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1.
Proc Natl Acad Sci U S A ; 121(28): e2402872121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38968126

RESUMO

Bioengineering of plant immune receptors has emerged as a key strategy for generating novel disease resistance traits to counteract the expanding threat of plant pathogens to global food security. However, current approaches are limited by rapid evolution of plant pathogens in the field and may lack durability when deployed. Here, we show that the rice nucleotide-binding, leucine-rich repeat (NLR) immune receptor Pik-1 can be engineered to respond to a conserved family of effectors from the multihost blast fungus pathogen Magnaporthe oryzae. We switched the effector binding and response profile of the Pik NLR from its cognate rice blast effector AVR-Pik to the host-determining factor pathogenicity toward weeping lovegrass 2 (Pwl2) by installing a putative host target, OsHIPP43, in place of the native integrated heavy metal-associated domain (generating Pikm-1OsHIPP43). This chimeric receptor also responded to other PWL alleles from diverse blast isolates. The crystal structure of the Pwl2/OsHIPP43 complex revealed a multifaceted, robust interface that cannot be easily disrupted by mutagenesis, and may therefore provide durable, broad resistance to blast isolates carrying PWL effectors in the field. Our findings highlight how the host targets of pathogen effectors can be used to bioengineer recognition specificities that have more robust properties compared to naturally evolved disease resistance genes.


Assuntos
Proteínas Fúngicas , Proteínas NLR , Oryza , Doenças das Plantas , Proteínas de Plantas , Oryza/microbiologia , Oryza/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Proteínas NLR/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/imunologia , Proteínas de Plantas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/imunologia , Interações Hospedeiro-Patógeno/imunologia , Resistência à Doença/imunologia , Imunidade Vegetal , Bioengenharia/métodos , Magnaporthe/imunologia , Magnaporthe/genética , Magnaporthe/metabolismo , Ligação Proteica , Receptores Imunológicos/metabolismo , Ascomicetos
2.
EMBO J ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020150

RESUMO

Plant intracellular nucleotide-binding and leucine-rich repeat immune receptors (NLRs) play a key role in activating a strong pathogen defense response. Plant NLR proteins are tightly regulated and accumulate at very low levels in the absence of pathogen effectors. However, little is known about how this low level of NLR proteins is able to induce robust immune responses upon recognition of pathogen effectors. Here, we report that, in the absence of effector, the inactive form of the tomato NLR Sw-5b is targeted for ubiquitination by the E3 ligase SBP1. Interaction of SBP1 with Sw-5b via only its N-terminal domain leads to slow turnover. In contrast, in its auto-active state, Sw-5b is rapidly turned over as SBP1 is upregulated and interacts with both its N-terminal and NB-LRR domains. During infection with the tomato spotted wilt virus, the viral effector NSm interacts with Sw-5b and disrupts the interaction of Sw-5b with SBP1, thereby stabilizing the active Sw-5b and allowing it to induce a robust immune response.

3.
Cureus ; 16(6): e62503, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39022525

RESUMO

Introduction Age-related macular degeneration, a chronic and progressive disease, is one of the leading causes of vision loss globally among the elderly population. Multiple hypotheses have been proposed regarding its pathogenesis, including the presence of lipid metabolism alteration. Dysfunctional lipid handling within retinal pigment epithelial cells has been implicated in the accumulation of lipofuscin and subsequent induction of oxidative stress and inflammation, all contributing to retinal degeneration. The present study aims to comparatively analyze the serum lipid fraction distributions in patients with neovascular age-related macular degeneration (AMD) and controls. Materials and methods A retrospective study was carried out between January 2021 and December 2023 on 91 naïve patients with neovascular AMD and 90 controls admitted for routine cataract surgery. All subjects underwent a comprehensive ophthalmological exam, including ophthalmoscopy and optical coherence tomography (OCT) with central macular thickness (CMT) measurement. A complete blood count with differential and lipid fractions values was analyzed. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were comparatively analyzed between the control group and the test group. Results The groups were comparable in terms of age (73.84 ±7.52 years for the neovascular AMD group vs 72.1±10.92 years in controls; p=0.8) and gender distribution (p=0.243). The mean NLR and PLR values were slightly higher in the AMD group but not statistically significant (p=0.51, p>0.99, respectively). Comparative analysis of lipid profile fractions showed significantly higher HDL-C values in the exudative AMD group compared to normal subjects (61.27±19.4 mg/dL vs 50.99±7.86 mg/dL, p=0.006). Also, the proportion of subjects with HDL-C>60 mg/dL was higher in the exudative AMD group (p=0.014). There were no significant differences in total cholesterol (189.77±53.39 mg/dL vs 190.43±37.84 mg/dL, p=0.681), LDL-C, and TG. Logistic regression analysis showed that serum HDL-C and HDL-C values >60 mg/dL are significantly associated factors with neovascular AMD. However, there is no statistical correlation between the values of these biochemical parameters and visual acuity or CMT in the neovascular AMD patient group. Conclusions There were no correlations between NLR and PLR with neovascular AMD in the study group. Higher HDL-C values exceeding 60 mg/dL were associated with neovascular age-related macular degeneration and could represent a possible therapeutic target in neovascular AMD.

4.
Bio Protoc ; 14(13): e5023, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39007158

RESUMO

In recent years, the increase in genome sequencing across diverse plant species has provided a significant advantage for phylogenomics studies, allowing the analysis of one of the most diverse gene families in plants: nucleotide-binding leucine-rich repeat receptors (NLRs). However, due to the sequence diversity of the NLR gene family, identifying key molecular features and functionally conserved sequence patterns is challenging through multiple sequence alignment. Here, we present a step-by-step protocol for a computational pipeline designed to identify evolutionarily conserved motifs in plant NLR proteins. In this protocol, we use a large-scale NLR dataset, including 1,862 NLR genes annotated from monocot and dicot species, to predict conserved sequence motifs, such as the MADA and EDVID motifs, within the coiled-coil (CC)-NLR subfamily. Our pipeline can be applied to identify molecular signatures that have remained conserved in the gene family over evolutionary time across plant species. Key features • Phylogenomics analysis of plant NLR immune receptor family. • Identification of functionally conserved sequence patterns among plant NLRs.

6.
Am J Cancer Res ; 14(6): 3130-3141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005676

RESUMO

To investigate the dynamics of inflammation and lipid-related indicators in lung cancer patients and their impact on treatment efficacy. A retrospective analysis was conducted on 133 lung cancer patients who seek for primary treatment at Wujin Hospital Affiliated to Jiangsu University from January 2019 to August 2022. The inflammation and blood lipid-related indicators were collected 1 week before treatment and after 2 cycles of treatment. We compared the changes in these indicators among patients with different treatment methods and outcomes. The diagnostic value of the dynamic changes in each index for disease progression was calculated using the ROC curve. The risk factors influencing disease development were identified using multifactorial logistic regression analysis. After 2 cycles of treatment, the white blood cell count (WBC, P<0.001), neutrophil count (NC, P<0.001), neutrophil-to-lymphocyte ratio (NLR, P<0.001) in the disease progression (PD) group were significantly increased, triglyceride (TG, P=0.023), apolipoprotein A1 (APO-A1, P=0.009) was significantly decreased. The results showed that ∆NC had the highest sensitivity (88.24%) in predicting disease progression, and ∆WBC had the best specificity (77.78%). Multivariate regression analysis showed that ΔWBC (P<0.001), ΔTG (P=0.041), and treatment method (P=0.010) were independent risk factors for disease progression (PD). The changes of WBC and TG before and after treatment are promising indicators for predicting the progression of lung cancer and may offer a new direction for lung cancer treatment.

7.
Cureus ; 16(6): e62360, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39006695

RESUMO

INTRODUCTION: Biomarkers like white blood cells, C-reactive protein, procalcitonin, and interleukin-1 are used in patients with sepsis for early diagnosis, differentiating various infections, making decisions to start antibiotics and evaluate their response, and to prognosticate morbidity and mortality. Despite the availability of these biomarkers, the prognosis of patients with sepsis in the ICU remains poor. Hence, this study was carried out to test the efficacy of procalcitonin and neutrophil-to-lymphocyte ratio (NLR) to prognosticate mortality and morbidity in terms of incidence of organ dysfunction and length of ICU stay in sepsis patients. METHODS: In this prospective observational study, we measured NLR and procalcitonin at days one, three, and seven of sepsis patients and divided them into four groups: low NLR and high procalcitonin (LNHP), high NLR and high procalcitonin (HNHP), high NLR and low procalcitonin (HNLP), and low NLR and low procalcitonin (LNLP). Mortality at 28 days was noted as the primary outcome. RESULTS: Out of 85 patients included in the study, five were lost to follow-up. Although no statistically significant difference was found in the primary outcome between all four groups, regression analysis showed that rising NLR and procalcitonin values were associated with a significant increase in mortality. CONCLUSION: Serial values of NLR and procalcitonin are more important in predicting severity in comparison to a single value at presentation and can be used as a prognostic marker in sepsis patients.

8.
Sci Rep ; 14(1): 15075, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956445

RESUMO

Sepsis is a severe disease characterized by high mortality rates. Our aim was to develop an early prognostic indicator of adverse outcomes in sepsis, utilizing easily accessible routine blood tests. A retrospective analysis of sepsis patients from the MIMIC-IV database was conducted. We performed univariate and multivariate regression analyses to identify independent risk factors associated with in-hospital mortality within 28 days. Logistic regression was utilized to combine the neutrophil-to-lymphocyte ratio (NLR) and the neutrophil-to-platelet ratio (NPR) into a composite score, denoted as NLR_NPR. We used ROC curves to compare the prognostic performance of the models and Kaplan-Meier survival curves to assess the 28 day survival rate. Subgroup analysis was performed to evaluate the applicability of NLR_NPR in different subpopulations based on specific characteristics. This study included a total of 1263 sepsis patients, of whom 179 died within 28 days of hospitalization, while 1084 survived beyond 28 days. Multivariate regression analysis identified age, respiratory rate, neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelet ratio (NPR), hypertension, and sequential organ failure assessment (SOFA) score as independent risk factors for 28 day mortality in septic patients (P < 0.05). Additionally, in the prediction model based on blood cell-related parameters, the combined NLR_NPR score exhibited the highest predictive value for 28 day mortality (AUC = 0.6666), followed by NLR (AUC = 0.6456) and NPR (AUC = 0.6284). Importantly, the performance of the NLR_NPR score was superior to that of the commonly used SOFA score (AUC = 0.5613). Subgroup analysis showed that NLR_NPR remained an independent risk factor for 28 day in-hospital mortality in the subgroups of age, respiratory rate, and SOFA, although not in the hypertension subgroup. The combined use of NLR and NPR from routine blood tests represents a readily available and reliable predictive marker for 28 day mortality in sepsis patients. These results imply that clinicians should prioritize patients with higher NLR_NPR scores for closer monitoring to reduce mortality rates.


Assuntos
Plaquetas , Mortalidade Hospitalar , Linfócitos , Neutrófilos , Sepse , Humanos , Sepse/sangue , Sepse/mortalidade , Sepse/diagnóstico , Masculino , Feminino , Prognóstico , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Plaquetas/patologia , Curva ROC , Fatores de Risco , Contagem de Plaquetas , Contagem de Linfócitos , Idoso de 80 Anos ou mais
9.
Ann Burns Fire Disasters ; 37(2): 124-129, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38974789

RESUMO

The aim of this study was to evaluate the characteristics and prognostic value of the neutrophil/lymphocyte ratio (NLR) in patients with severe burns. A retrospective study was conducted on 245 burn patients over 18 years old without comorbidity or combined injury, burn extent ≥20% TBSA, hospitalized within 24 hours after burn. The collected criteria included patient characteristics, NLR on admission, 3rd and 7th day after burn, and outcome. The results showed that NLR was higher than the normal value at all collected times. In addition, compared to the survivor group, NLR on admission, 3rd and 7th day after burn was significantly higher in the mortality group (p <.01). Multivariate analysis found that the NLR on the 7th day postburn was an independent factor associated with mortality (p <.05), along with the increase in age, burn extent, and presence of inhalation injury (AUC = .85; cut off: 14.13; sensitivity: 75% and specificity: 83.43%). In conclusion, NLR on the 7th day post burn may be used as a predictive factor for mortality amongst severe burn patients.


Le but de cette étude est d'évaluer les valeurs et l'intérêt pronostique du rapport neutrophiles/lymphocytes (RNL) chez le patient gravement brûlé. Il s'agit d'une étude rétrospective conduite auprès de 245 adultes (> 18 ans) brûlés sur >20% SCT, sans inhalation de fumée ni comorbidité, hospitalisés dans les 24h suivant le traumatisme. Nous avons examiné les caractéristiques du patient, les RNL à J3 et J7 ainsi que le devenir. Les RNL étaient systématiquement élevés, significativement plus chez ceux destinés à mourir (p <0,01). En analyse multivariée, la valeur de RNL à J7 est significativement corrélée à la mortalité (p <0,05), comme l'âge, la surface brûlée et l'inhalation. Au seuil de 14,13 on obtient une sensibilité de 75%, une spécificité de 83,43% et une AUC/ROC de 0,85. Le RNL à J7 peut être utilisé comme paramètre prédictif de mortalité chez les patients gravement brûlés.

10.
Heliyon ; 10(12): e32688, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975145

RESUMO

The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.

11.
Heliyon ; 10(12): e32393, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975159

RESUMO

Objectives: Chemerin, as a novel multifunctional adipokine, is proposed to be involved in high cancer risk and mortality. The present study was aimed to evaluate the prognostic value of serum Chemerin and neutrophils in patients with oral squamous cell carcinoma (OSCC). Materials and methods: 120 patients with OSCC were included in this prospective cohort study. The levels of serum Chemerin were measured by enzyme-linked immunosorbent assay (ELISA). We also explored the possible effects of Chemerin on neutrophils' chemokines in OSCC using a real-time PCR, western blotting. Results: Levels of serum Chemerin, neutrophils and NLR were significantly higher among non-survivors compared to survivors of OSCC (both P < 0.05). Higher serum Chemerin levels were associated with advanced TNM stage, lymph node metastasis, differentiation and tumor recurrence (both P < 0.05). Serum Chemerin levels correlated with neutrophils and NLR levels (r = 0.708, r = 0.578, both P < 0.05). Based on ROC analysis, Chemerin + NLR predicted OSCC patient mortality with 81.54 % sensitivity and 87.27 % specificity, with an AUC of 0.8898. In a Kaplan-Meier analysis, high serum Chemerin levels, high neutrophil levels and high NLR levels were associated with shorter overall and disease-free survival (both P < 0.05). A univariate and multivariate Cox regression analysis showed that serum Chemerin and neutrophils were independent risk factors for OSCC. (both P < 0.05). QRT-PCR and western blotting results showed that Chemerin upregulated the expression of chemokines IL-17 and CXCL-5 in neutrophils (both P < 0.05). Conclusions: Our study suggests that measurement of serum Chemerin and neutrophils might be a useful diagnostic and prognostic biomarker for OSCC patients. Chemerin may promote neutrophils infiltration in OSCC through upregulation of chemokines IL17 and CXCL-5.

12.
Cureus ; 16(6): e61733, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38975442

RESUMO

BACKGROUND: Over the last three years, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a global impact. COVID-19 has led to diagnostic and treatment delays in head and neck squamous cell cancers (HNSCCs). Both cancer and COVID-19 trigger systemic inflammatory responses that can result in cytokine storms, creating a favorable tumor microenvironment that supports tumor growth. Various studies have shown a positive association between increasing neutrophil-to-lymphocyte ratio (NLR) and disease severity in COVID-19. Studies have also shown that high NLR is associated with poor survival outcomes in cancer patients. Our aim is to investigate whether an increased NLR is linked to rapid tumor progression in patients with HNSCC who have also been affected by infections like COVID-19 in the pre-operative period. METHODS: This was a retrospective analysis of patients of HNSCC who were scheduled for surgery and had contracted COVID-19 in their pre-operative period between April 2021 and May 2021. The study analyzed pre- and post-COVID NLR in relation to disease progression in HNSCC. Statistical analysis was presented as an interquartile range and numbered with the percentage. Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 26.0, Armonk, NY) was utilized for the analysis. RESULTS: We evaluated 200 operable cases of which 38/200 (20%) patients with HNSCC were COVID-19 positive. Out of those COVID-19-positive patients, 27/38 (71%) patients got operated. Around, 11/38 (28.9%) patients were inoperable. And, 14/27 (53.8%) operated patients also had a change in treatment plan. The mean duration from the joint clinic treatment plan to the date of surgery was 25.18 days. Patients who had contracted COVID-19 and had a change in their treatment plan due to disease progression exhibited mean NLR values of 3.84 (pre-COVID) and 11.11 (post-COVID), with respective medians of 3.04 and 10.50. These differences showed a statistically significant p-value of 0.000. In contrast, patients who had no change in treatment plan displayed mean NLR values of 4.51 (pre-COVID) and 9.70 (post-COVID), with respective medians of 3.47 and 3.42, resulting in with a non-significant p-value of 0.082. CONCLUSION: This is a one-of-its-kind study that has evaluated the role of elevated NLR in patients with a COVID-19 virus infection and its relationship with the clinical progression of the disease. The findings suggest that elevated NLR in patients with HNSCC, along with concurrent SARS-CoV2 infection, may contribute to accelerated disease progression with an increase in tumor burden and nodal metastasis.

13.
Front Cardiovasc Med ; 11: 1397701, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962087

RESUMO

Objective: Leukocyte parameters are associated with cardiovascular diseases. The aim of the present study was to investigate the role of leukocyte parameters in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) with high thrombus burden (HTB). Methods: A total of 102 consecutive STEMI patients with HTB who underwent PPCI within 12 h from the onset of symptoms between June 2020 and September 2021 were enrolled in this study. In addition, 101 age- and sex-matched STEMI patients with low thrombus burden (LTB) who underwent PPCI within 12 h from the onset of symptoms were enrolled as controls. Leukocyte parameters, such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), were calculated at the time of admission. Results: The value of NLR and MLR were significantly higher in the HTB group than in the LTB group (6.24 ± 4.87 vs. 4.65 ± 3.47, p = 0.008; 0.40 ± 0.27 vs. 0.33 ± 0.20, p = 0.038). A cutoff value of >5.38 for NLR had a sensitivity and specificity of 53.9% and 74.3%, respectively, and MLR >0.29 had a sensitivity and specificity of 60.8% and 55.4%, respectively, for determining the STEMI patients with HTB [area under the receiver operating characteristic curve (AUC): 0.603, 95% confidence interval (CI): 0.524-0.681, p = 0.012; AUC: 0.578, 95% CI: 0.499-0.656, p = 0.046]. There was no significant difference of all-cause mortality rate and major adverse cardiac events (MACEs) between the STEMI patients with HTB or with LTB (3.92% in HTB group vs. 2.97% in LTB group, p = 0.712; 10.78% in HTB group vs. 8.91% in LTB group, p = 0.215). Compared with the HTB patients in the low NLR group, C-reactive protein, baseline troponin I, baseline brain natriuretic peptide, and leukocyte parameters, such as white blood cell, neutrophil, lymphocyte, NLR, PLR, and MLR, were also significantly higher in the high NLR group in STEMI patients who underwent PPCI with HTB (18.94 ± 19.06 vs. 35.23 ± 52.83, p = 0.037; 10.99 ± 18.07 vs. 21.37 ± 19.64, p = 0.007; 199.39 ± 323.67 vs. 430.72 ± 683.59, p = 0.028; 11.55 ± 3.56 vs. 9.31 ± 2.54, p = 0.001; 9.77 ± 3.17 vs. 5.79 ± 1.97, p = 0.000; 1.16 ± 0.44 vs. 2.69 ± 1.23, p = 0.000; 9.37 ± 4.60 vs 1.31 ± 2.58, p = 0.000; 200.88 ± 89.90 vs. 97.47 ± 50.99, p = 0.000; 0.52 ± 0.29 vs. 0.26 ± 0.14, p = 0.000, respectively). MACEs and heart failure in the high NLR group were significantly higher than that in the low NLR group of STEMI patients who underwent PPCI with HTB (20.45% vs. 4.25%, p = 0.041; 10.91% vs. 2.13%, p = 0.038). Conclusion: The value of NLR and MLR were higher in STEMI patients who underwent PPCI with HTB. In STEMI patients who underwent PPCI with HTB, a raised NLR could effectively predict the occurrence of MACEs and heart failure.

14.
Plant J ; 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972042

RESUMO

Nucleotide-binding leucine-rich repeat (NLR) proteins are crucial intracellular immune receptors in plants, responsible for detecting invading pathogens and initiating defense responses. While previous studies on the evolution and function of NLR genes were mainly limited to land plants, the evolutionary trajectory and immune-activating character of NLR genes in algae remain less explored. In this study, genome-wide NLR gene analysis was conducted on 44 chlorophyte species across seven classes and seven charophyte species across five classes. A few but variable number of NLR genes, ranging from one to 20, were identified in five chlorophytes and three charophytes, whereas no NLR gene was identified from the remaining algal genomes. Compared with land plants, algal genomes possess fewer or usually no NLR genes, implying that the expansion of NLR genes in land plants can be attributed to their adaptation to the more complex terrestrial pathogen environments. Through phylogenetic analysis, domain composition analysis, and conserved motifs profiling of the NBS domain, we detected shared and lineage-specific features between NLR genes in algae and land plants, supporting the common origin and continuous evolution of green plant NLR genes. Immune-activation assays revealed that both TNL and RNL proteins from green algae can elicit hypersensitive responses in Nicotiana benthamiana, indicating the molecular basis for immune activation has emerged in the early evolutionary stage of different types of NLR proteins. In summary, the results from this study suggest that NLR proteins may have taken a role as intracellular immune receptors in the common ancestor of green plants.

15.
Mol Cells ; : 100094, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39029627

RESUMO

FB_MR5 is an NLR protein identified from wild apple species Malus × robusta 5 conferring disease resistance to bacterial fire blight. FB_MR5 (hereafter MrMR5) recognizes the cysteine protease effector EaAvrRpt2 secreted from the causal agent of bacterial fire blight, Erwinia amylovora. We previously reported that MrMR5 is activated by the C-terminal cleavage product (ACP3) of Malus domestica RIN4 (MdRIN4) produced by EaAvrRpt2-directed proteolysis. Here, we show that MbMR5 from a wild apple species Malus baccata share 99.4% amino acid sequence identity with MrMR5. Surprisingly, transient expression of MbMR5 in Nicotiana benthamiana showed auto-activity in contrast to MrMR5. Domain swap and mutational analyses revealed that one amino acid polymorphism in the MbMR5 CC domain is critical in enhancing auto-activity. We further demonstrated that MrMR5 carrying seven amino acid polymorphisms present in MbMR5 is not activated by MdRIN4 ACP3 but recognizes AvrRpt2 without MdRIN4 in Nicotiana benthamiana. Our findings indicate that naturally occurring polymorphisms of MR5 natural variants can confer its cell death-inducing activity and the effector recognition mechanism likely due to altered compatibility with RIN4.

16.
Artigo em Inglês | MEDLINE | ID: mdl-39029649

RESUMO

Abnormal immune and inflammatory responses are considered to contribute to schizophrenia (SZ). The neutrophil/lymphocyte ratio (NLR) is an inexpensive and reproducible marker of systemic inflammatory responses. Accumulating studies have demonstrated that NLR values are increased in SZ compared to healthy controls and closely related to clinical symptoms in antipsychotic-naïve first-episode SZ (ANFES) patients. However, to our knowledge, only one study has examined NLR in relation to neurocognition in 27 first-episode psychosis patients and 27 controls. This study aimed to examine the relationship of NLR values with cognitive performances in ANFES patients with a larger sample size. Whole blood cell counts were measured in ninety-seven ANFES patients and fifty-six control subjects. The neurocognitive functions of all subjects were measured by the repeatable battery for the assessment of neuropsychological status (RBANS). ANFES patients performed worse on cognition and had increased NLR values relative to healthy controls. In addition, increased NLR was negatively associated with cognitive functions in ANFES patients. Lymphocyte count was positively correlated with cognitive functions in patients. These findings suggest that the abnormal immune and inflammation system indicated by NLR may be involved in the cognitive functions in ANFES patients.

17.
Sci Rep ; 14(1): 12634, 2024 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-38824158

RESUMO

Acute ST-segment elevation myocardial infarction (STEMI) is a severe cardiovascular disease that poses a significant threat to the life and health of patients. This study aimed to investigate the predictive value of triglyceride glucose index (TyG) combined with neutrophil-to-lymphocyte ratio (NLR) for in-hospital cardiac adverse event (MACE) after PCI in STEMI patients. From October 2019 to June 2023, 398 STEMI patients underwent emergency PCI in the Second People's Hospital of Hefei. Stepwise regression backward method and multivariate logistic regression analysis were used to screen the independent risk factors of MACE in STEMI patients. To construct the prediction model of in-hospital MACE after PCI in STEMI patients: Grace score model is the old model (model A); TyG combined with NLR model (model B); Grace score combined with TyG and NLR model is the new model (model C). We assessed the clinical usefulness of the predictive model by comparing Integrated Discrimination Improvement (IDI), Net Reclassification Index (NRI), Receiver Operating Characteristic Curve (ROC), and Decision Curve Analysis (DCA). Stepwise regression and multivariate logistic regression analysis showed that TyG and NLR were independent risk factors for in-hospital MACE after PCI in STEMI patients. The constructed Model C was compared to Model A. Results showed NRI 0.5973; NRI + 0.3036, NRI - 0.2937, IDI 0.3583. These results show that the newly developed model C predicts the results better than model A, indicating that the model is more accurate. The ROC analysis results showed that the AUC of Model A for predicting MACE in STEMI was 0.749. Model B predicted MACE in STEMI with an AUC of 0.685. Model C predicted MACE in STEMI with an AUC of 0.839. For DCA, Model C has a better net return between threshold probability 0.1 and 0.78, which is better than Model A and Model B. In this study, by combining TyG, NLR, and Grace score, it was shown that TyG combined with NLR could reasonably predict the occurrence of MACE after PCI in STEMI patients and the clinical utility of the prediction model.


Assuntos
Linfócitos , Neutrófilos , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Triglicerídeos , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Masculino , Feminino , Intervenção Coronária Percutânea/efeitos adversos , Pessoa de Meia-Idade , Triglicerídeos/sangue , Idoso , Fatores de Risco , Curva ROC , Glicemia/análise , Glicemia/metabolismo , Valor Preditivo dos Testes , Prognóstico , Contagem de Linfócitos , Estudos Retrospectivos
18.
Int J Gen Med ; 17: 2445-2453, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38826508

RESUMO

Background: This investigation evaluated the prognostic significance of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), and introduced a combined NLR-PLR score to evaluate the correlation between NLR-PLR score and hepatocellular carcinoma (HCC) recurrence. Material/Methods: We enrolled 110 patients who underwent orthotopic liver transplantation (LT) for HCC. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were assessed, and appropriate cut-off values were established. The NLR-PLR score ranged from 0 to 2 as follows: score of 2, high NLR (≥3.37) and high PLR (≥105.96); score of 1, either high NLR or high PLR; score of 0, neither high NLR nor high PLR. Results: The median overall survival (OS) of patients with NLR-PLR score of 0, 1 and 2 was 27, 26.5, and 6 months, respectively. The median OS of patients with NLR-PLR score of 2 was shorter than those with 0 (P < 0.001) and 1 (P < 0.001). The median disease-free survival (DFS) time of patients with NLR-PLR score of 0, 1 and 2 was 24.5, 24, and 6 months, The median DFS of patients with NLR-PLR score of 2 was shorter than those with 0 (P = 0.001) and 1 (P = 0.015). Multivariate analysis showed that NLR-PLR score was an independent risk factor for prognosis and survival. Conclusion: NLR, PLR and NLR-PLR score can predict the long-term survival of patients, and NLR-PLR score, having more predictive value than NLR and PLR alone is an independent risk factor for patient survival. more predictive value than NLR and PLR alone.

19.
Cureus ; 16(5): e60854, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38910647

RESUMO

Organophosphorus poisoning (OPP) poses a significant threat to human health, necessitating accurate prognostic markers for timely intervention and improved outcomes. This review evaluates the potential of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic indicator in acute organophosphorus poisoning (AOPP). A comprehensive analysis of existing literature reveals that elevated NLR values correlate with increased severity of poisoning and adverse clinical outcomes, including mortality and morbidity. NLR assessment offers valuable prognostic information beyond traditional markers, aiding risk stratification and guiding clinical decision-making. Integration of NLR into clinical practice holds promise for optimizing patient care through the early identification of high-risk individuals and tailored therapeutic interventions. Further research is needed to validate the utility of NLR in larger patient cohorts and standardize its incorporation into clinical guidelines. Leveraging NLR as a prognostic tool can enhance risk stratification, optimize treatment strategies, and ultimately improve outcomes in AOPP.

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