Bioactive peptides: an alternative therapeutic approach for cancer management.

Cancer is still considered a lethal disease worldwide and the patients' quality of life is affected by major side effects of the treatments including post-surgery complications, chemo-, and radiation therapy. Recently, new therapeutic approaches were considered globally for increasing conventional cancer therapy efficacy and decreasing the adverse effects. Bioactive peptides obtained from plant and animal sources have drawn increased attention because of their potential as complementary therapy. This review presents a contemporary examination of bioactive peptides derived from natural origins with demonstrated anticancer, ant invasion, and immunomodulation properties. For example, peptides derived from common beans, chickpeas, wheat germ, and mung beans exhibited antiproliferative and toxic effects on cancer cells, favoring cell cycle arrest and apoptosis. On the other hand, peptides from marine sources showed the potential for inhibiting tumor growth and metastasis. In this review we will discuss these data highlighting the potential befits of these approaches and the need of further investigations to fully characterize their potential in clinics.

CASP1 is a target for combination therapy in pancreatic cancer.

Gemcitabine (GEM) is commonly used as the first-line chemotherapeutic agent for treating pancreatic cancer (PC) patients. However, drug resistance is a major hurdle in GEM-based chemotherapy for PC. Recent studies have shown that pyroptosis, a type of programmed death, plays a significant regulatory role in cancer development and therapy. In this study, we observed an increase in the expression of Caspase-1(CASP1)/Gasdermin-D (GSDMD) in PC and found that high expression of CASP1 and GSDMD was associated with poor overall survival (OS) and progression-free survival (PFS) of PC patients. Knockdown of either CASP1 or GSDMD resulted in the inhibition of cell viability and migration in PC cells. More importantly, the knockdown of CASP1 or GSDMD enhanced GEM-induced cell death in PC cells. Interestingly, subsequent investigations demonstrated that enzymatically active CASP1 promoted GEM-induced cell death in PC cells. The activation of CASP1 by the DPP8/DPP9 inhibitor (Val-boroPro, VbP) increased GEM-induced cell death by inducing pyroptosis. These findings suggest that inhibiting CASP1 to suppress its oncogenic effects or activating it to promote cell pyroptosis both enhance the sensitivity of PC cells to GEM therapy.

Whole-Genome Sequencing Analysis of Non-Typhoidal Salmonella Isolated from Breeder Poultry Farm Sources in China, 2020-2021.

Non-typhoidal salmonellosis is a dangerous foodborne disease that causes enormous economic loss and threatens public health worldwide. The consumption of food, especially poultry or poultry products, contaminated with non-typhoidal Salmonella (NTS) is the main cause of human salmonellosis. To date, no research has identified the molecular epidemiological characteristics of NTS strains isolated from breeder chicken farms in different provinces of China. In our study, we investigated the antimicrobial resistance, phylogenetic relationships, presence of antimicrobial resistance and virulence genes, and plasmids of NTS isolates recovered from breeder chicken farms in five provinces of China between 2020 and 2021 by using a whole-genome sequencing (WGS) approach and phenotypic methods. All sequenced isolates belonged to six serovars with seven sequence types. Nearly half of the isolates (44.87%) showed phenotypic resistance to at least three classes of antimicrobials. Salmonella enterica serotype Kentucky harbored more antimicrobial resistance genes than the others, which was highly consistent with phenotypic resistance. Furthermore, the carried rate of 104 out of 135 detected virulence genes was 100%. Overall, our WGS results highlight the need for the continuous monitoring of, and additional studies on, the antimicrobial resistance of NTS.

Flaxseed Supplementation in Chicken Feed Accelerates Salmonella enterica subsp. enterica Serovar Enteritidis Clearance, Modulates Cecum Microbiota, and Influences Ovarian Gene Expression in Laying Hens.

Salmonella is a foodborne pathogen that poses a serious threat to both human and animal health and food safety. Flaxseed is rich in unsaturated fatty acids; has anti-metabolic syndrome, anti-inflammatory, and neuroprotective properties; and may be a potential source of feed additives. To investigate the impact of flaxseed on Salmonella-infected laying hens, we administered Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) after adding flaxseed to the feed of laying hens (15% [750 mg/kg]). S. Enteritidis colonization was reduced and its clearance was accelerated from the laying hens. Furthermore, flaxseed supplementation mitigated the damage to the ileum caused by S. Enteritidis. We analyzed alterations in intestinal flora through 16S rRNA amplicon sequencing. S. Enteritidis infection increased the abundance of Akkermansia and triggered the host inflammatory response. Conversely, the addition of flaxseed to the feed increased the abundance of beneficial intestinal bacteria, such as Lactobacilli and Bacteroides. Ovarian health is important for egg production performance in laying hens and our findings indicate that S. Enteritidis can persist in the ovaries for an extended period. Therefore, we further performed transcriptome sequencing analysis of ovarian tissues on day seven after S. Enteritidis infection. S. Enteritidis infection leads to altered ovarian gene expression, including the downregulation of lipid metabolism and growth and development genes and the upregulation of host immune response genes in laying hens. The upregulation of genes associated with growth and development may have stimulated ovarian growth and development.

Targeting NRF2 uncovered an intrinsic susceptibility of acute myeloid leukemia cells to ferroptosis.

Drug resistance and poor treatment response are major obstacles to the effective treatment of acute myeloid leukemia (AML). A deeper understanding of the mechanisms regulating drug resistance and response genes in AML is therefore urgently needed. Our previous research has highlighted the important role of nuclear factor E2-related factor 2 (NRF2) in AML, where it plays a critical role in detoxifying reactive oxygen species and influencing sensitivity to chemotherapy. In this study, we identify a core set of direct NRF2 targets that are involved in ferroptosis, a novel form of cell death. Of particular interest, we find that glutathione peroxidase 4 (GPX4) is a key ferroptosis gene that is consistently upregulated in AML, and high expression of GPX4 is associated with poor prognosis for AML patients. Importantly, simultaneous inhibition of NRF2 with ML385 and GPX4 with FIN56 or RSL3 synergistically targets AML cells, triggering ferroptosis. Treatment with ML385 + FIN56/RSL3 resulted in a marked reduction in NRF2 and GPX4 expression. Furthermore, NRF2 knockdown enhanced the sensitivity of AML cells to the ferroptosis inducers. Taken together, our results suggest that combination therapy targeting both NRF2 and GPX4 may represent a promising approach for the treatment of AML.

Analysis of N-of-1 trials using Bayesian distributed lag model with autocorrelated errors.

An N-of-1 trial is a multi-period crossover trial performed in a single individual, with a primary goal to estimate treatment effect on the individual instead of population-level mean responses. As in a conventional crossover trial, it is critical to understand carryover effects of the treatment in an N-of-1 trial, especially when no washout periods between treatment periods are instituted to reduce trial duration. To deal with this issue in situations where a high volume of measurements are made during the study, we introduce a novel Bayesian distributed lag model that facilitates the estimation of carryover effects, while accounting for temporal correlations using an autoregressive model. Specifically, we propose a prior variance-covariance structure on the lag coefficients to address collinearity caused by the fact that treatment exposures are typically identical on successive days. A connection between the proposed Bayesian model and penalized regression is noted. Simulation results demonstrate that the proposed model substantially reduces the root mean squared error in the estimation of carryover effects and immediate effects when compared to other existing methods, while being comparable in the estimation of the total effects. We also apply the proposed method to assess the extent of carryover effects of light therapies in relieving depressive symptoms in cancer survivors.

Sensitive detection of viable salmonella bacteria based on tertiary cascade signal amplification via splintR ligase ligation-PCR amplification-CRISPR/Cas12a cleavage.

Several viable Salmonella bacteria are capable of causing severe human diseases and huge economic losses. In this regard, viable Salmonella bacteria detection techniques that can identify small numbers of microbial cells are highly valuable. Here, we present a detection method (referred to as SPC) based on the amplification of tertiary signals using splintR ligase ligation, PCR amplification and CRISPR/Cas12a cleavage. The detection limit of the SPC assay was 6 copies (HilA RNA) and 10 CFU (cell). Based on Intracellular HilA RNA detection, this assay can be used to distinguish between viable and dead Salmonella. In addition, it is able to detect multiple serotypes of Salmonella and has been successfully used to detect Salmonella in milk or isolated from farms. Overall, this assay is a promising test for viable pathogens detection and biosafety control.

A Novel Nanobody-Horseradish Peroxidase Fusion Based-Competitive ELISA to Rapidly Detect Avian Corona-Virus-Infectious Bronchitis Virus Antibody in Chicken Serum.

Avian coronavirus-infectious bronchitis virus (AvCoV-IBV) is the causative agent of infectious bronchitis (IB) that has brought great threat and economic losses to the global poultry industry. Rapid and accurate diagnostic methods are very necessary for effective disease monitoring. At the present study, we screened a novel nanobody against IBV-N protein for development of a rapid, simple, sensitive, and specific competitive ELISA for IBV antibody detection in order to enable the assessment of inoculation effect and early warning of disease infection. Using the phage display technology and bio-panning, we obtained 7 specific nanobodies fused with horseradish peroxidase (HRP) which were expressed in culture supernatant of HEK293T cells. Out of which, the nanobody of IBV-N-Nb66-vHRP has highly binding with IBV-N protein and was easily blocked by the IBV positive serums, which was finally employed as an immunoprobe for development of the competitive ELISA (cELISA). In the newly developed cELISA, we reduce the use of enzyme-conjugated secondary antibody, and the time of whole operation process is approximately 1 h. Moreover, the IBV positive serums diluted at 1:1000 can still be detected by the developed cELISA, and it has no cross reactivity with others chicken disease serums including Newcastle disease virus, Fowl adenovirus, Avian Influenza Virus, Infectious bursal disease virus and Hepatitis E virus. The cut-off value of the established cELISA was 36%, and the coefficient of variation of intra- and inter-assay were 0.55-1.65% and 2.58-6.03%, respectively. Compared with the commercial ELISA (IDEXX kit), the agreement rate of two methods was defined as 98% and the kappa value was 0.96, indicating the developed cELISA has high consistency with the commercial ELISA. Taken together, the novel cELISA for IBV antibody detection is a simple, rapid, sensitive, and specific immunoassay, which has the potential to rapidly test IBV antibody contributing to the surveillance and control of the disease.

Development of nanobody-horseradish peroxidase-based sandwich ELISA to detect Salmonella Enteritidis in milk and in vivo colonization in chicken.

BACKGROUND: Salmonella Enteritidis (S. Enteritidis) being one of the most prevalent foodborne pathogens worldwide poses a serious threat to public safety. Prevention of zoonotic infectious disease and controlling the risk of transmission of S. Enteriditidis critically requires the evolution of rapid and sensitive detection methods. The detection methods based on nucleic acid and conventional antibodies are fraught with limitations. Many of these limitations of the conventional antibodies can be circumvented using natural nanobodies which are endowed with characteristics, such as high affinity, thermal stability, easy production, especially higher diversity. This study aimed to select the special nanobodies against S. Enteriditidis for developing an improved nanobody-horseradish peroxidase-based sandwich ELISA to detect S. Enteritidis in the practical sample. The nanobody-horseradish peroxidase fusions can help in eliminating the use of secondary antibodies labeled with horseradish peroxidase, which can reduce the time of the experiment. Moreover, the novel sandwich ELISA developed in this study can be used to detect S. Enteriditidis specifically and rapidly with improved sensitivity. RESULTS: This study screened four nanobodies from an immunized nanobody library, after four rounds of screening, using the phage display technology. Subsequently, the screened nanobodies were successfully expressed with the prokaryotic and eukaryotic expression systems, respectively. A sandwich ELISA employing the SE-Nb9 and horseradish peroxidase-Nb1 pair to capture and to detect S. Enteritidis, respectively, was developed and found to possess a detection limit of 5 × 104 colony forming units (CFU)/mL. In the established immunoassay, the 8 h-enrichment enabled the detection of up to approximately 10 CFU/mL of S. Enteriditidis in milk samples. Furthermore, we investigated the colonization distribution of S. Enteriditidis in infected chicken using the established assay, showing that the S. Enteriditidis could subsist in almost all parts of the intestinal tract. These results were in agreement with the results obtained from the real-time PCR and plate culture. The liver was specifically identified to be colonized with quite a several S. Enteriditidis, indicating the risk of S. Enteriditidis infection outside of intestinal tract. CONCLUSIONS: This newly developed a sandwich ELISA that used the SE-Nb9 as capture antibody and horseradish peroxidase-Nb1 to detect S. Enteriditidis in the spike milk sample and to analyze the colonization distribution of S. Enteriditidis in the infected chicken. These results demonstrated that the developed assay is to be applicable for detecting S. Enteriditidis in the spiked milk in the rapid, specific, and sensitive way. Meanwhile, the developed assay can analyze the colonization distribution of S. Enteriditidis in the challenged chicken to indicate it as a promising tool for monitoring S. Enteriditidis in poultry products. Importantly, the SE-Nb1-vHRP as detection antibody can directly bind S. Enteritidis captured by SE-Nb9, reducing the use of commercial secondary antibodies and shortening the detection time. In short, the developed sandwich ELISA ushers great prospects for monitoring S. Enteritidis in food safety control and further commercial production.

Rolling continual reassessment method with overdose control: An efficient and safe dose escalation design.

In phase 1 dose escalation studies, dose limiting toxicities (DLTs) are defined as adverse events of concern occurring during a predefined time window after first dosing of patients. Standard dose escalation designs, such as the continual reassessment method (CRM), only utilize this binary DLT information. Thus, late-onset DLTs are usually not accounted for when CRM guiding the dose escalation and finally defining the maximum tolerated dose (MTD) of the drug, which brings safety concerns for patients. Previously, several extensions of CRMs, such as the time-to-event CRM (TITE-CRM), fractional CRM (fCRM) and the data augmented CRM (DA-CRM), have been proposed to handle this issue without prolonging trial duration. However, among the model-based designs, none of the designs have explicitly controlled the risk of overdosing as in the escalation with overdose control (EWOC) design. Here we propose a novel dose escalation with overdose control design using a two-parameter logistic regression model for the probability of DLT depending on the dose and a piecewise exponential model for the time to DLT distribution, which we call rolling-CRM design. A comprehensive simulation study has been conducted to compare the performance of the rolling-CRM design with other dose escalation designs. Of note, the trial duration is significantly shorter compared to traditional CRM designs. The proposed design also retains overdose control characteristics, but might require a larger sample size compared to traditional CRM designs.

RGB-D Object SLAM Using Quadrics for Indoor Environments.

Indoor service robots need to build an object-centric semantic map to understand and execute human instructions. Conventional visual simultaneous localization and mapping (SLAM) systems build a map using geometric features such as points, lines, and planes as landmarks. However, they lack a semantic understanding of the environment. This paper proposes an object-level semantic SLAM algorithm based on RGB-D data, which uses a quadric surface as an object model to compactly represent the object's position, orientation, and shape. This paper proposes and derives two types of RGB-D camera-quadric observation models: a complete model and a partial model. The complete model combines object detection and point cloud data to estimate a complete ellipsoid in a single RGB-D frame. The partial model is activated when the depth data is severely missing because of illuminations or occlusions, which uses bounding boxes from object detection to constrain objects. Compared with the state-of-the-art quadric SLAM algorithms that use a monocular observation model, the RGB-D observation model reduces the requirements of the observation number and viewing angle changes, which helps improve the accuracy and robustness. This paper introduces a nonparametric pose graph to solve data associations in the back end, and innovatively applies it to the quadric surface model. We thoroughly evaluated the algorithm on two public datasets and an author-collected mobile robot dataset in a home-like environment. We obtained obvious improvements on the localization accuracy and mapping effects compared with two state-of-the-art object SLAM algorithms.

Meta-analysis of Ginkgo biloba Preparation for the Treatment of Alzheimer's Disease.

OBJECTIVE: The objective of this study was to investigate the efficacy and safety of Ginkgo biloba preparation for the treatment of Alzheimer disease (AD). METHODS: Both English (PubMed, Embase, Cochrane Library databases, and the Cochrane Controlled Trials Register) and Chinese (WanFang, Chinese Biomedical, CNKI, and VIP databases) databases were systematically and independently searched by 2 authors from their inception until July 3, 2019. All relevant studies included AD patients who were treated with Ginkgo biloba. The efficacy and safety of the medicine were used as the main measurement index. RESULTS: Seven studies (N = 939) were identified and analyzed. When compared with placebo, Ginkgo biloba showed exact validity in cognitive function and global clinical assessment (cognitive function section: risk ratio = 1.98, 95% confidence interval = 1.52-2.59, Z = 5.12, P < 0.001; according to Clinical Global Impression Change: odds ratio = 3.119, 95% confidence interval = 2.206-4.410, Z = 6.44, P < 0.001). Adverse events were mild. CONCLUSIONS: Ginkgo biloba preparation has reliable efficacy of cognitive function and global clinical assessment and safety in the treatment of AD.

Alteration of CTCF-associated chromatin neighborhood inhibits TAL1-driven oncogenic transcription program and leukemogenesis.

Aberrant activation of the TAL1 is associated with up to 60% of T-ALL cases and is involved in CTCF-mediated genome organization within the TAL1 locus, suggesting that CTCF boundary plays a pathogenic role in T-ALL. Here, we show that -31-Kb CTCF binding site (-31CBS) serves as chromatin boundary that defines topologically associating domain (TAD) and enhancer/promoter interaction required for TAL1 activation. Deleted or inverted -31CBS impairs TAL1 expression in a context-dependent manner. Deletion of -31CBS reduces chromatin accessibility and blocks long-range interaction between the +51 erythroid enhancer and TAL1 promoter-1 leading to inhibition of TAL1 expression in erythroid cells, but not T-ALL cells. However, in TAL1-expressing T-ALL cells, the leukemia-prone TAL1 promoter-IV specifically interacts with the +19 stem cell enhancer located 19 Kb downstream of TAL1 and this interaction is disrupted by the -31CBS inversion in T-ALL cells. Inversion of -31CBS in Jurkat cells alters chromatin accessibility, histone modifications and CTCF-mediated TAD leading to inhibition of TAL1 expression and TAL1-driven leukemogenesis. Thus, our data reveal that -31CBS acts as critical regulator to define +19-enhancer and the leukemic prone promoter IV interaction for TAL1 activation in T-ALL. Manipulation of CTCF boundary can alter TAL1 TAD and oncogenic transcription networks in leukemogenesis.

Point-Plane SLAM Using Supposed Planes for Indoor Environments.

Simultaneous localization and mapping (SLAM) is a fundamental problem for various applications. For indoor environments, planes are predominant features that are less affected by measurement noise. In this paper, we propose a novel point-plane SLAM system using RGB-D cameras. First, we extract feature points from RGB images and planes from depth images. Then plane correspondences in the global map can be found using their contours. Considering the limited size of real planes, we exploit constraints of plane edges. In general, a plane edge is an intersecting line of two perpendicular planes. Therefore, instead of line-based constraints, we calculate and generate supposed perpendicular planes from edge lines, resulting in more plane observations and constraints to reduce estimation errors. To exploit the orthogonal structure in indoor environments, we also add structural (parallel or perpendicular) constraints of planes. Finally, we construct a factor graph using all of these features. The cost functions are minimized to estimate camera poses and global map. We test our proposed system on public RGB-D benchmarks, demonstrating its robust and accurate pose estimation results, compared with other state-of-the-art SLAM systems.

A composite score to assess the burden of periodontal diseases and tooth loss.

BACKGROUND: Population studies of the prevalence of oral disease rely upon indices that summarize disease status. There is no universally accepted index that summarizes the burden of periodontal diseases, considering the number of teeth remaining in the mouth. METHODS: A new conceptual index was developed that includes consideration of the extent and severity of the periodontal diseases, the distribution of affected teeth, and tooth loss as a function of age. The index is referred to as the burden of periodontal diseases and tooth loss (BPT). RESULTS: A cohort of 1,097 individuals originally seen as new patients in a dental school clinic, and evaluated for undiagnosed dysglycemia, were studied. The BPT index was applied to this data set. A modifying effect of considering the number of lost teeth was observed. The distribution of scores w skewed to the left, which gradually shifted to the right when the most involved teeth (periodontal pathology, tooth loss) were weighted more heavily. This shift was not observed when missing teeth were not considered. CONCLUSIONS: This conceptual study illustrates that the extent and severity of periodontal pathology, and number and distribution of missing teeth, are important considerations when summarizing the condition of the mouth. The BPT provides a measure of the oral disease burden, as both periodontal pathology and tooth loss are associated with both functional impairment and reduced quality of life. The dental profession and dental research community must continually seek to develop new approaches to defining and summarizing the oral disease burden.

The Mechanism of Decreased IgG/IgE-Binding of Ovalbumin by Preheating Treatment Combined with Glycation Identified by Liquid Chromatography and High-Resolution Mass Spectrometry.

Ovalbumin is one of the most important sensitizing ingredients in allergens of egg albumin, which restricts the application of egg in the field of food processing. Previous research has indicated that glycation could cause the protein to partially expand, which may bring about the destruction of the structural IgG and IgE epitopes and induce the decline of the IgG- and IgE-binding ability of ovalbumin. In this research, the effect of a preheating treatment integrated with glycation on the IgG- and IgE-binding capability and the conformation changes of ovalbumin was studied by detecting the glycated sites and the values of degree of substitution per peptide (DSP) by liquid chromatography and high-resolution mass spectrometry (LC-HRMS). Interestingly, we found that a glycation site (K227) attached by two ribose molecules was detected in glycated ovalbumin with preheating treatment. In addition, a new glycation site (K323) appeared in G-60. The results displayed that preheating treament could strengthen the changes in the secondary and tertiary structure of ovalbumin by enhancing glycation and further reduce the IgG/IgE-binding ability by integrating with glycation because of the cover of IgG and IgE epitopes. Therefore, preheating treatment integrated with glycation may offer a way for ovalbumin to reduce sensitization.

LC-Orbitrap MS analysis of the glycation modification effects of ovalbumin during freeze-drying with three reducing sugar additives.

In general, the reducing sugars were extensively utilized as additives to prevent denaturation and inactivation during the freeze-drying process. However, different additives have unequal protective effects on the protein conformation. To evaluate the mechanism of protection the protein structure using different additives in the freeze-drying process, the glycated sites and degree of substitution per peptide (DSP) of each site were investigated by LC-Orbitrap MS. We found that the ovalbumin that was supplemented with ribose and then lyophilized (R-oval) have the highest extent of glycation modification. K227 was the most reactive glycated site in R-Oval, with a DSP of 0.83. The ovalbumin that was supplemented with lactose and then lyophilized (L-Oval) have the lowest degree of glycation, and K227 did not undergo the glycation reaction. It was hypothesized that the order impact of different additives on protection of the protein conformation were lactose > galactose > ribose during the freeze-drying process.

Downregulated miR-17, miR-29c, miR-92a and miR-214 may be related to BCL11B overexpression in T cell acute lymphoblastic leukemia.

AIM: BCL11B overexpression is a characteristic of most T cell acute lymphoblastic leukemia (T-ALL) cases, and downregulated BCL11B in leukemic T cells inhibits cell proliferation and induces apoptosis. The purpose of this study was to analyze the miRNA expression pattern that may be related to BCL11B regulation in T-ALL. METHODS: Quantitative real-time PCR was used to detect the miRNAs miR-17-3p, miR-17-5p, miR-29c-3p, miR-92a-3p, miR-214-3p and miR-214-5p, the BCL11B expression level in peripheral blood mononuclear cells which was obtained from 17 de novo and untreated T-ALL patients, and 15 healthy individuals (HIs) served as control. Correlations between the relative miRNA expression levels and BCL11B were analyzed. RESULTS: Based on the computational prediction that certain miRNAs bind the BCL11B 3'-UTR, miR-17-3p, miR-17-5p, miR-29c-3p, miR-92a-3p, miR-214-3p and miR-214-5p were found to be candidates for regulating BCL11B. The expression levels of the six miRNAs were decreased compared with HIs, and with the exception of miR-17-5p, statistically significant differences in expression levels were found in the T-ALL group. Moreover, while significantly higher BCL11B expression was found in the T-ALL group, a negative trend in the correlation level for all six miRNAs could be found in all groups; however, statistical significance was only found for miR-214-3p in the T-ALL group. CONCLUSION: miRNA downregulation together with BCL11B upregulation suggests that miR-17, miR-29c, miR-92a and miR-214 might be involved in BCL11B regulation. The therapeutic promise of regulating the expression of these miRNAs for T-ALL therapy may be considered in the future.

Different aberrant expression pattern of immune checkpoint receptors in patients with PTCL and NK/T-CL.

AIM: To better understand the T-cell immunodeficiency status in patients with peripheral T-cell lymphomas (PTCLs) and NK/T-cell lymphomas (NK/T-CLs), the T-cell inhibitory receptors expression pattern was investigated. METHODS: The expression levels of programmed death 1 (PD-1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), B/T lymphocyte attenuator (BTLA), lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin-3 (TIM-3), T-cell immunoglobulin and ITIM domain (TIGIT) genes were detected in peripheral blood mononuclear cells (PBMCs) from patients and healthy volunteers by quantitative real-time-PCR, the correlation between different gene expression levels was analyzed. RESULTS: Significantly higher expression of PD-1, CTLA-4, BTLA, LAG-3, TIM-3 and TIGIT can be observed as a common characteristic in patients with PTCL or NK/T-CL. However, the coexpression pattern seemed different between subtypes. Their overexpression is also related to disease progression stage. CONCLUSION: We first characterized the expression pattern of six T-cell inhibitory receptor genes in PTCL and NK/T-CL, which might work as immune biomarkers for evaluation the immunosuppression status and help to establish the precision targets of immunotherapy.