BACKGROUND Inflammatory myofibroblastic tumors(IMTs)are exceptionally rare neoplasms with intermediate malignant potential.Surgery is the accepted treatment option,aiming for complete resection with clear margins.CASE...BACKGROUND Inflammatory myofibroblastic tumors(IMTs)are exceptionally rare neoplasms with intermediate malignant potential.Surgery is the accepted treatment option,aiming for complete resection with clear margins.CASE SUMMARY A 39-year-old woman presented with a growing solitary pulmonary nodule measuring 2.0 cm in the right upper lobe(RUL)of the lung.The patient underwent a RUL anterior segmentectomy using uniportal video-assisted thoracoscopy.A preliminary tissue diagnosis indicated malignancy;however,it was later revised to an IMTs.Due to the absence of a minor fissure between the right upper and middle lobes,an alternative resection approach was necessary.Therefore,we utilized indocyanine green injection to aid in delineating the intersegmental plane.Following an uneventful recovery,the patient was discharged on the third postoperative day.Thereafter,annual chest tomography scans were scheduled to monitor for potential local recurrence.CONCLUSION This case underscores the challenges in diagnosing and managing IMTs,showing the importance of accurate pathologic assessments and tailored surgical strategies.展开更多
BACKGROUND Fibroblastic rheumatism(FR)is a rare fibroproliferative disease with an unknown etiology.The absence of typical symptoms makes early diagnosis challenging.This study aims to systematically review FR cases a...BACKGROUND Fibroblastic rheumatism(FR)is a rare fibroproliferative disease with an unknown etiology.The absence of typical symptoms makes early diagnosis challenging.This study aims to systematically review FR cases and present a case from our center to provide a comprehensive description of the clinical manifestations,diagnosis,and treatment,thereby assisting clinicians in early identification and timely management of FR,ultimately leading to improved prognosis.CASE SUMMARY FR is a rare fibroproliferative disease with an unknown etiology.It is characterized by rapidly progressive and destructive symmetrical inflammatory multiple arthritis.Here,we present a rare case of a 50-year-old female with symmetric inflammatory polyarthritis.We highlight the importance of a comprehensive medical history,histopathology,immunohistochemistry,and clinical manifestations of skin nodules,arthralgia,and arthritis for successful disease diagnosis.Despite employing non-steroidal anti-inflammatory drugs,corticosteroids,methotrexate,and tacrolimus,the patient's symptoms did not resolve,and joint destruction continued to progress.Early diagnosis,aggressive treatment with appropriate use of steroids and immunosuppressants,and further research to identify effective treatment strategies are crucial in preventing detrimental joint destruction and limb contractures.CONCLUSION A comprehensive review of the available literature emphasizes the importance of early and accurate diagnosis coupled with appropriate treatment for achieving favorable outcomes and preventing joint destruction and limb contractures.展开更多
A 54-year-old man was admitted for the evaluation of fever and abodominal pain. Radiological and endo- scopic examination revealed a lung nodule and multiple small intestine uclers. Clinical diagnosis such as tubercul...A 54-year-old man was admitted for the evaluation of fever and abodominal pain. Radiological and endo- scopic examination revealed a lung nodule and multiple small intestine uclers. Clinical diagnosis such as tuberculosis and Crohn＇s disease had been proposed. He developed intestine perforation after small bowel endoscopic procedure. During emergent surgery the involved intestinal segments were resected and a pathological diagnosis of fibroblastic histiocytic sarcoma （FBRC） was made. The patient died in the sixth month after the operation. The management of this cases highlig^t~ the ~rawback of pattern recogn^tio~ as the most commonly used clinical reasoning method, and the importance of histological investigation.展开更多
BACKGROUND Superficial CD34-positive fibroblast tumors(SCPFTs)are newly recognized fibroblast and myofibroblast tumors representing intermediate tumors.To the best of our knowledge,fewer than 50 cases have been report...BACKGROUND Superficial CD34-positive fibroblast tumors(SCPFTs)are newly recognized fibroblast and myofibroblast tumors representing intermediate tumors.To the best of our knowledge,fewer than 50 cases have been reported.Perianal SCPFT has not been previously reported.CASE SUMMARY A 55-year-old man was hospitalized upon discovering a painless perianal lump 10 d prior.Physical examination showed a lump of approximately 3 cm×4 cm in the 7 to 8 o’clock direction in the perianal area.Perianal abscess was considered the primary diagnosis.Lump removal surgery was performed under epidural anesthesia.Postoperative pathology showed a well-circumscribed,soft tissuederived,spindle-cell tumor with strong CD34 positivity by immunohistochemistry.The final diagnosis was perianal SCPFT.There were no complications,and the patient was followed for more than 8 mo without recurrence or metastasis.CONCLUSION We report a case of perianal superficial CD34-positive fibroblast tumor.This rare mesenchymal neoplasm has distinctive histomorphology,which is important for diagnosis.Comprehensive consideration of clinical information,imaging,histology,and immunohistochemistry is important for diagnosis.展开更多
In a groundbreaking study published in Cell,Onder and colleagues revealed the pivotal role of fibroblastic reticular cells(FRCs)in creating specialized niches,providing robust immune activation against non-small cell ...In a groundbreaking study published in Cell,Onder and colleagues revealed the pivotal role of fibroblastic reticular cells(FRCs)in creating specialized niches,providing robust immune activation against non-small cell lung cancer(NSCLC),which paves the way for innovative therapeutic strategies.^(1)展开更多
Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples...Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples from patients with different pathological processes were collected, and the correlations between the subsets of FLSs and STMs and pathological processes were analyzed via flow cytometry. In vitro experimental methods such as enzyme linked immunosorbent assay (ELISA), Western blotting, Transwell assays, CCK- 8 assays and cell coculture were used to assess cell proliferation, migration and secretion of inflammatory factors. A collagen- induced arthritis mouse model was constructed to investigate the therapeutic potential of emodin in RA by flow cytometry, micro- CT and staining. Results : Unique subsets of FLSs and STMs, namely, FAPα ^(+)THY1 − FLSs, FAPα ^(+)THY1 ^(+)FLSs, and MerTK ^(pos) TREM2 ^(high) STMs, were identified in synovial tissues from RA patients. The number of MerTK ^(pos) TREM2 ^(high) STMs was negatively correlated with the degree of damage in RA, while the number of FAPα ^(+)THY1 − FLSs was positively correlated with damage. On the one hand, emodin promoted the aggregation of MerTKposTREM2high STMs. Moreover, MerTK pos TREM2 high STM- mediated secretion of exosomes was promoted, which can inhibit the secretion of pro- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs and promote the secretion of anti- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs, thereby inhibiting FAPα ^(+)THY1 − FLS proliferation and migration, improving the local immune microenvironment, and inhibiting RA damage. Conclusion : Emodin was shown to regulate the aggregation of STM subsets and exosome secretion, affecting the secretion, proliferation and migration of inflammatory factors in FLS subsets, and ultimately achieving good therapeutic efficacy in RA patients, suggesting that it has important clinical value.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflamm...Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflammatory mediators in this process is well-established,the contribution of non-inflammatory regulators in SFs to joint pathology remains poorly understood.In this study,we investigated the non-inflammatory role of SFs in RA using a co-culture model,and found that SFs from RA patients promote apoptosis of human chondrocytes.Mechanistic investigations reveal that SFs can secrete small extracellular vesicles(sEVs),which are taken up by chondrocytes and induce chondrocyte apoptosis in both normal chondrocytes and chondrocytes from patients with RA.sEV-derived miRNA 15-29148 are identified as key signaling molecules mediating the apoptosis effects of chondrocytes.Further studies reveal that SF-derived miRNA 15-29148 targeting CIAPIN1 results in increased chondrocyte apoptosis.We further demonstrate that SF-derived miRNA 15-29148 is transferred to chondrocytes,exacerbating cartilage damage in vivo.Moreover,chondrocyte-specific aptamer-modified polyamidoamine nanoparticles not only ameliorated RA but also prevented its onset.This study suggests that,in RA,the secretion of specific sEV-miRNAs from SFs plays a crucial role in promoting chondrocyte apoptosis,potentially through non-inflammatory regulation,and that sEV-miRNA inhibition in SFs may represent an early preventive treatment strategy for cartilage degradation in RA.展开更多
Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have groupe...Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have grouped these two cell types together based on similarities in structure and function,an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes.In this study,we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury.Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury,gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed.Regarding macrophages,our findings highlighted abundant communication with other cells,including fibroblasts and neurons.Both pro-inflammatory and neuroprotective effects of macrophages were also identified;the pro-inflammatory effect may be related to integrin β2(Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway.These findings were validated by in vivo experiments.This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury,and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
Background:Lung cancer is a life-threatening disease that occurs worldwide,but is especially common in China.The crucial role of the tumour microenvironment(TME)in non-small cell lung cancer(NSCLC)has attracted recent...Background:Lung cancer is a life-threatening disease that occurs worldwide,but is especially common in China.The crucial role of the tumour microenvironment(TME)in non-small cell lung cancer(NSCLC)has attracted recent attention.Cancer-associated fibroblasts(CAFs)are the main factors that contribute to the TME function,and CAF exosomes are closely linked to NSCLC.Methods:The expression levels of miR-3124-5p and Toll-interacting protein(TOLLIP)were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot detection.Fibroblasts were isolated and identified from clinical NSCLC tissues.Transmission electron microscopy and Western Blot were used to identify exosomes from these cells.Changes in proliferation(CCK-8 and clone formation),migration(wound healing),and invasion(transwell)of NSCLC cells were measured.The Luciferase reporter test was applied to clarify the binding of miR-3124-5p to TOLLIP.The TOLLIP/TLR4/MyD88/NF-κB pathway proteins were determined using Western blot analysis.Results:MiR-3124-5p is overexpressed in clinical tissues and cells of NSCLC.MiR-3124-5p was dramatically enriched in CAF-derived exosomes.Cellular experiments revealed that CAFs delivered miR-3124-5p into NSCLC cells via exosomes,stimulating cancer cell progression.MiR-3124-5p acted as a sponge to negatively regulate TOLLIP expression,which activated the TLR4/MyD88/NF-κB axis to promote the occurrence and development of NSCLC.Functional salvage tests were performed to determine whether CAF-exosome-derived miR-3124-5p plays a pro-cancer role in NSCLC by affecting the TOLLIP signalling pathway.Conclusions:These results provide an interesting direction for the diagnosis and therapy of NSCLC.展开更多
Fibroblasts support a broad range of essential organ functions via microarchitectural,biomechanical,and biochemical cues.Despite great advances in fluorescence,photoacoustic conversion,and Raman scattering over the pa...Fibroblasts support a broad range of essential organ functions via microarchitectural,biomechanical,and biochemical cues.Despite great advances in fluorescence,photoacoustic conversion,and Raman scattering over the past decades,their invasiveness and limited spatial resolution hinder the characterization of fibroblasts in a single cell.Here,taking mouse embryonic fibroblasts(MEFs)as an example,we propose a novel noninvasive approach to investigate the compositional distribution of MEFs at the single-cell scale via terahertz(THz)nanos⁃copy.Compared to the topological morphology,THz nano-imaging enables the component-based visualization of MEFs,such as the membrane,cytoplasm,nucleus,and extracellular vesicles(EVs).Notably,we demonstrate the real-space observation of the influence of rapamycin treatment on the increase of EVs in MEFs.Moreover,the line-cut and area-statistical analysis establishes the relationship between the topological morphology and the THz near-field amplitudes for different cellular components of MEFs.This work provides a new pathway to char⁃acterize the effects of pharmaceutical treatments,with potential applications in disease diagnosis and drug devel⁃opment.展开更多
The objective of this research was to assess the potential of phosphatidylcholineencapsulated resveratrol as a cosmetic ingredient.The hydrogen peroxide(H_(2)O_(2))and ultraviolet A(UVA)induced human skin fibroblasts(...The objective of this research was to assess the potential of phosphatidylcholineencapsulated resveratrol as a cosmetic ingredient.The hydrogen peroxide(H_(2)O_(2))and ultraviolet A(UVA)induced human skin fibroblasts(HSF)models of skin damage were established to compare the antioxidant and anti-wrinkle properties between phosphatidylcholine-encapsulated resveratrol and unencapsulated resveratrol.The findings reveal that encapsulating resveratrol with phosphatidylcholine not only enhances skin absorption but also significantly improves its antioxidant capabilities.In the H2O2-induced HSF injury model,phosphatidylcholine-encapsulated resveratrol demonstrates a superior ability to neutralize reactive oxygen species(ROS)generated by H2O2 compared to the resveratrol group.Further analysis indicates that this enhanced functionality is associated with increased enzymatic activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and catalase(CAT)when treated with phosphatidylcholine-encapsulated resveratrol.Additionally,in UVA-irradiated HSF cells,phosphatidylcholine-encapsulated resveratrol effectively reduces the levels of matrix metalloproteinases-1 and-3(MMP-1 and MMP-3)and increased the contents of CollagenⅠand CollagenⅢ(Col-1 and Col-3),demonstrating significant anti-wrinkle effects.These findings provide critical evaluation criteria and application references for enhancing cosmetic ingredients through phosphatidylcholine encapsulation,thereby advancing skincare formulations.展开更多
Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a d...Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.展开更多
Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown rem...Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown remarkable potential in cancer theranostics.展开更多
Fibroblast growth factor(FGF)signaling encompasses a multitude of functions,including regulation of cell proliferation,differentiation,morphogenesis,and patterning.FGFs and their receptors(FGFR)are crucial for adult t...Fibroblast growth factor(FGF)signaling encompasses a multitude of functions,including regulation of cell proliferation,differentiation,morphogenesis,and patterning.FGFs and their receptors(FGFR)are crucial for adult tissue repair processes.Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage,bone loss,muscle reduction,and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis(OA),intervertebral disc degeneration(IVDD),osteoporosis(OP),and sarcopenia.In OA and IVDD pathologies specifically,FGF1,FGF2,FGF8,FGF9,FGF18,FGF21,and FGF23 regulate the synthesis,catabolism,and ossification of cartilage tissue.Additionally,the dysregulation of FGFR expression(FGFR1 and FGFR3)promotes the pathological process of cartilage degradation.In OP and sarcopenia,endocrine-derived FGFs(FGF19,FGF21,and FGF23)modulate bone mineral synthesis and decomposition as well as muscle tissues.FGF2 and other FGFs also exert regulatory roles.A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration.Moreover,an increasing number of potential targets within the FGF signaling have been identified,such as FGF9,FGF18,and FGF23.However,it should be noted that most of these discoveries are still in the experimental stage,and further studies are needed before clinical application can be considered.Presently,this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases.Besides,current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.展开更多
Interstitial hypertension and extracellular matrix(ECM)barriers imposed by cancer-associated fibroblasts(CAFs)at the tumor site significantly impede the retention of intratumorally administered oncolytic viruses(OVs)a...Interstitial hypertension and extracellular matrix(ECM)barriers imposed by cancer-associated fibroblasts(CAFs)at the tumor site significantly impede the retention of intratumorally administered oncolytic viruses(OVs)as well as their efficacy in infecting and eradicating tumor cells.Herein,a stable,controllable,and easily prepared hydrogel was developed for employing a differential release strategy to deliver OVs.The oncolytic herpes simplex virus-2(oH2)particles were loaded within sodium alginate(ALG),together with the small molecule drug PT-100 targeting CAFs.The rapid release of PT-100 functions as an anti-CAFs agent,reducing ECM,and alleviating interstitial pressure at the tumor site.Consequently,the delayed release of oH2 could more effectively invade and eradicate tumor cells while also facilitating enhanced infiltration of immune cells into the tumor microenvironment,thereby establishing an immunologically favorable milieu against tumors.This approach holds significant potential for achieving highly efficient oncolytic virus therapy with minimal toxicity,particularly in tumors rich in stromal components.展开更多
Melanoma is a malignant neoplasm with a high propensity to metastasize,arising from melanocytes and contributing significantly to global morbidity and mortality.Despite the demonstrated efficacy of many immunotherapy ap...Melanoma is a malignant neoplasm with a high propensity to metastasize,arising from melanocytes and contributing significantly to global morbidity and mortality.Despite the demonstrated efficacy of many immunotherapy approaches,these methods rely on direct destruction of tumor cells with minimal impact on the aggregate of nearby non-tumor cells,the extracellular matrix,and blood vessels that form the tumor microenvironment(TME).The TME is known to be heterogeneous and dynamic,exerting both antitumor and pro-tumor effects depending on the specific features and stage of carcinogenesis.TME has been shown in several studies to promote malignancy,angiogenesis,and metastasis in tumors in general and melanoma in particular.Consequently,a significant number of studies in thefield of melanoma therapy have been redirected to investigate the effects of individual TME constituents,their prognostic significance for patients,and the potential of therapeutic intervention to improve overall patient survival.This review highlights novel therapeutic approaches targeting two key resident cell types in the melanoma microenvironment:tumor-associated macrophages(TAMs)and cancer-associatedfibroblasts(CAFs).The review discusses their role in disease progression and summarizes the results of preclinical and clinical trials of targeted therapies against these cell types in the melanoma TME.展开更多
There is still no effective treatment for pancreatic cancer,one of the deadliest malignancies among the gastrointestinal diseases.Jiang et al demonstrated the presence of senescent cancer-associated fibroblasts(CAFs)i...There is still no effective treatment for pancreatic cancer,one of the deadliest malignancies among the gastrointestinal diseases.Jiang et al demonstrated the presence of senescent cancer-associated fibroblasts(CAFs)in pancreatic cancer tissues,supporting the use of CAFs as potential anti-cancer targets.The study indicated that a natural plant-derived compound resveratrol can reverse senescent CAF phenotype and decrease the growth,migration,and invasiveness of pancreatic cancer cells.Notably,the study indicated that resveratrol might be involved in regulating epithelial-to-mesenchymal transition in the tumor microenvironment.This editorial shares insights on the future investigation of resveratrol signaling in cancer cells and the tumor microenvironment,and discusses resveratrol-based treatment perspectives.展开更多
Head and neck squamous cell carcinoma(HNSCC)is a highly aggressive and devastating disease arising primarily from the mucosal epithelium of the oral cavity,pharynx,and larynx.HNSCC ranks as the sixth most common cance...Head and neck squamous cell carcinoma(HNSCC)is a highly aggressive and devastating disease arising primarily from the mucosal epithelium of the oral cavity,pharynx,and larynx.HNSCC ranks as the sixth most common cancer worldwide,carrying significant morbidity and mortality.HPV-positive HNSCC can be partially prevented with the FDA-approved HPV vaccine and generally exhibits a more favorable prognosis compared to HPV-negative cases.However,effective screening and treatment approaches remain elusive for HPV-negative HNSCC.While precancerous lesions may precede invasive cancer in certain situations,most patients present with advanced disease without prior indication of precancerous conditions.Despite robust immune cell infiltration in HNSCC tumors,the extent and composition of immune infiltration vary widely among patients,and these tumors often evade immune surveillance through diverse mechanisms.Given the heterogeneous nature of HNSCC influenced by anatomical location and etiological factors,precise identification of biomarkers and personalized treatment strategies are imperative.In this study,we aim to explore the possibility of establishing an effective treatment strategy to overcome obstacles to targeted treatment and enable long-term survival through detailed molecular characterization and immune profiling of HNSCC.展开更多
Pancreatic cancer is a highly aggressive malignancy with a poor prognosis and limited therapeutic options.The tumor microenvironment(TME),including cancer-associated fibroblasts(CAFs),plays a pivotal role in tumor pro...Pancreatic cancer is a highly aggressive malignancy with a poor prognosis and limited therapeutic options.The tumor microenvironment(TME),including cancer-associated fibroblasts(CAFs),plays a pivotal role in tumor progression and therapy resistance.Senescent CAFs,which exhibit a senescence-associated secretory phenotype(SASP),further exacerbate cancer growth through inflammatory cytokine secretion.This editorial highlights a study by Jiang et al,which investigates the potential of resveratrol,a natural polyphenolic compound,in targeting senescent CAFs to inhibit pancreatic cancer progression.The study demonstrates that resveratrol reduces senescent CAFs and downregulates SASP factors,thereby disrupting the pro-tumorigenic activities of these cells.Resveratrol’s ability to modulate the TME,induce apoptosis in pancreatic cancer cells,and inhibit metastasis underscores its potential as an adjunctive therapy.This research offers promising insights into novel strategies for improving therapeutic outcomes in pancreatic cancer by targeting the TME and senescent CAFs.展开更多
文摘BACKGROUND Inflammatory myofibroblastic tumors(IMTs)are exceptionally rare neoplasms with intermediate malignant potential.Surgery is the accepted treatment option,aiming for complete resection with clear margins.CASE SUMMARY A 39-year-old woman presented with a growing solitary pulmonary nodule measuring 2.0 cm in the right upper lobe(RUL)of the lung.The patient underwent a RUL anterior segmentectomy using uniportal video-assisted thoracoscopy.A preliminary tissue diagnosis indicated malignancy;however,it was later revised to an IMTs.Due to the absence of a minor fissure between the right upper and middle lobes,an alternative resection approach was necessary.Therefore,we utilized indocyanine green injection to aid in delineating the intersegmental plane.Following an uneventful recovery,the patient was discharged on the third postoperative day.Thereafter,annual chest tomography scans were scheduled to monitor for potential local recurrence.CONCLUSION This case underscores the challenges in diagnosing and managing IMTs,showing the importance of accurate pathologic assessments and tailored surgical strategies.
文摘BACKGROUND Fibroblastic rheumatism(FR)is a rare fibroproliferative disease with an unknown etiology.The absence of typical symptoms makes early diagnosis challenging.This study aims to systematically review FR cases and present a case from our center to provide a comprehensive description of the clinical manifestations,diagnosis,and treatment,thereby assisting clinicians in early identification and timely management of FR,ultimately leading to improved prognosis.CASE SUMMARY FR is a rare fibroproliferative disease with an unknown etiology.It is characterized by rapidly progressive and destructive symmetrical inflammatory multiple arthritis.Here,we present a rare case of a 50-year-old female with symmetric inflammatory polyarthritis.We highlight the importance of a comprehensive medical history,histopathology,immunohistochemistry,and clinical manifestations of skin nodules,arthralgia,and arthritis for successful disease diagnosis.Despite employing non-steroidal anti-inflammatory drugs,corticosteroids,methotrexate,and tacrolimus,the patient's symptoms did not resolve,and joint destruction continued to progress.Early diagnosis,aggressive treatment with appropriate use of steroids and immunosuppressants,and further research to identify effective treatment strategies are crucial in preventing detrimental joint destruction and limb contractures.CONCLUSION A comprehensive review of the available literature emphasizes the importance of early and accurate diagnosis coupled with appropriate treatment for achieving favorable outcomes and preventing joint destruction and limb contractures.
文摘A 54-year-old man was admitted for the evaluation of fever and abodominal pain. Radiological and endo- scopic examination revealed a lung nodule and multiple small intestine uclers. Clinical diagnosis such as tuberculosis and Crohn＇s disease had been proposed. He developed intestine perforation after small bowel endoscopic procedure. During emergent surgery the involved intestinal segments were resected and a pathological diagnosis of fibroblastic histiocytic sarcoma （FBRC） was made. The patient died in the sixth month after the operation. The management of this cases highlig^t~ the ~rawback of pattern recogn^tio~ as the most commonly used clinical reasoning method, and the importance of histological investigation.
文摘BACKGROUND Superficial CD34-positive fibroblast tumors(SCPFTs)are newly recognized fibroblast and myofibroblast tumors representing intermediate tumors.To the best of our knowledge,fewer than 50 cases have been reported.Perianal SCPFT has not been previously reported.CASE SUMMARY A 55-year-old man was hospitalized upon discovering a painless perianal lump 10 d prior.Physical examination showed a lump of approximately 3 cm×4 cm in the 7 to 8 o’clock direction in the perianal area.Perianal abscess was considered the primary diagnosis.Lump removal surgery was performed under epidural anesthesia.Postoperative pathology showed a well-circumscribed,soft tissuederived,spindle-cell tumor with strong CD34 positivity by immunohistochemistry.The final diagnosis was perianal SCPFT.There were no complications,and the patient was followed for more than 8 mo without recurrence or metastasis.CONCLUSION We report a case of perianal superficial CD34-positive fibroblast tumor.This rare mesenchymal neoplasm has distinctive histomorphology,which is important for diagnosis.Comprehensive consideration of clinical information,imaging,histology,and immunohistochemistry is important for diagnosis.
基金supported by the European Commission's Horizon 2021—Marie Sktodowska-Curie 101065013 to A.l.,the MICIU/AEl/10.13039/501100011033 and FEDER-EU(project PID2023-1487600B-I00)to A.V.,and the Excellence Cluster Cardio Pulmonary System(CPI)the DFG Collaborative Research Center 1531(TP B08)the LOEWE project iCANx to T.B.
文摘In a groundbreaking study published in Cell,Onder and colleagues revealed the pivotal role of fibroblastic reticular cells(FRCs)in creating specialized niches,providing robust immune activation against non-small cell lung cancer(NSCLC),which paves the way for innovative therapeutic strategies.^(1)
文摘Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples from patients with different pathological processes were collected, and the correlations between the subsets of FLSs and STMs and pathological processes were analyzed via flow cytometry. In vitro experimental methods such as enzyme linked immunosorbent assay (ELISA), Western blotting, Transwell assays, CCK- 8 assays and cell coculture were used to assess cell proliferation, migration and secretion of inflammatory factors. A collagen- induced arthritis mouse model was constructed to investigate the therapeutic potential of emodin in RA by flow cytometry, micro- CT and staining. Results : Unique subsets of FLSs and STMs, namely, FAPα ^(+)THY1 − FLSs, FAPα ^(+)THY1 ^(+)FLSs, and MerTK ^(pos) TREM2 ^(high) STMs, were identified in synovial tissues from RA patients. The number of MerTK ^(pos) TREM2 ^(high) STMs was negatively correlated with the degree of damage in RA, while the number of FAPα ^(+)THY1 − FLSs was positively correlated with damage. On the one hand, emodin promoted the aggregation of MerTKposTREM2high STMs. Moreover, MerTK pos TREM2 high STM- mediated secretion of exosomes was promoted, which can inhibit the secretion of pro- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs and promote the secretion of anti- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs, thereby inhibiting FAPα ^(+)THY1 − FLS proliferation and migration, improving the local immune microenvironment, and inhibiting RA damage. Conclusion : Emodin was shown to regulate the aggregation of STM subsets and exosome secretion, affecting the secretion, proliferation and migration of inflammatory factors in FLS subsets, and ultimately achieving good therapeutic efficacy in RA patients, suggesting that it has important clinical value.
基金the National Natural Science Foundation of China(82372412)the Social Development Project of Jiangsu Province(BE2022701)+4 种基金the Top Talent Support Program for Young and Middle-aged People of the Wuxi Health Committee(BJ2020044,BJ2020057,HB2020043)the Fundamental Research Funds of the Health and Family Planning Commission of Wuxi(M202024)the Special Program for Translational Medicine Research of the Wuxi Translational Medicine Center(2020DHYB07,2020DHYB03)the Key Special Project of Precision Medicine of the Wuxi Health Commission(J202101)peking union medical college hospital talent cultivation program(UHB50192).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflammatory mediators in this process is well-established,the contribution of non-inflammatory regulators in SFs to joint pathology remains poorly understood.In this study,we investigated the non-inflammatory role of SFs in RA using a co-culture model,and found that SFs from RA patients promote apoptosis of human chondrocytes.Mechanistic investigations reveal that SFs can secrete small extracellular vesicles(sEVs),which are taken up by chondrocytes and induce chondrocyte apoptosis in both normal chondrocytes and chondrocytes from patients with RA.sEV-derived miRNA 15-29148 are identified as key signaling molecules mediating the apoptosis effects of chondrocytes.Further studies reveal that SF-derived miRNA 15-29148 targeting CIAPIN1 results in increased chondrocyte apoptosis.We further demonstrate that SF-derived miRNA 15-29148 is transferred to chondrocytes,exacerbating cartilage damage in vivo.Moreover,chondrocyte-specific aptamer-modified polyamidoamine nanoparticles not only ameliorated RA but also prevented its onset.This study suggests that,in RA,the secretion of specific sEV-miRNAs from SFs plays a crucial role in promoting chondrocyte apoptosis,potentially through non-inflammatory regulation,and that sEV-miRNA inhibition in SFs may represent an early preventive treatment strategy for cartilage degradation in RA.
文摘Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have grouped these two cell types together based on similarities in structure and function,an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes.In this study,we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury.Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury,gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed.Regarding macrophages,our findings highlighted abundant communication with other cells,including fibroblasts and neurons.Both pro-inflammatory and neuroprotective effects of macrophages were also identified;the pro-inflammatory effect may be related to integrin β2(Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway.These findings were validated by in vivo experiments.This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury,and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
文摘Background:Lung cancer is a life-threatening disease that occurs worldwide,but is especially common in China.The crucial role of the tumour microenvironment(TME)in non-small cell lung cancer(NSCLC)has attracted recent attention.Cancer-associated fibroblasts(CAFs)are the main factors that contribute to the TME function,and CAF exosomes are closely linked to NSCLC.Methods:The expression levels of miR-3124-5p and Toll-interacting protein(TOLLIP)were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot detection.Fibroblasts were isolated and identified from clinical NSCLC tissues.Transmission electron microscopy and Western Blot were used to identify exosomes from these cells.Changes in proliferation(CCK-8 and clone formation),migration(wound healing),and invasion(transwell)of NSCLC cells were measured.The Luciferase reporter test was applied to clarify the binding of miR-3124-5p to TOLLIP.The TOLLIP/TLR4/MyD88/NF-κB pathway proteins were determined using Western blot analysis.Results:MiR-3124-5p is overexpressed in clinical tissues and cells of NSCLC.MiR-3124-5p was dramatically enriched in CAF-derived exosomes.Cellular experiments revealed that CAFs delivered miR-3124-5p into NSCLC cells via exosomes,stimulating cancer cell progression.MiR-3124-5p acted as a sponge to negatively regulate TOLLIP expression,which activated the TLR4/MyD88/NF-κB axis to promote the occurrence and development of NSCLC.Functional salvage tests were performed to determine whether CAF-exosome-derived miR-3124-5p plays a pro-cancer role in NSCLC by affecting the TOLLIP signalling pathway.Conclusions:These results provide an interesting direction for the diagnosis and therapy of NSCLC.
基金Supported by the National Natural Science Foundation of China(61988102,62401113,92463308)the National Safety Academic Fund(U2130113)+2 种基金the Sichuan Science and Technology Program(2022JDJQ0065)the Chengdu Science and Technology Program(2024-YF05-01803-SN)the Sichuan Provincial Administration of Traditional Chinese Medicine(2024MS512)and the from Key Laboratory of THz Technology,Ministry of Education.
文摘Fibroblasts support a broad range of essential organ functions via microarchitectural,biomechanical,and biochemical cues.Despite great advances in fluorescence,photoacoustic conversion,and Raman scattering over the past decades,their invasiveness and limited spatial resolution hinder the characterization of fibroblasts in a single cell.Here,taking mouse embryonic fibroblasts(MEFs)as an example,we propose a novel noninvasive approach to investigate the compositional distribution of MEFs at the single-cell scale via terahertz(THz)nanos⁃copy.Compared to the topological morphology,THz nano-imaging enables the component-based visualization of MEFs,such as the membrane,cytoplasm,nucleus,and extracellular vesicles(EVs).Notably,we demonstrate the real-space observation of the influence of rapamycin treatment on the increase of EVs in MEFs.Moreover,the line-cut and area-statistical analysis establishes the relationship between the topological morphology and the THz near-field amplitudes for different cellular components of MEFs.This work provides a new pathway to char⁃acterize the effects of pharmaceutical treatments,with potential applications in disease diagnosis and drug devel⁃opment.
文摘The objective of this research was to assess the potential of phosphatidylcholineencapsulated resveratrol as a cosmetic ingredient.The hydrogen peroxide(H_(2)O_(2))and ultraviolet A(UVA)induced human skin fibroblasts(HSF)models of skin damage were established to compare the antioxidant and anti-wrinkle properties between phosphatidylcholine-encapsulated resveratrol and unencapsulated resveratrol.The findings reveal that encapsulating resveratrol with phosphatidylcholine not only enhances skin absorption but also significantly improves its antioxidant capabilities.In the H2O2-induced HSF injury model,phosphatidylcholine-encapsulated resveratrol demonstrates a superior ability to neutralize reactive oxygen species(ROS)generated by H2O2 compared to the resveratrol group.Further analysis indicates that this enhanced functionality is associated with increased enzymatic activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and catalase(CAT)when treated with phosphatidylcholine-encapsulated resveratrol.Additionally,in UVA-irradiated HSF cells,phosphatidylcholine-encapsulated resveratrol effectively reduces the levels of matrix metalloproteinases-1 and-3(MMP-1 and MMP-3)and increased the contents of CollagenⅠand CollagenⅢ(Col-1 and Col-3),demonstrating significant anti-wrinkle effects.These findings provide critical evaluation criteria and application references for enhancing cosmetic ingredients through phosphatidylcholine encapsulation,thereby advancing skincare formulations.
基金Supported by National Key Research and Development Program Project,No.2017YFC1700601Shaanxi Provincial Key Research and Development Program Project,No.2018SF-350Leading Talents in Scientific and Technological Innovation of the Shaanxi Province Special Support Plan,No.00518。
文摘Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.
基金supported by the grants provided by Zhuhai People's Hospital,China(Grant No.:2021KYQD-03)the National Natural Science Foundation of China(Grant No.:22176016).
文摘Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown remarkable potential in cancer theranostics.
基金supported by the National Key R&D Program of China(2023YFC3603400)the National Natural Science Foundation of China(82072506,92268115)+2 种基金the Hunan Provincial Science Fund for Distinguished Young Scholars(2024JJ2089)the Science and Technology Innovation Program of Hunan Province(2021RC3025)the National Clinical Research Center for Geriatric Disorders(Xiangya Hospital,2021KF02).
文摘Fibroblast growth factor(FGF)signaling encompasses a multitude of functions,including regulation of cell proliferation,differentiation,morphogenesis,and patterning.FGFs and their receptors(FGFR)are crucial for adult tissue repair processes.Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage,bone loss,muscle reduction,and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis(OA),intervertebral disc degeneration(IVDD),osteoporosis(OP),and sarcopenia.In OA and IVDD pathologies specifically,FGF1,FGF2,FGF8,FGF9,FGF18,FGF21,and FGF23 regulate the synthesis,catabolism,and ossification of cartilage tissue.Additionally,the dysregulation of FGFR expression(FGFR1 and FGFR3)promotes the pathological process of cartilage degradation.In OP and sarcopenia,endocrine-derived FGFs(FGF19,FGF21,and FGF23)modulate bone mineral synthesis and decomposition as well as muscle tissues.FGF2 and other FGFs also exert regulatory roles.A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration.Moreover,an increasing number of potential targets within the FGF signaling have been identified,such as FGF9,FGF18,and FGF23.However,it should be noted that most of these discoveries are still in the experimental stage,and further studies are needed before clinical application can be considered.Presently,this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases.Besides,current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.
基金supported by the National Key R&D Program of China(No.2022YFC2403401)the National Natural Science Foundation of China(Nos.82073368,82303766)+2 种基金the Liaoning Revitalization Talents Program(No.XLYC2007071)the China Postdoctoral Science Foundation(No.2023M743908)the Joint Program of Science and Technology Program of Liaoning Province(No.2023JH2/101700094).
文摘Interstitial hypertension and extracellular matrix(ECM)barriers imposed by cancer-associated fibroblasts(CAFs)at the tumor site significantly impede the retention of intratumorally administered oncolytic viruses(OVs)as well as their efficacy in infecting and eradicating tumor cells.Herein,a stable,controllable,and easily prepared hydrogel was developed for employing a differential release strategy to deliver OVs.The oncolytic herpes simplex virus-2(oH2)particles were loaded within sodium alginate(ALG),together with the small molecule drug PT-100 targeting CAFs.The rapid release of PT-100 functions as an anti-CAFs agent,reducing ECM,and alleviating interstitial pressure at the tumor site.Consequently,the delayed release of oH2 could more effectively invade and eradicate tumor cells while also facilitating enhanced infiltration of immune cells into the tumor microenvironment,thereby establishing an immunologically favorable milieu against tumors.This approach holds significant potential for achieving highly efficient oncolytic virus therapy with minimal toxicity,particularly in tumors rich in stromal components.
基金performed at the expense of the subsidy allocated to Kazan Federal University for the fulfillment of the stated task in the field of scientific activity,No.FZSM-2023-0011.
文摘Melanoma is a malignant neoplasm with a high propensity to metastasize,arising from melanocytes and contributing significantly to global morbidity and mortality.Despite the demonstrated efficacy of many immunotherapy approaches,these methods rely on direct destruction of tumor cells with minimal impact on the aggregate of nearby non-tumor cells,the extracellular matrix,and blood vessels that form the tumor microenvironment(TME).The TME is known to be heterogeneous and dynamic,exerting both antitumor and pro-tumor effects depending on the specific features and stage of carcinogenesis.TME has been shown in several studies to promote malignancy,angiogenesis,and metastasis in tumors in general and melanoma in particular.Consequently,a significant number of studies in thefield of melanoma therapy have been redirected to investigate the effects of individual TME constituents,their prognostic significance for patients,and the potential of therapeutic intervention to improve overall patient survival.This review highlights novel therapeutic approaches targeting two key resident cell types in the melanoma microenvironment:tumor-associated macrophages(TAMs)and cancer-associatedfibroblasts(CAFs).The review discusses their role in disease progression and summarizes the results of preclinical and clinical trials of targeted therapies against these cell types in the melanoma TME.
文摘There is still no effective treatment for pancreatic cancer,one of the deadliest malignancies among the gastrointestinal diseases.Jiang et al demonstrated the presence of senescent cancer-associated fibroblasts(CAFs)in pancreatic cancer tissues,supporting the use of CAFs as potential anti-cancer targets.The study indicated that a natural plant-derived compound resveratrol can reverse senescent CAF phenotype and decrease the growth,migration,and invasiveness of pancreatic cancer cells.Notably,the study indicated that resveratrol might be involved in regulating epithelial-to-mesenchymal transition in the tumor microenvironment.This editorial shares insights on the future investigation of resveratrol signaling in cancer cells and the tumor microenvironment,and discusses resveratrol-based treatment perspectives.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(Nos.2022R1C1C1006181,RS-2023-00208416).
文摘Head and neck squamous cell carcinoma(HNSCC)is a highly aggressive and devastating disease arising primarily from the mucosal epithelium of the oral cavity,pharynx,and larynx.HNSCC ranks as the sixth most common cancer worldwide,carrying significant morbidity and mortality.HPV-positive HNSCC can be partially prevented with the FDA-approved HPV vaccine and generally exhibits a more favorable prognosis compared to HPV-negative cases.However,effective screening and treatment approaches remain elusive for HPV-negative HNSCC.While precancerous lesions may precede invasive cancer in certain situations,most patients present with advanced disease without prior indication of precancerous conditions.Despite robust immune cell infiltration in HNSCC tumors,the extent and composition of immune infiltration vary widely among patients,and these tumors often evade immune surveillance through diverse mechanisms.Given the heterogeneous nature of HNSCC influenced by anatomical location and etiological factors,precise identification of biomarkers and personalized treatment strategies are imperative.In this study,we aim to explore the possibility of establishing an effective treatment strategy to overcome obstacles to targeted treatment and enable long-term survival through detailed molecular characterization and immune profiling of HNSCC.
基金Supported by National Natural Science Foundation of China,No.82304151.
文摘Pancreatic cancer is a highly aggressive malignancy with a poor prognosis and limited therapeutic options.The tumor microenvironment(TME),including cancer-associated fibroblasts(CAFs),plays a pivotal role in tumor progression and therapy resistance.Senescent CAFs,which exhibit a senescence-associated secretory phenotype(SASP),further exacerbate cancer growth through inflammatory cytokine secretion.This editorial highlights a study by Jiang et al,which investigates the potential of resveratrol,a natural polyphenolic compound,in targeting senescent CAFs to inhibit pancreatic cancer progression.The study demonstrates that resveratrol reduces senescent CAFs and downregulates SASP factors,thereby disrupting the pro-tumorigenic activities of these cells.Resveratrol’s ability to modulate the TME,induce apoptosis in pancreatic cancer cells,and inhibit metastasis underscores its potential as an adjunctive therapy.This research offers promising insights into novel strategies for improving therapeutic outcomes in pancreatic cancer by targeting the TME and senescent CAFs.
