Latest Issue
Issue 1 ， 2020
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Lymphatic vessels, miRNAs, and CAR T cells in tumor immunology
Abstract：This special feature contains three review articles that summarize recent advances pertaining to tumor immunobiology. Normalization of antitumor immunity through checkpoint inhibitors has achieved significant clinical success and benefited many cancer patients. However, not all cancer patients respond to these treatments, and among the responders, some may develop resistance and others may suffer autoimmunity that requires intervention. Tumor immunotherapy holds promise for further improving the survival of cancer patients, but deeper understanding of immunological networks that regulate anti- and pro-tumor immunity is needed. The review papers collected in this issue cover a few topics that may stimulate future interest in the relevant research field.Keywords：Lymphatic;MicroRNA;Chimera antigen receptor T cell;Immunology- 23
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Published：2022-01-05
Editorial
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Lymphatic vasculature in tumor metastasis and immunobiology
Abstract：Lymphatic vessels are essential for tissue fluid homeostasis, immune cell trafficking, and intestinal lipid absorption. The lymphatics have long been recognized to serve as conduits for distant tumor dissemination. However, recent findings suggest that the regional lymphatic vasculature also shapes the immune microenvironment of the tumor mass and potentiates immunotherapy. This review discusses the role of lymphatic vessels in tumor metastasis and tumor immunity.Keywords：Lymphatic;Lymphatic endothelial cell (LEC);Cancer;Metastasis;Immunotherapy- 22
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Published：2022-01-05 -
MicroRNAs in tumor immunity: functional regulation in tumor-associated macrophages
Abstract：Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and are critical for cancer initiation and progression. MicroRNAs (miRNAs) could notably influence the phenotype of TAMs through various targets and signal pathways during cancer progression due to their post-transcriptional regulation. In this review, we discuss mainly the regulatory function of miRNAs on macrophage differentiation, functional polarization, and cellular crosstalk. Firstly, during the generation process, miRNAs take part in the differentiation from myeloid cells to mature macrophages, and this maturation process directly influences their recruitment into the TME, attracted by tumor cells. Secondly, macrophages in the TME can be either tumor-promoting or tumor-suppressing, depending on their functional polarization. Large numbers of miRNAs can influence the polarization of macrophages, which is crucial for tumor progression, including tumor cell invasion, intravasation, extravasation, and premetastatic site formation. Thirdly, crosstalk between tumor cells and macrophages is essential for TME formation and tumor progression, and miRNAs can be the mediator of communication in different forms, especially when encapsulated in microvesicles or exosomes. We also assess the potential value of certain macrophage-related miRNAs (MRMs) as diagnostic and prognostic markers, and discuss the possible development of MRM-based therapies.Keywords：MicroRNA;Tumor microenvironment;Tumor-associated macrophage;Functional polarization- 108
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Published：2022-01-05 -
Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma
Abstract：Multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approaches, chimeric antigen receptor (CAR) T-cell therapy is the most promising star, based on the results of previous success in B-cell neoplasms. In this immunotherapy, autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure. Tisagenlecleucel and Axicabtagene, targeting the CD19 antigen, are the two pacesetters of CAR T-cell products. They were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Their development enabled unparalleled efficacy in combating hematopoietic neoplasms. In this review article, we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.Keywords：Chimeric antigen receptor (CAR) T cells;Immunotherapy;Monoclonal antibody (mAb);Target antigen;Multiple myeloma- 34
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Published：2022-01-05
Review
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Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis
Abstract：Osteoarthritis (OA) is a degenerative articular disorder manifested by cartilage destruction, subchondral sclerosis, osteophytes, and synovitis, resulting in chronic joint pain and physical disability in the elderly. The purpose of this study was to investigate mitochondrial DNA copy number (mtDNACN) and inflammatory cytokines in primary knee OA patients and healthy volunteers. A total of 204 knee OA patients and 169 age-matched healthy volunteers were recruited. Their relative blood leukocyte mtDNACN was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), and ten inflammatory cytokines in their plasma were detected by multiplex immunoassay. Blood leukocyte mtDNACN in the OA group was significantly lower than that in the control group. Leukocyte mtDNACN in the control group was negatively correlated with their age (r=−0.380, P<0.0001), whereas mtDNACN in the OA group was positively correlated with their age (r=0.198, P<0.001). Plasma interleukin-4 (IL-4) and IL-6 were significantly higher in the knee OA group than in the control group. The plasma IL-6 level was positively correlated with blood leukocyte mtDNACN in the OA group (r=0.547, P=0.0014). IL-5 showed as a major factor (coefficient 0.69) in the second dimension of principle components analysis (PCA)-transformed data and was significantly higher in the OA group (P<0.001) as well as negatively correlated with mtDNACN (r=−0.577, P<0.001). These findings suggest that elevation of plasma IL-4 and IL-6 and a relative reduction in mtDNACN might be effective biomarkers for knee OA. IL-5 is a plausible factor responsible for decreasing blood leukocyte mtDNACN in knee OA patients.Keywords：Inflammatory cytokine;Blood leukocyte;Knee;Mitochondrial DNA copy number;Osteoarthritis- 125
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Published：2022-01-05 -
Psychophysiological and cognitive effects of strawberry plants on people in isolated environments
Abstract：In manned deep-space exploration, extremely isolated environments may adversely affect the mood and cognition of astronauts. Horticultural plants and activities have been proven to be effective in improving their physical, psychological, and cognitive states. To assess the effects of applying horticultural plants and activities in isolated environments, this study investigated the influence of viewing strawberry plants on the mood of people in a laboratory experiment as indicated by heart rate, salivary cortisol, and psychological scales. The results showed that heart rate and salivary cortisol were significantly decreased after viewing strawberry plants for 15 min. “Tension” and “confusion” scored using the Profile of Mood States negative mood subscales, and anxiety levels measured using the State-Trait Anxiety Inventory scale were also significantly reduced. This study further explored the impact of viewing strawberry plants on cognition. A notable reduction of the subjects’ reaction time after 15-min plant viewing was observed. Based on these findings, a long-duration isolated experiment in a bioregenerative life support system—“Lunar Palace I”—was conducted. A similar trend was obtained that crew members’ mood states were improved by viewing the strawberry plants, but no significant change was observed. This study provided some experimental evidence for the benefits of interacting with strawberry plants in isolated environments.Keywords：Isolated environment;Horticultural welfare;Strawberry;Mood;Cognition- 95
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Published：2022-01-05 -
Carfilzomib inhibits the growth of lung adenocarcinoma via upregulation of Gadd45a expression
Abstract：Proteasome inhibitors have shown remarkable success in the treatment of hematologic neoplasm. There has been a lot of attention to applying these drugs for solid tumor treatment. Recent preclinical study has signified the effectiveness on cell proliferation inhibition in lung adenocarcinoma treated by carfilzomib (CFZ), a second generation proteasome inhibitor. However, no insight has been gained regarding the mechanism. In this study, we have systematically investigated the CFZ functions in cell proliferation and growth, cell cycle arrest, and apoptosis in lung adenocarcinoma cells. Flow cytometry experiments showed that CFZ significantly induced G2/M cell cycle arrest and apoptosis in lung adenocarcinoma. MTS and colony formation assays revealed that CFZ substantially inhibited survival of lung adenocarcinoma cells. All results were consistently correlated to the upregulation expression of Gadd45a, which is an important gene in modulating cell cycle arrest and apoptosis in response to physiologic and environmental stresses. Here, upregulation of Gadd45a expression was observed after CFZ treatment. Knocking down Gadd45a expression suppressed G2/M arrest and apoptosis in CFZ-treated cells, and reduced cytotoxicity of this drug. The protein expression analysis has further identified that the AKT/FOXO3a pathway is involved in Gadd45a upregulation after CFZ treatment. These findings unveil a novel mechanism of proteasome inhibitor in anti-solid tumor activity, and shed light on novel preferable therapeutic strategy for lung adenocarcinoma. We believe that Gadd45a expression can be a highly promising candidate predictor in evaluating the efficacy of proteasome inhibitors in solid tumor therapy.Keywords：Carfilzomib;Lung adenocarcinoma;Gadd45a;Cell cycle arrest;Apoptosis- 18
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Published：2022-01-05 -
Toxicity and metabolism of 3-bromopyruvate in
Caenorhabditis elegans Abstract：In this study, we aimed to evaluate the toxic effects, changes in life span, and expression of various metabolism-related genes in Caenorhabditis elegans, using RNA interference (RNAi) and mutant strains, after 3-bromopyruvate (3-BrPA) treatment. C. elegans was treated with various concentrations of 3-BrPA on nematode growth medium (NGM) plates, and their survival was monitored every 24 h. The expression of genes related to metabolism was measured by the real-time fluorescent quantitative polymerase chain reaction (qPCR). Nematode survival in the presence of 3-BrPA was also studied after silencing three hexokinase (HK) genes. The average life span of C. elegans cultured on NGM with 3-BrPA was shortened to 5.7 d compared with 7.7 d in the control group. hxk-1, hxk-2, and hxk-3 were overexpressed after the treatment with 3-BrPA. After successfully interfering hxk-1, hxk-2, and hxk-3, the 50% lethal concentration (LC50) of all mutant nematodes decreased with 3-BrPA treatment for 24 h compared with that of the control. All the cyp35 genes tested were overexpressed, except cyp-35B3. The induction of cyp-35A1 expression was most obvious. The LC50 values of the mutant strains cyp-35A1, cyp-35A2, cyp-35A4, cyp-35B3, and cyp-35C1 were lower than that of the control. Thus, the toxicity of 3-BrPA is closely related to its effect on hexokinase metabolism in nematodes, and the cyp-35 family plays a key role in the metabolism of 3-BrPA.Keywords：3-Bromopyruvate;Caenorhabditis elegans;Hexokinase;Cytochrome P450- 48
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Published：2022-01-05
Article
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Modified stepwise mini-incision microdissection testicular sperm extraction: a useful technique for patients with a history of orchidopexy affected by non-obstructive azoospermia
Abstract：Non-obstructive azoospermia (NOA), which is defined as the absence of spermatozoa in the ejaculate secondary to impaired spermatogenesis within the testis, may be caused by a variety of etiologies, including varicocele-induced testicular damage, cryptorchidism, prior testicular torsion, post-pubertal mumps orchitis, gonadotoxic effects from medications, genetic abnormalities, chemotherapy/radiation, and other unknown causes currently classified as idiopathic (Cocuzza et al., 2013). The microdissection testicular sperm extraction (micro-TESE) technique involves a meticulous microsurgical exploration of the testicular parenchyma to identify and selectively extract larger seminiferous tubules that carry a higher probability of complete spermatogenesis (Schlegel, 1999). The Cornell group evaluated the efficacy of micro-TESE in 152 NOA patients with an associated history of cryptorchidism. In their series, spermatozoa were successfully retrieved in 116/181 attempts (64%), and the resulting pregnancy rate was 50% with a delivery rate of 38% (Dabaja and Schlegel, 2013). Franco et al. (2016) described a stepwise micro-TESE approach in NOA patients, which was considered to reduce the cost, time, and effort associated with the surgery. Alrabeeah et al. (2016) further reported that a mini-incision micro-TESE, carried through a 1-cm equatorial testicular incision, can be useful for micro-TESE candidates, particularly in patients with cryptozoospermia. We conducted a retrospective study of 20 consecutive NOA patients with a history of orchidopexy from May 2015 to March 2017.Keywords：Non-obstructive azoospermia;Microdissection testicular sperm extraction;Orchidopexy;Cryptorchidism- 26
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Published：2022-01-05
Correspondence
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