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1.
Drug Dev Res ; 85(2): e22166, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38424708

RESUMO

Hyperlipidemia is a common clinically encountered health condition worldwide that promotes the development and progression of cardiovascular diseases, including atherosclerosis. Berberine (BBR) is a natural product with acknowledged anti-inflammatory, antioxidant, and metabolic effects. This study evaluated the effect of BBR on lipid alterations, oxidative stress, and inflammatory response in rats with acute hyperlipidemia induced by poloxamer-407 (P-407). Rats were pretreated with BBR (25 and 50 mg/kg) for 14 days and acute hyperlipidemia was induced by a single dose of P-407 (500 mg/kg). BBR ameliorated hypercholesterolemia, hypertriglyceridemia, and plasma lipoproteins in P-407-adminsitered rats. Plasma lipoprotein lipase (LPL) activity was decreased, and hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was enhanced in hyperlipidemic rats. The expression of low-density lipoprotein receptor (LDL-R) and ATP-binding cassette transporter 1 (ABCA1) was downregulated in hyperlipidemic rats. BBR enhanced LPL activity, upregulated LDL-R, and ABCA1, and suppressed HMG-CoA reductase in P-407-administered rats. Pretreatment with BBR ameliorated lipid peroxidation, nitric oxide (NO), pro-inflammatory mediators (interleukin [IL]-6, IL-1ß, tumor necrosis factor [TNF]-α, interferon-γ, IL-4 and IL-18) and enhanced antioxidants. In addition, BBR suppressed lymphocyte ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase (E-ADA) as well as NO and TNF-α release by macrophages isolated from normal and hyperlipidemic rats. In silico investigations revealed the binding affinity of BBR toward LPL, HMG-CoA reductase, LDL-R, PSK9, ABCA1, and E-NTPDase. In conclusion, BBR effectively prevented acute hyperlipidemia and its associated inflammatory responses by modulating LPL, cholesterolgenesis, cytokine release, and lymphocyte E-NTPDase and E-ADA. Therefore, BBR is an effective and safe natural compound that might be employed as an adjuvant against hyperlipidemia and its associated inflammation.


Assuntos
Berberina , Hiperlipidemias , Ratos , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/patologia , Estresse Oxidativo , Interleucina-6/metabolismo , Antioxidantes/uso terapêutico , Linfócitos/metabolismo , Linfócitos/patologia , Fator de Necrose Tumoral alfa/metabolismo , Oxirredutases/metabolismo , Oxirredutases/farmacologia , Oxirredutases/uso terapêutico
2.
Sci Prog ; 107(1): 368504241231154, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425276

RESUMO

The underlying mechanisms for the beneficial effects exerted by bone marrow-mesenchymal stem cells (BM-MSCs) in treating repetitive traumatic brain injury (rTBI)-induced long-term sensorimotor/cognitive impairments are not fully elucidated. Herein, we aimed to explore whether BM-MSCs therapy protects against rTBI-induced long-term neurobehavioral disorders in rats via normalizing white matter integrity and gray matter microglial response. Rats were subjected to repeated mild lateral fluid percussion on day 0 and day 3. On the fourth day post-surgery, MSCs groups received MSCs (4 × 106 cells/ml/kg, intravenously) and were assessed by the radial maze, Y maze, passive avoidance tests, and modified neurological severity scores. Hematoxylin & eosin, and Luxol fast blue stainings were used to examine the histopathology and white matter thickness. At the same time, immunofluorescence staining was used to investigate the numbers of tumor necrosis factor-alpha (TNF-α)-containing microglia in gray matter. Three to nine months after neurotrauma, rats displayed sensorimotor and cognitive impairments, reduced thickness in white matter, and over-accumulation of TNF-α-containing microglia and cellular damage in gray matter. Therapy with BM-MSCs significantly attenuated the rTBI-induced sensorimotor and cognitive impairments and all their complications. Mesenchymal stem cell therapy might accelerate the recovery of sensorimotor and cognitive impairments in rats with rTBI via normalizing myelin integrity and microglia response.


Assuntos
Lesões Encefálicas Traumáticas , Disfunção Cognitiva , Células-Tronco Mesenquimais , Ratos , Animais , Bainha de Mielina , Microglia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologia , Lesões Encefálicas Traumáticas/terapia , Cognição
3.
Front Immunol ; 15: 1335602, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426108

RESUMO

Infection by an emerging bacterial pathogen Rahnella aquatilis caused enteritis and septicemia in fish. However, the molecular pathogenesis of enteritis induced by R. aquatilis infection and its interacting mechanism of the intestinal microflora associated with microRNA (miRNA) immune regulation in crucian carp Carassius auratus are still unclear. In this study, C. auratus intraperitoneally injected with R. aquatilis KCL-5 was used as an experimental animal model, and the intestinal pathological changes, microflora, and differentially expressed miRNAs (DEMs) were investigated by multi-omics analysis. The significant changes in histopathological features, apoptotic cells, and enzyme activities (e.g., lysozyme (LYS), alkaline phosphatase (AKP), alanine aminotransferase (ALT), aspartate transaminase (AST), and glutathione peroxidase (GSH-Px)) in the intestine were examined after infection. Diversity and composition analysis of the intestinal microflora clearly demonstrated four dominant bacteria: Proteobacteria, Fusobacteria, Bacteroidetes, and Firmicutes. A total of 87 DEMs were significantly screened, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the potential target genes were mainly involved in the regulation of lipid, glutathione, cytosine, and purine metabolism, which participated in the local immune response through the intestinal immune network for IgA production, lysosome, and Toll-like receptor (TLR) pathways. Moreover, the expression levels of 11 target genes (e.g., TLR3, MyD88, NF-κB, TGF-ß, TNF-α, MHC II, IL-22, LysC, F2, F5, and C3) related to inflammation and immunity were verified by qRT-PCR detection. The correlation analysis indicated that the abundance of intestinal Firmicutes and Proteobacteria was significantly associated with the high local expression of miR-203/NF-κB, miR-129/TNF-α, and miR-205/TGF-ß. These findings will help to elucidate the molecular regulation mechanism of the intestinal microflora, inflammation, and immune response-mediated miRNA-target gene axis in cyprinid fish.


Assuntos
Carpas , Enterite , Microbioma Gastrointestinal , MicroRNAs , Rahnella , Animais , Carpa Dourada/genética , Carpas/genética , Rahnella/genética , NF-kappa B , Multiômica , Fator de Necrose Tumoral alfa , Inflamação , Fator de Crescimento Transformador beta , MicroRNAs/genética
4.
Actas Esp Psiquiatr ; 52(1): 1-9, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38454896

RESUMO

BACKGROUND: Depression has become one of the most common mood disorders in adolescents, with an increasing incidence each year. Abnormal activation of peripheral immunity causes an increase in pro-inflammatory factors, which in turn affects neuroendocrine dysfunction and alters neurobiochemistry, leading to depression. In this study, we aimed to explore the relationship between inflammatory immune function and intestinal flora in adolescents with first-episode depression. METHODS: A total of 170 cases of adolescent patients with first-episode depression who attended our hospital from January 2020 to March 2023 were retrospectively selected as the observation group. Simultaneously, 170 individuals who underwent a healthy physical examination during the same period were chosen as the control group. The enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), substance P (SP), neuropeptide Y (NPY), serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 in the patients. Flow cytometry was utilized to assess the levels of T-lymphocytes CD3+, CD4+, and CD8+ cells. The levels of 16S ribosomal RNA (16SrRNA) method were used to determine the intestinal flora of the subjects in both groups. Inflammatory factor levels, immune function, and intestinal flora expression were observed, and correlation analysis was performed. RESULTS: The levels of 5-HT and NPY in the observation group were lower than those in the control group. The SP level was significantly higher in the observation group compared to the control group (p < 0.05). The observation group demonstrated significantly higher TNF-α, IL-1ß, and IL-6 levels than the control group (p < 0.05). The values of CD3+, CD4+, CD4+/CD8+ in the observation group were lower than those in the control group (p < 0.05), whereas the CD8+ values were notably higher (p < 0.05). Bifidobacterium, Escherichia coli, Lactobacillus, and Bacteroides in the observation group were less than those in the control group (p < 0.05). The content of Bifidobacterium was negatively correlated with the level of TNF-α (r = -0.358, p < 0.001), positively correlated with the level of CD3+, CD4+, CD4+/CD8+ (r = 0.490, 0.169, 0.165, p < 0.05), and negatively correlated with the level of CD8+ (r = -0.154, p < 0.05). The level of Escherichia coli content was negatively correlated with the levels of IL-6, CD3+, CD4+, CD4+/CD8+ (r = -0.483, -0.548, -0.317, -0.328, p < 0.001), and positively correlated with the levels of CD8+ (r = 0.325, p < 0.001). The content of Lactobacillus was positively correlated with the levels of CD3+, CD4+, CD4+/CD8+ (r = 0.552, 0.188, 0.194, p < 0.05), and negatively correlated with the level of CD8+ (r = -0.186, p < 0.05). The content of Bacteroides was positively correlated with the level of CD3+, CD4+, CD4+/CD8+ (r = -0.570, -0.183, -0.193, p < 0.05), and negatively correlated with the level of CD8+ levels were positively correlated (r = 0.187, p < 0.05). CONCLUSIONS: The intestinal flora is related to the level of inflammatory factors and immune function. Further study on the relationship between intestinal flora, inflammatory immune function, and depression could offer novel insights for the prevention and treatment of depressive disorders.


Assuntos
Microbioma Gastrointestinal , Fator de Necrose Tumoral alfa , Humanos , Adolescente , Interleucina-6 , Depressão , Estudos Retrospectivos , Serotonina , Escherichia coli , Imunidade
5.
Zhongguo Zhen Jiu ; 44(3): 261-265, 2024 Mar 12.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38467499

RESUMO

OBJECTIVES: To observe the clinical effect of the modified painless blistering moxibustion with wheat-grain sized moxa cone on cough variant asthma (CVA) differentiated as pathogenic wind attacking the lung and explore the influences on eosinophil count (EOS) in the peripheral blood and the content of interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α) in the serum of patients. METHODS: Ninety-two patients with CVA of pathogenic wind attacking the lung were randomly divided into an observation group and a control group, 46 cases in each group. In the observation group, the modified painless blistering moxibustion with wheat-grain sized moxa cone was applied to the unilateral Feishu (BL 13), Gaohuang (BL 43) and Zusanli (ST 36) in each session of treatment, once every 3 days. In the control group, budesonide and formoterol powder inhaler was delivered, 4.5 µg per inhalation, once every half an hour after breakfast and dinner; one more time of inhalation needed if the symptoms were not well controlled, but less than 6 times of inhalation per day. The duration of treatment was 8 weeks in both groups. Separately, before and after treatment, and during the 1-month follow-up after treatment completion, the score of the symptoms of traditional Chinese medicine (TCM) was observed in the two groups; using the lung function detector, the indexes of pulmonary function (forced expiratory volume in one second [FEV1], FEV1/forced vital capacity [FVC] and peak expiratory flow [PEF]) were determined, and the count of EOS in the peripheral blood and the content of IL-4 and TNF-α in the serum were determined before and after treatment; and the clinical effect was compared between the two groups. RESULTS: After treatment and in follow-up, the TCM symptom scores were decreased compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that of the control group in follow-up (P<0.05). After treatment, FEV1, FEV1/FVC and PEF were increased when compared with those before treatment in the two groups (P<0.05), and the count of EOS in the peripheral blood and the content of IL-4 and TNF-α in the serum were reduced (P<0.05); there was no statistical difference in these indexes between the two groups (P>0.05). After treatment, the total effective rate of the observation group was 95.7% (44/46), which was not different statistically in comparison with the control group (93.5% [43/46], P>0.05). In the follow-up, the total effective rate of the observation group was 95.7% (44/46), which was higher than that of the control group (78.3% [36/46], P<0.05). CONCLUSIONS: The modified painless blistering moxibustion with wheat-grain sized moxa cone may ameliorate the symptoms of CVA of pathogenic wind attacking the lung and improve the pulmonary functions, which is probably related to the regulation of the count of EOS in the peripheral blood and the content of IL-4 and TNF-α in the serum, thereby, reducing the inflammatory response.


Assuntos
Moxibustão , Humanos , Triticum , Interleucina-4 , Fator de Necrose Tumoral alfa , Vento , Pulmão
6.
Zhongguo Zhen Jiu ; 44(3): 295-302, 2024 Mar 12.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38467504

RESUMO

OBJECTIVES: To explore the effect and mechanism of acupuncture at "Feishu" (BL 13) and "Dingchuan" (EX-B 1), and "Kongzui" (LU 6) and "Yuji" (LU 10) for relaxing the airway smooth muscle in the rats during acute asthma attack and compare the effect among the two pairs of acupoints and the acupoints combination. METHODS: Forty SD male rats with SPF grade were randomly divided into a blank group, a model group, a pair-point A group (acupuncture at "Feishu" [BL 13] and "Dingchuan" [EX-B 1]), a pair-point B group (acupuncture at "Kongzui" [LU 6] and "Yuji" [LU 10]) and a point combination group (acupuncture at "Feishu" [BL 13] , "Dingchuan" [EX-B 1], "Kongzui" [LU 6] and "Yuji" [LU 10]), with 8 rats in each group. Except the rats in the blank group, the model of acute asthma attack was induced by ovalbumin (OVA) combined with aluminum hydroxide gel in the rest groups. Started on the 15th day of modeling, except in the blank group and the model group, acupuncture was delivered in the other groups, 30 min in each intervention, once daily, for 14 days. In each group, the latent period of asthma inducing was measured; the lung resistance (LR) and dynamic lung compliance (Cdyn) were determined using lung function detector; the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in serum and bronchoalveolar lavage fluid (BALF) were measured by ELISA; with Masson staining and electron microscopy adopted, the morphology and ultrastructure of airway smooth muscle of the rats were observed; the mRNA and protein expressions of ET-1 and beta-2 adrenergic receptor (ß2-AR) were detected by quantitative real-time fluorescence and Western blot, respectively. RESULTS: Compared with the blank group, the latent period of asthma inducing was shortened (P<0.05), RL increased and Cdyn decreased (P<0.05) with the different concentrations of methacholine (0.025 mg/kg, 0.05 mg/kg, 0.1 mg/kg, 0.2 mg/kg) in the model group. In the pair-point A group, the pair-point B group and the point combination group, the latent period of asthma inducing was prolonged (P<0.05), RL decreased and Cdyn increased (P<0.05) with different concentrations of methacholine when compared with those in the model group; and the latent period of asthma inducing in the point combination group was longer than that in the pair-point A group (P<0.05). Compared with the blank group, the levels of ET-1, TNF-α and cGMP in the serum and BALF were elevated (P<0.05), and those of cAMP reduced (P<0.05) in the model group. The levels of ET-1, TNF-α and cGMP in the serum and BALF were reduced (P<0.05), and those of cAMP elevated (P<0.05) in the pair-point A group, the pair-point B group and the point combination group when compared with those in the model group. In the blank group, the lung tissue was normal structurally. In the model group, the collagen fibers were proliferated increasingly, the smooth muscle was thickened, the mitochondria were swollen, and their cristae disrupted and reduced massively. In the pair-point B group, the collagen fibers were proliferated, the smooth muscle was thicker compared with that in the blank group, the mitochondria were mildly swollen and their cristae disrupted partially. In the pair-point A group and the point combination group, the lung tissue changes were obviously alleviated in comparison with the model group, the mitochondria were slightly swollen and their cristae disrupted occasionally. Compared with the blank group, the mRNA and protein expression of ET-1 increased and that of ß2-AR decreased in the lung tissue of the model group (P<0.05). In the pair-point A group, the pair-point B group and the point combination group, the mRNA and protein expression of ET-1 was reduced and that of ß2-AR elevated in the lung tissue when compared with those in the model group (P<0.05). In comparison with the pair-point A group, the mRNA expression of ß2-AR was elevated in the point combination group (P<0.05). When compared with the pair-point B group, the mRNA expression of ß2-AR increased, the protein expression of ET-1 decreased (P<0.05) in the point combination group. CONCLUSIONS: Acupuncture at "Feishu" (BL 13) and "Dingchuan" (EX-B 1), "Kongzui" (LU 6) and "Yuji" (LU 10), two pairs of acupoints relieves the airway smooth muscle spasm in the rats during acute asthma attack, which may be related to inhibiting the mRNA and protein expression of ET-1 to reduce the excretion of ET-1 and TNF-α; while enhancing the mRNA and protein expression of ß2-AR to balance the levels of cAMP and cGMP. The effect is optimal when acupuncture is delivered at two pairs of acupoints simultaneously.


Assuntos
Terapia por Acupuntura , Asma , Ratos , Masculino , Animais , Fator de Necrose Tumoral alfa/metabolismo , Cloreto de Metacolina/metabolismo , Asma/terapia , Asma/metabolismo , Pulmão , RNA Mensageiro/metabolismo , Colágeno/metabolismo
7.
Am J Reprod Immunol ; 91(3): e13833, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38467595

RESUMO

BACKGROUND: Endometritis is an inflammatory reaction of the lining of uterus, leading to the occurrence of infertility. Platelet rich plasma (PRP) has been proven to exhibit extremely effective for the treatment of endometrium-associated infertility, but the mechanism of its prevention for endometritis remains unclear. OBJECTIVE: The present study aimed to investigate the protective effect of PRP against endometritis induced by lipopolysaccharide (LPS) and elucidate the mechanism underlying these effects. METHODS: Mouse model of endometritis was established by intrauterine perfusion of LPS. PRP intrauterine infusion was administered at 24 h after LPS induction. After another 24 h, the uterine tissues were harvested to observe histopathological changes, production of proinflammatory cytokines, variation of the Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) signaling pathways, and validated the anti-inflammatory effect of PRP. The myeloperoxidase (MPO) activity and concentration of nitric oxide (NO) were determined using assay kit. Proinflammatory chemokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)) were measured by ELISA and Real-Time PCR. The activity of TLR4/NF-κB pathway in uterine tissues was measured by Western blotting. RESULTS: Hematoxylin-eosin staining (H&E) appeared that PRP remarkably relieved the impairment of uterine tissues. Detection of MPO activity and concentration of NO revealed that PRP treatment distinctly mitigated infiltration of inflammatory cells in mice with endometritis induced by LPS. PRP treatment significantly affected the expression of TNF-α, IL-1ß, and IL-6. PRP was also found to suppress LPS-induced activation of TLR4/NF-κB pathway. CONCLUSION: PRP effectively alleviates LPS-induced endometritis via restraining the signal pathway of TLR4/NF-κB. These findings provide a solid foundation for PRP as a potential therapeutic agent for endometritis.


Assuntos
Endometrite , Infertilidade , Plasma Rico em Plaquetas , Humanos , Feminino , Animais , Camundongos , NF-kappa B/metabolismo , Endometrite/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Interleucina-6 , Receptor 4 Toll-Like/metabolismo , Transdução de Sinais , Interleucina-1beta/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologia , Óxido Nítrico/uso terapêutico , Plasma Rico em Plaquetas/metabolismo
8.
Adv Exp Med Biol ; 1444: 129-143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467977

RESUMO

Necroptosis is a regulated form of cell death involved in the development of various pathological conditions. In contrast to apoptosis, plasma membrane rupture (PMR) occurs in cells in the relatively early stage of necroptosis; therefore, necroptosis induces a strong inflammatory response. Stimuli, including tumor necrosis factor (TNF), interferon (IFN)α/ß, lipopolysaccharide, polyI:C, and viral infection, induce the formation of necrosomes that lead to membrane rupture and the release of intracellular contents, termed danger-associated molecular patterns (DAMPs). DAMPs are the collective term for molecules that normally reside in the cytoplasm or nucleus in living cells without inducing inflammation but induce strong inflammatory responses when released outside cells. Recent studies have provided a better understanding of the mechanisms underlying PMR and the release of DAMPs. Moreover, necroptosis is involved in various pathological conditions, and mutations in necroptosis-related genes can cause hereditary autoinflammatory syndromes. Thus, manipulating necroptosis signaling pathways may be useful for treating diseases involving necroptosis.


Assuntos
Apoptose , Necroptose , Humanos , Necrose/metabolismo , Apoptose/fisiologia , Morte Celular , Fator de Necrose Tumoral alfa/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
9.
Ann Ital Chir ; 95(1): 22-29, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469616

RESUMO

BACKGROUND: Cancer-related fatigue (CRF) stands out as one of the most prevalent subjective adverse reactions experienced by patients following chemotherapy, often resulting in unfavorable symptoms for elderly non-small cell lung cancer (NSCLC) patients during chemotherapy. Hence, the aim of this study was to explore the fluctuations in CRF levels among elderly NSCLC patients undergoing chemotherapy. METHODS: This retrospective study involved 400 elderly patients diagnosed with NSCLC. Standardized guidelines were employed to direct patient care following lung cancer surgery (T0), subsequent to the first (T1), second (T2), third (T3), and fourth (T4) cycles of chemotherapy. At various intervals, all patients underwent assessments utilizing the Piper Fatigue Scale, Karnofsky Performance Status (KPS) Scale, Pittsburgh Sleep Quality Index (PSQI) Scale, and Connor-Davidson Resilience Scale. Additionally, serum levels of IL-6 and TNF-α were quantified using enzyme-linked immunosorbent assay (ELISA). RESULTS: Throughout the treatment regimen, patients exhibited a declining trend in CRF, CD-RISC, and KPS scores (p < 0.05, T0 vs T4), whereas the PSQI score demonstrated a notable increase (p < 0.05, T0 vs T4). Furthermore, ELISA results revealed that as treatment advanced, the average levels of inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor (TNF)-α during the T4 period significantly decreased compared to those at T0 (p < 0.05). CONCLUSION: As the number of chemotherapy treatments for elderly NSCLC patients increased, the severity of CRF and the manifestations of sleep disorders were escalated. Additionally, physical function, psychological resilience, as well as IL-6 and TNF-α levels, exhibited a downward trend.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Testes Psicológicos , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Interleucina-6 , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Estudos Longitudinais , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/uso terapêutico , Estudos Retrospectivos , Fadiga/induzido quimicamente , Resiliência Psicológica
10.
Ann Ital Chir ; 95(1): 42-48, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469613

RESUMO

BACKGROUND: Intrahepatic bile duct stones, a prevalent condition within hepato-biliary diseases, present a considerable challenge due to the high rates of recurrence, complications, and difficulty in treatment. Selecting an optimal surgical approach is vital for effective stone clearance and minimizing patient morbidity. While laparoscopic hepatectomy and percutaneous transhepatic choledochoscopy are established modalities, their comparative efficacy and safety profiles necessitate further investigation to inform clinical decision-making. OBJECTIVE: To explore the effectiveness and safety of different surgical methods for intrahepatic bile duct stones.  Methods: The clinical data of 65 patients with intrahepatic bile duct stones admitted to Nanchong Central Hospital, China, from January 2021 to January 2022 were retrospectively analyzed. According to the differences in surgical methods, patients undergoing laparoscopic hepatectomy were included in the laparoscopic group (n = 33), and patients undergoing percutaneous transhepatic choledochoscopy were included in the percutaneous transhepatic group (n = 32). The differences in perioperative indicators, inflammatory factors, postoperative complications, and one-year follow-up recurrence rates between the two groups were compared. RESULTS: Compared with percutaneous transhepatic group, laparoscopic group had significantly shorter operation time and hospitalization time (p < 0.05), and significantly higher blood loss (p < 0.05). After the operation, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the laparoscopic and percutaneous transhepatic groups were significantly lower than those in the same group before the operation (p < 0.05). CRP, TNF-α, and IL-6 in the laparoscopic group were significantly lower than in the percutaneous transhepatic group (p < 0.05). There was no significant difference in the incidence of postoperative complications and the recurrence rate of one-year follow-up between the laparoscopic group and the percutaneous transhepatic puncture group (p > 0.05). CONCLUSION: Laparoscopic hepatectomy and percutaneous transhepatic choledochoscopy are both practical and safe, and the appropriate surgical scheme should be selected according to the patient's specific condition.


Assuntos
Interleucina-6 , Fator de Necrose Tumoral alfa , Humanos , Estudos Retrospectivos , Ductos Biliares Intra-Hepáticos/cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
11.
Hum Exp Toxicol ; 43: 9603271241235408, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38472141

RESUMO

INTRODUCTION: Organophosphate pesticides (Ops) like diazinon (DZN) have well-known neurotoxic effects and low-level chronic exposure has been linked to detrimental neurobehavioral impairments and memory deficits. However, it's not entirely clear how DZN-induced biological changes, particularly in the prefrontal cortex (PFC) contribute to these effects. The purpose of this study is to investigate the impact of DZN exposure on inhibitory avoidance (IA) memory function, amyloid precursor expression (APP), and proinflammatory tumor necrosis factor-α (TNF-α) levels in the rat cortex. MATERIALS AND METHODS: Rats were divided into 4 groups and recived 2 mg/kg DZN for 5-days or 12-weeks and two control groups recived the same volume of vehicle. IA memory was assesed using the shuttle box apparatus. Rats were sacrificed and the prefrontal cortex PFC were removed. Real-time PCR and Western blotting were used to messure TNF-α, and amyloid protein precursors gene expression and protein levels. RESULTS: Our findings indicated that DZN caused body weight loss and a notable decline in performance on the IA memory. Additionally, 5-days exposure increased APP and APLP2 protein levels in the PFC, while 12-weeks exposure decreased these levels. Furthermore, expression of APP and APLP2 gens were decreased in PFC. TNF-α levels increased as a result of 5-days exposure to DZN, but these levels dropped to normal after 12-weeks administration, and this observation was significant. CONCLUSION: Taken together, exposure to low doses of DZN leads to disturbances in IA memory performance and also alternations in amyloid beta precursors that can be related to increased risk of Alzheimer's disease.


Assuntos
Diazinon , Inseticidas , Ratos , Animais , Diazinon/toxicidade , Fator de Necrose Tumoral alfa , Peptídeos beta-Amiloides , Estresse Oxidativo , Inseticidas/toxicidade , Córtex Pré-Frontal
12.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(1): 37-45, 2024 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38475949

RESUMO

OBJECTIVES: This study aimed to investigate the effects of sitagliptin on the proliferation, apoptosis, inflammation, and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in lipopolysaccharide (LPS)-induced inflammatory microenvironment and its molecular mechanism. METHODS: hPDLSCs were cultured in vitro and treated with different concentrations of sitagliptin to detect cell viability and subsequently determine the experimental concentration of sitagliptin. An hPDLSCs inflammation model was established after 24 h of stimulation with 1 µg/mL LPS and divided into blank, control, low-concentration sitagliptin (0.5 µmol/L), medium-concentration sitagliptin (1 µmol/L), and high-concentration sitagliptin (2 µmol/L), high-concentrationsitagliptin+stromal cell derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) pathway inhibitor (AMD3100) (2 µmol/L+10 µg/mL) groups. A cell-counting kit-8 was used to detect the proliferation activity of hPDLSCs after 24, 48, and 72 h culture. The apoptosis of hPDLSCs cultured for 72 h was detected by flow cytometry. After inducing osteogenic differentiation for 21 days, alizarin red staining was used to detect the osteogenic differentiation ability of hPDLSCs. The alkaline phosphatase (ALP) activity in hPDLSCs was determined using a kit. The levels of inflammatory factors [tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6] in the supernatant of hPDLSCs culture were detected by enzyme-linked immunosorbent assay. The mRNA expressions of osteogenic differentiation genes [Runt-associated transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN)], SDF-1 and CXCR4 in hPDLSCs were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Western blot analysis was used to determine SDF-1 and CXCR4 protein expression in hPDLSCs. RESULTS: Compared with the blank group, the proliferative activity, number of mineralized nodules, staining intensity, ALP activity, and RUNX2, OCN, OPN mRNA, SDF-1, and CXCR4 mRNA and protein expression levels of hPDLSCs in the control group significantly decreased. The apoptosis rate and levels of TNF-α, IL-1ß, and IL-6 significantly increased (P<0.05). Compared with the control group, the proliferative activity, number of mineralized nodule, staining intensity, ALP activity, and RUNX2, OCN, OPN mRNA, SDF-1, and CXCR4 mRNA and protein expression levels of hPDLSCs in low-, medium-, and high-concentration sitagliptin groups increased. The apoptosis rate and levels of TNF-α, IL-1ß, and IL-6 decreased (P<0.05). AMD3100 partially reversed the effect of high-concentration sitagliptin on LPS-induced hPDLSCs (P<0.05). CONCLUSIONS: Sitagliptin may promote the proliferation and osteogenic differentiation of hPDLSCs in LPS-induced inflammatory microenvironment by activating the SDF-1/CXCR4 signaling pathway. Furthermore, it inhibited the apoptosis and inflammatory response of hPDLSCs.


Assuntos
Benzilaminas , Ciclamos , Lipopolissacarídeos , Ligamento Periodontal , Humanos , Ligamento Periodontal/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Receptores CXCR4/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Osteogênese , Transdução de Sinais , Inflamação/metabolismo , Células-Tronco , RNA Mensageiro/metabolismo , Apoptose , Proliferação de Células , Células Estromais/metabolismo , Diferenciação Celular , Células Cultivadas
13.
Gynecol Endocrinol ; 40(1): 2325000, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38477938

RESUMO

OBJECTIVE: To investigate the target and mechanism of action of Bushen Huoxue Recipe (BSHX) for the treatment of infertility in polycystic ovary syndrome (PCOS), to provide a basis for the development and clinical application of herbal compounds. METHODS: Prediction and validation of active ingredients and targets of BSHX for the treatment of PCOS by using network pharmacology-molecular docking technology. In an animal experiment, the rats were randomly divided into four groups (control group, model group, BSHX group, metformin group, n = 16 in each group), and letrozole combined with high-fat emulsion gavage was used to establish a PCOS rat model. Body weight, vaginal smears, and number of embryos were recorded for each group of rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of ovarian and endometrial tissues, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the serum inflammatory factor levels. Expression levels of transforming growth factor-ß (TGF-ß), transforming growth factor beta activated kinase 1 (TAK1), nuclear factor kappa-B (NF-κB), Vimentin, and E-cadherin proteins were measured by western blot (WB). RESULTS: Ninety active pharmaceutical ingredients were obtained from BSHX, involving 201 protein targets, of which 160 were potential therapeutic targets. The active ingredients of BSHX exhibited lower binding energy with tumor necrosis factor-α (TNF-α), TGF-ß, TAK1, and NF-κB protein receptors (< -5.0 kcal/mol). BSHX significantly reduced serum TNF-α levels in PCOS rats (p < .01), effectively regulated the estrous cycle, restored the pathological changes in the ovary and endometrium, improved the pregnancy rate, and increased the number of embryos. The results of WB suggested that BSHX can down-regulate protein expression levels of TGF-ß and NF-κB in endometrial tissue (p < .05), promote the expression level of E-cadherin protein (p < .001), intervene in the endometrial epithelial-mesenchymal transition (EMT) process. CONCLUSIONS: TGF-ß, TAK1, NF-κB, and TNF-α are important targets of BSHX for treating infertility in PCOS. BSHX improves the inflammatory state of PCOS, intervenes in the endometrial EMT process through the TGF-ß/NF-κB pathway, and restores endometrial pathological changes, further improving the pregnancy outcome in PCOS.


Assuntos
Medicamentos de Ervas Chinesas , Infertilidade , Síndrome do Ovário Policístico , Feminino , Humanos , Animais , Gravidez , Ratos , NF-kappa B , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa , Fatores de Transcrição , Caderinas , Endométrio , Transição Epitelial-Mesenquimal , Fator de Crescimento Transformador beta , Fatores de Crescimento Transformadores
14.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473703

RESUMO

Multiple sclerosis (MS) is the most common autoimmune demyelinating disease of the central nervous system (CNS), consisting of heterogeneous clinical courses varying from relapsing-remitting MS (RRMS), in which disability is linked to bouts of inflammation, to progressive disease such as primary progressive MS (PPMS) and secondary progressive MS (SPMS), in which neurological disability is thought to be linked to neurodegeneration. As a result, successful therapeutics for progressive MS likely need to have both anti-inflammatory and direct neuroprotective properties. The modulation of sphingosine-1-phosphate (S1P) receptors has been implicated in neuroprotection in preclinical animal models. Siponimod/BAF312, the first oral treatment approved for SPMS, may have direct neuroprotective benefits mediated by its activity as a selective (S1P receptor 1) S1P1 and (S1P receptor 5) S1P5 modulator. We showed that S1P1 was mainly present in cortical neurons in lesioned areas of the MS brain. To gain a better understanding of the neuroprotective effects of siponimod in MS, we used both rat neurons and human-induced pluripotent stem cell (iPSC)-derived neurons treated with the neuroinflammatory cytokine tumor necrosis factor-alpha (TNF-α). Cell survival/apoptotic assays using flow cytometry and IncuCyte live cell analyses showed that siponimod decreased TNF-α induced neuronal cell apoptosis in both rat and human iPSCs. Importantly, a transcriptomic analysis revealed that mitochondrial oxidative phosphorylation, NFκB and cytokine signaling pathways contributed to siponimod's neuroprotective effects. Our data suggest that the neuroprotection of siponimod/BAF312 likely involves the relief of oxidative stress in neuronal cells. Further studies are needed to explore the molecular mechanisms of such interactions to determine the relationship between mitochondrial dysfunction and neuroinflammation/neurodegeneration.


Assuntos
Azetidinas , Compostos de Benzil , Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Fármacos Neuroprotetores , Humanos , Animais , Ratos , Receptores de Esfingosina-1-Fosfato , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Fator de Necrose Tumoral alfa/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Morte Celular
15.
BMC Cardiovasc Disord ; 24(1): 153, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481148

RESUMO

BACKGROUND: The current study was conducted aimed atexploring the effects of staged rehabilitation training on the levels of inflammatory factors and red blood cell distribution in patients who underwent cardiac valve replacement. METHODS: A total of 140 patients who underwent cardiac valve replacement at The First Hospital of Hebei Medical University between April 2021 and November 2022 were included in this study. During the postoperative rehabilitation phase, the patients were randomly assigned to either the control group or the experimental group. The experimental group received staged rehabilitation training (n = 70), while the control group received conventional care and rehabilitation suggestions without specialized staged rehabilitation training (n = 70). Informed consent was obtained from all patients prior to theirinclusion in the study. Clinical data of the patients were collected andanalyzed. RDW was measured using an automated blood cell analyzer on postoperative day 1, 14, and 28. Levels ofTNF-α, IL-6 and CRP were measured using ELISA. Quality of life was evaluated usingthe WHOQOL-BREF questionnaire. The effects of postoperative rehabilitation were assessed using the 6MWD test. The occurrence of adverse events in the postoperative periodwas alsoanalyzed. RESULTS: There were no significant differences in the general characteristics of the two groups of patients (P > 0.05). On the first day after surgery, no significant differences were seen in RDW between the two groups (P > 0.05). However, on the 14th and 28th day after surgery, the experimental group exhibited a significant reduction in RDW compared to the control group (P < 0.05). On the first day after surgery, the levels of serum TNF-α, IL-6 and CRP were comparable between the two groups (P > 0.05). However, on the 14th and the 28th after surgery, the experimental group showed evidently lower levels of TNF-α, IL-6 and CRP compared to the control group (P < 0.05). The experimental group demonstrated higher scores in the domains of physical health, psychological state, social relationships, and environment in the WHOQOL-BREF questionnaire compared to the control group (P < 0.05). Furthermore, the experimental group exhibited increased average,minimum,maximum walking distances in the6-minute walking test compared to the control group (P < 0.05). There were no significant differences in the incidence of postoperative adverse events between the two groups of patients (P > 0.05). CONCLUSION: Staged rehabilitation training exerteda positive effect on the levels of inflammatory factors and red blood cell distribution in patients following cardiac valve replacement. This type of rehabilitation training facilitated the patient's recovery process by reducing the inflammatory response and improving the condition of red blood cells. Additionally, it enhanced the quality of life and rehabilitation outcomes for patients.


Assuntos
Qualidade de Vida , Fator de Necrose Tumoral alfa , Humanos , Interleucina-6 , Índices de Eritrócitos , Eritrócitos
16.
Arthritis Res Ther ; 26(1): 68, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38481302

RESUMO

OBJECTIVE: To investigate the clinical phenotype and treatment response in patients with rheumatoid arthritis (RA) with and without concomitant Sjögren's disease (SjD). METHODS: In this observational cohort study, patients with RA from the Swiss Clinical Quality Management in Rheumatic Diseases registry were categorised according to the presence or absence of SjD. To assess treatment effectiveness, drug retention of tumor necrosis factor-α-inhibitors (TNFi) was compared to other mode of action (OMA) biologics and Janus kinase-inhibitors (JAKi) in RA patients with and without SjD. Adjusted hazard ratios (HR) for time to drug discontinuation were compared in crude and adjusted Cox proportional regression models for potential confounders. RESULTS: We identified 5974 patients without and 337 patients with concomitant SjD. Patients with SjD were more likely to be female, to have a positive rheumatoid factor, higher disease activity scores, and erosive bone damage. For treatment response, a total of 6781 treatment courses were analysed. After one year, patients with concomitant SjD were less likely to reach DAS28 remission with all three treatment modalities. Patients with concomitant SjD had a higher hazard for stopping TNFi treatment (adjusted HR 1.3 [95% CI 1.07-1.6]; OMA HR 1.12 [0.91-1.37]; JAKi HR 0.97 [0.62-1.53]). When compared to TNFi, patients with concomitant SjD had a significantly lower hazard for stopping treatment with OMA (adjusted HR 0.62 [95% CI 0.46-0.84]) and JAKi (HR 0.52 [0.28-0.96]). CONCLUSION: RA patients with concomitant SjD reveal a severe RA phenotype, are less responsive to treatment, and more likely to fail TNFi.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Feminino , Masculino , Antirreumáticos/uso terapêutico , Suíça/epidemiologia , Fator de Necrose Tumoral alfa , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Resultado do Tratamento , Biomarcadores
17.
Oncoimmunology ; 13(1): 2326694, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481728

RESUMO

Pancreatic cancer is characterized by extreme therapeutic resistance. In pancreatic cancers harboring high-risk genomes, we describe that cancer cell-neutrophil signaling circuitry provokes neutrophil-derived transmembrane (tm)TNF-TNFR2 interactions that dictate inflammatory polarization in cancer-associated fibroblasts and T-cell dysfunction - two hallmarks of therapeutic resistance. Targeting tmTNF-TNFR2 signaling may sensitize pancreatic cancer to chemo±immunotherapy.


Assuntos
Neoplasias Pancreáticas , Receptores Tipo II do Fator de Necrose Tumoral , Humanos , Receptores Tipo II do Fator de Necrose Tumoral/genética , Fator de Necrose Tumoral alfa , Transdução de Sinais
18.
Arch Virol ; 169(4): 74, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480558

RESUMO

Triple motif protein 21 (TRIM21) has an antiviral function that inhibits various viral infections. However, its role in the progress of influenza A virus (IAV) infection is unclear. In this study, we investigated the role and molecular mechanism of TRIM21 in IAV infection. RT-qPCR was used to determine the level of TRIM21 mRNA, and ELISA was used to measure the levels of IFN-α, IFN-ß, IL-6, and TNF-α. The levels of the TRIM21, NP, TBK1, IRF3, p-TBK1, and p-IRF3 proteins were estimated by Western blot. The results showed that, after IAV infection, TRIM21 was upregulated in clinical patient serum and A549 cells, and this was correlated with the IFN response. Overexpression of TRIM21 reduced IAV replication and transcription in in vitro cell experiments. TRIM21 also increased IFN-α and IFN-ß levels and decreased IL-6 and TNF-α levels in A549 cells. In addition, overexpression of TRIM21 inhibited IAV-induced apoptosis. Further experiments demonstrated that TBK1-IRF3 signaling was activated by TRIM21 and was involved in the inhibitory effect of TRIM21 on virus replication. In summary, our study suggests that TRIM21 inhibits viral replication by activating the TBK1-IRF3 signaling pathway, further inhibiting the infection process of IAV.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Influenza Humana , Humanos , Células A549 , Inflamação , Vírus da Influenza A/metabolismo , Vírus da Influenza A Subtipo H1N1/metabolismo , Influenza Humana/genética , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Interferon-alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo
19.
CNS Neurosci Ther ; 30(3): e14666, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38468126

RESUMO

AIM: To explore the neuroprotective potential of hyperforin and elucidate its underlying molecular mechanisms involved in its therapeutic effects against vascular cognitive impairment (VCI). METHODS: The active compounds and possible targets of Hypericum perforatum L. that may be effective against VCI were found by network pharmacology in this research. We utilized bilateral common carotid artery occlusion (BCCAO) surgery to induce a VCI mouse model. Morris water maze (MWM) and Y-maze tests were used to assess VCI mice's cognitive abilities following treatment with hyperforin. To evaluate white matter lesions (WMLs), we utilized Luxol fast blue (LFB) stain and immunofluorescence (IF). Neuroinflammation was assessed using IF, western blot (WB), and enzyme-linked immunosorbent assay (ELISA). The effects of hyperforin on microglia were investigated by subjecting the BV2 microglial cell line to oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The expressions of VEGFR2 , p-SRC, SRC, VEGFA, and inflammatory markers including IL-10, IL-1ß, TNF-α, and IL-6 were subsequently assessed. RESULTS: The VEGFR2 /SRC signaling pathway is essential for mediating the protective properties of hyperforin against VCI according to network pharmacology analysis. In vivo findings demonstrated that hyperforin effectively improved BCCAO-induced cognitive impairment. Furthermore, staining results showed that hyperforin attenuated WMLs and reduced microglial activation in VCI mice. The hyperforin treatment group's ELISA results revealed a substantial decrease in IL-1ß, IL-6, and TNF-α levels. According to the results of in vitro experiments, hyperforin decreased the release of pro-inflammatory mediators (TNF-α, IL-6, and IL-1ß) and blocked microglial M1-polarization by modulating the VEGFR2 /SRC signaling pathway. CONCLUSION: Hyperforin effectively modulated microglial M1 polarization and neuroinflammation by inhibiting the VEGFR2 /SRC signaling pathways, thereby ameliorating WMLs and cognitive impairment in VCI mice.


Assuntos
Disfunção Cognitiva , Floroglucinol/análogos & derivados , Terpenos , Substância Branca , Camundongos , Animais , Microglia , Doenças Neuroinflamatórias , Fator de Necrose Tumoral alfa/metabolismo , Substância Branca/metabolismo , Interleucina-6/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo
20.
Genome Biol ; 25(1): 68, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468286

RESUMO

BACKGROUND: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. RESULTS: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.


Assuntos
Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Membrana Sinovial , Linfócitos B , Fator de Necrose Tumoral alfa , Fenótipo
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