CD31 and CD34 highlighted an abundant vascular network. NGS revealed TSC1 gene alterations in all 3 cases, with no VHL gene mutation detected.</div></div><div><h3>Conclusions</h3><div>Primary renal HB is a rare mesenchymal tumor that requires differentiation from clear cell renal cell carcinoma (CCRCC) using morphological, IHC markers, and genetic testing when necessary. TSC1 could be a specific molecular hallmark of renal HB. Additional case data is required to better understand the molecular genetic alterations of the disease.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155817"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Livia Maccio , Antonio Travaglino , Emma Bragantini , Antonio Raffone , Susanna Ronchi , Eleonora Di Lauro , Carla Facco , Jvan Casarin , Angela Santoro , Francesca Addante , Nadine Narducci , Giulia Scaglione , Damiano Arciuolo , Caterina Fulgione , Stefano La Rosa , Gian Franco Zannoni
{"title":"Immunophenotype of uterine tumor resembling ovarian sex cord tumor (UTROSCT): Case series and meta-analysis of the literature","authors":"Livia Maccio , Antonio Travaglino , Emma Bragantini , Antonio Raffone , Susanna Ronchi , Eleonora Di Lauro , Carla Facco , Jvan Casarin , Angela Santoro , Francesca Addante , Nadine Narducci , Giulia Scaglione , Damiano Arciuolo , Caterina Fulgione , Stefano La Rosa , Gian Franco Zannoni","doi":"10.1016/j.prp.2025.155822","DOIUrl":"10.1016/j.prp.2025.155822","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to define the frequency of positivity of several immunohistochemical markers in uterine tumor resembling ovarian sex cord tumor (UTROSCT).</div></div><div><h3>Methods</h3><div>All consecutive UTROSCT cases were retrieved from consultation files of one of the authors. Histological and immunohistochemical slides were reviewed. In addition, three electronic databases were searched from their inception to January 2024 for all studies assessing the immunophenotype of UTROSCT. Exclusion criteria were: sample size < 10 patients, overlapping patient data, reviews. Endometrial stromal tumors with sex cord-like areas (formerly called “type I UTROSCT”) were excluded. Immunohistochemical markers assessed in ≥ 10 cases in at least 3 different series were included. For each marker, pooled positivity rate was calculated by using a random effect model; mean labeling index was calculated for Ki67.</div></div><div><h3>Results</h3><div>Thirty UTROSCT cases were retrieved Six studies were included, and 30 new cases were obtained, with a total of 181 UTROSCTs. Fourteen immunohistochemical markers were assessed. Pooled positivity rates were (in descending order): CD56 = 97 %, progesterone receptor = 91 %, estrogen receptor = 85.5 %, WT1 = 84 %, wide-spectrum cytokeratins = 78.7 %, CD99 = 77 %, desmin = 74.5 %, calretinin = 70.6 %, smooth muscle actin = 56.4 %, inhibin = 44.5 %, CD10 = 41 %, caldesmon = 21.9 %, Melan-A/MART-1 = 10.4 %. Mean Ki67 labeling index was 8.7 %.</div></div><div><h3>Conclusions</h3><div>Immunophenotypically, UTROSCT is less consistent than ovarian sex cord tumors and overlaps with other mesenchymal and epithelial tumors; an integrated clinico-pathological and immunohistochemical evaluation appears necessary for a correct diagnosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155822"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MLH1 gene promoter methylation status partially overlaps with CpG methylator phenotype (CIMP) in colorectal adenocarcinoma","authors":"Carlotta Ceccon , Chiara Borga , Valentina Angerilli , Francesca Bergamo , Giada Munari , Marianna Sabbadin , Jessica Gasparello , Francesca Schiavi , Stefania Zovato , Marco Scarpa , Emanuele Damiano Luca Urso , Angelo Paolo Dei Tos , Claudio Luchini , Federica Grillo , Sara Lonardi , Paola Parente , Matteo Fassan","doi":"10.1016/j.prp.2024.155786","DOIUrl":"10.1016/j.prp.2024.155786","url":null,"abstract":"<div><h3>Background</h3><div><em>RAS</em>/<em>BRAF</em> mutations, mismatch DNA repair complex deficiency (MMRd)/microsatellite instability (MSI), and CpG methylator phenotype (CIMP) are key molecular actors in colorectal carcinogenesis. To date, conflicting evidence about the correlations between these molecular features has been reported.</div></div><div><h3>Materials and methods</h3><div>A retrospectively selected cohort of 123 CRCs was divided into 3 groups based on the molecular characteristics: MMR proficient (MMRp)/<em>BRAF</em> p.V600E mutated (<em>BRAF</em><sup><em>mut</em></sup>), MMRd/<em>BRAF</em><sup><em>mut</em></sup>, and MMRd/<em>BRAF wild type (BRAF</em><sup><em>wt</em></sup><em>)</em>. <em>MLH1</em> promoter (p<em>MLH1</em>) methylation status was assessed by pyrosequencing. For 82 samples the CIMP phenotype was evaluated using the EpiTect® MethyLight kit.</div></div><div><h3>Results</h3><div>The MMRd/<em>BRAF</em><sup><em>mut</em></sup> group showed a higher p<em>MLH1</em> methylation rate compared to both the MMRd/<em>BRAF</em><sup><em>wt</em></sup> and the MMRp/<em>BRAF</em><sup><em>mut</em></sup> groups. Overall, the two MMRd groups had a higher methylation rate compared to the MMRp cases independently from the mutational status of <em>BRAF</em> (<em>p</em>-value <0.0001). The MMRd/<em>BRAF</em><sup><em>mut</em></sup> group was characterized by a 90.0 % of CIMP high (CIMP-H) tumors of which 97.2 % were p<em>MLH1</em> methylated. Instead, the MMRd/<em>BRAF</em><sup><em>wt</em></sup> group presented 50.0 % of CIMP-H adenocarcinomas.</div></div><div><h3>Conclusions</h3><div>Our study demonstrates that p<em>MLH1</em> hypermethylation, MMRd, <em>BRAF</em><sup><em>mut</em></sup> and CIMP phenotype do not completely overlap in CRC. These findings further refine the knowledge on the molecular landscape of CRC and may have critical implications also for the clinical management of the disease.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155786"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enas A. El Saftawy , Basma Emad Aboulhoda , Marwa Ali AbdElkhalek , Mansour A. Alghamdi , Nashwah Samir AlHariry
{"title":"Non-coding RNAs in urinary bladder cancer microenvironment: Diagnostic, therapeutic, and prognostic perspective","authors":"Enas A. El Saftawy , Basma Emad Aboulhoda , Marwa Ali AbdElkhalek , Mansour A. Alghamdi , Nashwah Samir AlHariry","doi":"10.1016/j.prp.2025.155815","DOIUrl":"10.1016/j.prp.2025.155815","url":null,"abstract":"<div><div>Urinary bladder cancer (UBC) is the ninth most common cancer worldwide. Despite the reliance of UBC therapy on definite pathological grading and classifications, the clinical response among patients varies widely. The molecular basis of this type of cancer appeals to considerable research; hence, new diagnostic and therapeutic options are introduced. Convenient keywords were searched in Google Scholar, PubMed, the Egyptian Knowledge Bank (EKB), and Web of Science. The recent era of UBC research is concerned with non-coding RNAs (ncRNAs), predominantly, microRNAs (miRNAs) and long non-coding RNA (lncRNAs). In addition, snoRNAs, PIWI-interacting RNAs, mitochondrial RNAs, circular, and <em>Schistosoma haematobium</em>-related ncRNAs appeared to contribute to the pathogenesis of the UBC. This review underscored the recently studied ncRNAs and their importance in the pathogenesis of UBC. Besides, we introduced the prospectives regarding their diagnostic, therapeutic, and prognostic significance in UBC clinical settings. <strong>Conclusion</strong>. Oncogenic and oncosuppressor ncRNAs’ definite balances and interaction within the TME of UBC are key players in the fate of the tumor. Thus, profiling ncRNA in-depth inspects the TME of the UBC for better clinical insights.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155815"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tikam Chand Dakal , Reya Rene Philip , Ravi Bhushan , Priyanka Vijay Sonar , Senthilkumar Rajagopal , Abhishek Kumar
{"title":"Genetic and epigenetic regulation of non-coding RNAs: Implications in cancer metastasis, stemness and drug resistance","authors":"Tikam Chand Dakal , Reya Rene Philip , Ravi Bhushan , Priyanka Vijay Sonar , Senthilkumar Rajagopal , Abhishek Kumar","doi":"10.1016/j.prp.2024.155728","DOIUrl":"10.1016/j.prp.2024.155728","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) have a crucial function in the initiation, advancement, and resistance to therapy of tumors. Recent findings indicate that non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a complex role in controlling the features of cancer stem cells (CSCs). Non-coding RNAs (ncRNAs) play a crucial role in controlling important characteristics of stem cells, such as their ability to renew themselves, differentiate into distinct cell types, and resist therapy. This article provides an overview of the current understanding of the complex relationship between non-coding RNAs (ncRNAs), namely microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and cancer stem cells (CSCs). Particular microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are involved in regulating important signaling pathways like as Wnt, Notch, and Hedgehog, which control stem cell-like characteristics. The miR-34, miR-200, and let-7 families specifically aim at inhibiting the process of self-renewal and epithelial-to-mesenchymal transition. On the other hand, long non-coding RNAs (lncRNAs) such as H19, HOTAIR, and MALAT1 play a role in modifying the epigenetic landscape, hence enhancing the characteristics of stemness. This article also offers a thorough examination of the role of non-coding RNAs (ncRNAs) in regulating cancer stemness, emphasizing their impact on crucial biochemical pathways, epigenetic changes, and therapeutic implications. Comprehending the interaction between non-coding RNAs (ncRNAs) and cancer stem cells (CSCs) provides fresh perspectives on possible focused treatments for fighting aggressive and resistant malignancies. Gaining a comprehensive understanding of the connection between non-coding RNA (ncRNA) and cancer stem cells (CSC) offers valuable insights for the development of novel and precise treatments to combat aggressive cancers that are resistant to conventional therapies. In addition, the combination of ncRNA therapies with conventional methods like as chemotherapy or epigenetic medicines could result in synergistic effects. Nevertheless, there are still obstacles to overcome in terms of delivery, effectiveness, and safety. In summary, the interaction between non-coding RNA and cancer stemness shows potential as a targeted treatment approach in the field of precision oncology. This calls for additional investigation and use in clinical settings.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155728"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriele De Rubis , Keshav Raj Paudel , Sofia Kokkinis , Tammam El-Sherkawi , Jessica Katrine Datsyuk , Prakash Salunke , Joachim Gerlach , Kamal Dua
{"title":"Potent phytoceuticals cocktail exhibits anti-inflammatory and antioxidant activity on LPS-triggered RAW264.7 macrophages in vitro","authors":"Gabriele De Rubis , Keshav Raj Paudel , Sofia Kokkinis , Tammam El-Sherkawi , Jessica Katrine Datsyuk , Prakash Salunke , Joachim Gerlach , Kamal Dua","doi":"10.1016/j.prp.2024.155770","DOIUrl":"10.1016/j.prp.2024.155770","url":null,"abstract":"<div><div>Chronic inflammatory conditions, which include respiratory diseases and other ailments, are characterized by persistent inflammation and oxidative stress, and represent a significant health burden, often inadequately managed by current therapies which include conventional inhaled bronchodilators and oral or inhaled corticosteroids in the case of respiratory disorders. The present study explores the potential of Vedicinals®9 Advanced, a polyherbal formulation, to mitigate LPS-induced inflammation and oxidative stress in RAW264.7 mouse macrophages. The cells were pre-treated with Vedicinals®9 Advanced, followed by exposure to LPS to induce an inflammatory response. Key experimental outcomes were assessed, including nitric oxide (NO) and reactive oxygen species (ROS) production, as well as the expression of inflammatory and oxidative stress-related genes and proteins. Vedicinals®9 Advanced significantly reduced LPS-induced NO and ROS production, indicating strong anti-inflammatory and antioxidant properties. Additionally, the formulation downregulated the LPS-upregulated mRNA expression of pro-inflammatory cytokines, such as TNF-α and CXCL1, and oxidative stress markers, including GSTP1 and NQO1. Furthermore, Vedicinals®9 Advanced downregulated the LPS-induced protein expression of the chemokines CCL2 and CCL6, the LPS co-receptor, CD14, and the pro-inflammatory cytokines G-CSF and IL-1β. These findings highlight the potential of Vedicinals®9 Advanced as a therapeutic option for managing CRDs and other inflammatory conditions. The formulation’s ability to simultaneously target inflammation and oxidative stress suggests it may offer advantages over existing treatments, with potential for broader application in inflammatory diseases.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155770"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}