The roles of voltage-dependent K^+ channels during activation and damage in alveolar macrophages (AMs) exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage,...The roles of voltage-dependent K^+ channels during activation and damage in alveolar macrophages (AMs) exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage, and were adjusted to 5× 10^5/mL. After AMs were exposed to different concentrations (0, 25, 50, 100, 200 μg/mL) of quartz particles and 100 μg/mL amorphous silica particles for 24 h, the voltage-depended K^+ current in AMs was measured by using patch clamp technique. Meanwhile the leakage of lactate dehydrogenase (LDH) and the viability of AMs were detected respectively. Patch clamp studies demonstrated that AMs possessed outward delayed and inward rectifying K^+ current. Exposure to quartz particles increased the outward delayed K^+ current but it had no effect on inward rectifier K^+ current in AMs. Neither of the two K^+ channels in AMs was affected by amorphous silica particles. Cytotoxicity test showed that both silica particles could damage AM membrane and result in significant leakage of LDH (P〈0.05). MTT studies, however, showed that only quartz particles reduced viability of AMs (P〈0.05). It is concluded that quartz parti- cles can activate the outward delayed K^+ channel in AMs, which may act as an activating signal in AMs to initiate an inflammatory response during damage and necrosis in AMs induced by exposure to quartz particle. K^+ channels do not contribute to the membrane damage of AMs.展开更多
Background: Our previous study showed that 3 plant extracts enhanced the immune responses and growth efficiency of weaned pigs infected with porcine reproductive and respiratory syndrome virus(PRRSV), which is one of ...Background: Our previous study showed that 3 plant extracts enhanced the immune responses and growth efficiency of weaned pigs infected with porcine reproductive and respiratory syndrome virus(PRRSV), which is one of the most economically important disease in swine industry. However, each plant extract differently effected on growth efficiency and immune responses. Therefore, the objective of this study was conducted to characterize the effects and investigate the potential underlying mechanisms of 3 plant extracts on gene expression of alveolar macrophages in weaned pigs experimentally infected with PRRSV.Results: PRRSV infection altered(P < 0.05) the expression of 1,352 genes in pigs fed the control(CON;755 up, 597 down). Compared with the infected CON, feeding capsicum(CAP), garlic botanical(GAR), or turmeric oleoresin(TUR) altered the expression of 46 genes(24 up, 22 down), 134 genes(59 up, 75 down), or 98 genes(55 up, 43 down) in alveolar macrophages of PRRSV-infected pigs, respectively. PRRSV infection up-regulated(P < 0.05) the expression of genes related to cell apoptosis, immune system process, and response to stimulus, but downregulated(P < 0.05) the expression of genes involved in signaling transduction and innate immune response.Compared with the infected CON, feeding TUR or GAR reduced(P < 0.05) the expression of genes associated with antigen processing and presentation, feeding CAP up-regulated(P < 0.05) the expression of genes involved in antigen processing and presentation. Supplementation of CAP, GAR, or TUR also enhanced(P < 0.05) the expression of several genes related to amino acid metabolism, steroid hormone synthesis, or RNA degradation, respectively.Conclusions: The results suggest that 3 plant extracts differently regulated the expression of genes in alveolar macrophages of PRRSV-infected pigs, especially altering genes involved in immunity.展开更多
Alveolar macrophages (AM) from BCG activated Wistar rat were irradiated with different doses of Gamma rays in vitro. The effects of radiation on their immunological functions and membrane damage were studied. The non-...Alveolar macrophages (AM) from BCG activated Wistar rat were irradiated with different doses of Gamma rays in vitro. The effects of radiation on their immunological functions and membrane damage were studied. The non-specific cytotoxicity and specific phagocytosis of AM irradiated with dose of 0, 100, 300 and 500 Gy decreased with the increase in dose. The relative fractions of Lactate Dehydrogenase and Beta-glucuronidase (β-glu) activity in supernatant increased with the increase in dose. There was a correlation between the suppression of immunological functions and the degree of damage of cytoplasmic and lysosomal membranes of AM after irradiation. Na2SeO3, a protective agent of cell membranes, alleviated this effect on the suppressive cytotoxicity indices of irradiated AM.展开更多
To study the effects of tumor necrosis factor (TNF)-α on matrix metalloproteinase (MMP)-9 expression and activity in alveolar macrophages (AM) and to investigate the role of NF-κB in the induction, AM were col...To study the effects of tumor necrosis factor (TNF)-α on matrix metalloproteinase (MMP)-9 expression and activity in alveolar macrophages (AM) and to investigate the role of NF-κB in the induction, AM were collected from bronchoalveolar lavage fluid (BALF) of healthy subjects and patients with chronic obstructive pulmonary disease (COPD). MMP-9 expression and activity were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and zymography. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA). MMP-9 expression and activity induced by TNF-α in AM from healthy subjects or patients with COPD were significantly increased in a dose-dependent manner (P〈0.05). NF-κB activity induced by TNF-α was significantly increased in AM from patients with COPD, and pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC) significantly inhibited the activation of NF-κB induced by TNF-α (P〈0.05). The presents study suggested that the expression and activity of MMP-9 from AM can be induced by TNF-α, and TNF-α/NF-κB signal pathway may play an important role in the induction.展开更多
To explore the effects of bilirubin on alveolar macrophages (AM) and expression of iNOS and NO in them in emphysema model, the rats were pretreated with bilirubin before exposed to smoke. AM were isolated from broncho...To explore the effects of bilirubin on alveolar macrophages (AM) and expression of iNOS and NO in them in emphysema model, the rats were pretreated with bilirubin before exposed to smoke. AM were isolated from bronchoalveolar lavage fluid (BALF) and cultured. Pathological microscopic examination of AM and immunohistochemical analysis of iNOS were performed. Nitric oxide (NO) content in the samples was determined by nitrate reductase technique. The results showed both alveoli and alveolar septum appeared normal in size and shape in normal group. AM showed kidney-shaped nucleus and were rich in Golgi complexes and primary lysosomes in the cytoplasm. The inner membrane of mitochondrion was continuous. Most cristae of the mitochondria were intact. In model group, the alveoli were expanded, ruptured and bullaes were formed. Both the population and sizes of AM increased significantly. Secondary lysosomes were rich in the cytoplasm. Deformation and pyknosis of the nucleus, swelling of the mitochondrions and rupture of the inner mitochondrial membrane could also be seen. At high magnification, most of the mitochondrial cristae were broken, or completely lost at certain points. In bilirubin group, alveoli partly expanded and the population of AM also increased, with morphological changes being slighter than that in model group. Both NO contents and expression of iNOS in model group were higher than those in normal group (P<0.05). In bilirubin group the two indice were lower than those in model group (P<0.05). Our findings suggested that high expression of iNOS and high NO content in AM accelerate the development of emphysema associated with smoking in rats. Bilirubin may exert protective effects on AM and retards the development of emphysema in rats.展开更多
Background: Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE2(supporting both inflammation and resolution) makes it a potent regulator of immune...Background: Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE2(supporting both inflammation and resolution) makes it a potent regulator of immune cell function. Therefore, the use of dietary long chain n-6 PUFA to enhance PGE2 effects merits investigation.Methods: Day-old pigs(n = 60) were allotted to one of three dietary groups for 21 d(n = 20/diet), and received either a control diet(CON, arachidonate = 0.5% of total fatty acids), an arachidonate(ARA)-enriched diet(LC n-6,ARA = 2.2%), or an eicosapentaenoic(EPA)-enriched diet(LC n-3, EPA = 3.0%). Alveolar macrophages and lung parenchymal tissue were collected for fatty acid analysis. Isolated alveolar macrophages were stimulated with LPS in situ for 24 h, and m RNA was isolated to assess markers associated with inflammation and eicosanoid production.Culture media were collected to assess PGE2 secretion. Oxidative burst in macrophages was measured by: 1)oxygen consumption and extracellular acidification(via Seahorse), 2) cytoplasmic oxidation and 3) nitric oxide production following 4, 18, and 24 h of LPS stimulation.Results: Concentration of ARA(% of fatty acids, w/w) in macrophages from pigs fed LC n-6 was 86% higher than CON and 18% lower in pigs fed LC n-3(P < 0.01). Following LPS stimulation, abundance of COX-2 and TNF-α mRNA(P < 0.0001), and PGE2 secretion(P < 0. 01) were higher in LC n-6 PAM vs. CON. However, ALOX5 abundance was1.6-fold lower than CON. Macrophages from CON and LC n-6 groups were 4-fold higher in ALOX12/15 abundance(P < 0.0001) compared to LC n-3. Oxygen consumption and extracellular acidification rates increased over 4 h following LPS stimulation(P < 0.05) regardless of treatment. Similarly, increases in cytoplasmic oxidation(P < 0.001)and nitric oxide production(P < 0.002) were observed after 18 h of LPS stimulation but were unaffected by diet.Conclusions: We infer that enriching diets with arachidonic acid may be an effective means to enhance a stronger innate immunologic response to respiratory challenges in neonatal pigs. However, further work is needed to examine long-term safety, clinical efficacy and economic viability.展开更多
Objective: To explore the effect of tumor necrosis factor (TNF)-α on matrix metalloproteinase-9 (MMP-9) expression and activity in alveolar macrophages (AM) from patients with chronic obstructive pulmonary dis...Objective: To explore the effect of tumor necrosis factor (TNF)-α on matrix metalloproteinase-9 (MMP-9) expression and activity in alveolar macrophages (AM) from patients with chronic obstructive pulmonary disease (COPD) and study its associated signal pathway. Methods: AM were collected from bronchoalveolar lavage fluid in patients with COPD. The AM were incubated for 1.5 h with pyrrolidine dithiocarbamate(PDTC) at concentrations from 0 μmol/L to 50μmol/L and then stimulated for 24 h by TNF-α at 10 ng/ml. MMP-9 expression and activity were respectively detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and Zymography. NF-κB activity was investigated by electrophoretic mobility shift assay (EMSA). Results: Both the mRNA and protein levels of MMP-9 induced by TNF-α in AM were significantly elevated in a dose dependent manner ( P 〈 0.05). The level of MMP-9 activity was also correspondingly significantly elevated in the induction ( P 〈 0.05), which was possibly related with the over-expression of MMP-9. NF-κB activity was significantly increased when AM were stimulated by 10 ng/mL TNF-α ( P 〈 0.05). The expression of MMP-9 induced by TNF-α could be significantly inhibited by PDTC (P 〈 0.05 ). Conclusion: The expression and activity of MMP-9 from AM could be induced by TNF-α, and NF-κB signal pathway played an important role in the induction.展开更多
Tuberculosis(TB),is an infectious disease caused by Mycobacterium tuberculosis(M.tuberculosis),and presents with high morbidity and mortality.Alveolar macrophages play an important role in TB pathogenesis although the...Tuberculosis(TB),is an infectious disease caused by Mycobacterium tuberculosis(M.tuberculosis),and presents with high morbidity and mortality.Alveolar macrophages play an important role in TB pathogenesis although there is heterogeneity and functional plasticity.This study aimed to show the characteristics of alveolar macrophages from bronchioalveolar lavage fluid(BALF)in active TB patients.Single-cell RNA sequencing(scRNA-seq)was performed on BALF cells from three patients with active TB and additional scRNA-seq data from three healthy adults were established as controls.Transcriptional profiles were analyzed and compared by differential gene expression and functional enrichment analysis.We applied pseudo-temporal trajectory analysis to investigate correlations and heterogeneity within alveolar macrophage subclusters.Alveolar macrophages from active TB patients at the single-cell resolution are described.We found that TB patients have higher cellular percentages in five macrophage subclusters.Alveolar macrophage subclusters with increased percentages were involved in inflammatory signaling pathways as well as the basic macrophage functions.The TB-increased alveolar macrophage subclusters might be derived from M1-like polarization state,before switching to an M2-like polarization state with the development of M.tuberculosis infection.Cell-cell communications of alveolar macrophages also increased and enhanced in active TB patients.Overall,our study demonstrated the characteristics of alveolar macrophages from BALF in active TB patients by using scRNA-seq.展开更多
Objective:To explore the expression of microRNA(miRNA) let-7c and its function in chronic obstructive pulmonary disease(COPD) and alveolar macrophage cells.Methods:Real time PCR was performed to detect the expression ...Objective:To explore the expression of microRNA(miRNA) let-7c and its function in chronic obstructive pulmonary disease(COPD) and alveolar macrophage cells.Methods:Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice.MiRNA let-7c was overexpresscd in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3(STAT3) as well as phosphorylation level of STAT3 after LPS stimulation.Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3.Results:MiRNA let-7c expression was significantly lower in patients with COPD compared with control group,and the similar result was found in COPD mice and LPS stimulated alveolar macrophages.Overexpression of miRNA lct-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha,interleukin-6 and interleukin-1β.Luciferase assay showed STAT3 was a targeting of miRNA lct-7c in alveolar macrophages.Conclusions:MiRNA lct-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage,which may provide a new target for COPD treatment strategies.展开更多
BACKGROUND Pulmonary alveolar proteinosis(PAP)and X-linked agammaglobulinemia(XLA)are rare diseases in children.Many theories infer that immunodeficiency can induce PAP,but these reports are almost all review articles...BACKGROUND Pulmonary alveolar proteinosis(PAP)and X-linked agammaglobulinemia(XLA)are rare diseases in children.Many theories infer that immunodeficiency can induce PAP,but these reports are almost all review articles,and there is little clinical evidence.We report the case of a child with both PAP and XLA.CASE SUMMARY A 4-month-old boy sought medical treatment due to coughing and difficulty in breathing for>2 wk.He had been hospitalized multiple times due to respiratory infections and diarrhea.Chest computed tomography and alveolar lavage fluid showed typical PAP-related manifestations.Genetic testing confirmed that the boy also had XLA.Following total lung alveolar lavage and intravenous immunoglobulin replacement therapy,the boy recovered and was discharged.During the follow-up period,the number of respiratory infections was significantly reduced,and PAP did not recur.CONCLUSION XLA can induce PAP and improving immune function contributes to the prognosis of children with this type of PAP.展开更多
Tumor-associated macrophages(TAMs)are emerging as targets for tumor therapy because of their primary role in promoting tumor progression.Several studies have been conducted to target TAMs by reducing their infiltratio...Tumor-associated macrophages(TAMs)are emerging as targets for tumor therapy because of their primary role in promoting tumor progression.Several studies have been conducted to target TAMs by reducing their infiltration,depleting their numbers,and reversing their phenotypes to suppress tumor progression,leading to the development of drugs in preclinical and clinical trials.However,the heterogeneous characteristics of TAMs,including their ontogenetic and functional heterogeneity,limit their targeting.Therefore,in-depth exploration of the heterogeneity of TAMs,combined with immune checkpoint therapy or other therapeutic modalities could improve the efficiency of tumor treatment.This review focuses on the heterogeneous ontogeny and function of TAMs,as well as the current development of tumor therapies targeting TAMs and combination strategies.展开更多
Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide ...Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.展开更多
The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its ...The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its potential molecular mechanism were investigated.Results showed that SCP3 at 25-100μg/m L increased viability and improved phagocytosis of RAW264.7 cells.Meanwhile,SCP3 could activate mitogen-activated protein kinase(MAPK)and nuclear factor kappa B(NF-κB)signaling pathways,which increased the phosphorylation of Erk1/2,JNK,p38 and NF-κB p65,promoting secretion of cytokines tumor necrosis factorα(TNF-α),interleukin 6(IL-6)and nitric oxide(NO)as well as the production of reactive oxygen species(ROS).In addition,Toll-like receptor 4(TLR4)receptor inhibitors were able to block the production of NO and TNF-αby SCP3-stimulated macrophages.Based on Western blot analysis and validation using specific inhibitors against MAPK and NF-κB signaling pathways,the results demonstrated that SCP3 induced macrophages activation and enhanced TNF-αand NO production via TLR4-mediated MAPK and NF-κB pathways.In summary,SCP3 has significant immunomodulatory potential.The underlying molecular mechanism was that SCP3 activates macrophages via TLR4 receptors to promote ROS production,which in turn activates the downstream MAPK/NF-κB signaling pathway and then increases the secretion levels of cytokines and NO.展开更多
BACKGROUND Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis(AE).Currently,there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of pati...BACKGROUND Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis(AE).Currently,there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial.Radical hepatectomy combined with regional lymph node dissection is a better treatment.AIM To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy.METHODS A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed.Fifty-five patients with combined lymph node metastasis were analysed for their clinical data,diagnosis and treatment methods,follow-up efficacy,and characteristics of lymph node metastasis.Finally,we comparatively analysed the lymph node metastasis rates at different sites.Categorical variables are expressed as frequencies and percentages,and the analysis of difference was performed using theχ2 test.The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables.RESULTS A lymph node metastasis rate of 8.8%(55/623)was reported in patients with hepatic AE,with a female predilection(69.1%)and a statistically significant sex difference(χ2=8.018,P=0.005).Of the 55 patients with lymph node metastasis,72.7%had a parasite lesion,neighbouring organ invasion,and metastasis stage of P3N1M0 and above,of which 67.3%,78.2%,and 34.5%of hepatic AE lesions invaded the bile ducts,blood vessels,and distant metastases,respectively.Detection rates of lymph node metastasis of 16.4%,21.7%,and 34.2%were reported for a preoperative abdominal ultrasound,magnetic resonance imaging,and computed tomography examinations.All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection.After surgery,a routine pathological examination was conducted on the resected lymph nodes.A total of 106 positive lymph nodes were detected in six groups at various sites,including 51 single-group metastasis cases and four multi-group metastasis cases.When the metastasis rates at different sites were statistically analysed,we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites(χ^(2)=128.089,P=0.000<0.05).No statistical difference was observed in the metastasis rate between the five other groups.Clavien-Dindo grade IIIa complication occurred in 14 cases,which improved after administering symptomatic treatment.Additionally,lymph node dissection-related complications were not observed.Recurrence after 2 years was observed in one patient.CONCLUSION Lymph node metastasis is a rare form of metastasis in hepatic AE,which is more frequent in women.Parahepatoduodenal ligament lymph nodes are commonly observed.Radical hepatectomy combined with regional lymph node dissection is a safe,effective,and feasible treatment for liver AE combined with lymph node metastasis.展开更多
The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bon...The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.展开更多
BACKGROUND Extraction of impacted third molars often leads to severe complications caused by damage to the inferior alveolar nerve(IAN).AIM To proposes a method for the partial grinding of an impacted mandibular third...BACKGROUND Extraction of impacted third molars often leads to severe complications caused by damage to the inferior alveolar nerve(IAN).AIM To proposes a method for the partial grinding of an impacted mandibular third molar(IMM3)near the IAN to prevent IAN injury during IMM3 extraction.METHODS Between January 1996 and March 2022,25 patients with IMM3 roots near the IAN were enrolled.The first stage of the operation consisted of grinding a major part of the IMM3 crown with a high-speed turbine dental drill to achieve sufficient space between the mandibular second molar and IMM3.After 6 months,when the root tips were observed to be away from the IAN on X-ray examination,the remaining part of the IMM3 was completely removed.RESULTS All IMM3s were extracted easily without symptoms of IAN injury after extraction.CONCLUSION Partial IMM3 grinding may be a good alternative treatment option to avoid IAN injury in high-risk cases.展开更多
BACKGROUND Hepatic cystic and alveolar echinococcosis coinfections,particularly with concurrent abscesses and sinus tract formation,are extremely rare.This article presents a case of a patient diagnosed with this uniq...BACKGROUND Hepatic cystic and alveolar echinococcosis coinfections,particularly with concurrent abscesses and sinus tract formation,are extremely rare.This article presents a case of a patient diagnosed with this unique presentation,discussing the typical imaging manifestations of both echinococcosis types and detailing the diagnosis and surgical treatment experience thereof.CASE SUMMARY A 39-year-old Tibetan woman presented with concurrent hepatic cystic and alveolar echinococcosis,accompanied by abdominal wall abscesses and sinus tract formation.Initial conventional imaging examinations suggested only hepatic cystic echinococcosis,but intraoperative and postoperative pathological examination revealed the coinfection.Following radical resection of the lesions,the patient’s condition improved,and she was discharged soon thereafter.Subsequent outpatient follow-ups confirmed no recurrence of the hydatid lesion and normal surgical wound healing.Though mixed hepatic cystic and alveolar echinococcosis with abdominal wall abscesses and sinus tract formations are rare,the general treatment approach remains consistent with that of simpler infections of alveolar echinococcosis.CONCLUSION Lesions involving the abdominal wall and sinus tract formation,may require radical resection.Long-term prognosis includes albendazole and follow-up examinations.展开更多
BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can sign...BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.展开更多
Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classica...Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classically activated macrophage(M1)polarization.In this study,we established THP-1-derived testing state macrophages(M0),M1 macrophages,and alternately activated macrophages(M2).Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages.Flow cytometry was used to detect phenotypic proteins(CD11b,CD38,CD80).We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048.Flow cytometry,western blot,and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response,while over-expression of lnc_000048 led to the opposite effect.Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization.Moreover,catRAPID prediction,RNA-pull down,and mass spectrometry were used to identify and screen the protein kinase RNA-activated(PKR),then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR.Immunofluorescence(IF)-RNA fluorescence in situ hybridization(FISH)double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage.We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation,leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression.Taken together,these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.展开更多
Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challe...Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.展开更多
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30671743)
文摘The roles of voltage-dependent K^+ channels during activation and damage in alveolar macrophages (AMs) exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage, and were adjusted to 5× 10^5/mL. After AMs were exposed to different concentrations (0, 25, 50, 100, 200 μg/mL) of quartz particles and 100 μg/mL amorphous silica particles for 24 h, the voltage-depended K^+ current in AMs was measured by using patch clamp technique. Meanwhile the leakage of lactate dehydrogenase (LDH) and the viability of AMs were detected respectively. Patch clamp studies demonstrated that AMs possessed outward delayed and inward rectifying K^+ current. Exposure to quartz particles increased the outward delayed K^+ current but it had no effect on inward rectifier K^+ current in AMs. Neither of the two K^+ channels in AMs was affected by amorphous silica particles. Cytotoxicity test showed that both silica particles could damage AM membrane and result in significant leakage of LDH (P〈0.05). MTT studies, however, showed that only quartz particles reduced viability of AMs (P〈0.05). It is concluded that quartz parti- cles can activate the outward delayed K^+ channel in AMs, which may act as an activating signal in AMs to initiate an inflammatory response during damage and necrosis in AMs induced by exposure to quartz particle. K^+ channels do not contribute to the membrane damage of AMs.
文摘Background: Our previous study showed that 3 plant extracts enhanced the immune responses and growth efficiency of weaned pigs infected with porcine reproductive and respiratory syndrome virus(PRRSV), which is one of the most economically important disease in swine industry. However, each plant extract differently effected on growth efficiency and immune responses. Therefore, the objective of this study was conducted to characterize the effects and investigate the potential underlying mechanisms of 3 plant extracts on gene expression of alveolar macrophages in weaned pigs experimentally infected with PRRSV.Results: PRRSV infection altered(P < 0.05) the expression of 1,352 genes in pigs fed the control(CON;755 up, 597 down). Compared with the infected CON, feeding capsicum(CAP), garlic botanical(GAR), or turmeric oleoresin(TUR) altered the expression of 46 genes(24 up, 22 down), 134 genes(59 up, 75 down), or 98 genes(55 up, 43 down) in alveolar macrophages of PRRSV-infected pigs, respectively. PRRSV infection up-regulated(P < 0.05) the expression of genes related to cell apoptosis, immune system process, and response to stimulus, but downregulated(P < 0.05) the expression of genes involved in signaling transduction and innate immune response.Compared with the infected CON, feeding TUR or GAR reduced(P < 0.05) the expression of genes associated with antigen processing and presentation, feeding CAP up-regulated(P < 0.05) the expression of genes involved in antigen processing and presentation. Supplementation of CAP, GAR, or TUR also enhanced(P < 0.05) the expression of several genes related to amino acid metabolism, steroid hormone synthesis, or RNA degradation, respectively.Conclusions: The results suggest that 3 plant extracts differently regulated the expression of genes in alveolar macrophages of PRRSV-infected pigs, especially altering genes involved in immunity.
文摘Alveolar macrophages (AM) from BCG activated Wistar rat were irradiated with different doses of Gamma rays in vitro. The effects of radiation on their immunological functions and membrane damage were studied. The non-specific cytotoxicity and specific phagocytosis of AM irradiated with dose of 0, 100, 300 and 500 Gy decreased with the increase in dose. The relative fractions of Lactate Dehydrogenase and Beta-glucuronidase (β-glu) activity in supernatant increased with the increase in dose. There was a correlation between the suppression of immunological functions and the degree of damage of cytoplasmic and lysosomal membranes of AM after irradiation. Na2SeO3, a protective agent of cell membranes, alleviated this effect on the suppressive cytotoxicity indices of irradiated AM.
文摘To study the effects of tumor necrosis factor (TNF)-α on matrix metalloproteinase (MMP)-9 expression and activity in alveolar macrophages (AM) and to investigate the role of NF-κB in the induction, AM were collected from bronchoalveolar lavage fluid (BALF) of healthy subjects and patients with chronic obstructive pulmonary disease (COPD). MMP-9 expression and activity were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and zymography. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA). MMP-9 expression and activity induced by TNF-α in AM from healthy subjects or patients with COPD were significantly increased in a dose-dependent manner (P〈0.05). NF-κB activity induced by TNF-α was significantly increased in AM from patients with COPD, and pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC) significantly inhibited the activation of NF-κB induced by TNF-α (P〈0.05). The presents study suggested that the expression and activity of MMP-9 from AM can be induced by TNF-α, and TNF-α/NF-κB signal pathway may play an important role in the induction.
文摘To explore the effects of bilirubin on alveolar macrophages (AM) and expression of iNOS and NO in them in emphysema model, the rats were pretreated with bilirubin before exposed to smoke. AM were isolated from bronchoalveolar lavage fluid (BALF) and cultured. Pathological microscopic examination of AM and immunohistochemical analysis of iNOS were performed. Nitric oxide (NO) content in the samples was determined by nitrate reductase technique. The results showed both alveoli and alveolar septum appeared normal in size and shape in normal group. AM showed kidney-shaped nucleus and were rich in Golgi complexes and primary lysosomes in the cytoplasm. The inner membrane of mitochondrion was continuous. Most cristae of the mitochondria were intact. In model group, the alveoli were expanded, ruptured and bullaes were formed. Both the population and sizes of AM increased significantly. Secondary lysosomes were rich in the cytoplasm. Deformation and pyknosis of the nucleus, swelling of the mitochondrions and rupture of the inner mitochondrial membrane could also be seen. At high magnification, most of the mitochondrial cristae were broken, or completely lost at certain points. In bilirubin group, alveoli partly expanded and the population of AM also increased, with morphological changes being slighter than that in model group. Both NO contents and expression of iNOS in model group were higher than those in normal group (P<0.05). In bilirubin group the two indice were lower than those in model group (P<0.05). Our findings suggested that high expression of iNOS and high NO content in AM accelerate the development of emphysema associated with smoking in rats. Bilirubin may exert protective effects on AM and retards the development of emphysema in rats.
基金funded in part by the North Carolina State University Agricultural Foundation,USDA-NIFA Animal Health Program
文摘Background: Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE2(supporting both inflammation and resolution) makes it a potent regulator of immune cell function. Therefore, the use of dietary long chain n-6 PUFA to enhance PGE2 effects merits investigation.Methods: Day-old pigs(n = 60) were allotted to one of three dietary groups for 21 d(n = 20/diet), and received either a control diet(CON, arachidonate = 0.5% of total fatty acids), an arachidonate(ARA)-enriched diet(LC n-6,ARA = 2.2%), or an eicosapentaenoic(EPA)-enriched diet(LC n-3, EPA = 3.0%). Alveolar macrophages and lung parenchymal tissue were collected for fatty acid analysis. Isolated alveolar macrophages were stimulated with LPS in situ for 24 h, and m RNA was isolated to assess markers associated with inflammation and eicosanoid production.Culture media were collected to assess PGE2 secretion. Oxidative burst in macrophages was measured by: 1)oxygen consumption and extracellular acidification(via Seahorse), 2) cytoplasmic oxidation and 3) nitric oxide production following 4, 18, and 24 h of LPS stimulation.Results: Concentration of ARA(% of fatty acids, w/w) in macrophages from pigs fed LC n-6 was 86% higher than CON and 18% lower in pigs fed LC n-3(P < 0.01). Following LPS stimulation, abundance of COX-2 and TNF-α mRNA(P < 0.0001), and PGE2 secretion(P < 0. 01) were higher in LC n-6 PAM vs. CON. However, ALOX5 abundance was1.6-fold lower than CON. Macrophages from CON and LC n-6 groups were 4-fold higher in ALOX12/15 abundance(P < 0.0001) compared to LC n-3. Oxygen consumption and extracellular acidification rates increased over 4 h following LPS stimulation(P < 0.05) regardless of treatment. Similarly, increases in cytoplasmic oxidation(P < 0.001)and nitric oxide production(P < 0.002) were observed after 18 h of LPS stimulation but were unaffected by diet.Conclusions: We infer that enriching diets with arachidonic acid may be an effective means to enhance a stronger innate immunologic response to respiratory challenges in neonatal pigs. However, further work is needed to examine long-term safety, clinical efficacy and economic viability.
文摘Objective: To explore the effect of tumor necrosis factor (TNF)-α on matrix metalloproteinase-9 (MMP-9) expression and activity in alveolar macrophages (AM) from patients with chronic obstructive pulmonary disease (COPD) and study its associated signal pathway. Methods: AM were collected from bronchoalveolar lavage fluid in patients with COPD. The AM were incubated for 1.5 h with pyrrolidine dithiocarbamate(PDTC) at concentrations from 0 μmol/L to 50μmol/L and then stimulated for 24 h by TNF-α at 10 ng/ml. MMP-9 expression and activity were respectively detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and Zymography. NF-κB activity was investigated by electrophoretic mobility shift assay (EMSA). Results: Both the mRNA and protein levels of MMP-9 induced by TNF-α in AM were significantly elevated in a dose dependent manner ( P 〈 0.05). The level of MMP-9 activity was also correspondingly significantly elevated in the induction ( P 〈 0.05), which was possibly related with the over-expression of MMP-9. NF-κB activity was significantly increased when AM were stimulated by 10 ng/mL TNF-α ( P 〈 0.05). The expression of MMP-9 induced by TNF-α could be significantly inhibited by PDTC (P 〈 0.05 ). Conclusion: The expression and activity of MMP-9 from AM could be induced by TNF-α, and NF-κB signal pathway played an important role in the induction.
基金funded by grants from the National Natural Science Foundation of China (Grant No. 81800090)the Key Project of National Science & Technology for Infectious Diseases of China (Grant No. 2018ZX10722301-002)
文摘Tuberculosis(TB),is an infectious disease caused by Mycobacterium tuberculosis(M.tuberculosis),and presents with high morbidity and mortality.Alveolar macrophages play an important role in TB pathogenesis although there is heterogeneity and functional plasticity.This study aimed to show the characteristics of alveolar macrophages from bronchioalveolar lavage fluid(BALF)in active TB patients.Single-cell RNA sequencing(scRNA-seq)was performed on BALF cells from three patients with active TB and additional scRNA-seq data from three healthy adults were established as controls.Transcriptional profiles were analyzed and compared by differential gene expression and functional enrichment analysis.We applied pseudo-temporal trajectory analysis to investigate correlations and heterogeneity within alveolar macrophage subclusters.Alveolar macrophages from active TB patients at the single-cell resolution are described.We found that TB patients have higher cellular percentages in five macrophage subclusters.Alveolar macrophage subclusters with increased percentages were involved in inflammatory signaling pathways as well as the basic macrophage functions.The TB-increased alveolar macrophage subclusters might be derived from M1-like polarization state,before switching to an M2-like polarization state with the development of M.tuberculosis infection.Cell-cell communications of alveolar macrophages also increased and enhanced in active TB patients.Overall,our study demonstrated the characteristics of alveolar macrophages from BALF in active TB patients by using scRNA-seq.
基金founded by the Medical Scientific Research Projects of Health Family Planning Commission of Chongqing(20142019)
文摘Objective:To explore the expression of microRNA(miRNA) let-7c and its function in chronic obstructive pulmonary disease(COPD) and alveolar macrophage cells.Methods:Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice.MiRNA let-7c was overexpresscd in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3(STAT3) as well as phosphorylation level of STAT3 after LPS stimulation.Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3.Results:MiRNA let-7c expression was significantly lower in patients with COPD compared with control group,and the similar result was found in COPD mice and LPS stimulated alveolar macrophages.Overexpression of miRNA lct-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha,interleukin-6 and interleukin-1β.Luciferase assay showed STAT3 was a targeting of miRNA lct-7c in alveolar macrophages.Conclusions:MiRNA lct-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage,which may provide a new target for COPD treatment strategies.
基金Supported by Sanitation Research Project of Kunming Municipal Health Commission,No.2020-06-01-119.
文摘BACKGROUND Pulmonary alveolar proteinosis(PAP)and X-linked agammaglobulinemia(XLA)are rare diseases in children.Many theories infer that immunodeficiency can induce PAP,but these reports are almost all review articles,and there is little clinical evidence.We report the case of a child with both PAP and XLA.CASE SUMMARY A 4-month-old boy sought medical treatment due to coughing and difficulty in breathing for>2 wk.He had been hospitalized multiple times due to respiratory infections and diarrhea.Chest computed tomography and alveolar lavage fluid showed typical PAP-related manifestations.Genetic testing confirmed that the boy also had XLA.Following total lung alveolar lavage and intravenous immunoglobulin replacement therapy,the boy recovered and was discharged.During the follow-up period,the number of respiratory infections was significantly reduced,and PAP did not recur.CONCLUSION XLA can induce PAP and improving immune function contributes to the prognosis of children with this type of PAP.
基金This work was supported by the National Natural Science Foundation of China(82003018).
文摘Tumor-associated macrophages(TAMs)are emerging as targets for tumor therapy because of their primary role in promoting tumor progression.Several studies have been conducted to target TAMs by reducing their infiltration,depleting their numbers,and reversing their phenotypes to suppress tumor progression,leading to the development of drugs in preclinical and clinical trials.However,the heterogeneous characteristics of TAMs,including their ontogenetic and functional heterogeneity,limit their targeting.Therefore,in-depth exploration of the heterogeneity of TAMs,combined with immune checkpoint therapy or other therapeutic modalities could improve the efficiency of tumor treatment.This review focuses on the heterogeneous ontogeny and function of TAMs,as well as the current development of tumor therapies targeting TAMs and combination strategies.
基金supported by the National Natural Science Foundation of China,No.32371048(to YK)the Peking University People’s Hospital Research and Development Funds,No.RDX2021-01(to YK)the Natural Science Foundation of Beijing,No.7222198(to NH)。
文摘Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.
基金the financial supports by the National Natural Science Foundation of China(82060594)the Natural Science Foundation of Jiangxi Province,China(20202BAB205006)。
文摘The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its potential molecular mechanism were investigated.Results showed that SCP3 at 25-100μg/m L increased viability and improved phagocytosis of RAW264.7 cells.Meanwhile,SCP3 could activate mitogen-activated protein kinase(MAPK)and nuclear factor kappa B(NF-κB)signaling pathways,which increased the phosphorylation of Erk1/2,JNK,p38 and NF-κB p65,promoting secretion of cytokines tumor necrosis factorα(TNF-α),interleukin 6(IL-6)and nitric oxide(NO)as well as the production of reactive oxygen species(ROS).In addition,Toll-like receptor 4(TLR4)receptor inhibitors were able to block the production of NO and TNF-αby SCP3-stimulated macrophages.Based on Western blot analysis and validation using specific inhibitors against MAPK and NF-κB signaling pathways,the results demonstrated that SCP3 induced macrophages activation and enhanced TNF-αand NO production via TLR4-mediated MAPK and NF-κB pathways.In summary,SCP3 has significant immunomodulatory potential.The underlying molecular mechanism was that SCP3 activates macrophages via TLR4 receptors to promote ROS production,which in turn activates the downstream MAPK/NF-κB signaling pathway and then increases the secretion levels of cytokines and NO.
基金Supported by Natural Science Foundation of Xinjiang Uygur Autonomous Region,China,No.2022D01D17.
文摘BACKGROUND Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis(AE).Currently,there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial.Radical hepatectomy combined with regional lymph node dissection is a better treatment.AIM To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy.METHODS A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed.Fifty-five patients with combined lymph node metastasis were analysed for their clinical data,diagnosis and treatment methods,follow-up efficacy,and characteristics of lymph node metastasis.Finally,we comparatively analysed the lymph node metastasis rates at different sites.Categorical variables are expressed as frequencies and percentages,and the analysis of difference was performed using theχ2 test.The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables.RESULTS A lymph node metastasis rate of 8.8%(55/623)was reported in patients with hepatic AE,with a female predilection(69.1%)and a statistically significant sex difference(χ2=8.018,P=0.005).Of the 55 patients with lymph node metastasis,72.7%had a parasite lesion,neighbouring organ invasion,and metastasis stage of P3N1M0 and above,of which 67.3%,78.2%,and 34.5%of hepatic AE lesions invaded the bile ducts,blood vessels,and distant metastases,respectively.Detection rates of lymph node metastasis of 16.4%,21.7%,and 34.2%were reported for a preoperative abdominal ultrasound,magnetic resonance imaging,and computed tomography examinations.All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection.After surgery,a routine pathological examination was conducted on the resected lymph nodes.A total of 106 positive lymph nodes were detected in six groups at various sites,including 51 single-group metastasis cases and four multi-group metastasis cases.When the metastasis rates at different sites were statistically analysed,we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites(χ^(2)=128.089,P=0.000<0.05).No statistical difference was observed in the metastasis rate between the five other groups.Clavien-Dindo grade IIIa complication occurred in 14 cases,which improved after administering symptomatic treatment.Additionally,lymph node dissection-related complications were not observed.Recurrence after 2 years was observed in one patient.CONCLUSION Lymph node metastasis is a rare form of metastasis in hepatic AE,which is more frequent in women.Parahepatoduodenal ligament lymph nodes are commonly observed.Radical hepatectomy combined with regional lymph node dissection is a safe,effective,and feasible treatment for liver AE combined with lymph node metastasis.
基金Supported by the National Key Research and Development Program of China,No.2023YFC2508806Key Research and Development Project in Henan Province,No.231111310500+4 种基金Young Elite Scientists Sponsorship Program by CAST,No.2021-QNRC2-A06Scientific Research Project of Henan Zhongyuan Medical Science and Technology Innovation and Development Foundation,No.ZYYC2023ZDYouth Science Award Project of the Provincial-Level Joint Fund for Science and Technology Research and Development Project in Henan Province,No.225200810084Special Project on Training Top Talents in Traditional Chinese Medicine in Henan Province,No.2022ZYBJ242023 Hunan University of Chinese Medicine Postgraduate Innovation Project,No.2023CX64。
文摘The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.
文摘BACKGROUND Extraction of impacted third molars often leads to severe complications caused by damage to the inferior alveolar nerve(IAN).AIM To proposes a method for the partial grinding of an impacted mandibular third molar(IMM3)near the IAN to prevent IAN injury during IMM3 extraction.METHODS Between January 1996 and March 2022,25 patients with IMM3 roots near the IAN were enrolled.The first stage of the operation consisted of grinding a major part of the IMM3 crown with a high-speed turbine dental drill to achieve sufficient space between the mandibular second molar and IMM3.After 6 months,when the root tips were observed to be away from the IAN on X-ray examination,the remaining part of the IMM3 was completely removed.RESULTS All IMM3s were extracted easily without symptoms of IAN injury after extraction.CONCLUSION Partial IMM3 grinding may be a good alternative treatment option to avoid IAN injury in high-risk cases.
基金Supported by National Natural Science Foundation of China,No.82260412.
文摘BACKGROUND Hepatic cystic and alveolar echinococcosis coinfections,particularly with concurrent abscesses and sinus tract formation,are extremely rare.This article presents a case of a patient diagnosed with this unique presentation,discussing the typical imaging manifestations of both echinococcosis types and detailing the diagnosis and surgical treatment experience thereof.CASE SUMMARY A 39-year-old Tibetan woman presented with concurrent hepatic cystic and alveolar echinococcosis,accompanied by abdominal wall abscesses and sinus tract formation.Initial conventional imaging examinations suggested only hepatic cystic echinococcosis,but intraoperative and postoperative pathological examination revealed the coinfection.Following radical resection of the lesions,the patient’s condition improved,and she was discharged soon thereafter.Subsequent outpatient follow-ups confirmed no recurrence of the hydatid lesion and normal surgical wound healing.Though mixed hepatic cystic and alveolar echinococcosis with abdominal wall abscesses and sinus tract formations are rare,the general treatment approach remains consistent with that of simpler infections of alveolar echinococcosis.CONCLUSION Lesions involving the abdominal wall and sinus tract formation,may require radical resection.Long-term prognosis includes albendazole and follow-up examinations.
文摘BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2020MH138(to XZ).
文摘Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classically activated macrophage(M1)polarization.In this study,we established THP-1-derived testing state macrophages(M0),M1 macrophages,and alternately activated macrophages(M2).Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages.Flow cytometry was used to detect phenotypic proteins(CD11b,CD38,CD80).We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048.Flow cytometry,western blot,and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response,while over-expression of lnc_000048 led to the opposite effect.Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization.Moreover,catRAPID prediction,RNA-pull down,and mass spectrometry were used to identify and screen the protein kinase RNA-activated(PKR),then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR.Immunofluorescence(IF)-RNA fluorescence in situ hybridization(FISH)double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage.We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation,leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression.Taken together,these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.
基金supported by Shanghai Sailing Program(22YF1438700)National Key Research and Development Program of China(2021YFA1201303)+5 种基金National Natural Science Foundation of China(82172511,81972121,81972129,82072521,82011530023,and 82111530200)Sanming Project of Medicine in Shenzhen(SZSM201612078)the Introduction Project of Clinical Medicine Expert Team for Suzhou(SZYJTD201714)Shanghai Talent Development Funding Scheme 2020080Shanghai Sailing Program(21YF1404100 and 22YF1405200)Research Project of Shanghai Science and Technology Commission(22DZ2204900)。
文摘Skeletal muscle has a robust regeneration ability that is impaired by severe injury,disease,and aging.resulting in a decline in skeletal muscle function.Therefore,improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders.Owing to their significant role in tissue regeneration,implantation of M2 macrophages(M2MФ)has great potential for improving skeletal muscle regeneration.Here,we present a short-wave infrared(SWIR)fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2MФtransplantation.SWIR fluorescence imaging was employed to track implanted M2MФin the injured skeletal muscle of mouse models.It is found that the implanted M2MФaccumulated at the injury site for two weeks.Then,SWIR fluorescence imaging of blood vessels showed that M2MФimplantation could improve the relative perfusion ratio on day 5(1.09±0.09 vs 0.85±0.05;p=0.01)and day 9(1.38±0.16 vs 0.95±0.03;p=0.01)post-injury,as well as augment the degree of skeletal muscle regencration on day 13 post-injury.Finally,multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration.These results provide more in vivo details about M2MФin skeletal muscle regeneration and confirm that M2MФcould promote angiogenesis and improve the degree of skeletal muscle repair,which will guide the research and development of M2MФimplantation to improve skeletal muscle regeneration.