51 results
Search Results
2. Mitochondrial control of antigen presentation in cancer cells.
- Author
-
Soler-Agesta, Ruth, Anel, Alberto, and Galluzzi, Lorenzo
- Subjects
- *
ANTIGEN presentation , *CANCER cells , *T cell receptors , *MITOCHONDRIA , *T cells - Abstract
Cytotoxic T lymphocytes recognize and kill cancer cells when the latter present antigenic epitopes complexed with MHC class I molecules on their surface. In a recent Science paper, Mangalhara et al. show that alterations of the mitochondrial electron flow upregulate multiple factors involved in antigen presentation via a succinate-dependent epigenetic mechanism. Cytotoxic T lymphocytes recognize and kill cancer cells when the latter present antigenic epitopes complexed with MHC class I molecules on their surface. In a Science paper, Mangalhara et al. show that alterations of the mitochondrial electron flow upregulate multiple factors involved in antigen presentation via a succinate-dependent epigenetic mechanism. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
3. A "scoping" review of prostate brachytherapy and immune responses.
- Author
-
Nguyen, Anthony T., Liu, Chung-Tang Spencer, and Kamrava, Mitchell
- Subjects
- *
RADIOISOTOPE brachytherapy , *IMMUNE response , *PROSTATE , *T cells , *TREATMENT effectiveness - Abstract
Whether prostate brachytherapy (BT) results in opportunistic biological changes that can improve clinical outcomes is not well studied. We sought to investigate the impact of prostate BT on the immune system. A scoping review was performed using PubMed/Scopus for papers published between 2011-2021. Search terms were "brachytherapy" AND "immune" AND "prostate". A total of 81 records were identified and 6 were selected for further review. 2 low-dose-rate BT papers (n=68) evaluated changes in the peripheral blood following I-125 monotherapy. Both showed significant increases in peripheral CD3+ and CD4+ T cells post-BT. One also demonstrated significant increases in Treg subsets up to 150 days post-BT. 4 high-dose-rate (HDR) studies (n=37) were identified, and all were done in combination with EBRT. The largest study (n=24) showed a single 10 Gy fraction of HDR converted 80% of "cold" tumors into an "intermediate" or "hot" state, based on a tumor inflammation signature when comparing a pre-BT biopsy to one prior to a second HDR fraction. Prostate BT can invoke an immune activating phenotype; however, changes in immunosuppressive cells are also seen. Additional data is needed to understand how to promote synergy between BT and the immune system. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
4. CAR-T cell therapy: Efficacy in management of cancers, adverse effects, dose-limiting toxicities and long-term follow up.
- Author
-
Elmarasi, Mohamed, Elkonaissi, Islam, Elsabagh, Ahmed Adel, Elsayed, Engy, Elsayed, Abdelrahman, Elsayed, Basant, Elmakaty, Ibrahim, and Yassin, Mohamed
- Subjects
- *
CELLULAR therapy , *CHIMERIC antigen receptors , *HEMATOLOGIC malignancies , *CYTOKINE release syndrome , *T cells , *B cells - Abstract
• CAR-T therapy offers durable remissions in refractory hematological malignancies. • Meta-analyses show significant efficacy in various hematologic cancers. • CAR T-cell therapy improves quality of life for blood cancer patients. • Encouraging results in CD22-targeting CAR T-cell therapy for B-cell malignancies. • Long-term studies reveal durable remissions but also persistent adverse effects. Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a groundbreaking and highly promising approach for the management of cancer. This paper reviews the efficacy of CAR-T therapy in the treatment of various hematological malignancies, also, with a mention of its effect on solid tumors, for which they have not received FDA approval yet. Different common and uncommon side effects are also discussed in this paper, with attention to the effect of each drug separately. By reviewing the recommendations of the FDA for CAR-T therapy research, we have extensively discussed dose-limiting toxicities. This further highlights the need for precise dosing strategies, striking a balance between therapeutic benefits and potential risks. Additionally, we reviewed the long-term follow-up of patients receiving CAR-T therapy to gain valuable insights into response durability and late-onset effects. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Electrochemical immuno-biosensors for the detection of the tumor marker alpha-fetoprotein: A review.
- Author
-
Shan, Chen-Wei, Chen, Zhencheng, Han, Guo-Cheng, Feng, Xiao-Zhen, and Kraatz, Heinz-Bernhard
- Subjects
- *
BIOSENSORS , *TUMOR markers , *ALPHA fetoproteins , *T cells , *METHYLENE blue , *DETECTION limit - Abstract
Alpha-fetoprotein (AFP) is a glycoprotein that has many important physiological functions, including transportation, immunosuppression, and induction of apoptosis by T lymphocytes. AFP is closely related to the development of hepatocellular carcinoma and many kinds of tumors, all of which can show high concentrations, so it is used as a positive test indicator for many kinds of tumors. This paper reviews recent advances in the detection of the tumor marker AFP based on three immuno-biosensors: electrochemical (EC), photoelectrochemical (PEC), and electrochemical luminescence (ECL). The electrodes are modified by different materials or homemade composites, different signaling molecules are selected as single probes or dual probes for the detection of AFP. The detection limit was as low as 3 fg/mL, which indicated that the AFP immunosensor had achieved highly sensitive detection. In addition, we also reviewed and summarized the current development status and application prospect of AFP immunoelectrochemical sensors. There are not too many researches on immunosensors based on dual-signal ratios, and the commonly used probes are methylene blue (MB) and ferrocene (Fc). It would be more innovative to have more novel signaling molecules as probes to prepare dual-signal ratio sensors. This paper reviews recent advances in the detection of the tumor marker AFP in recent years based on three different types of electrochemical biosensors: electrochemical (EC) immunosensors, photoelectrochemical (PEC) sensors, and electrochemical luminescence (ECL) sensors. Among them, EC sensors are classified as single-probe and dual-probe. [Display omitted] • This manuscript reviews recent research on the detection of AFP. • The review describes three immunobiosensors: EC, PEC and ECL. • A comprehensive summary and comparison of three sensors for AFP detection. • This review provides guidelines for future research on immunobiosensors. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. On the approximate solution of dynamic systems derived from the HIV infection of CD[formula omitted]T cells using the LRBF-collocation scheme.
- Author
-
Asadi-Mehregan, Fatemeh, Assari, Pouria, and Dehghan, Mehdi
- Subjects
- *
HIV infections , *RADIAL basis functions , *DYNAMICAL systems , *HIV , *PARTIAL differential equations , *T cells , *COMPUTATIONAL neuroscience - Abstract
Human immunodeficiency virus (HIV) infection may cause death by damaging some of the patient's vital organs through weakening the body's immune system, including CD 4 + T cells. In the meantime, mathematical models can be useful in dealing with this deadly virus by providing effective strategies based on the examination of different infection states. The major aim pursued in this paper is to present a computational algorithm for solving nonlinear systems of ordinary and partial differential equations resulting from the HIV infection models of CD 4 + T cells. The offered method is developed according to the use of local radial basis functions (LRBFs) as shape functions in the discrete collocation scheme. The new technique approximates the solution by a small set of nodes instead of all points located in the domain where the HIV mathematical model is given. Thus the presented method uses less computing volume compared to the globally supported radial basis functions, and as a result, its algorithm can be quickly run on a computer with relatively low memory. The computational efficiency of the scheme is studied by several test examples. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Therapeutic modulation of V Set and Ig domain-containing 4 (VSIG4) signaling in immune and inflammatory diseases.
- Author
-
Li, You, Wang, Qi, Li, Jiaxin, Li, Aohan, Wang, Qianqian, Zhang, Qinggao, and Chen, Yingqing
- Subjects
- *
CELL anatomy , *POLLUTANTS , *WOUNDS & injuries , *THERAPEUTICS , *HOMEOSTASIS , *EMOTIONAL trauma - Abstract
Inflammation is the result of acute and chronic stresses, caused by emotional or physical trauma, or nutritional or environmental pollutants, and brings serious harm to human life and health. As an important cellular component of the innate immune barrier, the macrophage plays a key role in maintaining tissue homeostasis and promoting tissue repair by controlling infection and resolving inflammation. Several studies suggest that V Set and Ig domain-containing 4 is specifically expressed in tissue macrophages and is associated with a variety of inflammatory diseases. In this paper, we mainly summarize the recent research on V Set and Ig domain-containing 4 structures, functions, function and roles in acute and chronic inflammatory diseases, and provide a novel therapeutic avenue for the treatment of inflammatory diseases, including nervous system, urinary, respiratory and metabolic diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
8. CD8 cell counting in whole blood by a paper-based time-resolved fluorescence lateral flow immunoassay.
- Author
-
Xiao, Wei, Liang, Jiajie, Zhang, Ying, Zhang, Yan, Teng, Peijun, Cao, Dongni, Zou, Siyi, Xu, Tao, Zhao, Jianfu, and Tang, Yong
- Subjects
- *
BLOOD cell count , *IMMUNOASSAY , *T cells , *FLUORESCENCE , *SOCIOECONOMIC status , *CELL physiology - Abstract
The number of CD8+ T lymphocytes (CD8 cells) in peripheral blood can directly reflect the immune status of the body and is widely used for auxiliary diagnosis and prognostic evaluation of diseases. There is an urgent need to develop a simple CD8 cell-counting platform to meet clinical needs. Our group designed a paper-based cell-counting method based on a blocking competition strategy. In addition, we developed a time-resolved fluorescence-blocking competitive lateral flow immunoassay (TRF-BCLFIA) for point-of-care CD8 cell counting that functions by measuring europium nanoparticle (EuNP)-labeled CD8 antibody probes that are not captured by CD8 cells, and we indirectly calculated the concentration of CD8 cells in samples. Within 30 min, four operation steps can provide an accurate CD8 cell count for a 75-μL whole-blood sample, and this approach can be implemented on a handheld device. The TRF-BCLFIA reliably quantified CD8 cells in whole-blood samples, in which the assay exhibited a linear correlation (R2 = 0.989) readout for CD8 cell concentrations ranging from 137 to 821 cells/μL. To validate this approach, our newly developed CD8 cell-counting tool was used to assess 33 tumor patient blood samples. The results showed a high consistency with a flow cytometry-based absolute count. This analysis approach is a promising alternative for the costly standard flow cytometry-based tools for CD8 cell counting in tumor patients in community clinics, small hospitals, and low medical resource regions. This technology would deliver simple diagnostics to patients anywhere in the world, regardless of geography or socioeconomic status. [Display omitted] • We developed a CD8 cell-counting tool that called time-resolved fluorescence-blocking competitive lateral flow immunoassay. • The probes labeled CD8 antibody was europium nanoparticle (EuNP). • Within 30 min, the TRF-BCLFIA reliably quantified CD8 cells in whole-blood samples with a good a linear correlation. • The TRF-BCLFIA showed a high consistency with a flow cytometry-based absolute count. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
9. Circuit-level design of radiation tolerant memory cell.
- Author
-
Pandey, Monalisa and Islam, Aminul
- Subjects
- *
STATIC random access memory , *SINGLE event effects , *ASTROPHYSICAL radiation , *PARTICLE tracks (Nuclear physics) , *T cells , *SPACE environment , *ELECTROSTATIC discharges - Abstract
As transistors shrink in size, the integration density of memory circuits like Static Random Access Memory (SRAM) cells rises, making them increasingly susceptible to Single Event Effects (SEE). In the space environment, memory circuits face stability and reliability challenges due to the presence of various charged particles such as α-particles, neutrons, electrons, heavy ions, and photons. These high-energy particles create ion tracks when they strike the memory device, leading to upsets in the storage bits. Conventional 6 T SRAM cells are susceptible to these upsets. As a solution this paper proposes a new Radiation Tolerable (RT 13 T) SRAM cell that is better suited for deep-space applications compared to other memory cell. RT13T has been validated to withstand radiation hazards through Critical Charge (Q Crit) analysis, which shows that it exhibits 1.17×, 1.1×, 1.94× and 1.06× highest Q Crit than QUCCE 10 T/12 T,traditional 6 T and LIOR 13 T memory cells, respectively. As the comparison made, our Proposed RT 13 T saved by5.1 %,9.9 %, 20.1 % and 7 % of the power consumption compared to QUCCE10T/12 T/LIOR 13 T/SERSC-16 T SRAM cells at a nominal supply voltage of 0.7 V. It also exhibits shorter read delay (T RA) 10.6 %, 1.34 %, 9.6 %, 22.16 %compared to QUCCE 10 T/12 T,6T, SERSC-16Tmemory cells, respectively. In terms of stability,our proposed RT13T SRAM cell exhibits 2.32×/2.05×/2.9×/1.05×/1.01 × higher read stability as compared with QUCCE10T/12 T/6T/LIOR 13 T/SERSC-16 T memory cells during the read operation. The our proposed RT13T shows improvements in design metrics are at the expense of a longer write delay. To characterize the performances of the proposed RT13T, 16-nm CMOS predictive technology model and validated through extensive simulation with licensed PrimeSim HSPICE of Synopsys. The results of our proposed RT13T cell are compared with some other previously proposed memory cells such as 6 T, QUCCE 10 T, QUCCE 12 T, LIOR 13 T and SERSC-16 T memory cells. The obtained results are tabulated and plotted for graphical analysis. In terms of area consumption our proposed 13 T consumes 0.9×/0.6 × lesser area than QUCCE 12 T/SERSC-16 T memory cells but our proposed circuit consumes 3.1×/1.08×/1.05 × more area than QUCCE10T/conventional 6 T/LIOR 13 T because QUCCE10T and 6 T consist of less number of transistors in memory cells.The cell proposed in this paper demonstrates strong radiation-hardened capabilities and excellent overall performance, making it well-suited for aerospace electronic devices and ensuring stable operation in space radiation environments. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
10. Ephedrae Herba polysaccharides inhibit the inflammation of ovalbumin induced asthma by regulating Th1/Th2 and Th17/Treg cell immune imbalance.
- Author
-
Zhang, Beibei, Zeng, Mengnan, Zhang, Qinqin, Wang, Ru, Jia, Jufang, Cao, Bing, Liu, Meng, Guo, Pengli, Zhang, Yuhan, Zheng, Xiaoke, and Feng, Weisheng
- Subjects
- *
KILLER cells , *IMMUNOGLOBULIN E , *TUMOR necrosis factors , *TRANSFORMING growth factors , *POLYSACCHARIDES , *T helper cells , *T cells , *NEUTROPHILS - Abstract
This study aimed to investigate the anti-asthma effects of Ephedrae Herba polysaccharides (PE) and possible mechanisms related to immune inflammatory response. An asthma model was established in rats using ovalbumin (OVA). Seventy rats were randomly assigned to five groups: control, model, dexamethasone (DEX, 0.075 mg/kg), low dose polysaccharides (LPE, 137.71 mg/kg) and high dose polysaccharides (HPE, 275.42 mg/kg). The cough and asthma were used to evaluate the basic state of asthmatic rats. Histological studies were evaluated by hematoxylin and eosin (H&E), Masson, and periodic acid-schiff (PAS) staining. The levels of interferon-γ (IFN-γ), interleukin (IL)-4, immunoglobulin E (IgE), tumor necrosis factor α (TNF-α), and IL-17A in bronchoalveolar lavage fluid (BALF), and the levels of transforming growth factor β1 (TGF-β1), IL-6, and IL-10 in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of Ifn-γ , Il-4 , Tgf-β1 , Il-6 , Il-10 , Tnf-α , Il-13 , and Il-17a were evaluated by quantitative real-time reverse transcription (qRT)-PCR. The dendritic cell (DCs), T helper cell (Th), natural killer cell (NK), regulatory T cell (Treg), and Th17 cells in blood, the lymphocytes, macrophages and neutrophils in spleen, and cell apoptosis and reactive oxygen species (ROS) in lung were analysed by flow cytometry (FCM). Immunohistochemistry (IHC) was used to stain DCs (CD11c+, CD86+, and CD80+), macrophages (CD68+), and neutrophils (MPO+) in the spleen and lung. The protein levels of IL-17A, CD11c, CD86, and CD80 in lung were measured by western blot. Our study demonstrated that PE could effectively improve the symptoms of asthmatic rats, ameliorate the lung pathological injury, inhibit inflammation, apoptosis and oxidative stress, regulate the levels of macrophages, neutrophils, DCs, NK, Thc, Treg and Th17 cells. PE could collectively inhibit the inflammation, apoptosis and ROS in asthma rats induced by OVA via regulating Th1/Th2 and Th17/Treg cell immune imbalance. [Display omitted] • This paper is the first to explore the intervention effect and mechanism of polysaccharides in Ephedrae Herba on OVA-induced allergic asthma. • Ephedrae Herba polysaccharides may treat OVA-induced allergic asthma by modulating inflammation and immunity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
11. Meet the authors: Dr. Clint Allen and Dr. Sandro Santagata.
- Author
-
Allen, Clint and Santagata, Sandro
- Subjects
- *
HEAD & neck cancer , *PHENOTYPIC plasticity , *LUNGS , *CYTOTOXIC T cells , *T cells - Abstract
In this Q&A, Cell Press Community Review Scientific Editor Leia Judge talks to Dr. Clint Allen and Dr. Sandro Santagata about their new papers "Phenotypic plasticity and reduced tissue retention of exhausted tumor-infiltrating T cells following neoadjuvant immunotherapy in head and neck cancer" and "Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma" and their experiences with publishing through Cell Press Community Review. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
12. Tracking down tumor-specific T cells.
- Author
-
Reading, James, Foster, Kane, Joshi, Kroopa, and Chain, Benny
- Subjects
- *
CANCER cells , *T cells - Abstract
Two papers published in this edition of Cancer Cell (Zheng et al., 2022 and Veatch et al., 2022) provide an elegant illustration of how single-cell sequencing can be used to define a molecular phenotype which identifies tumor-specific T cells. Two papers published in this edition of Cancer Cell (Zheng et al., 2022 and Veatch et al., 2022) provide an elegant illustration of how single-cell sequencing can be used to define a molecular phenotype which identifies tumor-specific T cells. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
13. Babesia bovis AMA-1, MSA-2c and RAP-1 contain conserved B and T-cell epitopes, which generate neutralizing antibodies and a long-lasting Th1 immune response in vaccinated cattle.
- Author
-
Hidalgo-Ruiz, Mario, Mejia-López, Susana, Pérez-Serrano, Rosa M., Zaldívar-Lelo de Larrea, Guadalupe, Ganzinelli, Sabrina, Florin-Christensen, Monica, Suarez, Carlos E., Hernández-Ortiz, Rubén, Mercado-Uriostegui, Miguel A., Rodríguez-Torres, Angelina, Carvajal-Gamez, Bertha I., Camacho-Nuez, Minerva, Wilkowsky, Silvina E., and Mosqueda, Juan
- Subjects
- *
IMMUNE response , *T cells , *EPITOPES , *HUMORAL immunity , *IMMUNOGLOBULINS , *BABESIA - Abstract
Vaccines against bovine babesiosis must, ideally, induce a humoral immune response characterized by neutralizing antibodies against conserved epitopes and a cellular Th1 immune response. In Babesia bovis , proteins such as AMA-1, MSA-2c, and RAP-1 have been characterized and antibodies against these proteins have shown a neutralizing effect, demonstrating the implication of B and T-cell epitopes in the immune response. There is evidence of the existence of B and T-cell epitopes in these proteins, however, it remains to be defined, the presence of conserved peptides in strains from around the world containing B and T-cell epitopes, and their role in the generation of a long-lasting immunity. The aim in this paper was to identify peptides of Babesia bovis AMA-1, MSA-2c, and RAP-1 that elicit a neutralizing and long-lasting Th1 immune response. Peptides containing B-cell epitopes of AMA-1, MSA-2c and RAP-1, were identified. The immune response generated by each peptide was characterized in cattle. All peptides tested induced antibodies that recognized intraerythrocytic parasites, however, only 5 peptides generated neutralizing antibodies in vitro : P2AMA-1 (6.28%), P3MSA-2c (10.27%), P4MSA-2c (10.42%), P1RAP-1 (32.45%), and P4RAP-1 (36.98%). When these neutralizing antibodies were evaluated as a pool, the inhibition percentage of invasion increased to 52.37%. When the T cellular response was evaluated, two peptides: P3MSA2c and P2AMA1 induced a higher percentage (>70%) of activated CD4 +/CD45RO+ T cells than unstimulated cells. Additionally, both peptides induced the production of gamma interferon (IFN−) in PBMCs from vaccinated cattle after one year proving the implication of a long-lasting Th1 immune response. In conclusion, we identified conserved peptides containing B and T-cell epitopes in antigens of B. bovis that elicit a Th1 immune response and showed evidence that peptides from the same protein elicit different immune responses, which has implication for vaccine development in bovine babesiosis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
14. ESTABLISHMENT OF A DOUBLE-HUMANIZED MOUSE MODEL USING PATIENT-DERIVED XENOGRAFT BLADDER CANCER TUMOR CELL LINE AND HUMAN γδ T-CELLS.
- Author
-
Trecarten, Shaun, Svatek, Robert S., Ji, Niannian, Shu, Zhen-Ju, Curiel, Tyler J., Mukherjee, Neelam, and Furman, Jamie
- Subjects
- *
GENE expression , *GRAFT versus host disease , *CELL lines , *LABORATORY mice , *T cells , *BLADDER cancer , *IPILIMUMAB - Abstract
Despite recent breakthroughs of immune-checkpoint inhibitors in the management of bladder cancer (BC), only 20% of patients with non-muscle invasive BC (NMIBC) completely respond, leaving room for improvement. Due to challenges in developing a preclinical model which reflects the heterogeneity and biology of bladder tumors, patient-derived xenograft (PDX) models were created. PDX models involve implanting tumor extracted from patients into immunocompromised mice, which therefore keep the morphology and genomic fidelity of their parental patient cancers. The state of immunodeficiency, however, precludes study of immunotherapy and consequently humanized mice models engrafted with a human immune system were developed, though this led to spontaneous xenogenic graft vs host disease (GVHD). As a potential solution to GVHD in humanized mouse models, this paper describes successful creation of a double-humanized mouse (DHM) by simultaneously engrafting human immune cells and human tumors from the same donor. BC tissue was processed +/- digested into single-cell suspensions (SCS, F0 tissue) and injected orthotopically or subcutaneously into flanks of NSG™ mice. Subsequent tumor growth (PDX-F1) was measured, and PDX-F1 tumors reaching >200mm3 were processed into SCS and reimplanted subcutaneously into a new NSG™ (PDX-F2). Continuous passages (PDX-Fn) were repeated.; Extra SCS-F1 and Fn was analyzed for human epithelial cell adhesion molecule (EpCAM) expression. From an individual F1, a stable cell line (PDX257S) was cultured, and also analyzed for EpCAM expression by flow cytometry. For the DHM model, autologous γδ T-cells expanded in vitro from PDX257S donors were injected with PDX257S cells (effector: target = 2:1) into the NSG™ flanks and were observed for body condition/hematuria for 45 days. Total RNA-sequencing was performed on F0, PDX-Fn and PDX257S cell line. Tumor growth curves were analyzed with 2-way analysis of variance (ANOVA). F0 tissue was obtained from 60 patients. Tumor acceptance in orthotopic injection was not observed in the first 11 suitable tumors, and this method was ceased. Subcutaneous tumor acceptance rate improved with digestion and processing of F0 rather than processing alone (11% vs 5%). EpCAM expression was 98% vs 70% in PDX257S vs its F1 tissue, and < 30% in F1 tissue from other donors that did not yield further passages. In the DHM, while tumor growth was significantly reduced compared to control group after 45 days (mean vol 200 mm3 vs 580 mm3, p=0.02) post injection, it was not completely suppressed. RNA sequencing revealed increased expression of genes including BCL2L1, KRAS, MYC, E2F1, and E2F4 in both PDX257 subcutaneous tumor and cell line compared with donor tumor tissue, and very low/no expression of CDKN2A and FHIT genes in both PDX257 cell line and donor tumor tissue. Creation of a double-humanized mouse model is feasible, and tumor growth is not completely suppressed with the addition of autologous γδ T-cells. PDX257S tumor and cell line is associated with increased EpCAM expression and on RNA sequencing, increased expression of BCL2L1, KRAS, MYC, E2F1, and E2F4. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
15. Azo-based hypoxic-activated 6-diazo-5-oxo-L-norleucine (DON) prodrug combined with vascular disrupting agent nanoparticles for tumor-selective glutamine metabolism blockade.
- Author
-
Xu, Hang, Zheng, Mengfei, Yang, Chenguang, Wang, Kun, Lv, Zheng, Liu, Zhilin, Tang, Zhaohui, and Chen, Xuesi
- Subjects
- *
GLUTAMINE , *TUMOR microenvironment , *CELL metabolism , *METABOLISM , *T cells , *COLON cancer , *WEIGHT loss , *NANOMEDICINE - Abstract
Highly expressed azo-reductase (AZOR) selectively reduces Azo-DON to DON in hypoxic tumor environments, impair glutamine metabolism in cancer cells, and promote tumor cell death without affecting T cell metabolism and proliferation, thereby generating strong antitumor immune responses. CB-PLG nanoparticles (CBP) mentioned in the paper can enhance the degree of hypoxia in normoxic tumors, which is conducive to efficient reduction of Azo-DON at tumor sites. [Display omitted] • Azo-DON is a novel hypoxia-active prodrug of glutamine antagonist. • Azo-DON selectively blocks tumor glutamine metabolism after reducing to DON. • T cells continue to proliferate and remain active when Azo-DON is reduced to DON. • CBP nanoparticles increase tumor hypoxia and facilitate the reduction of Azo-DON. Glutamine antagonists, such as 6-diazo-5-oxo-L-norleucine (DON), have demonstrated remarkable anti-tumor effects by blocking tumor glutamine metabolism, but their use is frequently causing toxicity. Despite the existence of multiple glutamine antagonist prodrug designs, a tumor-selective prodrug has yet to be developed. Herein, a novel prodrug of DON, Azo-DON, has been developed, which remains stable and inactive in normal tissues with sufficient oxygen levels, while can be selectively reduced to DON by highly expressed azo-reductase in hypoxic tumor environments. This leads to blockade of glutamine metabolism in cancer cells and promotes cell death without affecting T cell proliferation. In a high-hypoxic H22 hepatoma cancer model, Azo-DON showed a 1.8-fold enhancement in glutamine blockade compared to the control group, resulting in a tumor suppression rate (TSR) of 84.2% in vivo with no significant weight loss. In a low-hypoxic CT26 colon cancer model, when combined with vascular disrupting agent nanoparticles (CBP) to induce a hypoxic environment, Azo-DON exhibited a 4.6-fold enhancement in glutamine blockade over the control group, resulted in a remarkable TSR of 96.6% in vivo. This innovative approach represents a promising strategy for the application of broad-spectrum metabolic inhibitors in the field of precision cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
16. Inhibitory receptors and checkpoints on NK cells: Implications for cancer immunotherapy.
- Author
-
Li, Lingfei, Li, Ang, Jin, Hai, Li, Mingyang, and Jia, Qingge
- Subjects
- *
KILLER cells , *CANCER cells , *PROGRAMMED cell death 1 receptors , *T cells , *IMMUNOTHERAPY , *TUMOR treatment - Abstract
With the success of immunosuppressive checkpoint in tumor therapy, the corresponding adverse response and drug resistance defects have been exposed. T cells and NK cells are the body's immune system of the two substantial main forces. in recent years, study of T cell checkpoints appeared a certain block, such as PD-1 the effect not benign, on the distribution of NK cell surface excitatory and inhibitory receptors under normal conditions to maintain steady, could be targeted in the tumor treatment blockade have therapeutic effect. This paper reviews the function of NK cells and the effects of corresponding receptors in various types of tumors, providing a direction for the selection of appropriate gate control sites for future treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
17. T cells and monocyte-derived myeloid cells mediate immunotherapy-related hepatitis in a mouse model.
- Author
-
Llewellyn, Heather P., Arat, Seda, Gao, Jingjin, Wen, Ji, Xia, Shuhua, Kalabat, Dalia, Oziolor, Elias, Virgen-Slane, Richard, Affolter, Timothy, and Ji, Changhua
- Subjects
- *
MYELOID cells , *LABORATORY mice , *T cells , *DRUG side effects , *T helper cells , *CHRONIC active hepatitis - Abstract
Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) which are more severe when ICIs are used in combination. We aimed to use a mouse model to elucidate the molecular mechanisms of immune-related hepatitis, one of the common irAEs associated with ICIs. Immune phenotyping and molecular profiling were performed on Pdcd1 -/- mice treated with anti-CTLA4 and/or the IDO1 inhibitor epacadostat or a 4-1BB agonistic antibody. ICI combination-induced hepatitis and 4-1BB agonist-mediated hepatitis share similar features yet maintain distinct immune signatures. Both were characterized by an expansion of periportal infiltrates and pan-zonal inflammation albeit with different morphologic characteristics. In both cases, infiltrates were predominantly CD4+ and CD8+ T cells with upregulated T-cell activation markers, ICOS and CD44. Depletion of CD8+ T cells abolished ICI-mediated hepatitis. Single-cell transcriptomics revealed that the hepatitis induced by combination ICIs is associated with a robust immune activation signature in all subtypes of T cells and T helper 1 skewing. Expression profiling revealed a central role for IFNγ and liver monocyte-derived macrophages in promoting a pro-inflammatory T-cell response to ICI combination and 4-1BB agonism. We developed a novel mouse model which offers significant value in yielding deeper mechanistic insight into immune-mediated liver toxicity associated with various immunotherapies. Hepatitis is one of the common immune-related adverse events in cancer patients receiving immune checkpoint inhibitor (ICI) therapy. The mechanisms of ICI-induced hepatitis are not well understood. In this paper, we identify key molecular mechanisms mediating immune intracellular crosstalk between liver T cells and macrophages in response to ICI in a mouse model. [Display omitted] • P dcd 1 -/- mouse can be utilized as a model for immune checkpoint inhibitor-mediated liver injury. • Single-cell immune transcriptional profiling revealed a landscape of molecular pathways responding to inhibition of PD1, CTLA4 and IDO1. • We identified a subset-specific T cell activation signature and common IFNγ signature. • Monocyte-derived macrophages coordinate the T cell response to immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
18. Antitumor and immunoregulatory activities of a novel polysaccharide from Astragalus membranaceus on S180 tumor-bearing mice.
- Author
-
Yu, Juan, Dong, Xiao-dan, Jiao, Jian-shuang, Ji, Hai-yu, and Liu, An-jun
- Subjects
- *
ASTRAGALUS membranaceus , *WESTERN immunoblotting , *CELL cycle , *B cells , *ANIMAL disease models , *T cells , *DIETARY supplements - Abstract
The Astragalus membranaceus polysaccharide (APS4) with direct cytotoxicity on various cancer cells has been prepared in our previous study, while the underlying therapeutic role of APS4 on solid tumors in vivo hasn't been investigated yet. Therefore, in this paper, the lymphocytes-mediated antitumor and immunoregulatory activities of APS4 were researched by establishing S180 tumor-bearing mice model. Flow cytometry analysis revealed that APS4 could effectively regulate the percentages of CD3+, CD4+, CD8+ T cells and CD19+ B cells in thymus, peripheral blood and spleen of S180 tumor-bearing mice, dose-dependently. H&E staining and cell cycle determination of solid tumors manifested that APS4 treatment could significantly inhibit the growth of solid tumors by inducing cells apoptosis. Furthermore, two-dimensional electrophoresis and western blot analysis further demonstrated that APS4 could activate antitumor-related immune cells and promote anaerobic metabolism of tumor microenvironment, thereby causing the apoptosis of S180 tumor cells. These data implicated that APS4 could be used as a potential dietary supplement for immune enhancement. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
19. B cells masquerade as dendritic cells.
- Author
-
Denzin, Lisa K.
- Subjects
- *
B cells , *DENDRITIC cells , *T cells - Abstract
In a recent paper, Schriek et al. show that, in a complement-dependent reaction, marginal zone B cells (MZBs) steal MHC class II (MHCII) from dendritic cells (DCs). Activation of T cells by stolen MHCII complexes potentially allows MZBs to augment or regulate T cell activation in ways that are distinct from DCs. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
20. Biophysiology of in ovo administered bioactive substances to improve gastrointestinal tract development, mucosal immunity, and microbiota in broiler chicks.
- Author
-
Ayalew, Habtamu, Wang, Jing, Wu, Shugeng, Qiu, Kai, Tekeste, Ayalsew, Xu, Changchun, Lamesgen, Dessalegn, Cao, Sumei, Qi, Guanghai, and Zhang, Haijun
- Subjects
- *
CHICKS , *GASTROINTESTINAL system , *PHAGOCYTOSIS , *CELL receptors , *LYMPHOCYTE count , *T cells , *IMMUNITY , *PROBIOTICS - Abstract
Early embryonic exogenous feeding of bioactive substances is a topic of interest in poultry production, potentially improving gastrointestinal tract (GIT) development, stimulating immunization, and maximizing the protection capability of newly hatched chicks. However, the biophysiological actions and effects of in ovo administered bioactive substances are inconsistent or not fully understood. Thus, this paper summarizes the functional effects of bioactive substances and their interaction merits to augment GIT development, the immune system, and microbial homeostasis in newly hatched chicks. Prebiotics, probiotics, and synbiotics are potential bioactive substances that have been administered in embryonic eggs. Their biological effects are enhanced by a variety of mechanisms, including the production of antimicrobial peptides and antibiotic responses, regulation of T lymphocyte numbers and immune-related genes in either up- or downregulation fashion, and enhancement of macrophage phagocytic capacity. These actions occur directly through the interaction with immune cell receptors, stimulation of endocytosis, and phagocytosis. The underlying mechanisms of bioactive substance activity are multifaceted, enhancing GIT development, and improving both the innate and adaptive immune systems. Thus summarizing these modes of action of prebiotics, probiotics and synbiotics can result in more informed decisions and also provides baseline for further research. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
21. An intimate encounter: DC3s empower anti-tumor CTLs.
- Author
-
Stojanovic, Ana and Cerwenka, Adelheid
- Subjects
- *
CELL survival , *HOMEOSTASIS , *CELL physiology , *CELL communication , *CYTOTOXIC T cells , *CELL proliferation , *T cells - Abstract
Discrete tissue niches are emerging as essential prerequisites enabling cell communication and function in both homeostasis and disease. In a recent Cell paper, Di Pilato et al. identify a unique dendritic cell-cytotoxic T cell crosstalk within the perivascular space that facilitates T cell survival and proliferation and drives anti-tumor activity. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
22. Modeling the cytotoxicity of Romidepsin reveals the ineffectiveness of this drug in the "shock and kill" strategy.
- Author
-
Deng, Qi, Guo, Ting, Qiu, Zhipeng, and Chen, Yuming
- Subjects
- *
HIV , *T cells , *HIV infections , *VIRAL load , *MULTISCALE modeling - Abstract
The "shock and kill" strategy is being widely explored to purge Human Immunodeficiency Virus (HIV) latent reservoirs. Romidepsin, a kind of latency-reversing agents (LRAs), has been shown to induce HIV RNA transcription. However, several clinical trials testing this drug have resulted in limited effect in reducing the HIV latent reservoirs. To understand the mechanisms underlying such limited effect, we develop a multi-scale model that incorporates pharmacokinetics and considers the toxicity of romidepsin to T cells in this paper. By fitting the model to the viral load data from plasma of six patients received romidepsin, we find that the model with T cell toxicity of romidepsin can well explain the clinical data. The dynamics of latently infected cells during romidepsin administration are explored using the best-fit parameter values. The results show that latently infected cells decrease very slowly and remain very stable overall in four of the six participants under the assumption of T cell toxicity of romidepsin. This implies that the ineffectiveness of romidepsin on latent reservoirs can be explained by its toxicity to T cells. In the remaining two participants, however, latently infected cells are quite stable without T cell toxicity of LRAs. It is found that the estimated activation rate of latently infected cells by romidepsin and the estimated elimination rate of romidepsin on immune cells for these two patients are very different from those for the other four patients. Thus we speculate that the heterogeneous response to romidepsin across participants may also be a determining factor of the effectiveness of romidepsin. These results may have significant implications in the search for the control of HIV infection. • An HIV model is proposed to understand the cause of ineffectiveness of romidepsin in the "shock and kill" strategy. • The model has a good fit to patients' data when T cell toxicity of romidepsin is considered. • The toxicity of romidepsin to T cell may contribute to the ineffectiveness of "shock and kill" strategy concerning romidepsin. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
23. Multiple bifurcations in a mathematical model of glioma-immune interaction.
- Author
-
Ma, Linyi, Hu, Dongpo, Zheng, Zhaowen, Ma, Cui-Qin, and Liu, Ming
- Subjects
- *
MATHEMATICAL models , *HOPF bifurcations , *GLIOMAS , *CANCER cells , *CONTINUOUS time models , *T cells - Abstract
In this paper, a mathematical model describing the interaction of malignant glioma cells, macrophages and glioma specific CD8+T cells is discussed. The biologically feasible equilibria and corresponding local stability are deduced. The bifurcations and related dynamical behaviors of this model are further studied thoroughly. The existence of transcritical bifurcation and saddle–node bifurcation is derived based on Sotomayor's theorem and Hopf bifurcation is well discussed. The codimension 2 bifurcation such as Bogdanov–Takens bifurcation is investigated using the normal form theory and center manifold theorem in more detail. Finally, numerical simulations are obtained to validate our analytical findings by varying the parameters. • The dynamics of a mathematical model describing the interaction of malignantglioma cells, macrophages and glioma specific CD8+T cells are discussed. • The co-existence of equilibria of the model are obtained by numerical simulation. • The existence of codimension 1 and codimension 2 bifurcations is investigated. • Extensive numerical simulations are obtained to validate our analytical findings. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
24. The interactions of docetaxel with tumor microenvironment.
- Author
-
Gupta, Reena, Kadhim, Mustafa M., Turki Jalil, Abduladheem, Qasim Alasheqi, Mohammed, Alsaikhan, Fahad, Khalimovna Mukhamedova, Nurkhan, Alexis Ramírez-Coronel, Andrés, Hassan Jawhar, Zanko, Ramaiah, Pushpamala, and Najafi, Masoud
- Subjects
- *
DOCETAXEL , *TUMOR microenvironment , *TUBULINS , *KILLER cells , *ANTINEOPLASTIC agents , *T cells - Abstract
• Docetaxel boosted anticancer effects of NK cells and CD8 + T lymphocytes. • Docetaxel stimulated the recruitment of tumor-associated macrophages. • Targeting some molecules such as PD-1 enhanced the anticancer activity of docetaxel. There are several interactions within the tumor microenvironment (TME) that affect the response of cancer cells to therapy. There are also a large number of cells and secretions in TME that increase resistance to therapy. Following the release of immunosuppressive, pro-angiogenic, and metastatic molecules by certain cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and cancer cells, immune evasion, angiogenesis, and metastasis may be induced. However, natural killer (NK) cells and cytotoxic CD8 + T lymphocytes (CTLs) can responsively release anticancer molecules. In addition, anticancer drugs can modulate these cells and their interactions in favor of either cancer resistance or therapy. Docetaxel belongs to taxanes, a class of anti-tumor drugs, which acts through the polymerization of tubulin and the induction of cell cycle arrest. Also, it has been revealed that taxanes including docetaxel affect cancer cells and the other cells within TME through some other mechanisms such as modulation of immune system responses, angiogenesis, and metastasis. In this paper, we explain the basic mechanisms of docetaxel interactions with malignant cells. Besides, we review the diverse effects of docetaxel on TME and cancer cells in consequence. Lastly, the modulatory effects of docetaxel alone or in conjunction with other anticancer agents on anti-tumor immunity, cancer cell resistance, angiogenesis, and metastasis will be discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
25. Indoleamine 2,3-dioxygenase 1 in circumventing checkpoint inhibitor responses: Updated.
- Author
-
Charehjoo, Arian, Majidpoor, Jamal, and Mortezaee, Keywan
- Subjects
- *
INDOLEAMINE 2,3-dioxygenase , *DIOXYGENASES , *CYTOTOXIC T lymphocyte-associated molecule-4 , *REGULATORY T cells , *T cells , *IMMUNE checkpoint inhibitors , *ENDOENZYMES - Abstract
[Display omitted] • IDO1 induces immune tolerance within TME. • Serum profiling of IDO1 metabolites is of prognostic value. • IDO1 upregulation occurs after ICI therapy. • IDO1 inhibitors can be used safely with ICI therapy. • Epacadostat plus ICI renders promising clinical responses. • Clinical efficacy of anti-PD-L1/IDO inhibitor vaccination is promising. Metabolic alterations occur commonly in tumor cells as a way to adapt available energetic sources for their proliferation, survival and resistance. Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular enzyme catalyzing tryptophan degradation into kynurenine. IDO1 expression shows a rise in the stroma of many types of human cancers, and it provides a negative feedback mechanism for cancer evasion from immunosurveillance. Upregulation of IDO1 correlates with cancer aggression, poor prognosis and shortened patient survival. The increased activity of this endogenous checkpoint impairs effector T cell function, increases regulatory T cell (Treg) population and induces immune tolerance, so its inhibition potentiates anti-tumor immune responses and reshapes immunogenic state of tumor microenvironment (TME) presumably through normalizing effector T cell activity. A point is that the expression of this immunoregulatory marker is upregulated after immune checkpoint inhibitor (ICI) therapy, and that it has inducible effect on expression of other checkpoints. These are indicative of the importance of IDO1 as an attractive immunotherapeutic target and rationalizing combination of IDO1 inhibitors with ICI drugs in patients with advanced solid cancers. In this review, we aimed to discuss about the impact of IDO1 on tumor immune ecosystem, and the IDO1-mediated bypass of ICI therapy. The efficacy of IDO1 inhibitor therapy in combination with ICIs in advanced/metastatic solid tumors is also a focus of this paper. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
26. Novel evidence of Thymosin α1 immunomodulatory properties in SARS-CoV-2 infection: Effect on innate inflammatory response in a peripheral blood mononuclear cell-based in vitro model.
- Author
-
Ricci, Daniela, Etna, Marilena Paola, Severa, Martina, Fiore, Stefano, Rizzo, Fabiana, Iannetta, Marco, Andreoni, Massimo, Balducci, Stefano, Stefanelli, Paola, Palamara, Anna Teresa, and Coccia, Eliana Marina
- Subjects
- *
MONONUCLEAR leukocytes , *THYMOSIN , *SARS-CoV-2 , *T-cell exhaustion , *INFLAMMATION , *T cells - Abstract
[Display omitted] • SARS-CoV-2 promotes an inflammatory phenotype in human monocytes. • In SARS-CoV-2 stimulated PBMC Tα1 mitigates monocyte and myeloid DC activation. • Tα1 dampens SARS-CoV-2 mediated induction of pro-inflammatory cytokines. • Tα1 promotes release of the anti-inflammatory factors IL-10 from SARS-CoV- 2-stimulated PBMC. The peculiar property of Thymosin alpha 1 (Tα1) to act as master regulator of immune homeostasis has been successfully defined in different physiological and pathological contexts ranging from cancer to infection. Interestingly, recent papers also demonstrated its mitigating effect on the "cytokine storm" as well as on the T-cell exhaustion/activation in SARS-CoV-2 infected individuals. Nevertheless, in spite of the increasing knowledge on Tα1-induced effects on T cell response confirming the distinctive features of this multifaceted peptide, little is known on its effects on innate immunity during SARS-CoV-2 infection. Here, we interrogated peripheral blood mononuclear cell (PBMC) cultures stimulated with SARS-CoV-2 to disclose Tα1 properties on the main cell players of early response to infection, namely monocytes and myeloid dendritic cells (mDC). Moving from ex vivo data showing an enhancement in the frequency of inflammatory monocytes and activated mDC in COVID-19 patients, a PBMC-based experimental setting reproduced in vitro a similar profile with an increased percentage of CD16+ inflammatory monocytes and mDC expressing CD86 and HLA-DR activation markers in response to SARS-CoV-2 stimulation. Interestingly, the treatment of SARS-CoV-2-stimulated PBMC with Tα1 dampened the inflammatory/activation status of both monocytes and mDC by reducing the release of pro-inflammatory mediators, including TNF-α, IL-6 and IL-8, while promoting the production of the anti-inflammatory cytokine IL-10. This study further clarifies the working hypothesis on Tα1 mitigating action on COVID-19 inflammatory condition. Moreover, these evidence shed light on inflammatory pathways and cell types involved in acute SARS-CoV-2 infection and likely targetable by newly immune-regulating therapeutic approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
27. Immune system activation in polymyalgia rheumatica: Which balance between autoinflammation and autoimmunity? A systematic review.
- Author
-
Hysa, Elvis, Gotelli, Emanuele, Sammorì, Silvia, Cimmino, Marco Amedeo, Paolino, Sabrina, Pizzorni, Carmen, Sulli, Alberto, Smith, Vanessa, and Cutolo, Maurizio
- Subjects
- *
TALL-1 (Protein) , *IMMUNE system , *POLYMYALGIA rheumatica , *GROWTH factors , *AUTOIMMUNE diseases , *AUTOIMMUNITY , *ENDOTHELIUM diseases - Abstract
Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease that is common in elderly people. Its classification in the spectrum of autoinflammatory and autoimmune diseases is difficult because of its only partially understood immune-mediated mechanisms. The literature concerning the innate and adaptive immune system activation in PMR was systematically reviewed highlighting the relative weight of autoinflammation and autoimmunity in its pathogenesis and disease progression. A literature search on PubMed Central and Embase scientific databases was performed by two independent reviewers. To be eligible, the studies needed to fully satisfy our initial PICO framework: a primary diagnosis of PMR as a population, the search for immune/inflammatory cells, cytokines and autoantibodies as an intervention, a control group consisting in healthy controls, patients with other inflammatory rheumatic diseases or PMR patients in remission after treatment and as outcomes the results of the investigations in the analyzed tissue samples. The most relevant data of the included papers were extracted by using a standardized template. Of the 933 screened abstracts, 52 papers were included in the systematic review and categorized depending on their primary research objectives. The hyper-activity of neutrophils and monocytes, expressing toll-like receptor 7 in active disease, an impaired phagocytosis and endothelial dysfunction, as well as an increased count of innate T cells in patients with remission emerged among the major derangements of the innate immune response in PMR. Among the cytokines profile, interleukin-6 plays a key role but other pro-inflammatory mediators and angiogenesis markers such as chemokines, B-cell activating factor, vascular endothelial growth factor and angiopoietins seem to be involved in refractory or glucocorticoid-resistant PMR. The aberrant adaptive immune response was documented by tissue and serum findings of polarized T cells towards T helper 1 and 17 phenotypes, an increased expression of immunosenescent surface markers and a downregulated immunoregulatory response. The altered distribution of peripheral B cells, detected during active disease, suggested their peripheral migration towards unidentified sites. The interaction between innate and adaptive immune response was documented by a synovial infiltrate of macrophages and T cells. Despite multiple autoantibodies have been detected in PMR patients, none proved to correlate with disease activity seeming to be reactive to the marked inflammation or antigenic determinants provided by environmental triggers or tissue/cell damage. The complex network between innate and adaptive immune system in PMR is supported by findings at molecular and cellular levels. By considering both the ends of the pathophysiological spectrum of immune-mediated rheumatic diseases, PMR may be regarded as an inflammatory immune-mediated disease with mixed mechanisms in a background of genetic and epigenetic factors together with immunological and endocrine senescence. • High concentrations of serum pro-inflammatory cytokines and cell growth factors identify active PMR patients • Innate immune cells might play a role both in PMR disease activity and sub-clinical ongoing inflammation. • T cells are dysregulated in PMR for a hyper-expression of immunosenescent markers and deficient immunoregulatory pathways. • B cells peripheral distribution is altered during active disease suggesting an inflammatory-driven compartmentalization. • Autoantibodies do not seem pathogenetic in PMR but may be reactive to external triggers or damaged tissues self-antigens. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
28. Dendritic cell-targeting polymer nanoparticle-based immunotherapy for cancer: A review.
- Author
-
Hu, Yeye, Zhang, Wei, Chu, Xiaozhong, Wang, Aoran, He, Ziliang, Si, Chuan-Ling, and Hu, Weicheng
- Subjects
- *
DENDRITIC cells , *IMMUNOLOGICAL adjuvants , *NANOMEDICINE , *POLYMERS , *IMMUNE response , *IMMUNOTHERAPY , *T cells - Abstract
Created with BioRender.com [Display omitted] Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
29. Area-efficient radiation-hardened 6 T SOI SRAM cell design using TDBC Transistors.
- Author
-
Lv, Yinghuan, Xie, Tiantian, Liu, Yulan, Ren, Zhipeng, and Chen, Jing
- Subjects
- *
STATIC random access memory , *TRANSISTORS , *FLOATING bodies , *THRESHOLD energy , *PULSED lasers , *T cells - Abstract
Single event upset (SEU) is a critical issue for the static random access memory (SRAM) exposed to irradiated environments. In this paper, an area-efficient 6 T SRAM cell design based on partially depleted silicon-on-insulator (PDSOI) technology is proposed to improve the ability to resist SEU using tunnel-diode body-contact (TDBC) transistors. The proposed cell and 6 T floating body (FB) SOI SRAM cell are fabricated using 130 nm PDSOI technology for comparison purposes. Pulsed laser experiments show that, at the nominal supply voltage of 1.2 V, the energy threshold of the proposed cell increases by 25.2 % compared to the 6 T FB SOI cell with a similar area. The energy threshold of the traditional T-gate body-contact (TB) cell is also compared with that of the proposed cell. • An area-efficient 6 T SRAM cell design based on PDSOI technology is proposed to improve the ability of resisting SEU. • The proposed cell and 6 T floating body SOI SRAM cell are fabricated using 130 nm PDSOI technology for comparison purposes. • The energy threshold of the proposed cell increases by 25.2 % compared to the 6 T FB SOI cell with a similar area. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
30. Host immunity to Plasmodium infection: Contribution of Plasmodium berghei to our understanding of T cell-related immune response to blood-stage malaria.
- Author
-
Ibraheem, Yarob, Bayarsaikhan, Ganchimeg, and Inoue, Shin-Ichi
- Subjects
- *
PLASMODIUM berghei , *T helper cells , *CYTOTOXIC T cells , *IMMUNE response , *PLASMODIUM , *T cells - Abstract
Malaria is a life-threatening disease caused by infection with Plasmodium parasites. The goal of developing an effective malaria vaccine is yet to be reached despite decades of massive research efforts. CD4+ helper T cells, CD8+ cytotoxic T cells, and γδ T cells are associated with immune responses to both liver-stage and blood-stage Plasmodium infection. The immune responses of T cell-lineages to Plasmodium infection are associated with both protection and immunopathology. Studies with mouse model of malaria contribute to our understanding of host immune response. In this paper, we focus primarily on mouse malaria model with blood-stage Plasmodium berghei infection and review our knowledge of T cell immune responses against Plasmodium infection. Moreover, we also discuss findings of experimental human studies. Uncovering the precise mechanisms of T cell-mediated immunity to Plasmodium infection can be accomplished through further investigations using mouse models of malaria with rodent Plasmodium parasites. Those findings would be invaluable to advance the efforts for development of an effective malaria vaccine. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
31. Stability and Hopf bifurcation of a tumor–immune system interaction model with an immune checkpoint inhibitor.
- Author
-
Shi, Shujing, Huang, Jicai, Kuang, Yang, and Ruan, Shigui
- Subjects
- *
IMMUNE checkpoint inhibitors , *HOPF bifurcations , *T cells , *HOPFIELD networks , *ORBITS (Astronomy) , *INTRAVENOUS injections , *TUMOR growth - Abstract
In this paper we study a three-dimensional tumor–immune system interaction model consisted of tumor cells, activated T cells, and immune checkpoint inhibitor anti-PD-1. Based on the uncontrollable character of tumor cells in the absence of immune response and treatment, the growth of tumor cells is assumed to be exponential. We discuss the distribution of equilibria qualitatively and study the stability of all possible equilibria with and without anti-PD-1 drug. When no drug is applied, the model has a tumor-free equilibrium and at most one tumorous equilibrium. Biologically, there exists a threshold d T 1 for the death rate d T of T cells: when d T ≥ d T 1 tumor cells will keep growing; when d T < d T 1 tumor cells may be eradicated for some positive initial values and keep growing for some other positive initial values. For the case with anti-PD-1 treatment, the model has at most five tumor-free equilibria and two interior equilibria. Our analysis indicates that there exists a threshold γ A 1 for the intravenous continuous injection γ A : when γ A ≤ γ A 1 the fate of tumor cells is the same as the case with no drug applied; when γ A > γ A 1 the model may exhibit bistable phenomena and periodic orbits. Furthermore, we establish the existence of local Hopf bifurcation around the interior equilibrium and determine the stability of the bifurcating periodic orbits. Our simulations show that the model exhibits a stable periodic orbit which implies the long term coexistence and balance of the tumor and immune system. • Study a tumor–immune system interaction model with an immune checkpoint inhibitor. • Discuss the number and stability of all possible equilibria. • Establish the existence of Hopf bifurcation and the stability of the periodic orbit. • Carry out numerical simulations to illustrate the theoretical results. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
32. The effect of hepatitis B virus on T lymphocyte and its subsets in chronic hepatitis B patients in different ALT stages: A new concept ALT in HBV infection.
- Author
-
Gao, Peng, Luo, Yanping, Chen, Lin, Yang, Zhongxia, He, Qiang, and Li, Junfeng
- Subjects
- *
CHRONIC hepatitis B , *LYMPHOCYTE subsets , *HEPATITIS B virus , *HEPATITIS associated antigen , *TH2 cells , *T cells , *HEPATITIS B - Abstract
• This paper compares and analyzes the difference of immune status of T lymphocytes and their subsets in hepatitis B patients under different ALT conditions for the first time. • For the first time, this paper reveals the changes of immune status and the effects of antiviral therapy on immune function when ALT is greater than or equal to 2 times the normal upper limit. • This paper puts forward for the first time the significance of using ALT as a node to judge the immune function of the body. The aim of the present study was to explore the effect of hepatitis B virus on T lymphocyte and its subsets in different ALT states, and elucidate the immunological mechanism of ALT basing antiviral therapy for hepatitis B. 363 chronic hepatitis B patients were selected as the study subjects. According to ALT abnormalities, the patients were divided into three study groups. ALT normal group 131 cases, normal≦ ALT < 2 times of upper limit group 110 cases, ALT ≥ 2 times of upper limit group 122 cases. Entecavir was given to the ALT ≥ 2 times of upper limit group patients and followed up for 24 weeks. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the hepatitis B virus load were measured by quantitative PCR analyzer, T lymphocytes were detected by flow cytometry, the level of IL-2, IFN-γ, IL-4 and IL-10 were detected by enzyme-linked immunosorbent assay. Detecting the influence of different hepatitis B viru loads in different groups on immunological indexes, and the virological and immunological indexes changes in before and after antiviral therapy patients. In the ALT normal group, different virus load hepatitis B virus had minor effect on T lymphocytes and their subsets (P > 0.05). In the ALT ≥ double upper limit of normal group. with the virus load increased, The total number of T lymphocytes, CD3+ CD4 + T lymphocytes decreased, (P < 0.05)CD3+ CD8 + T lymphocytes increased(P < 0.05). With the virus load increased the cytokines IL-2, IFN-γ which reflect the Th1 lymphocytes increased(P < 0.05), the cytokines IL-4、IL-10 which reflect the Th2 lymphocytes decreased(P < 0.05). Before and after 24 weeks of entecavir treatment, the patient's HBV-DNA decreased significantly(P < 0.05) and the body's immune function improved significantly. (P < 0.05)The influence of hepatitis B virus on immune function is different in different ALT states. Therefore, the scientific significance of ALT grouping in the hepatitis B treatment can be clarified from the immunological point. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
33. The role of dendritic cells in allergic diseases.
- Author
-
Liu, Peng, Kang, Chenglin, Zhang, Jin, Liu, Yue, Liu, Jiangqi, Hu, Tianyong, Zeng, Xianhai, and Qiu, Shuqi
- Subjects
- *
ALLERGIES , *DENDRITIC cells , *IMMUNOREGULATION , *T cells , *T helper cells , *BIOLOGICAL classification , *ALLERGIC rhinitis , *FOOD allergy - Abstract
• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
34. Application of network composite module analysis and verification to explore the bidirectional immunomodulatory effect of Zukamu granules on Th1 / Th2 cytokines in lung injury.
- Author
-
Li, Yixuan, Li, Siyu, Gu, Min, Liu, Guoxiu, Li, Yanan, Ji, Zhihong, Li, Keao, Wang, Yanping, Zhai, Huaqiang, and Wang, Yongyan
- Subjects
- *
CYTOKINES , *LUNG injuries , *STAT proteins , *HERBAL medicine , *IDIOPATHIC pulmonary fibrosis , *IMMUNOGLOBULINS , *ANIMAL experimentation , *IMMUNOMODULATORS , *REGULATORY T cells , *IMMUNE system , *CELLULAR signal transduction , *T cells , *CHINESE medicine , *ACUTE diseases , *MICE - Abstract
Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
35. A sub-threshold 10T FinFET SRAM cell design for low-power applications.
- Author
-
Dolatshah, Amir, Abbasian, Erfan, Nayeri, Maryam, and Sofimowloodi, Sobhan
- Subjects
- *
STATIC random access memory , *COLUMNS , *T cells , *PSYCHOLOGICAL feedback - Abstract
This paper presents a high-stability low-power 10 T (HSLP10T) sub-threshold SRAM cell with single-ended operations. The HSLP10T cell uses a decoupled read path, formed by a transmission gate and a dynamic inverter, thereby, resulting in read stability improvement. In addition, it employs a feedback-cutting transistor to facilitate the write operation, which increases writability. Due to single-ended operations, direct-write on complementary node, floated bitline, and use of more p-type transistors, the power consumption reduces in the proposed cell. Simulated results in the 7-nm FinFET technology indicate that at a 300 mV supply voltage, the read stability/writability of the proposed HSLP10T cell is 2.06X/1.31X as that of the conventional 6 T cell. Moreover, the dynamic/leakage power consumption is reduced by 1.82X/2.92X when compared with the conventional 6 T SRAM. The proposed HSLP10T SRAM bitcell has a layout area of 0.047 µm2, which is 1.67 × larger than the conventional 6 T SRAM. However, the highest ON-to-OFF currents ratio related to the proposed design compensates for this area overhead by connecting more number of cells to the same bitline in the columns of the SRAM array. Moreover, the minimum operation voltage is reduced by 48.28 % using proposed design compared to the conventional 6 T SRAM. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
36. The role of dendritic cells in allergic diseases.
- Author
-
Liu, Peng, Kang, Chenglin, Zhang, Jin, Liu, Yue, Liu, Jiangqi, Hu, Tianyong, Zeng, Xianhai, and Qiu, Shuqi
- Subjects
- *
ALLERGIES , *DENDRITIC cells , *IMMUNOREGULATION , *T cells , *T helper cells , *BIOLOGICAL classification , *ALLERGIC rhinitis , *FOOD allergy - Abstract
• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
37. Recent advances in the production, reprogramming, and application of CAR-T cells for treating hematological malignancies.
- Author
-
Vandghanooni, Somayeh, Eskandani, Morteza, Sanaat, Zohreh, and Omidi, Yadollah
- Subjects
- *
HEMATOLOGIC malignancies , *MONONUCLEAR leukocytes , *T cells , *CHIMERIC antigen receptors , *CURRENT good manufacturing practices - Abstract
As genetically engineered cells, chimeric antigen receptor (CAR)-T cells express specific receptors on their surface to target and eliminate malignant cells. CAR proteins are equipped with elements that enhance the activity and survival of T cells. Once injected, CAR-T cells act as a "living drug" against tumor cells in the body. Up to now, CAR-T cell therapy has been demonstrated as a robust adoptive cell transfer (ACT) immunotherapeutic modality for eliminating tumor cells in refractory hematological malignancies. CAR-T cell therapy modality involves several steps, including the collecting of the blood from patients, the isolation of peripheral blood mononuclear cells (PBMCs), the enrichment of CD4+/CD8+ T cell, the genetic reprogramming, the expansion of modified T cells, and the injection of genetically engineered T cells. The production of CAR-T cells is a multi-step procedure, which needs precise and safety management systems, including good manufacturing practice (GMP), and in-line quality control and assurance. The current study describes the structure of CARs and concentrates on the next generations of CARs that are engaged in enhancing the anti-tumor responses and safety of the engineered T cells. This paper also highlights the important concerns in quality control and nonclinical research of CAR-T cells, as well as general insights into the manufacture, reprogramming, and application of CAR-T cells based on new and enhanced techniques for treating hematological malignancies. Besides, the application of the CRISPR-Cas9 genome editing technology and nanocarrier-based delivery systems containing CAR coding sequences to overcome the limitations of CAR-T cell therapy has also been explained. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
38. Bessel-quasilinearization technique to solve the fractional-order HIV-1 infection of CD[formula omitted] T-cells considering the impact of antiviral drug treatment.
- Author
-
Yüzbaşı, Şuayip and Izadi, Mohammad
- Subjects
- *
T cells , *QUASILINEARIZATION , *ANTIVIRAL agents , *HIV , *NONLINEAR equations , *LINEAR equations - Abstract
• Two numerical methods are developed for solving the fractional-order HIV-1 infection model of CD4 + T-cells. • Two method (Bessel matrix method and Bessel quasilinearization method) are based on the novel Bessel polynomials. • Error and convergence analysis are studied. • Numerical applications and comparisons show that methods are effective. • In the comparison of the two methods used, the Bessel-QLM method gives better results. In this paper, two numerical methods based on the novel Bessel polynomials are developed to solve the fractional-order HIV-1 infection model of CD 4 + T-cells considering the impact of antiviral drug treatment. In first of these methods, by using the Bessel polynomial and collocation points, we transform the HIV problem into a system of nonlinear algebraic equations. And this method, which is the method of direct solution is called as Bessel matrix method. The second method, which is called the Bessel-QLM method converts firstly HIV problem to a sequence of linear equations by using the technique of quasilinearization and then the reduced problem is solved by the direct Bessel matrix method. Error and convergence analysis are studied for the Bessel method. Finally, the applications are made on the numerical examples and also the numerical results are compared with the results of other available techniques. It is observed from applications that the presented results are better than the results of other existing methods and also the Bessel-QLM method is more efficient than the direct Bessel method. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
39. T cells direct microglial repair of white matter after stroke.
- Author
-
Zera, Kristy A. and Buckwalter, Marion S.
- Subjects
- *
WHITE matter (Nerve tissue) , *REGULATORY T cells , *T cells , *MICROGLIA , *ISCHEMIC stroke - Abstract
A recent paper by Shi et al. defines the role of regulatory T cells (Tregs) in white matter recovery after ischemic stroke. This study elucidates the mechanisms by which Tregs direct microglia to alter their phenotype to support oligodendrogenesis, thereby improving white matter integrity and functional recovery after stroke in mice. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
40. Rules of thumb to obtain, isolate, and preserve porcine peripheral blood mononuclear cells.
- Author
-
Díaz, Ivan
- Subjects
- *
MONONUCLEAR leukocytes , *T cells , *PORCINE reproductive & respiratory syndrome - Abstract
One of the most used biospecimens in immunology are peripheral blood mononuclear cells (PBMC). PBMC are particularly useful when evaluating immunity through responses of circulating B- and T-cells, during an infection, or after a vaccination. While several reviews and research papers have been published aiming to point out critical steps when sampling, isolating, and cryopreserving human PBMC -or even analyzing any parameter before sampling that could impair the immune assays' outcomes-, there are almost no publications in swine research dealing with these topics. As it has been demonstrated, several factors, such as stress, circadian rhythmicity, or the anticoagulant used have serious negative impact, not only on the separation performance of PBMC, but also on the ulterior immune assays. The present review aims to discuss studies carried out in humans that could shed some light for swine research. When possible, publications in pigs are also discussed. The main goal of the review is to encourage swine researchers to standardize protocols to obtain, manage and preserve porcine PBMC, as well as to minimize, or at least to consider, the bias that some parameters might induce in their studies before, during and after isolating PBMC. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
41. Design of high stability, low power and high speed 12 T SRAM cell in 32-nm CNTFET technology.
- Author
-
Mani, Elangovan, Abbasian, Erfan, Gunasegeran, Muthukumaran, and Sofimowloodi, Sobhan
- Subjects
- *
STATIC random access memory , *T cells , *FIELD-effect transistors - Abstract
Many researchers are trying to create a low power, high stability, and high-speed static random access memory (SRAM) cell. This paper introduces an SRAM cell consisting of 12 transistors (12 T) developed by carbon nanotube field-effect transistor (CNTFET) to support such an endeavor and be a milestone in creating a better SRAM cell. The proposed 12 T CNTFET SRAM cell is a modified Schmitt-trigger (ST)-based SRAM cell design. The ST-based SRAM cell feedback-cutting and single-ended read decupled techniques are introduced to improve the SRAM cell's static noise margin (SNM) and access time. The presence of stacked N-CNTFETs reduces the proposed cell's power consumption. In addition to conventional 6 T [9] and 8 T [10] SRAM cells, it has been compared with some of the existing SRAM cells such as 12 T SRAM [11] , 12 T SRAM [12] , 12 T SRAM [13] and 12 T SRAM [14] , for calculating the relative performance of the proposed 12 T CNTFET SRAM cell design in terms of fundamental design metrics. The simulation results at 0.9 V show that compared to the afromentioned bit cells, the proposed design accomplishes low power consumption while writing, reading, and holding modes of operation. It has a high SNM during all the operations. The proposed cell has the least read access time. The power, SNM, and access time performance of the bit cells are evaluated for the variation of CNTFET parameters and reported in this article. The proposed cell is also implemented using MOSFET, and the performance of MOSFET and CNTFET is compared. The simulation is done with the HSPICE simulation tool using the Stanford University 32 nm CNTFET model. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
42. CD38: An important regulator of T cell function.
- Author
-
Li, Wentao, Liang, Lin, Liao, Qianjin, Li, Yanling, and Zhou, Yanhong
- Subjects
- *
T cells , *CELL physiology , *CD38 antigen , *EXTRACELLULAR enzymes , *CHIMERIC antigen receptors - Abstract
Cluster of differentiation 38 (CD38) is a multifunctional extracellular enzyme on the cell surface with NADase and cyclase activities. CD38 is not only expressed in human immune cells, such as lymphocytes and plasma cells, but also is abnormally expressed in a variety of tumor cells, which is closely related to the occurrence and development of tumors. T cells are one of the important immune cells in the body. As NAD consuming enzymes, CD38, ART2, SIRT1 and PARP1 are closely related to the number and function of T cells. CD38 may also influence the activity of ART2, SIRT1 and PARP1 through the CD38-NAD+ axis to indirectly affect the number and function of T cells. Thus, CD38-NAD+ axis has a profound effect on T cell activity. In this paper, we reviewed the role and mechanism of CD38+ CD4+ T cells / CD38+ CD8+ T cells in cellular immunity and the effects of the CD38-NAD+ axis on T cell activity. We also summarized the relationship between the CD38 expression level on T cell surface and disease prediction and prognosis, the effects of anti-CD38 monoclonal antibodies on T cell activity and function, and the role of anti-CD38 chimeric antigen receptor (CAR) T cell therapy in tumor immunity. This will provide an important theoretical basis for a comprehensive understanding of the relationship between CD38 and T cells. [Display omitted] • As a NAD consuming enzyme, CD38 is closely related to the number and function of T cells. • The expression of CD38 in CD4+ T cells and CD8+ T cell affects the function of CD4+T cell. • The expression level of CD38 on T cell surface is associated with disease prediction and prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
43. Synthesis and biological evaluation of artemisinin derivatives as potential MS agents.
- Author
-
Zhang, Yan, Lv, Jie, Zhang, Suqing, Yang, Hanxi, Shen, Jingshan, Du, Changsheng, Jiang, Xiangrui, and Aisa, Haji A.
- Subjects
- *
ARTEMISININ derivatives , *BIOSYNTHESIS , *MYELIN oligodendrocyte glycoprotein , *T cells , *MULTIPLE sclerosis - Abstract
[Display omitted] In this paper, a series of artemisinin derivatives were synthesized and evaluated. Studies have shown that IFN-γ produced by Th1 CD4+ T cells and IL-17A secreted by Th17 CD4+ T cells played critical roles in the treatment of multiple sclerosis. We used different concentrations of artemisinin derivatives to inhibit Th1 / Th17 differentiation in naive CD4+ T cells and to characterize IFN-γ / IL-17A in in vitro experiments. The preliminary screening results showed that ester compound 5 exhibited obvious inhibitory activities on Th1 and Th17 (IFN-γ decreased from 41% to 3% and IL-17A decreased from 24% to 8% at the concentration of 10 nM to 10 μM), and carbamate compounds also had obvious inhibitory activities against Th17 at high concentration. Moreover, we investigated the effect of compound 5 on myelin oligodendrocyte glycoprotein (MOG)-induced mice experimental autoimmune encephalomyelitis (EAE) model in vivo. 100 mg/kg compound 5 effectively reduced the disease severity of EAE compared with the vehicle group. This research revealed that compound 5 could be a promising avenue as potential MS inhibitor. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
44. Dynamics of a reaction-diffusion fractional-order model for M1 oncolytic virotherapy with CTL immune response.
- Author
-
Younoussi, Majda El, Hajhouji, Zakaria, Hattaf, Khalid, and Yousfi, Noura
- Subjects
- *
CYTOTOXIC T cells , *ONCOLYTIC virotherapy , *IMMUNE response , *T cells , *PARTIAL differential equations , *FRACTIONAL differential equations - Abstract
• A reaction-diffusion fractional-order model for M1 oncolytic virotherapy with CTL immune response is presented. • Threshold parameters and equilibria are determined. • Stability analysis are rigorously established. • Numerical simulations are given to illustrate the analytical results. Despite many years of research, cancer continues to be a major worldwide concern. Several researchers proposed their mathematical models to understand and describe the dynamics of tumor cells under some cancer treatments. In this paper, we present a fractional partial differential equation system to describe the dynamics in space and time of the concentration of normal cells, tumor cells, nutrient, M1 virus, and cytotoxic T lymphocytes (CTL) cells, as well as the interaction between them. We study and analyze the equilibrium points of the presented system. The global stability of these equilibrium points is proved by constructing adequate Lyapunov functional for each equilibrium point. Furthermore, we give some numerical simulations to illustrate our results. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
45. Hopf bifurcation and chaos of tumor-Lymphatic model with two time delays.
- Author
-
Wang, Jingnan, Shi, Hongbin, Xu, Li, and Zang, Lu
- Subjects
- *
HOPF bifurcations , *T cells , *BIFURCATION theory , *LYMPHATICS , *CELL proliferation , *IMMUNE system - Abstract
• Obtain threshold values and formulas of the Hopf bifurcation. • Show the interesting chaotic attractors and the periodic oscillation. • Use bifurcation theory to explain the chaotic attractor formation. • Obtain the biomedical significance corresponding to model dynamics. In this paper, a tumor and Lymphatic immune system interaction model with two time delays is discussed in which the delays describe the proliferation of tumor cells and the transmission from immature T lymphocytes to mature T lymphocytes respectively. Conditions for the asymptotic stability of the equilibrium and the existence of Hopf bifurcations are obtained by analyzing the roots of a characteristic equation. The computing formulas for the stability and the direction of the Hopf bifurcating periodic solutions are given. Numerical simulation show that different values of time delays can generate different behaviors, including the stable-state, the periodic oscillation and the chaotic attractors, as well as the coexistence of two periodic oscillations. These theoretical and numerical results not only can be useful for explaining the occurrence of chaotic attractors, but also can help for understanding the biomedical significance corresponding to the interaction dynamics of tumor cells and T lymphocytes. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
46. Superior low-immunogenicity of tilapia type I collagen based on unique secondary structure with single calcium binding motif over terrestrial mammals by inhibiting activation of DC intracellular Ca2+-mediated STIM1-Orai1/NF-кB pathway.
- Author
-
Xu, Xiao, Sui, Baiyan, Liu, Xin, and Sun, Jiao
- Subjects
- *
AMINO acid sequence , *TILAPIA , *COLLAGEN , *T cells , *INTRACELLULAR calcium , *CLINICAL medicine , *CELLULAR signal transduction - Abstract
The reason for low- or non-immunogenicity of fish collagens is still in doubt, which, to some extent, bottlenecks their production and clinical application as biomaterials. Employing bovine or porcine type I collagens (BCI or PCI) as controls in this paper, we intensively investigate the influence of tilapia type I collagens (TCI) on the function of dendritic cells (DCs) and T cells. From bio-informatic analyses, as well as data obtained in vitro and in vivo , we find the variations in amino acid sequences lead to only one calcium binding motif in the secondary structure of TCI, compared with three in BCI or PCI. So when TCI (together with the minor amount of Ca2+ they take) are uptaken, intracellular [Ca2+] remains stable and DCs maintain immature. On the contrary, those that have uptaken PCI or BCI experience not only increased [Ca2+] in the plasma but also phosphorylation of p65, resulting in activation of STIM1-Orai1/NF-кB signaling pathway and DC maturation. We fully prove our results on mice models, with no obvious cellular and humoral immune reactions. Our study primarily reveal the underlying mechanisms why TCI, different from BCI or PCI, show almost non-immunogenicity. Our findings are of great importance for the promotion and wide application of TCI in biomedicine. [Display omitted] • Tilapia type I collagens (TCI) do not induce DC maturation. • TCI do not enhance intracellular [Ca2+] by not activating STIM1-Orai1/NF-кB pathway. • Variations in amino acid sequences result in different numbers of calcium ligands. • TCI show lower immunogenicity than terrestrial mammals both in vitro and in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
47. Intelligent photothermal dendritic cells restart the cancer immunity cycle through enhanced immunogenic cell death.
- Author
-
Sun, Zhihong, Deng, Guanjun, Peng, Xinghua, Xu, Xiuli, Liu, Lanlan, Peng, Jiaofeng, Ma, Yifan, Zhang, Pengfei, Wen, Austin, Wang, Yifan, Yang, Zhaogang, Gong, Ping, Jiang, Wen, and Cai, Lintao
- Subjects
- *
DENDRITIC cells , *CELL death , *T cells , *CANCER cells , *IMMUNITY , *HEAT shock proteins , *IMMUNOLOGICAL tolerance - Abstract
Dendritic cells (DCs) play a pivotal role in initiating antigen-specific tumor immunity. However, the abnormal function of DCs owing to the immunosuppressive tumor microenvironment (TME) and the insufficient number of tumor infiltrating DCs could promote immune tolerance and tumor immune escape. Thus, there is great potential to employ DCs to induce efficient antitumor immunity. In this paper, we developed intelligent DCs (iDCs), which consist of nanoparticles loaded with photothermal agents (IR-797) and coated with a mature DC membrane. The DC cell membrane on the surface of iDCs preserves the ability to present antigens and prime T cells. The iDCs can also enter the lymph node and stimulate T cells. The activated T cells reduced the expression of heat shock proteins (HSPs) in tumor cells, rendering them more sensitive to heat stress. Subsequently, we used mild photothermal therapy (42–45 °C) to induce immunogenic cell death and contribute to a synergistic antitumor effect. iDCs as a refined and precise system in combination with DC-based immunotherapy and thermal therapy can be stored long-term and on a large scale, so they can be applied in many patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
48. The interactions between major immune effector cells and Hepatocellular Carcinoma: A systematic review.
- Author
-
Schoenberg, Markus Bo, Li, Xiaokang, Li, Xinyu, Han, Yongsheng, Börner, Nikolaus, Koch, Dominik, Guba, Markus Otto, Werner, Jens, and Bazhin, Alexandr V.
- Subjects
- *
T cells , *KILLER cells , *HEPATOCELLULAR carcinoma , *TUMOR-infiltrating immune cells , *CYTOTOXIC T cells , *CELL communication , *LIVER tumors - Abstract
• Major immune effector cells like CD8+ T lymphocytes and natural killer cells are able to kill or inhibit Hepatocellular carcinoma (HCC) cells and their cytotoxic ability can be enhanced or down-regulated by certain cytokines or drugs. • HCC cells can impair the function of major immune effector cells through a variety of mechanisms. • Organoids or direct contact cell co-culture especially with primary HCC cells and tumor infiltrating lymphocytes provide better understanding of cell–cell interactions between major immune effector cells and HCC cells. • Immunotherapy like checkpoint inhibitors and adoptive cell transfer showed notable effectiveness and safety in preventing HCC recurrence as adjuvant therapy. Hepatocellular carcinoma (HCC) is the most common liver neoplasm with high morbidity and mortality. Tumor immunotherapy might be promising adjuvant therapy for HCC after surgery. To better develop HCC immunotherapy, comprehensive understanding of cell–cell interactions between immune effector cells and HCC cells remains crucial. To review the existing studies to summarize the cell–cell interactions between major immune effector cells and HCC cells providing new data for HCC immunotherapy. A systematic review was conducted by searching PubMed database covering all papers published in recent five years up to January 2020. The guidelines of the preferred reporting items for systematic reviews were firmly followed. There are 9 studies researching the interactions between CD8+ T lymphocytes and HCC cells and 22 studies researching that between natural killer (NK) cells and HCC cells. Among the 9 studies, 6 studies reported that CD8+ T lymphocytes showed cytotoxicity towards HCC cells while 3 studies found CD8+ T lymphocytes were impaired by HCC cells. Among the 22 studies, 20 studies presented that NK cells could inhibit HCC cells. Two studies were found to report NK cell dysfunction in HCC. Based on the systematic analysis, we concluded that CD8+ T lymphocytes and NK cells can inhibit HCC cells. While in turn, HCC cells can also result in the dysfunction of those effector cells through various mechanisms. Organoids and direct contact cell co-culture with primary HCC cells and TILs should be the most innovative way to investigate the interactions and develop novel immunotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
49. Analysis of Th1/Th2 response pattern with Treg cell inhibition and stochastic effect.
- Author
-
Liang, Qiantong and Lo, Wing-Cheong
- Subjects
- *
REGULATORY T cells , *TH2 cells , *TH1 cells , *CELLULAR control mechanisms , *CELL aggregation , *T cells - Abstract
• A mathematical model of the interactions between Th1 and Th2 cells with Treg cell inhibition and stochastic effects is developed. • Sufficient conditions for different asymptotic phases of Th1 and Th2 responses under the Treg cell regulation are obtained. • Numerical simulations are performed to identify the basins of attraction of different steady states and illustrate different dynamical scenarios. • The effect of stochastic effect under the Treg cell regulation is discussed. • The switching probability and the mean residence time are applied to study the effect of noise. T cells differentiate into Th1 or Th2 cells upon maturation to influence different patterns of the immune response. Th1 and Th2 cells regulate each other and their responses are inhibited by Treg cells. With noisy external stimulation, Th1/Th2 cell differentiation can be dynamically balanced. The underlying mechanisms of Th cell differentiation under Treg cell inhibition and the extrinsic noise effects are not yet completely understood. In this paper, a mathematical model of the interactions between Th1 and Th2 cells with Treg cell inhibition and stochastic effects is developed to study the preference of outcomes and the noise-induced hopping among different states. First, we provide the conditions for different asymptotic phases of Th1 and Th2 responses under Treg cell regulation. Numerical simulations are applied to calculate the switching probability and the mean residence time to study how the noise affects the attractiveness of different states. Our results support that due to the stronger inhibitory effect of Treg cells on Th1 cell development, the high-Th2-low-Th1 state is more attractive under small noise effects. Additionally, we show that the attractiveness of the states is affected mainly by the extrinsic noise in Th2 cell signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
50. Dynamical behaviour of HIV Infection with the influence of variable source term through Galerkin method.
- Author
-
Attaullah, Jan, Rashid, and Yüzbaşı, Şuayip
- Subjects
- *
GALERKIN methods , *HIV , *HUMAN body , *T cells , *THYMUS , *HTLV - Abstract
In this paper, we formulate the intricate process of Human Immunodeficiency Virus (HIV) infection in a mathematical model. In the formulation of the model, the density of CD 4 + T-cells is categorized into healthy and infected classes while the density of free HIV viruses in the human host's blood is considered a separate class. It is reported that when HIV enters a human's body, it infects a large amount of CD 4 + T-cells and unbalance the supply of new cells from the thymus. Therefore, we incorporate variable source term relying on the viral load for the supply of new cells instead of using a fixed value for the supply of these cells. We implement a continuous Galerkin Petrov time discretization scheme, particularly cGP(2)-scheme to visualize the dynamical behavior of the mentioned model and a detailed description of the effects of different physical parameters of interest are depicts graphically and discuss that how the level of healthy, infected CD 4 + T-cells and free HIV particles varies concerning the emerging parameters in the model. In the proposed cGP(2)-method, two unknowns terms can be found by solving a 2 × 2 block system. This method is accurate of order 3 in the whole time interval and shows even superconvergence of order 4 in the discrete-time points. Furthermore, determine the solution of the model utilizing the fourth-order Runge-Kutta (RK4)-method and find out the absolute errors between the solutions obtained from both approaches. Finally, the validity and reliability of the proposed scheme are verified by comparing the numerical and graphical results with the RK-4 method. We examine the accuracy of the cGP(2)-sheme and observe that it produces more accurate results at relatively larger step sizes as in comparison to RK-4 scheme. Correspondence between the findings of cGP(2)-method and RK4-method reveal that the new technique is a promising tool for obtaining approximate solutions to the nonlinear systems of real-world problems. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.