Uniportal video-assisted thoracoscopic fissureless right upper lobe anterior segmentectomy for inflammatory myofibroblastic tumor:A case report

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.

Systematic review of fibroblastic rheumatism:A case report

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.

Fibroblastic reticular cell sarcoma of the small intestine:a very rare case report and clinicopathological diagnosis

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.

Perianal superficial CD34-positive fibroblastic tumor: A case 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.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

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.

Inhibitory effect of ferroptosis inhibitor toxicity induced by cobalt nanoparticles through reactive oxygen species

BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400μmol/L cobalt nanoparticles and 25μmol/L deferiprone),the deferiprone group(25μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P<0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factorα,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factorα,interleukin-1β,and interleukin-6)significantly decreased(P<0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P<0.05),while deferiprone inhibited this effect(P<0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.

Sclerosing epithelioid fibrosarcoma of the pancreas:A case report

BACKGROUND A sclerosing epithelioid fibrosarcoma(SEF)is a rare malignant fibroblastic soft tissue tumor that rarely occurs in intra-abdominal organs.A case of a SEF in the pancreatic head is reported herein,including its clinical manifestations,preoperative imaging features,gross specimen and pathological findings.CASE SUMMARY A 33-year-old male patient was admitted to Peking Union Medical College Hospital in December 2023 due to a one-year history of intermittent upper abdominal pain and the discovery of a pancreatic mass.The patient underwent an enhanced computed tomography scan of the abdomen,which revealed a welldefined,round mass with clear borders and calcifications in the pancreatic head.The mass exhibited progressive,uneven mild enhancement,measuring approximately 6.6 cm×6.3 cm.The patient underwent laparoscopic pylorus-preserving pancreaticoduodenectomy.Postoperative pathological examination revealed that the lesion was consistent with a SEF.At the 3-month postoperative follow-up,the patient did not report any short-term complications,and there were no signs of tumor recurrence.CONCLUSION SEFs are rare malignant fibrous soft tissue tumors.SEFs rarely develop in the pancreas,and its preoperative diagnosis depends on imaging findings,with confirmation depending on pathological examination and immunohistochemistry.Currently,only four cases of pancreatic SEF have been reported in studies written in English.This case is the first reported case of a pancreatic SEF by a clinical physician.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

RNA sequencing of exosomes secreted by fibroblast and Schwann cells elucidates mechanisms underlying peripheral nerve regeneration

Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.

Computed tomography-based radiomics predicts the fibroblastrelated gene EZH2 expression level and survival of hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of liver cancer.The primary treatment strategies for HCC currently include liver transplantation and surgical resection.However,these methods often yield unsatisfactory outcomes,leading to a poor prognosis for many patients.This underscores the urgent need to identify and evaluate novel therapeutic targets that can improve the prognosis and survival rate of HCC patients.AIM To construct a radiomics model that can accurately predict the EZH2 expression in HCC.METHODS Gene expression,clinical parameters,HCC-related radiomics,and fibroblastrelated genes were acquired from public databases.A gene model was developed,and its clinical efficacy was assessed statistically.Drug sensitivity analysis was conducted with identified hub genes.Radiomics features were extracted and machine learning algorithms were employed to generate a radiomics model related to the hub genes.A nomogram was used to illustrate the prognostic significance of the computed Radscore and the hub genes in the context of HCC patient outcomes.RESULTS EZH2 and NRAS were independent predictors for prognosis of HCC and were utilized to construct a predictive gene model.This model demonstrated robust performance in diagnosing HCC and predicted an unfavorable prognosis.A negative correlation was observed between EZH2 expression and drug sensitivity.Elevated EZH2 expression was linked to poorer prognosis,and its diagnostic value in HCC surpassed that of the risk model.A radiomics model,developed using a logistic algorithm,also showed superior efficiency in predicting EZH2 expression.The Radscore was higher in the group with high EZH2 expression.A nomogram was constructed to visually demonstrate the significant roles of the radiomics model and EZH2 expression in predicting the overall survival of HCC patients.CONCLUSION EZH2 plays significant roles in diagnosing HCC and therapeutic efficacy.A radiomics model,developed using a logistic algorithm,efficiently predicted EZH2 expression and exhibited strong correlation with HCC prognosis.

Roles of fibroblast growth factors in the treatment of diabetes

Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.

Lysine demethylase 5B transcriptionally regulates TREM1 in human cardiac fibroblasts

Background:A differential gene,triggering receptor expressed on myeloid cells 1(TREM1),was identified in blood sequencing datasets from myocardial infarction patients and healthy controls.Myocardialfibrosis following myocardial infarction significantly contributes to cardiac dysfunction.Objectives:This study aimed to unveil the intrinsic regulatory mechanism of TREM1 in myocardialfibrosis.Methods:Mimicking pathology by angiotensin II(Ang II)treatment of human cardiacfibroblasts(HCFs),the impacts of TREM1 knockdown on its proliferation,migration,and secretion of the pro-fibrotic matrix were identified.Using the Human Transcription Factor Database(HumanTFDB)website,lysine-specific demethylase 5B(KDM5B)was found to bind to the TREM1 promoter,which was further validated through luciferase reporter and chromatin immunoprecipitation(ChIP).By promoting KDM5B overexpression,its effect on the regulation of TREM1 was examined.Results:TREM1 knockdown suppressed the proliferation,migration,and secretion of the pro-fibrotic matrix in HCFs upon Ang II treatment.KDM5B bound to the TREM1 promoter and upregulated its transcriptional expression.Furthermore,KDM5B overexpression reversed the regulation of the above cellular phenotypes by TREM1 knockdown.Conclusion:This study sheds light on the positive regulation of TREM1 by KDM5B,demonstrating their role in promoting myocardialfibrosis.Thisfinding provides a theoretical foundation for understanding disease pathology and potentially advancing the development of new targeted therapies.

Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

Resveratrol inhibits pancreatic cancer proliferation and metastasis by depleting senescent tumor-associated fibroblasts

BACKGROUND Pancreatic cancer,a formidable gastrointestinal neoplasm,is characterized by its insidious onset,rapid progression,and resistance to treatment,which often lead to a grim prognosis.While the complex pathogenesis of pancreatic cancer is well recognized,recent attention has focused on the oncogenic roles of senescent tumor-associated fibroblasts.However,their precise role in pancreatic cancer remains unknown.Resveratrol is a natural polyphenol known for its multifaceted biological actions,including antioxidative and neuroprotective properties,as well as its potential to inhibit tumor proliferation and migration.Our current investigation builds on prior research and reveals the remarkable ability of resveratrol to inhibit pancreatic cancer proliferation and metastasis.AIM To explore the potential of resveratrol in inhibiting pancreatic cancer by targeting senescent tumor-associated fibroblasts.METHODS Immunofluorescence staining of pancreatic cancer tissues revealed prominent coexpression ofα-SMA and p16.HP-1 expression was determined using immunohistochemistry.Cells were treated with the senescence-inducing factors known as 3CKs.Long-term growth assays confirmed that 3CKs significantly decreased the CAF growth rate.Western blotting was conducted to assess the expression levels of p16 and p21.Immunofluorescence was performed to assess LaminB1 expression.Quantitative real-time polymerase chain reaction was used to measure the levels of several senescence-associated secretory phenotype factors,including IL-4,IL-6,IL-8,IL-13,MMP-2,MMP-9,CXCL1,and CXCL12.A scratch assay was used to assess the migratory capacity of the cells,whereas Transwell assays were used to evaluate their invasive potential.RESULTS Specifically,we identified the presence of senescent tumor-associated fibroblasts within pancreatic cancer tissues,linking their abundance to cancer progression.Intriguingly,Resveratrol effectively eradicated these fibroblasts and hindered their senescence,which consequently impeded pancreatic cancer progression.CONCLUSION This groundbreaking discovery reinforces Resveratrol's stature as a potential antitumor agent and positions senescent tumor-associated fibroblasts as pivotal contenders in future therapeutic strategies against pancreatic cancer.

Unraveling the role of cancer-associated fibroblasts in colorectal cancer

Within the intricate milieu of colorectal cancer(CRC)tissues,cancer-associated fibroblasts(CAFs)act as pivotal orchestrators,wielding considerable influence over tumor progression.This review endeavors to dissect the multifaceted functions of CAFs within the realm of CRC,thereby highlighting their indispensability in fostering CRC malignant microenvironment and indicating the development of CAFs-targeted therapeutic interventions.Through a comprehensive synthesis of current knowledge,this review delineates insights into CAFsmediated modulation of cancer cell proliferation,invasiveness,immune evasion,and neovascularization,elucidating the intricate web of interactions that sustain the pro-tumor metabolism and secretion of multiple factors.Additionally,recognizing the high level of heterogeneity within CAFs is crucial,as they encompass a range of subtypes,including myofibroblastic CAFs,inflammatory CAFs,antigen-presenting CAFs,and vessel-associated CAFs.Innovatively,the symbiotic relationship between CAFs and the intestinal microbiota is explored,shedding light on a novel dimension of CRC pathogenesis.Despite remarkable progress,the orchestrated dynamic functions of CAFs remain incompletely deciphered,underscoring the need for continued research endeavors for therapeutic advancements in CRC management.

Skin care efficacy study of recombinant humanized collagen based on in vitro level

Studying the skin care efficacy of recombinant humanized collagen based on in vitro level.The stability of the recombinant humanized collagen was first analyzed by treating at different temperatures,then its skincare efficacy based on in vitro level was evaluated by detecting the inhibition rate of elastase,the inhibition rate of collagenase,the protein content of type I collagen in human fibroblasts,the inhibition of reactive oxygen species(ROS)with human keratinocytes,and the effects of the recombinant humanized collagen on the expression of hyaluronic acid(HA),filaggrin(FLG)and transglutaminase 1(TGM1)in keratinocytes.The results showed that recombinant humanized collagen was able to maintain stability at temperatures below 70℃.With regard to its skincare efficacy,recombinant humanized collagen could inhibit elastase and collagenase activities and promote the increase of type I collagen content in human fibroblasts.It also showed good inhibition of ROS in keratinocytes in vitro and could increase the expression of HA,FLG,and TGM1 in keratinocytes.In short,the recombinant humanized collagen exhibited a favourable skin care effect in vitro level.This study proved that it has potential firming,anti-wrinkle,moisturizing,and repairing efficacy,and is a valuable cosmetic raw material.

Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression

Colorectal cancer(CRC)remains one of the most commonly diagnosed and deadliest types of cancer worldwide.CRC displays a desmoplastic reaction(DR)that has been inversely associated with poor prognosis;less DR is associated with a better prognosis.This reaction generates excessive connective tissue,in which cancer-associated fibroblasts(CAFs)are critical cells that form a part of the tumor microenvironment.CAFs are directly involved in tumorigenesis through different mechanisms.However,their role in immunosuppression in CRC is not well understood,and the precise role of signal transducers and activators of transcription(STATs)in mediating CAF activity in CRC remains unclear.Among the myriad chemical and biological factors that affect CAFs,different cytokines mediate their function by activating STAT signaling pathways.Thus,the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors.Here,we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse

BACKGROUND Pelvic organ prolapse(POP)involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity,and vaginal structure is an essential factor.In POP,the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions.The intricate etiology of POP and the prohibition of trans-vaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development.Human umbilical cord mesenchymal stromal cells(hucMSCs)present limitations,but their exosomes(hucMSC-Exo)are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.suppressed inflammation in POP group fibroblasts,stimulated primary fibroblast growth,and elevated collagen I(Col1)production in vitro.High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11(MMP11)expression.CONCLUSION HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro.Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression.HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.

Clinical evaluation of sintilimab in conjunction with bevacizumab for advanced colorectal cancer with microsatellite stable-type after failure of first-line therapy

BACKGROUND At present,immune checkpoint inhibitors(ICIs)remain the 1st-line therapy me-thod for patients suffering from high microsatellite instability/deficient misma-tch repair metastatic colorectal cancer(mCRC).However,ICI treatments demon-strate minimal therapeutic efficacy against microsatellite stable(MSS)/proficient mismatch repair(pMMR)CRC.This is mainly because this type of tumor is a“cold tumor”with almost no lymphocyte infiltration.Anti-angiogenic drugs have been found to improve the immune microenvironment by promoting many immune cells to enter the immune microenvironment,thereby exerting anti-tumor effects.AIM To investigate the effects of ICIs combined with bevacizumab monoclonal anti-body on tumor immune cells in MSS/pMMR advanced CRC patients with first-line treatment failure.METHODS A total of 110 MSS/pMMR patients with advanced CRC after first-line treatment failure in the Affiliated Hospital of Qinghai University were enrolled for a ran-domized controlled trial.In short,patients in the experimental group(n=60)were given sintilimab plus bevacizumab for 4 cycles,and those in the control group(n=50)patients were treated with FOLFIRI combined with bevacizumab for 4 cycles.The expression levels of cluster of differentiation(CD)8(+)T cells,tumor-associated macrophages(TAMs),and cancer-associated fibroblasts(CAFs)were comprehensively evaluated to assess the effects of sintilimab combined with bevacizumab on MSS/pMMR advanced CRC sufferers following failure of 1st-line therapy.RESULTS The positive expression rates of CD8(+)T lymphocytes(30%vs 50%),TAMs(23.30%vs 60%),and CAFs(23.30%vs 50%)before and after treatment in both groups exhibited statistical significance(P<0.05).Additionally,the therapeutic effects of both groups(partial remission:26.67%vs 10%;objective response rate:26.70%vs 10%)were significantly different(P<0.05).Although the experimental group showed a higher progression-free survival,median progression-free survival,and disease control rate than the control group,the difference was not statist-ically significant.Moreover,no significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups was found(P>0.05).CONCLUSION ICIs in combination with bevacizumab can not only improve the patient’s prognosis but also yield safe and controllable adverse drug reactions in patients suffering from MSS/pMMR advanced CRC after failure to a 1st-line therapy.