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1.
Front Immunol ; 14: 1130662, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122742

RESUMO

Introduction: Macrophages are central cells in mediating the inflammatory response. Objective and Methods: We evaluated the effect of high glucose conditions on the inflammatory profile and the autophagy pathway in Bone-Marrow Derived Macrophages (BMDM) from diabetic (D-BMDM) (alloxan: 60mg/kg, i.v.) and non-diabetic (ND-BMDM) C57BL/6 mice. BMDM were cultured in medium with normal glucose (5.5 mM), or high glucose (25 mM) concentration and were primed with Nigericin (20µM) stimulated with LPS (100 ng/mL) at times of 30 minutes; 2; 4; 6 and 24 hours, with the measurement of IL-6, IL-1ß and TNF-α cytokines. Results: We have further identified changes in the secretion of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α, where BMDM showed increased secretion of these cytokines after LPS + Nigericin stimulation. In addition, changes were observed in the autophagy pathway, where the increase in the autophagic protein LC3b and Beclin-1 occurred by macrophages of non-diabetic animals in hyperglycemic medium, without LPS stimulation. D-BMDM showed a reduction on the expression of LC3b and Beclin-1, suggesting an impaired autophagic process in these cells. Conclusion: The results suggest that hyperglycemia alters the inflammatory pathways in macrophages stimulated by LPS, playing an important role in the inflammatory response of diabetic individuals.


Assuntos
Interleucina-6 , Fator de Necrose Tumoral alfa , Camundongos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Proteína Beclina-1/metabolismo , Nigericina/farmacologia , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Citocinas/metabolismo , Autofagia , Glucose/metabolismo
2.
Regen Biomater ; 10: rbad033, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122820

RESUMO

Recently, evidence has suggested that chronic endometritis (CE) is a crucial factor associated with infertility and failure of assisted reproductive techniques, prompting concern in the reproductive field. Studies have shown that persistent infiltered immune cells stimulation result in the disturbance of endometrial immune microenvironment could lead to the infertility of CE patients finally. Conventional treatments are limited because they lack immune regulation, so it is urgent to develop a novel approach to treat CE and promote embryo implantation in patients with CE. Herein, we prepared recombinant humanized type III collagen (rhCol III) with high cell adhesion activity to regulate macrophages and repair the endometrium. In this study, M1 macrophages and M1 macrophages cultured medium and lipopolysaccharide (LPS) co-stimulated inflammatory endometrium stromal cells (ESCs) were established in vitro to mimic CE condition. rhCol III promoted M1 macrophages toward M2 phenotype, improved cell migration, viability and collagen components of inflammatory ESCs. Also, the inflammatory response of inflammatory ESCs was downregulated after rhCol III treatment. Subsequently, LPS was used for CE rat model and a 28-day observation was performed; inflammatory cells' infiltration, endometrium repair, extracellular matrix (ECM) remodeling and pregnancy outcomes were promoted after rhCol III endometrial infusion. In conclusion, rhCol III promoted (i) macrophage polarization toward M2 macrophages, (ii) pro-inflammatory cytokine production and anti-inflammatory cytokine reduction, (iii) ECM remodeling and (iv) fertility restoration. Meanwhile, rhCol III enhanced cell biological functions by interacting with discoidin domain receptors, regulated cell metabolism and reduced the inflammatory response through the inhibition of the NF-κB/YAP signaling pathway. Overall, the results illustrated the potential therapeutic prospects of rhCol III for CE treatment.

3.
World J Gastrointest Oncol ; 15(4): 596-616, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37123058

RESUMO

Many digestive system malignant tumors are characterized by high incidence and mortality rate. Increasing evidence has revealed that the tumor microenvironment (TME) is involved in cancer initiation and tumor progression. Tumor-associated macrophages (TAMs) are a predominant constituent of the TME, and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer. TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype. The latter especially are crucial drivers of tumor invasion, growth, angiogenesis, metastasis, immunosuppression, and resistance to therapy. TAMs are of importance in the occurrence, development, diagnosis, prognosis, and treatment of common digestive system malignant tumors. In this review, we summarize the role of TAMs in common digestive system malignant tumors, including esophageal, gastric, colorectal, pancreatic and liver cancers. How TAMs promote the development of tumors, and how they act as potential therapeutic targets and their clinical applications are also described.

4.
Exp Ther Med ; 25(5): 219, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37123212

RESUMO

The present study investigated the immunostimulatory activity and anti-obesity activity of Adenocaulon himalaicum leaf extracts (AHL) in RAW264.7 cells and 3T3-L1 cells. AHL increased the production of immunostimulatory factors, such as NO, inducible nitric oxide synthase (iNOS), IL-1ß, IL-6 and TNF-α and activated the phagocytotic activity in RAW264.7 cells. Inhibition of Toll-like receptor 4 (TLR4) attenuated the AHL-mediated production of immunostimulatory factors and activation of phagocytic activity in RAW264.7 cells. Inhibition of p38 and JNK blocked the AHL-mediated production of immunostimulatory factors, whereas inhibition of TLR4 suppressed the AHL-mediated phosphorylation of p38 and JNK. Additionally, AHL blocked the lipid accumulation in 3T3-L1 cells. AHL downregulated proliferator-activated receptor γ, CCAAT enhancer binding protein α and perilipin-1 levels, while upregulating adipose triglyceride lipase, phosphorylated (p-)hormone-sensitive lipase, p-adenosine monophosphate activated protein kinase, uncoupling protein 1, peroxisome-proliferator-activated receptor-γ coactivator-1 α and PR domain containing 16 levels in 3T3-L1 cells. These findings suggested that AHL may exert immunostimulatory activity through macrophages via TLR4-mediated activation of p38 and JNK and anti-obesity activity by blocking lipid accumulation via the inhibition of adipogenesis and induction of lipolysis and browning of white adipocytes.

5.
Int Immunopharmacol ; 119: 110137, 2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37126984

RESUMO

Extracellular vesicles (EVs) exhibit pivotal functions in cancer via intercellular communication through shuttling microRNA (miRNA) and protein. Therefore, we aim to elucidate the function of EVs containing miR-143-3p derived from M2 macrophages in colorectal cancer (CRC). EVs derived from M2 macrophages were isolated and characterized. Expression changes in miR-143-3p were calculated in the EVs. The effects of M2 macrophage-derived EV carrying miR-143-3p on cell biological processes and in vivo tumorigenic ability concerning ZC3H12A were examined. EVs derived from M2 macrophages could stimulate the aggressive tumor biology of CRC cells. Meanwhile, in vivo results showed that M2 macrophage-derived EVs facilitated tumor growth and epithelial-mesenchymal transition. M2 macrophage-secreted EVs could transfer miR-143-3p to CRC cells, in which miR-143-3p bound to the 3'UTR of ZC3H12A and inhibited its expression, leading to elevation of the expression of transcription factor C/EBPß. Overall, M2 macrophage-derived EV miR-143-3p inhibits ZC3H12A gene and increases C/EBPß expression to facilitate the development of CRC, which provides novel targets for the molecular treatment of CRC.

6.
Artigo em Inglês | MEDLINE | ID: mdl-37128912

RESUMO

BACKGROUND: Obesity and diabetes are associated with elevated free fatty acids like palmitic acid (PA), which promote chronic inflammation and impaired inflammation resolution associated with cardiometabolic disorders. Long noncoding RNAs (lncRNAs) are implicated in inflammatory processes; however, their roles in PA-regulated inflammation and resolution are unclear. METHODS: We performed RNA-sequencing analysis to identify PA-regulated coding genes and novel lncRNAs in CD14+ monocytes from healthy volunteers. We investigated the regulation and function of an uncharacterized PA-induced lncRNA PARAIL (PA-regulated anti-inflammatory lncRNA). We examined its role in inflammation resolution by employing knockdown and overexpression strategies in human and mouse macrophages. We also used RNA pulldown coupled with mass spectrometry to identify PARAIL interacting nuclear proteins and their mechanistic involvement in PARAIL functions in human macrophages. RESULTS: Treatment of human CD14+ monocytes with PA-induced several lncRNAs and genes associated with inflammatory phenotype. PA strongly induced lncRNA PARAIL expressed near RIPK2. PARAIL was also induced by cytokines and infectious agents in human monocytes/macrophages and was regulated by NF-κB (nuclear factor-kappa B). Time course studies showed PARAIL was induced during inflammation resolution phase in PA-treated macrophages. PARAIL knockdown with antisense oligonucleotides upregulated key inflammatory genes and vice versa with PARAIL overexpression. We found that PARAIL interacts with ELAVL1 (ELAV-like RNA-binding protein 1) protein via AREs (AU-rich elements). ELAVL1 knockdown inhibited the anti-inflammatory functions of PARAIL. Moreover, PARAIL knockdown increased cytosolic localization of ELAVL1 and increased the stability of ARE-containing inflammatory genes. Mouse orthologous Parail was downregulated in macrophages from mice with diabetes and atherosclerosis. Parail overexpression attenuated proinflammatory genes in mouse macrophages. CONCLUSIONS: Upregulation of PARAIL under acute inflammatory conditions contributes to proresolution mechanisms via PARAIL-ELAVL1 interactions. Conversely, PARAIL downregulation in cardiometabolic diseases enhances ELAVL1 function and impairs inflammation resolution to further augment inflammation. Thus, inflammation-resolving lncRNAs like PARAIL represent novel targets to combat inflammatory cardiometabolic diseases.

7.
Future Med Chem ; 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37129027

RESUMO

Background: Sepsis is a syndrome due to microbial infection causing impaired multiorgan function. Its underlying cause is immune dysfunction and macrophages play an essential role. Methods: TIRAP interaction with PKCδ in macrophage was studied, revealing downstream signaling by Western blot and quantitative reverse transcriptase PCR. Dorzolamide (DZD) disrupting TIRAP-PKCδ interaction was identified by virtual screening and validated in vitro and in septic mice. Results: The study highlights the indispensable role of TIRAP-PKCδ in p38 MAPK-activation, NF-κB- and AP-1-mediated proinflammatory cytokines expression, whereas DZD significantly attenuated the signaling. Conclusion: Targeting TIRAP-PKCδ interaction by DZD is a novel therapeutic approach for treating sepsis.

8.
Immunol Invest ; : 1-25, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37129471

RESUMO

Adipose tissue macrophages (ATM) are an essential type of immune cells in adipose tissue. Obesity induces the inflammation of adipose tissues, as expressed by ATM accumulation, that is more likely to become a source of systemic metabolic diseases, including insulin resistance. The process is characterized by the transcriptional regulation of inflammatory pathways by virtue of signaling molecules such as cytokines and free fatty acids. Notably, posttranslational modification (PTM) is a key link for these signaling molecules to trigger the proinflammatory or anti-inflammatory phenotype of ATMs. This review focuses on summarizing the functions and molecular mechanisms of ATMs regulating inflammation in obese adipose tissue. Furthermore, the role of PTM is elaborated, hoping to identify new horizons of treatment and prevention for obesity-mediated metabolic disease.

9.
Cell Biochem Biophys ; 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37129843

RESUMO

This study aimed to investigate the role of PPARγ and underlying mechanisms in myocardial ischemia/reperfusion injury (IRI). IRI was surgically induced in mice and neonatal rat cardiomyocytes (NRCM) were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). Quantitative genetic analysis and western blotting were performed to assess mRNA and protein levels, respectively, of PPARγ, as well as of different inflammatory, fibrosis, and apoptosis markers in cells and tissues. PPARγ was overexpressed in the heart of mice and NRCMs by viral transfection. Apoptosis and fibrosis were detected by TUNEL and Masson's trichrome staining, respectively. Enzyme-linked immunosorbent assay was performed to detect M1 and M2 macrophage-related inflammatory factors present in mouse sera. PPARγ overexpression significantly inhibited OGD/R- and IRI-induced cardiomyocyte apoptosis and fibrosis in vitro and in vivo. Moreover, PPARγ overexpression inhibited IRI-induced secretion of M1-related proinflammatory factors, whereas it supported the secretion of M2-related anti-inflammatory factors. Notably, these events were found to be mediated by the JAK/STAT pathway. In conclusion, PPARγ regulates macrophage polarization upon IRI via the JAK/STAT pathway, which will in turn prevent myocardial apoptosis and fibrosis. Hence, PPARγ may represent a valuable target for myocardial IRI treatment.

10.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(2): 384-391, 2023 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-37139773

RESUMO

Macrophages are important immune effector cells with significant plasticity and heterogeneity in the body immune system, and play an important role in normal physiological conditions and in the process of inflammation. It has been found that macrophage polarization involves a variety of cytokines and is a key link in immune regulation. Targeting macrophages by nanoparticles has a certain impact on the occurrence and development of a variety of diseases. Due to its characteristics, iron oxide nanoparticles have been used as the medium and carrier for cancer diagnosis and treatment, making full use of the special microenvironment of tumors to actively or passively aggregate drugs in tumor tissues, which has a good application prospect. However, the specific regulatory mechanism of reprogramming macrophages using iron oxide nanoparticles remains to be further explored. In this paper, the classification, polarization effect and metabolic mechanism of macrophages were firstly described. Secondly, the application of iron oxide nanoparticles and the induction of macrophage reprogramming were reviewed. Finally, the research prospect and difficulties and challenges of iron oxide nanoparticles were discussed to provide basic data and theoretical support for further research on the mechanism of the polarization effect of nanoparticles on macrophages.


Assuntos
Nanopartículas , Neoplasias , Humanos , Macrófagos/metabolismo , Citocinas , Inflamação , Neoplasias/metabolismo , Nanopartículas Magnéticas de Óxido de Ferro , Microambiente Tumoral
11.
Avian Dis ; 67(1): 80-88, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37140115

RESUMO

Clostridial dermatitis (CD), caused by Clostridium septicum and Clostridium perfringens, is an economically important emerging disease of turkeys characterized by sudden deaths and necrotic dermatitis. Immune responses in CD-affected commercial turkeys are poorly understood. In the present study, C. septicum was isolated from CD-affected commercial turkeys during a recent outbreak, and the tissues (skin, muscle, and spleen) were collected and analyzed for immune gene expression, along with samples from clinically healthy birds. The results showed that CD-affected turkeys had significantly higher levels of IL-1ß, IL-6, IFNγ, and iNOS transcripts in the skin, muscle, and spleen tissues compared to healthy birds. Affected turkeys also had a significantly elevated transcription of toll-like receptor (TLR21) gene in the skin and spleen tissues, suggesting a role for this receptor in the immune recognition. The expression of IL-4 and IL-13 genes in the spleen and muscle was also significantly higher in the affected birds. Additional birds from the same affected and healthy farms examined for serology revealed that the CD-affected turkeys had significantly higher levels of serum IgM and IgY antibodies. Furthermore, in vitro stimulation of MQ-NCSU macrophages with C. septicum led to a significant transcriptional upregulation of IL-1ß and IFNγ genes, while the IL-10 gene expression was downregulated. The surface expression of MHC-II protein and cellular production of nitric oxide were also significantly increased in the C. septicum-stimulated macrophages, indicating cellular activation. Collectively, our findings suggest that the host responses in CD-affected turkeys involve a robust inflammatory response as well as a response mediated by IL4/IL-13 cytokines that may aid in antibody-mediated immunity.


Evaluación de la respuesta inmune en pavos comerciales afectados por dermatitis clostridial. La dermatitis clostridial (CD), causada por Clostridium septicum y Clostridium perfringens, es una enfermedad emergente económicamente importante de los pavos caracterizada por muerte súbitas y dermatitis necrótica. Se conoce poco acerca de las respuestas inmunitarias en pavos comerciales afectados por dermatitis clostridial. En el presente estudio, se aisló C. septicum de pavos comerciales afectados por dermatitis clostridial durante un brote reciente, y los tejidos (piel, músculo y bazo) se recolectaron y analizaron para determinar la expresión de genes inmunitarios junto con muestras de aves clínicamente sanas. Los resultados mostraron que los pavos afectados por dermatitis clostridial tenían niveles significativamente más altos de transcritos de IL-1ß, IL-6, IFNγ, and iNOS en los tejidos de la piel, los músculos y el bazo en comparación con las aves sanas. Los pavos afectados también tenían una transcripción significativamente elevada del gene del receptor tipo toll (TLR21) en los tejidos de la piel y el bazo, lo que sugiere un papel de este receptor en el reconocimiento inmunitario. La expresión de los genes IL-4 e IL-13 en el bazo y el músculo también fue significativamente mayor en las aves afectadas. Aves adicionales de las mismas granjas afectadas y sanas que fueron examinadas por serología revelaron que los pavos afectados por dermatitis clostridial tenían niveles significativamente más altos de anticuerpos séricos IgM e IgY. Además, la estimulación in vitro de los macrófagos MQ-NCSU con C. septicum condujo a una regulación transcripcional significativamente al alza de los genes IL-1ß and IFNγ, mientras que la expresión del gene IL-10 se reguló a la baja. La expresión superficial de la proteína MHC-II y la producción celular de óxido nítrico también aumentaron significativamente en los macrófagos estimulados por C. septicum, lo que indica activación celular. Colectivamente, estos hallazgos sugieren que las respuestas del huésped en pavos afectados por dermatitis clostridial implican una respuesta inflamatoria robusta, así como una respuesta mediada por citoquinas IL4/IL-13 que pueden ayudar en la inmunidad mediada por anticuerpos.


Assuntos
Infecções por Clostridium , Dermatite , Doenças das Aves Domésticas , Animais , Infecções por Clostridium/veterinária , Perus , Interleucina-13 , Doenças das Aves Domésticas/epidemiologia , Clostridium , Dermatite/veterinária , Imunidade
12.
J Clin Invest ; 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37140985

RESUMO

Neurofibromatosis Type 1 (NF1) is one of the most common tumor-predisposing genetic disorders. Neurofibromas are NF1-associated benign tumors. A hallmark feature of neurofibromas is an abundant collagen-rich extracellular matrix (ECM) that constitutes >50% of the tumor dry weight. However, little is known about the mechanism underlying ECM deposition during neurofibroma development and treatment response. We performed a systematic investigation of ECM enrichment during plexiform neurofibroma (pNF) development, and identified basement membrane (BM) proteins, rather than major collagen isoforms, as the most upregulated ECM component. Following MEK inhibitor treatment, the ECM profile displayed an overall down-regulation signature, suggesting ECM reduction as a therapeutic benefit of MEK inhibition. Through these proteomic studies, TGF-ß1 signaling was identified as playing a role in ECM dynamics. Indeed, TGF-ß1 overexpression promoted pNF progression in vivo. Furthermore, by integrating single-cell RNA-sequencing, we found that immune cells including macrophages and T cells produce TGF-ß1 to induce Schwann cells to produce and deposit BM proteins for ECM remodeling. Following Nf1 loss, neoplastic Schwann cells further increased BM protein deposition in response to TGF-ß1. Our data delineate the regulation governing ECM dynamics in pNF and suggest that BM proteins could serve as markers for disease diagnosis and treatment response.

13.
ACS Appl Bio Mater ; 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37145591

RESUMO

Atherosclerosis is one of the most urgent global health subjects, causes millions of deaths worldwide, and is associated with enormous healthcare costs. Macrophages are the root cause for inflammatory onset and progression of the disease but are not addressed by conventional therapy. Therefore, we used pioglitazone, which is a drug initially used for diabetes therapies, but at the same time has great potential regarding the mitigation of inflammation. As yet, this potential of pioglitazone cannot be exploited, as drug concentrations at the target site in vivo are not sufficient. To overcome this shortcoming, we established PEG-PLA/PLGA-based nanoparticles loaded with pioglitazone and tested them in vitro. Encapsulation of the drug was analyzed by HPLC and revealed an outstanding encapsulation efficiency of 59% into the nanoparticles, which were 85 nm in size and had a PDI of 0.17. Further, uptake of our loaded nanoparticles in THP-1 macrophages was comparable to the uptake of unloaded nanoparticles. On the mRNA level, pioglitazone-loaded nanoparticles were superior to the free drug by 32% in increasing the expression of the targeted receptor PPAR-γ. Thereby the inflammatory response in macrophages was ameliorated. In this study, we take the first step toward an anti-inflammatory, causal antiatherosclerotic therapy, using the potential of the already established drug pioglitazone, and enable it to enrich at the target site by using nanoparticles. An additional crucial feature of our nanoparticle platform is the versatile modifiability of ligands and ligand density, to achieve an optimal active targeting effect in the future.

14.
J Neuroinflammation ; 20(1): 104, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37138291

RESUMO

BACKGROUND: Increasing pre-clinical evidence suggests that aerobic exercise positively modulates neuroimmune responses following traumatic nerve injury. However, meta-analyses on neuroimmune outcomes are currently still lacking. This study aimed to synthesize the pre-clinical literature on the effects of aerobic exercise on neuroimmune responses following peripheral nerve injury. METHODS: MEDLINE (via Pubmed), EMBASE and Web of Science were searched. Controlled experimental studies on the effect of aerobic exercise on neuroimmune responses in animals with a traumatically induced peripheral neuropathy were considered. Study selection, risk of bias assessment and data extraction were performed independently by two reviewers. Results were analyzed using random effects models and reported as standardized mean differences. Outcome measures were reported per anatomical location and per class of neuro-immune substance. RESULTS: The literature search resulted in 14,590 records. Forty studies were included, reporting 139 comparisons of neuroimmune responses at various anatomical locations. All studies had an unclear risk of bias. Compared to non-exercised animals, meta-analyses showed the following main differences in exercised animals: (1) in the affected nerve, tumor necrosis factor-α (TNF-α) levels were lower (p = 0.003), while insulin-like growth factor-1 (IGF-1) (p < 0.001) and Growth Associated Protein 43 (GAP43) (p = 0.01) levels were higher; (2) At the dorsal root ganglia, brain-derived neurotrophic factor (BDNF)/BDNF mRNA levels (p = 0.004) and nerve growth factor (NGF)/NGF mRNA (p < 0.05) levels were lower; (3) in the spinal cord, BDNF levels (p = 0.006) were lower; at the dorsal horn, microglia (p < 0.001) and astrocyte (p = 0.005) marker levels were lower; at the ventral horn, astrocyte marker levels (p < 0.001) were higher, and several outcomes related to synaptic stripping were favorably altered; (4) brainstem 5-HT2A receptor levels were higher (p = 0.001); (5) in muscles, BDNF levels (p < 0.001) were higher and TNF-α levels lower (p < 0.05); (6) no significant differences were found for systemic neuroimmune responses in blood or serum. CONCLUSION: This review revealed widespread positive modulatory effects of aerobic exercise on neuroimmune responses following traumatic peripheral nerve injury. These changes are in line with a beneficial influence on pro-inflammatory processes and increased anti-inflammatory responses. Given the small sample sizes and the unclear risk of bias of the studies, results should be interpreted with caution.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Traumatismos dos Nervos Periféricos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator de Crescimento Neural/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Corno Dorsal da Medula Espinal/metabolismo , Exercício Físico , RNA Mensageiro/metabolismo
15.
Neuron ; 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37148871

RESUMO

Spinal cord injury (SCI) causes lifelong debilitating conditions. Previous works demonstrated the essential role of the immune system in recovery after SCI. Here, we explored the temporal changes of the response after SCI in young and aged mice in order to characterize multiple immune populations within the mammalian spinal cord. We revealed substantial infiltration of myeloid cells to the spinal cord in young animals, accompanied by changes in the activation state of microglia. In contrast, both processes were blunted in aged mice. Interestingly, we discovered the formation of meningeal lymphatic structures above the lesion site, and their role has not been examined after contusive injury. Our transcriptomic data predicted lymphangiogenic signaling between myeloid cells in the spinal cord and lymphatic endothelial cells (LECs) in the meninges after SCI. Together, our findings delineate how aging affects the immune response following SCI and highlight the participation of the spinal cord meninges in supporting vascular repair.

16.
Int Immunopharmacol ; 119: 110213, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37137266

RESUMO

P-Hydroxylcinnamaldehyde (CMSP) was firstly isolated from Chinese medicine Cochinchinnamomordica seed (CMS) by our team and has been verified to have growth-inhibiting abilities in malignant tumors including esophageal squamous cell carcinoma (ESCC). However, the detailed mechanism of its function is still unclear. Tumor-associated macrophages (TAMs) are an essential component of the tumor microenvironment (TME), playing important roles in tumor growth, metastasis, angiogenesis, and epithelial-mesenchymal transition (EMT). In the present study, we found that the percentage of M1-like macrophages was significantly increased in TME of ESCC cell derivedxenograft tumor model after CMSP treatment, while the ratios of other immune cells showed relatively low variation. To confirm these results, we further examined the effect of CMSP on macrophage polarization in vitro. The results revealed that CMSP also could induce phorbol-12-myristate-13-acetate (PMA)-induced M0 macrophages from THP-1 and mouse peritoneal macrophages toward the M1-like macrophages. Furthermore, CMSP could exert anti-tumor effect through TAMs in vitro co-culture model, in addition, the growth inhibition effect of CMSP was partly abolished in macrophage depletion model. To determine the potential pathway of CMSP induced polarization, we used quantitative proteomics (label-free) technology to explore the proteomic changes under CMSP treatment. The results revealed that immune-activating protein and M1 macrophage biomarkers were significantly increased after CMSP treatment. More importantly, CMSP stimulated pathways related to M1 macrophage polarization, such as the NF-κB signaling pathway and Toll-like receptor pathway, indicating that CMSP might induce M1-type macrophage polarization through these pathways. In conclusion, CMSP can regulate immune microenvironment in vivo and induce TAM polarization toward the M1 type by promoting proteomic changes, and exert anti-tumor effect through TAMs.

17.
Artigo em Russo | MEDLINE | ID: mdl-37141524

RESUMO

Laser therapy as a physiotherapeutic method has been successfully used for a long time in the treatment of various pathologies, but the action mechanisms of low level laser therapy (LLLT) remain understudied. OBJECTIVE: To perform the analysis of published results of LLLT investigations, to describe the physical principles of photobiomodulation, its action mechanisms on various cells and tissues, therapeutic intervention and efficiency of the technique. MATERIAL AND METHODS: The search of articles was done for the period from 2014 to 2022. The preference was given to the articles for the last 5 years in the PubMed database depending on keywords: low level laser therapy, photobiomodulation, exosomes, monocytes, macrophages. RESULTS AND DISCUSSION: This article represents the current conceptions about the action mechanisms and reproduced effects of low level laser therapy, the photobiomodulation influence on the inflammation and reparative processes in human body by intervention on cells and their signal pathways. The discussion of research results and probable causes of conflicting data are performed, as well as the efficacy assessment of laser irradiation in different conditions and diseases is made. CONCLUSION: Laser therapy has certain variety of advantages, among which: non-invasiveness and availability, long-term service of equipment, stable intensity of light radiation and the ability to use in various wavelength ranges. The technique efficacy was proven for a large number of diseases. However, for the successful application of photobiomodulation in clinical practice in current evidence-based medicine, additional investigations are necessary to determine the best dosimetric radiation parameters, as well as further study of action mechanisms on various human cells and tissues.


Assuntos
Terapia com Luz de Baixa Intensidade , Humanos , Terapia com Luz de Baixa Intensidade/métodos , Medicina Baseada em Evidências , Anti-Inflamatórios
18.
Biomark Res ; 11(1): 49, 2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37147740

RESUMO

Chimeric antigen receptor (CAR) T cell therapy, in which a patient's own T lymphocytes are engineered to recognize and kill cancer cells, has achieved striking success in some hematological malignancies in preclinical and clinical trials, resulting in six FDA-approved CAR-T products currently available in the market. Despite impressive clinical outcomes, concerns about treatment failure associated with low efficacy or high cytotoxicity of CAR-T cells remain. While the main focus has been on improving CAR-T cells, exploring alternative cellular sources for CAR generation has garnered growing interest. In the current review, we comprehensively evaluated other cell sources rather than conventional T cells for CAR generation.

19.
J Cancer Res Ther ; 19(Supplement): S300-S305, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37148007

RESUMO

Background: Tumor-associated macrophages (TAM) are the main component of inflammation along with leukocytes, endothelial cells and fibroblasts together form a tumor microenvironment, with immune cells representing its vital component. Many studies suggested that TAMs cumulating in tumors correlate with a poor prognosis. In prostate cancer, TAMs can increase cancer cell invasion by stimulating tumor angiogenesis, degrading the extracellular matrix, and also suppresses the antitumor functions of cytotoxic T cells resulting in poor prognosis. Aims and Objectives: : 1. To determine the expression of M1 (CD68) and M2 (CD163) in prostate carcinoma (Pca). 2. To find the association between M1, M2 macrophage with Gleason's score and stage of Pca. Materials and Methods: : This is a retrospective observational study. All transurethral resection prostatic (TURP) chips positive for Pca and the clinical details were collected. Radiologic findings with respect to stage of disease, size of lesion, were noted. Results: Among the 62 cases studied, majority of the cases were in-between the age of 61-70 years. Highest cases were seen in Gleason's score 8, 9, and 10 (62%), prostatic specific antigen (PSA) levels 20-80 ng/mL (64%), tumor size 3-6 cm (51.6%), T3 stage (40.3%), N1 lymph node stage (70.9%). M1 stage of (31%). CD68 and CD163 expression was analyzed with Gleason's score, TNM stage and PSA levels. CD68 score 3 correlated with low distant and nodal metastasis 6.2% and 6.8%, respectively. CD163 score 3 correlated with high metastasis to lymph nodes and distant metastasis of 86.3% and 25%, respectively. On further analysis, statistically convincing association between the CD163 expression and Gleason's score, PSA levels, nodal and distant metastasis was found. Conclusion: CD68 expression was correlated with good prognosis with less nodal and distant metastasis and Cd163 expression has poor outcome with increased chances of nodal and distant metastasis. Further exploration of TAM mechanisms and immune checkpoints in the prostate tumor microenvironment can furnish new light and motives for the treatment of Pca.


Assuntos
Carcinoma , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Antígeno Prostático Específico , Macrófagos Associados a Tumor/patologia , Próstata/patologia , Células Endoteliais , Neoplasias da Próstata/patologia , Prognóstico , Microambiente Tumoral
20.
Int Immunopharmacol ; 119: 110232, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37150017

RESUMO

Although the impact of Zika virus (ZIKV) infection on human health has been well documented, we still have no vaccine or effective treatment. This fact highlights the importance of searching for alternative therapy for treating ZIKV. To search for ZIKV antivirals, we examined the effect of vitamin D in monocyte-derived macrophages (MDMs) differentiated in the presence of vitamin D (D3-MDM) and explored the molecular mechanisms by analyzing transcriptional profiles. Our data show the restriction of ZIKV infection in D3-MDMs as compared to MDMs. Transcriptional profiles show that vitamin D alters about 19% of Zika response genes (8.2% diminished and 10.8% potentiated). Among the genes with diminished expression levels, we found proinflammatory cytokines and chemokines such as IL6, TNF, IL1A, IL1B, and IL12B, CCL1, CCL4, CCL7, CXCL3, CXCL6, and CXCL8. On the other hand, genes with potentiated expression were related to degranulation such as Lysozyme, cathelicidin (CAMP), and Serglycin. Since the CAMP gene encodes the antimicrobial peptide LL-37, we treated MDMs with LL-37 and infected them with ZIKV. The results showed a decrease in the proportion of infected cells. Our data provide new insights into the role of vitamin D in restricting ZIKV infection in macrophages that are mediated by induction of cathelicidin/LL-37 expression and downregulation of proinflammatory genes. Results highlight the biological relevance of vitamin D-inducible peptides as an antiviral treatment for Zika fever.

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