bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune-related arthritis following pelvic radiation therapy in a patient with lung cancer receiving long-term immune checkpoint blocker treatment: Case report
Authors: Aldea Mihaela , Belkhir Rakiba , Colomba Emeline , Blanchard Pierre , Danlos Francois-Xavier , Botticella Angela , Terlizzi Mario , Deutsch Eric , Le Péchoux Cecile , Planchard David , Michot Jean-Marie , Besse Benjamin , Levy Antonin
Published: October 2022

Radiotherapy can trigger immune-related out-of-field “abscopal” response. We report a patient with advanced NSCLC (non-small cell lung cancer) receiving long-term anti-PD1 (programmed cell death protein 1) who have developed out-of-field immune-related arthritis following pelvic irradiation.
Endostatin induces normalization of blood vessels in colorectal cancer and promotes infiltration of CD8+ T cells to improve anti-PD-L1 immunotherapy
Authors: Chu Xiao-Dong , Bao Hui , Lin Yu-Jian , Chen Ruo-Xi , Zhang Yi-Ran , Huang Ting , He Jia-Shuai , Huangfu Shu-Chen , Pan Yun-Long , Ding Hui
Published: October 2022

Introduction

The purpose of this study was to evaluate recombinant human endostatin (rHE)-induced normalization of the tumor vasculature in colorectal cancer (CRC) and to evaluate the therapeutic effects of combined treatment with rHE and a programmed death ligand-1 (PD-L1) inhibitor.

Methods

A mouse subcutaneous tumorigenesis model was established to evaluate the antitumor effects of endostatin combined with a PD-L1 inhibitor on CRC. Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DW MRI) was used to evaluate changes in the intratumor microcirculation in response to combined treatment with endostatin and a PD-L1 inhibitor. The infiltration density and function of CD8+ T cells in tumors were evaluated using flow cytometry. Finally, clinical specimens were used to evaluate the expression area of tumor vascular pericytes and CD8+ T cells in tumor tissues.

Results

The antitumor effects of endostatin combined with a PD-L1 inhibitor were significantly greater than those of endostatin or a PD-L1 inhibitor alone. On the ninth day of intervention, the endostatin group showed significantly higher pseudo diffusion parameter (D*) and microvascular volume fraction (F) values in tumors than those in the control group or PD-L1 group. After 27 days of intervention, the endostatin groups showed significantly lower levels of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β than those in the control group. Treatment of CD8+ T cells with endostatin for 24 h did not alter the expression levels of markers of reduced T-cell activity. However, endostatin reversed the VEGF-mediated inhibition of the secretion of interferon (IFN)-γ from T cells. The results in CRC clinical samples showed that treatment with endostatin induced significantly higher infiltration of CD8+ T cells compared with treatment that did not include endostatin. Furthermore, the expression area of pericytes was significantly positively related to the infiltration density of CD8+ T cells and overall survival time.

Conclusion

Endostatin improved the antitumor effects of PD-L1 inhibitors on CRC, significantly increased the activity of CD8+ T cells, and synergistically improved the tumor treatment effect of the two inhibitors.
Hunting down NLRP3 inflammasome: An executioner of radiation-induced injury
Authors: Cheng Han , Chen Lingling , Huang Minchun , Hou Jin , Chen Zhifeng , Yang Xiaojun
Published: October 2022

Radiotherapy is one of the mainstream treatment modalities for several malignancies. However, radiation-induced injury to surrounding normal tissues limits its efficacy. The NLRP3 inflammasome is an essential mechanism of innate immunity that reacts to challenges from endogenous danger signals and pathological microbes. A growing body of evidence has demonstrated a key role of NLRP3 inflammasome in the pathogenesis of radiation-induced tissue injury. Despite accumulating evidence, the potential value of the NLRP3 inflammasome in the management of radiation-induced tissue injury is not adequately recognized. We conducted a literature review to characterize the relationship between NLRP3 inflammasome and radiation injury. By analyzing recent evidence, we identify NLRP3 inflammasome as one of the executioners of radiation-induced injury, since it responds to the challenges of radiation, induces cell pyroptosis and tissue dysfunction, and initiates non-resolving inflammation and fibrosis. Based on these concepts, we propose early intervention/prevention strategies targeting NLRP3 inflammasome in a radiation context, which may help resolve imperative clinical problems.
In-silico evaluation of adenoviral COVID-19 vaccination protocols: Assessment of immunological memory up to 6 months after the third dose
Authors: Stolfi Paola , Castiglione Filippo , Mastrostefano Enrico , Di Biase Immacolata , Di Biase Sebastiano , Palmieri Gianna , Prisco Antonella
Published: October 2022

Background

The immune response to adenoviral COVID-19 vaccines is affected by the interval between doses. The optimal interval is unknown.

Aim

We aim to explore in-silico the effect of the interval between vaccine administrations on immunogenicity and to analyze the contribution of pre-existing levels of antibodies, plasma cells, and memory B and T lymphocytes.

Methods

We used a stochastic agent-based immune simulation platform to simulate two-dose and three-dose vaccination protocols with an adenoviral vaccine. We identified the model’s parameters fitting anti-Spike antibody levels from individuals immunized with the COVID-19 vaccine AstraZeneca (ChAdOx1-S, Vaxzevria). We used several statistical methods, such as principal component analysis and binary classification, to analyze the correlation between pre-existing levels of antibodies, plasma cells, and memory B and T cells to the magnitude of the antibody response following a booster dose.

Results and conclusions

We find that the magnitude of the antibody response to a booster depends on the number of pre-existing memory B cells, which, in turn, is highly correlated to the number of T helper cells and plasma cells, and the antibody titers. Pre-existing memory T cytotoxic cells and antibodies directly influence antigen availability hence limiting the magnitude of the immune response. The optimal immunogenicity of the third dose is achieved over a large time window, spanning from 6 to 16 months after the second dose. Interestingly, after any vaccine dose, individuals can be classified into two groups, sustainers and decayers, that differ in the kinetics of decline of their antibody titers due to differences in long-lived plasma cells. This suggests that the decayers may benefit from a tailored boosting schedule with a shorter interval to avoid the temporary loss of serological immunity.
Prospective surveillance of Zika virus at the end of the Americas’ outbreak: An unexpected outcome
Authors: Rivas Enrique , Ojeda Joyce , Garcia-Rivera Enid J. , Rivera Doris M. , Arredondo José L. , Medina Eduardo López , Aguirre Floriberto , Bernal Luis , Chen Zhenghong , Petit Celine , Guranathan Sanjay , Heinrichs Jon H. , Áñez Germán , Noriega Fernando
Published: October 2022

Objective

The French Polynesia Zika virus (ZIKV) outbreak (2013–2014) broadened the known manifestations of ZIKV disease (ZVD) to include neural and congenital syndromes. A subsequent epidemic in the Americas (2015–2016) caused >685,000 suspected/confirmed cases before seemingly disappearing as fast as it expanded. A study was implemented (2017–2018) to detect ZVD cases in the region (Mexico, Honduras, Colombia and Puerto Rico), with the aim of validating surveillance methodology so as to increase sensitivity in case detection, which would have potential application for future vaccine development endeavors.

Study design and setting

To identify potential cases, we focused on signs/symptoms that were frequently associated with ZVD for confirmation by PCR. Serostatus and seroconversion were evaluated by ZIKV non-structural protein 1 blockade-of-binding enzyme-linked immunosorbent assay (BOB ELISA) and microneutralization assay.

Results

Overall, 2,400 participants aged 15–40 years were enrolled; 959 (40.0%) had signs/symptoms that could be associated with ZVD: axillary temperature ≥37°C (64.3%), myalgia (60.8%) and arthralgia (58.6%). Three suspected cases were virologically confirmed. Zika seroprevalence was high at study initiation (52.6% [BOB ELISA] and 56.0% [microneutralization assay]). In participants who were Zika seronegative, low seroconversion rates were observed after one year follow-up (3.6% [BOB ELISA] and 3.1% [microneutralization assay]).

Conclusion

The ZIKV continued to circulate in the Americas at very low levels following the 2015–2016 outbreak. The epidemiological factors driving Zika’s rapid rise and decline remain poorly understood.

Clinical trial registration

Clinicaltrials.gov: NCT03158233 BARDA (Contract # HHSO100201600039C) WHO Universal Trial Number: U1111-1183-5687.
Correlation analysis between foveal avascular zone and near peripheral retinal hypoperfusion in multiple sclerosis: a wide field optical coherence tomography angiography study
Authors: Montorio Daniela , Cennamo Gilda , Carotenuto Antonio , Petracca Maria , Brescia Morra Vincenzo , Costagliola Ciro
Published: October 2022

The identification of non-invasive biomarkers to investigate and monitor retinal structural and vascular changes in multiple sclerosis (MS) represents an interesting source of debate. Until now optical coherence tomography angiography (OCTA) evaluated the foveal avascular zone (FAZ) and areas of retinal non-perfusion only in the macular region in MS patients. It could be interesting to identify possible biomarkers, useful in assessing the ischemic areas also in the near peripheral retina, since FAZ enlargement and the areas of peripheral retinal non-perfusions share common pathogenic processes. In this cross-sectional study, we investigated the correlation between the FAZ area and retinal vessel density (VD) in the near peripheral retina by new wide-field optical coherence tomography angiography (OCTA) in patients affected by relapsing-remitting multiple sclerosis (RR-MS). Moreover, we compared the FAZ area and the VD of superficial and deep capillary plexuses in the fovea region and in the near peripheral retina (6.4 × 6.4 mm) between RR-MS patients and healthy controls by means of a Solix full-range OCTA. Last, we also detected the changes in structural OCT parameters (ganglion cell complex and retinal nerve fiber layer). Thirty-three eyes of 33 RR-MS patients and 35 eyes of 35 healthy controls were enrolled. RR-MS patients showed a lower VD in the superficial capillary plexus and a significant increase in the FAZ area compared with controls. The deep capillary plexus revealed a reduced VD although not statistically significant in patients with respect to controls. In the patients' group, the FAZ area showed significantly negative correlations with VD of superficial capillary plexuses in the foveal and whole region, while the FAZ area did not negatively correlate with the VD of the deep capillary plexus. The significant correlations among OCTA parameters could demonstrate the FAZ area as a possible biomarker for assessing the perfusion status in the near peripheral retina, useful in RR-MS management. These findings could confirm the role of vascular dysfunction in the pathogenetic mechanisms of MS.
Development of combinatorial antibody therapies for diffuse large B cell lymphoma
Authors: Geanes Eric S. , Krepel Stacey A. , McLennan Rebecca , Pierce Stephen , Khanal Santosh , Bradley Todd
Published: October 2022

Diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma, is typically treated with chemotherapy combined with the immunotherapy rituximab, an antibody targeting the B cell receptor, CD20. Despite the success of this treatment regimen, approximately a third of DLBCL patients experience either relapse or have refractory disease that is resistant to rituximab, indicating the need for alternative therapeutic strategies. Here, we identified that CD74 and IL4R are expressed on the cell surface of both CD20 positive and CD20 negative B cell populations. Moreover, genes encoding CD74 and IL4R are expressed in lymphoma biopsies isolated from all stages of disease. We engineered bispecific antibodies targeting CD74 or IL4R in combination with rituximab anti-CD20 (anti-CD74/anti-CD20 and anti-IL4R/anti-CD20). Bispecific antibody function was evaluated by measuring direct induction of apoptosis, antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity in both rituximab-sensitive and rituximab-resistant DLBCL cell lines. Both anti-CD74/anti-CD20 and anti-IL4R/anti-CD20 were able to mediate ADCC and ADCP, but CD74-targeting therapeutic antibodies could also mediate direct cytotoxicity. Overall, this study strongly indicates that development of bispecific antibodies that target multiple B cell receptors expressed by lymphoma could provide improved defense against relapse and rituximab resistance.
Effects of Danggui Buxue decoction on host gut microbiota and metabolism in GK rats with type 2 diabetes
Authors: Wang Wen-kai , Fan Lu , Ge Fan , Li Zihang , Zhu Jingtian , Yin Kai , Xia Jinyan , Xue Mei
Published: October 2022

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by persistent abnormally elevated blood sugar levels. T2DM affects millions of people and exerts a significant global public health burden. Danggui Buxue decoction (DBD), a classical Chinese herbal formula composed of Astragalus membranaceus (Huangqi) and Angelica sinensis (Danggui), has been widely used in the clinical treatment of diabetes and its complications. However, the effect of DBD on the gut microbiota of individuals with diabetes and its metabolism are still poorly understood. In this study, a T2DM model was established in Goto-Kakizaki (GK) rats, which were then treated with a clinical dose of DBD (4 g/kg) through tube feeding for 6 weeks. Next, we used 16S rRNA sequencing and untargeted metabolomics by liquid chromatography with mass spectrometry (LC–MS) to detect changes in the composition of the microbiota and cecal metabolic products. Our data show that DBD mediates the continuous increase in blood glucose in GK rats, improves insulin sensitivity, reduces expression of inflammatory mediators, and improves systemic oxidative stress. Moreover, DBD also improves microbial diversity (e.g., Romboutsia, Firmicutes, and Bacilli) in the intestines of rats with T2DM. Further, DBD intervention also regulates various metabolic pathways in the gut microbiota, including alanine, aspartate, and glutamate metabolism. In addition, arginine biosynthesis and the isoflavone biosynthesis may be a unique mechanism by which DBD exerts its effects. Taken together, we show that DBD is a promising therapeutic agent that can restore the imbalance found in the gut microbiota of T2DM rats. DBD may modify metabolites in the microbiota to realize its antidiabetic and anti-inflammatory effects.
Gut microbiota diversity and specific composition during immunotherapy in responders with non-small cell lung cancer
Authors: Shoji Fumihiro , Yamaguchi Masafumi , Okamoto Masaki , Takamori Shinkichi , Yamazaki Koji , Okamoto Tatsuro , Maehara Yoshihiko
Published: October 2022

Cancer immunotherapy including immune checkpoint inhibitors (ICI) has revolutionized non-small cell lung cancer (NSCLC) therapy. Recently, the microbiota status “before” initiation of ICI therapy has been emphasized as a predictive biomarker in patients undergoing ICI therapy. However, the microbiota diversity and composition “during” ICI therapy is unknown. This multicenter, prospective observational study analyzed both saliva and feces from 28 patients with NSCLC. We performed 16S ribosomal RNA gene sequencing, then analyzed associations of oral and gut microbiota diversity or composition with ICI response. At the genus level, the alpha diversity of the gut microbiota was significantly greater in responders (n = 17) than in non-responders (n = 11) (Chao 1, p = 0.0174; PD whole tree, p = 0.0219; observed species, p = 0.0238; Shannon, p = 0.0362), while the beta diversity of the gut microbiota was significantly different (principal coordinates analysis, p = 0.035). Compositional differences in the gut microbiota were observed between the two groups; in particular, g_Blautia was enriched in responders, whereas o_RF32 order unclassified was enriched in non-responders. The progression-free survival (PFS) of patients enriched gut microbiota of g_Blautia was significantly longer [median survival time (MST): not reached vs. 549 days, p = 0.0480] and the PFS of patients with gut microbiota of o_RF32 unclassified was significantly shorter (MST: 49 vs. 757 days, p = 0.0205). There were no significant differences between groups in the oral microbiota. This study revealed a strong association between gut microbiota diversity and ICI response in NSCLC patients. Moreover, specific gut microbiota compositions may influence the ICI response. These findings might be useful in identifying biomarkers to predict ICI response.
The identification of the key residues E829 and R845 involved in transient receptor potential melastatin 2 channel gating
Authors: Luo Yuhuan , Chen Shijia , Wu Fei , Jiang Chunming , Fang Marong
Published: October 2022

Transient receptor potential melastatin 2 (TRPM2), a non-selective cation channel, is involved in many physiological and pathological processes, including temperature sensing, synaptic plasticity regulation, and neurodegenerative diseases. However, the gating mechanism of TRPM2 channel is complex, which hinders its functional research. With the discovery of the Ca2+ binding site in the S2–S3 domain of TRPM2 channel, more and more attention has been drawn to the role of the transmembrane segments in channel gating. In this study, we focused on the D820-F867 segment around the S2 domain, and identified the key residues on it. Functional assays of the deletion mutants displayed that the deletions of D820-W835 and L836-P851 destroyed channel function totally, indicating the importance of these two segments. Sequence alignments on them found three polar and charged residues with high conservation (D820, E829, and R845). D820A, E829A, and R845A which removed the charge and the side chain of the residues were tested by 500 μM adenosine diphosphate-ribose (ADPR) or 50 mM Ca2+. E829A and R845A affected the characteristic of channel currents, while D820A behaved similarly to WT, indicating the participations of E829 and R845 in channel gating. The charge reversing mutants, E829K and R845D were then constructed and the electrophysiological tests showed that E829A and E829K made the channel lose function. Interestingly, R845A and R845D exhibited an inactivation process when using 500 μM ADPR, but activated normally by 50 mM Ca2+. Our data suggested that the negative charge at E829 took a vital part in channel activation, and R845 increased the stability of the Ca2+ combination in S2-S3 domain, thus guaranteeing the opening of TRPM2 channel. In summary, our identification of the key residues E829 and R845 in the transmembrane segments of TRPM2. By exploring the gating process of TRPM2 channel, our work helps us better understand the mechanism of TRPM2 as a potential biomarker in neurodegenerative diseases, and provides a new approach for the prediction, diagnosis, and prognosis of neurodegenerative diseases.
Association of sleep quality with lower urinary tract symptoms/benign prostatic hyperplasia among men in China: A cross-sectional study
Authors: Li Yifan , Zhou Xianghong , Qiu Shi , Cai Boyu , Wang Sheng , Chen Lei , Hu Dan , Jiang Zhongyuan , Wang Mingda , Xiong Xingyu , Jin Kun , Wei Qiang , Yang Lu , Ma Li
Published: October 2022

Objective

As the population aged, voiding dysfunction has been steadily rising among males during the past decade. Increasing evidence showed that sleep disorders are associated with an increasing risk of various diseases, but the association between sleep disorders and lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) among Chinese males have not been well characterized.

Materials and methods

We conducted a cross-sectional analysis of data from West China Natural Population Cohort Study (WCNPCS) 2019–2021. Sleep quality was assessed by Pittsburgh sleep quality index (PSQI) in Chinese version. LUTS/BPH as a dependent variable of a binary variable, assessed by a self-reported questionnaire. Multivariate logistic regression analysis were performed to evaluate the correlation between sleep disorders and the risk of LUTS/BPH after adjusting for confounding factors.

Results

11,824 eligible Chinese men participated in this cross-sectional survey. In multivariate logistic regression analysis, after adjusting for confounding variables, global PSQI score (OR: 1.257, 1.119–1.411, p < 0.001) and its six compounds (Subjective sleep quality: OR: 1.376, 1.004–1.886, p = 0.048; Sleep latency: OR: 0.656, 0.557–0.773, p < 0.001; Sleep duration: OR: 1.441, 1.189–1.745, p < 0.001; Habitual sleep efficiency: OR: 1.369, 1.193–1.570, p < 0.001; Daytime dysfunction: OR: 1.702, 1.278–2.267, p < 0.001) except the use of sleep drug subgroup were significantly positively correlated with LUTS/BPH prevalence. Significant interaction effects were observed in age subgroups (age-young group: age < 51; age-middle group: 51 ≤ age ≤ 61; age-older group: age > 61) (P < 0.05). Among older participants, sleep disorders were more significantly associated with the risk of LUTS/BPH.

Conclusion

There was a significant association between poor sleep quality and increased prevalence of LUTS/BPH, especially among the elderly male population, suggesting an important role of healthy sleep in reducing prostate disease burden.
Essential oils of Zingiber officinale: Chemical composition, in vivo alleviation effects on TPA induced ear swelling in mice and in vitro bioactivities
Authors: Zhang Silu , Zhang Lijun , Yu Mengjie , Luo Donghui , Chen Shuai , Liu Weifeng , Zhang Yehui , Zhang Lanyue , Zhao Tiantian
Published: October 2022

Zingiber officinale (ZO) is a traditional food condiment. The essential oils of Z. officinale (ZOEOs) are known to have multiple bioactivities. In this study, gas chromatography mass spectrometer (GC-MS) analytical method was used to identify active ingredient present in ZOEOs. A total of 41 compounds were identified in ZOEOs. Major components in ZOEOs were zingiberene (19.71%), (+)-β-cedrene (12.85%), farnesene (12.17%), α-curcumene (10.18%) and β-elemene (3.54%). Experimental results of 12-O-tetradecanoylphorbol-13 acetate (TPA) induced ear swelling validation mice model showed that ZOEOs treatment has better anti-inflammatory effect compared with ibuprofen (positive control) at high concentrations. Histological and immunohistochemical analysis showed that ZOEOs significantly decreased COX-2, IL-6 and NF-κB expression in a dose dependent manner. The mRNA levels of COX-2 and NF-κB were also down regulated by the application of ZOEOs. This indicated that ZOEOs exhibited positive effects in ear skin protection. Antibacterial experimental results showed that EOZOs had anti-bacterial effects on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. DPPH radical scavenging, A549 cell line and LNCaP cell line inhibition results indicated that ZOEOs exhibited potential antioxidant and anti-tumor properties. The findings of these study provide scientific basis on therapeutic use of ZO in food, cosmetic and pharmaceutical industries.
A multi-network comparative analysis of whole-transcriptome and translatome reveals the effect of high-fat diet on APP/PS1 mice and the intervention with Chinese medicine
Authors: Gao Wenya , Zhou Junyi , Gu Xinru , Zhou Yanyan , Wang Linna , Si Nan , Fan Xiaorui , Bian Baolin , Wang Hongjie , Zhao Haiyu
Published: October 2022

Different studies on the effects of high-fat diet (HFD) on Alzheimer’s disease (AD) pathology have reported conflicting findings. Our previous studies showed HFD could moderate neuroinflammation and had no significant effect on amyloid-β levels or contextual memory on AD mice. To gain more insights into the involvement of HFD, we performed the whole-transcriptome sequencing and ribosome footprints profiling. Combined with competitive endogenous RNA analysis, the transcriptional regulation mechanism of HFD on AD mice was systematically revealed from RNA level. Mmu-miR-450b-3p and mmu-miR-6540-3p might be involved in regulating the expression of Th and Ddc expression. MiR-551b-5p regulated the expression of a variety of genes including Slc18a2 and Igfbp3. The upregulation of Pcsk9 expression in HFD intervention on AD mice might be closely related to the increase of cholesterol in brain tissues, while Huanglian Jiedu Decoction significantly downregulated the expression of Pcsk9. Our data showed the close connection between the alterations of transcriptome and translatome under the effect of HFD, which emphasized the roles of translational and transcriptional regulation were relatively independent. The profiled molecular responses in current study might be valuable resources for advanced understanding of the mechanisms underlying the effect of HFD on AD.
Identification and validation of novel biomarker TRIM8 related to cervical cancer
Authors: Zhang Li , Dan Youli , Ou Chaoyang , Qian Hongyan , Yin Yi , Tang Min , He Qian , Peng Chen , He Aiqin
Published: October 2022

Background

Cervical cancer, as a common gynecological disease, endangers female health. Give the lack of effective biomarkers for the diagnosis and treatment of cervical cancer, this paper aims to analyze the Gene Expression Omnibus (GEO) data sets using comprehensive bioinformatics tools, and to identify biomarkers associated with the cancer in patient samples.

Methods

The bioinformatics methods were used to extract genes related to cervical cancer from GSE39001, while the GEO2R online tool to elaborate on differentially expressed genes (DEGs) in normal and cancer samples, and to clarify related genes and functions. The results were verified by IHC, WB, CCK-8, clone formation and flow cytometry experiments.

Results

A total of 2,859 DEGs were identified in the GEO microarray dataset. We extracted genes associated with both ubiquitination and autophagy from the key modules of weighted gene co-expression network analysis (WGCNA), and the analysis showed that TRIM8 was of great significance for the diagnosis and prognosis of cervical cancer. Besides, experimental validation showed the high TRIM8 expression in cervical cancer, as well as its involvement in the proliferation of cervical cancer cells.

Conclusion

We identified a biomarker (TRIM8) that may be related to cervical cancer through a series of analyses on the GEO dataset. Experimental verification confirmed the inhibition of cervical cancer cells proliferation by lowering TRIM8 expression. Therefore, TRIM8 can be adopted as a new biomarker of cervical cancer to develop new therapeutic targets.
A multicenter study of ICU resource utilization in pediatric, adolescent and young adult patients post CAR-T therapy
Authors: Ragoonanan Dristhi , Bhar Saleh , Mohan Gopi , Beltramo Fernando , Khazal Sajad J. , Hurley Caitlin , Andersen Clark , Margossian Steven , Neelapu Sattva S. , Shpall Elizabeth , Gutierrez Cristina , Tewari Priti , Shoberu Basirat , Talleur Aimee , McCall David , Nunez Cesar , Cuglievan Branko , Tambaro Francesco Paolo , Petropoulos Demetrios , Abdel-Azim Hisham , Mahadeo Kris M.
Published: October 2022

Tisagenlecleucel is associated with remarkable outcomes in treating patients up to the age of 25 years with refractory B-cell acute lymphoblastic leukemia (ALL). Yet, due to unique and potentially life-threatening complications, access remains limited to higher-resource and certified centers. Reports of inequity and related disparities in care are emerging. In this multicenter study of ALL patients admitted for anti-leukemia therapy, who required pediatric intensive care (ICU) support (n = 205), patients receiving tisagenlecleucel (n = 39) were compared to those receiving conventional chemotherapy (n = 166). The median time to ICU transfer was 6 (0–43) versus 1 (0–116) days, respectively (p < 0.0001). There was no difference in the use of vasopressor, ionotropic, sedating, and/or paralytic agents between groups, but use of dexamethasone was higher among tisagenlecleucel patients. Patients receiving tisagenlecleucel were more likely to have cardiorespiratory toxicity (p = 0.0002), but there were no differences in diagnostic interventions between both groups and/or differences in ICU length of stay and/or overall hospital survival. Toxicities associated with tisagenlecleucel are generally reversible, and our findings suggest that resource utilization once admitted to the ICU may be similar among patients with ALL receiving tisagenlecleucel versus conventional chemotherapy. As centers consider improved access to care and the feasibility of tisagenlecleucel certification, our study may inform strategic planning.
Oncolytic herpes simplex virus delivery of dual CAR targets of CD19 and BCMA as well as immunomodulators to enhance therapeutic efficacy in solid tumors combined with CAR T cell therapy
Authors: Liu Yuanyuan , Zheng Yanxin , Deng Tianyi , Huang Yue , Liu Ziwen , Zhan Borui , Zhou Xusha , Yan Runbin , Ren Jiangtao , Xing Yun , Wu Guixing , Zheng Biao , Hu Guang , Wang Wen , Liu Yonghong , Zhao Jing , Chen Xiaoqing , Zhou Grace Guoying
Published: October 2022

Background

The CAR T-cell therapy is a promising approach to treating hematologic malignancies. However, the application in solid tumors still has many tough challenges, including heterogenicity in antigen expressions and immunosuppressive tumor microenvironment (TME). As a new cancer treatment modality, oncolytic virotherapy can be engineered to circumvent these obstacles for CAR T cell therapy in solid tumors.

Methods

In this study, an oHSV T7011 is engineered to drive ectopic expression of dual-antigens, extracellular domains of CD19 and BCMA, on the solid tumor cell surface to be targeted by approved CAR T cells. In addition, multiple immunomodulators, CCL5, IL-12, and anti-PD-1 antibody are also included to modulate the TME. The antitumor activities of T7011 in combination with CD19 or BCMA CAR T-cell were evaluated in vitro and in vivo.

Results

The expression of CD19 or BMCA on the tumor cell surface could be detected after T7011 infection. The level of CCL5 in TME was also increased. Efficacy studies demonstrated that combination with T7011 and CAR-TCD19 or CAR-TBCMA cells showed significant synergistic anti-tumor responses in several solid tumor models.

Conclusion

These studies indicated that the new generation of oHSV T7011 can be a promising combinational therapy with CD19 or BCMA-specific CAR T cells for the treatment of a broad range of solid tumors.
CD19 chimeric antigen receptor T-cell therapy following autologous stem cell transplantation against relapsed or refractory Burkitt lymphoma/leukemia: A case report and literature review
Authors: Ye Mingyu , Gao Lei , Wang Tao , Yu Jiechen , Gui Jiaping , Yang Jianmin
Published: October 2022

Burkitt lymphoma or leukemia (BL) is a highly aggressive non-Hodgkin lymphoma. Older age (over 60 years old) and the presence of high-risk factors (such as abdominal mass, high levels of the serum lactic dehydrogenase, Ann Arbor stage II-IV and so on) usually predict a poorer outcome. Chimeric antigen receptor T cells (CART) have achieved remarkable success in the treatment of B-cell leukemia and lymphoma. Here, for the first time, we report a 61-year-old, high-risk BL patient with autologous stem cell transplantation (ASCT) bridging therapy prior to CART as consolidation therapy. Our findings demonstrate that the combination of ASCT and CART for BL is safe and feasible.
Immune cell-lipoprotein imbalance as a marker for early diagnosis of non-small cell lung cancer metastasis
Authors: Zhang Wei , Wang Weiwei , Wu Junlu , Tian Jiale , Yan Wenhui , Yuan Yi , Yao Yiwen , Shang Anquan , Quan Wenqiang
Published: October 2022

The underlying molecular mechanisms and evolutionary patterns of lung cancer metastasis remain unclear, resulting in a lack of effective indicators for early diagnosis of metastasis. We retrospectively analyzed 117 patients with primary non-small cell lung cancer (NSCLC) admitted to Tongji Hospital of Tongji University in 2021, of which 93 patients with tumor metastasis were set as the metastasis group. 24 patients without metastasis were set as the non-metastasis group. The differences of each index in the two groups of patients and the expression levels in different TNM stages were compared. This study intends to evaluate the diagnostic value and net clinical benefit of common blood-related indicators Neutrophil/lymphocyte (NLR), lymphocyte/monocyte (LMR), High density lipoprotein/neutrophil (HNR), High density lipoprotein/monocyte (HMR) and combined assays in NSCLC metastasis for the early diagnosis of patients with NSCLC metastasis. It was found that the level of NLR was higher in metastatic NSCLC than non-metastatic, but the level of LMR, HNR and HMR was lower. The levels of NLR, LMR, HNR and HMR in patients with different TNM stages showed that NLR levels increased with TNM stage, while LMR, HNR and HMR levels decreased. The threshold probability range of the 4 combined tests was greater and the overall clinical benefit rate was higher compared to the individual tests. Our findings suggest that NLR, LMR, HNR and HMR have better diagnostic value for NSCLC metastasis. This study provides a clinical basis for investigating the mechanisms by which immune cells and lipid metabolism-related proteins remodel the microenvironment prior to NSCLC metastasis.
Regulation of autophagy by non-coding RNAs in gastric cancer
Authors: Wang Zijian , Liu Jiarui , Xie Jingri , Yuan Xingxing , Wang Bingyu , Shen Wenjuan , Zhang Yang
Published: October 2022

Autophagy is a conserved cellular self-digesting process that degrades obsoleting proteins and cellular components and plays a crucial role in the tumorigenesis, metastasis, and drug resistance of various tumors such as gastric cancer (GC). As a hotspot in molecular biology, non-coding RNAs (ncRNAs) are involved in the regulation of multiple biological processes, such as autophagy. Increasing evidence indicate that various ncRNAs exert double roles in the initiation and progression of GC, either serve as oncogenes or tumor suppressors. Recent studies have shown that some ncRNAs could modulate autophagy activity in GC cells, which would affect the malignant transformation and drug resistance. Whether the function of ncRNAs in GC is dependent on autophagy is undefined. Therefore, identifying the underlying moleculr targets of ncRNAs in autophagy pathways and the role of ncRNA-regulated autophagy in GC could develop new treatment interventions for this disease. This review summarizes the autophagy process and its role in GC, and the regulatory mechanisms of ncRNAs, as well as focuses on the dual role of ncRNAs-mediated autophagy in GC, for the development of potential therapeutic strategies in GC patients.
Angioimmunoblastic T-cell lymphoma with extensive follicular dendritic cell and fibroblastic reticular cell network proliferation mimicking follicular dendritic cell sarcoma: A case report with pathologic, immunophenotypic, and molecular findings
Authors: Zhang Fen , Li Wenyu , Cui Qian , Chen Yu , Liu Yanhui
Published: October 2022

Angioimmunoblastic T-cell lymphoma (AITL) is a common type of nodal peripheral T-cell lymphoma, which always presents with extensive follicular dendritic cell (FDC) meshwork. Here, we report a case of AITL combined with extensive spindle cell meshwork. Spindle cells occupied were positive for the FDC markers CD21, CD23, and CD35. Furthermore, some cells were positive for desmin and smooth muscle actin (SMA), suggesting the differentiation of fibroblastic reticular cell (FRC). Interestingly, the proliferation of spindle cells was so extensive that was easily misdiagnosed as FDC sarcoma (FDCS). Next-generation sequencing showed that the common mutations reported in AITL, including RHOA, TET2, and IDH2, were also detected in this case, while the genes that are recurrently mutated in FDCS were not detected. Regrettably, the patient died 19 months later. Overall, we highlight the unusual morphologic features in an AITL patient with extensive FDC and FRC network that may be misdiagnosed as FDCS, and careful morphological observation and immunochemical and molecular examinations are crucial for an accurate diagnosis.
The diagnostic significance of blood-derived circRNAs in NSCLC: Systematic review and meta-analysis
Authors: Yu Weijie , Liu Ruixue , Miao Zhoulin , Zhang Liwei , Sheyhidin Ilyar , Ainiwaer Julaiti
Published: October 2022

Background

Using blood-derived circular RNAs (circRNAs) may be an efficient tool for noninvasive fluid biopsy in diagnosing non-small cell lung cancer (NSCLC). However, no relevant systemic meta-analysis has been conducted so far to support the diagnostic value of using blood-derived circRNAs in NSCLC clinically. The aim of this study is to clarify the issue through a meta-analysis.

Methods

A systematic search strategy was used to search relevant literature in the databases of PubMed, Web of Science, and Cochrane Library from 2017 to 2022. The relationship between the diagnostic accuracy of circRNAs and NSCLC was analyzed. For the purpose of evaluating the quality of the literature, Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used. Statistical analyses were assessed using Stata software (version 17.0) and META-DISC (version 1.4).

Results

The meta-analysis included 1,093 patients with NSCLC and 959 controls. Results are as follows: pooled sensitivity, 0.78 (95% CI = 0.71–0.83, I2 = 71.86); pooled specificity, 0.76 (95% CI = 0.70–0.82, I2 = 70.12); pooled positive likelihood ratio (PLR), 3.3 (95% CI = 2.6–4.2, I2 = 37.56); pooled negative likelihood ratio (NLR), 0.29 (95% CI = 0.23–0.37, I2 = 64.67); diagnostic odds ratio (DOR), 11.42 (95% CI = 7.88–16.56, I2 = 99.05); area under the receiver operating characteristic curve (AUC), 0.84 (95% CI = 0.80–0.87). Based on the subgroup analysis, it appears that the heterogeneity is primarily caused by the NSCLC subgroup.

Conclusion

circRNAs are highly useful diagnostic biomarkers for NSCLC in China. Further prospective studies on the diagnostic value of circRNAs should be conducted in multiple countries.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022323804.
Considerations for future studies on the effect of late phase oxygen strategies on retinopathy of prematurity
Authors: Nusman Charlotte M. , Schalij-Delfos Nicoline E. , Groenwold Rolf H. H. , Onland Wes
Published: October 2022

Strategies to ensure high intraocular oxygen delivery to the developing retina after 32 weeks gestational age, such as higher saturation targets and/or higher hemoglobin levels, are hypothesized to prevent ophthalmological treatment for retinopathy of prematurity (ROP). This short report summarizes the current evidence of these strategies, and discusses possibilities of future studies. A large sample size would be required and therefore the feasibility of a future randomized controlled trial is questioned.
Naoxintong Capsule Alternates Gut Microbiota and Prevents Hyperlipidemia in High-Fat-Diet Fed Rats
Authors: Lu Yihang , Wan Haofang , Wu Yujia , Yang Jiehong , Yu Li , He Yu , Wan Haitong , Li Chang
Published: October 2022

Background: Naoxintong Capsule (NXT) is a formulated Traditional Chinese Medicine (TCM) widely applied in the treatment of cardiovascular and metabolic diseases, most of which are closely related to hyperlipidemia as a major risk factor. Given the current limited understandings to the role of gut microbiota in the lipid-lowering effect of NXT and other TCM products, this study investigated the regulation of gut microbiota and lipid metabolism by NXT, and their potential relationship.

Methods: The chemical components of NXT were firstly analyzed with HPLC-MS method. In high fat diet (HFD)-fed rat models, as well as normal rats as control, the histopathological and biochemical changes of serum and liver were examined, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). In addition, the gut microbiota community was analyzed using 16S rRNA sequencing technique, the fecal levels of gut microbiota related metabolites, including bile acids (BAs) and short chain fatty acids (SCFAs) were determined with HPLC-MS. The correlations of the clinical indicators and gut microbiota related indicators were then investigated statistically.

Results: The results showed that NXT exerted potential preventive effect on hyperlipidemia. Specifically, NXT significantly reduced the body weight, TC, TG and LDL-C in serum, increased HDL-C in serum, reduced the TC and TG in liver, as well as protected liver. The body weight, serum lipid levels and liver function were all significantly alleviated. The gut microbiota of the HFD-fed rats was reconstituted with supplementation of NXT. The fecal levels of gut microbiota related metabolites, including BAs and SCFAs were also altered. The correlation between the gut microbiota and clinical/metabolomic parameters was then studied. As the result, the amount of propionic aicd, Firmicutes/Bacteroidetes ratio (F/B) and the relative abundance of Collinsella in feces are the most possibly potential therapeutic biomarkers of NXT.

Conclusion: NXT was effective in regulation of gut microbiota and prevention of hyperlipidemia in HFD fed rats. The present work might provide novel insights into the anti-hyperlipidemia effect of TCM and afford new scientific evidence for clinical application of TCM.
The molecular mechanisms and intervention strategies of mitophagy in cardiorenal syndrome
Authors: Yao Mengying , Liu Yong , Sun Mengjia , Qin Shaozong , Xin Wang , Guan Xu , Zhang Bo , He Ting , Huang Yinghui
Published: October 2022

Cardiorenal syndrome (CRS) is defined as a disorder of the heart and kidney, in which acute or chronic injury of one organ may lead to acute or chronic dysfunction of the other. It is characterized by high morbidity and mortality, resulting in high economic costs and social burdens. However, there is currently no effective drug-based treatment. Emerging evidence implicates the involvement of mitophagy in the progression of CRS, including cardiovascular disease (CVD) and chronic kidney disease (CKD). In this review, we summarized the crucial roles and molecular mechanisms of mitophagy in the pathophysiology of CRS. It has been reported that mitophagy impairment contributes to a vicious loop between CKD and CVD, which ultimately accelerates the progression of CRS. Further, recent studies revealed that targeting mitophagy may serve as a promising therapeutic approach for CRS, including clinical drugs, stem cells and small molecule agents. Therefore, studies focusing on mitophagy may benefit for expanding innovative basic research, clinical trials, and therapeutic strategies for CRS.
Antiquated ejection fraction: Basic research applications for speckle tracking echocardiography
Authors: Sturgill Sarah L. , Shettigar Vikram , Ziolo Mark T.
Published: October 2022

For years, ejection fraction has been an essentially ubiquitous measurement for assessing the cardiovascular function of animal models in research labs. Despite technological advances, it remains the top choice among research labs for reporting heart function to this day, and is often overstated in applications. This unfortunately may lead to misinterpretation of data. Clinical approaches have now surpassed research methods, allowing for deeper analysis of the tiers of cardiovascular performance (cardiovascular performance, heart performance, systolic and diastolic function, and contractility). Analysis of each tier is crucial for understanding heart performance, mechanism of action, and disease diagnosis, classification, and progression. This review will elucidate the differences between the tiers of cardiovascular function and discuss the benefits of measuring each tier via speckle tracking echocardiography for basic scientists.
Fungal isolates influence the quality of Peucedanum praeruptorum Dunn
Authors: Liu Li , Wang Xuejun , Chen Shaotong , Liu Dong , Song Cheng , Yi Shanyong , Zhu Fucheng , Wang Wei , Wang Fang , Wang Guanglin , Song Xiangwen , Jia Bin , Chen Cunwu , Peng Huasheng , Guo Lanping , Han Bangxing
Published: October 2022

The symbiotic relationship between beneficial microorganisms and plants plays a vital role in natural and agricultural ecosystems. Although Peucedanum praeruptorum Dunn is widely distributed, its development is greatly limited by early bolting. The reason for early bolting in P. praeruptorum remains poorly characterized. We focus on the plant related microorganisms, including endophytes and rhizosphere microorganisms, by combining the traditional isolation and culture method with metagenomic sequencing technology. We found that the OTUs of endophytes and rhizosphere microorganisms showed a positive correlation in the whole growth stage of P. praeruptorum. Meanwhile, the community diversity of endophytic and rhizosphere fungi showed an opposite change trend, and bacteria showed a similar change trend. Besides, the microbial communities differed during the pre- and post-bolting stages of P. praeruptorum. Beneficial bacterial taxa, such as Pseudomonas and Burkholderia, and fungal taxa, such as Didymella and Fusarium, were abundant in the roots in the pre-bolting stage. Further, a strain belonging to Didymella was obtained by traditional culture and was found to contain praeruptorin A, praeruptorin B, praeruptorin E. In addition, we showed that the fungus could affect its effective components when it was inoculated into P. praeruptorum. This work provided a research reference for the similar biological characteristics of perennial one-time flowering plants, such as Saposhnikovia divaricate, Angelica sinensis and Angelica dahurica.
Multi-stage resistance to Zymoseptoria tritici revealed by GWAS in an Australian bread wheat diversity panel
Authors: Yang Nannan , Ovenden Ben , Baxter Brad , McDonald Megan C. , Solomon Peter S. , Milgate Andrew
Published: October 2022

Septoria tritici blotch (STB) has been ranked the third most important wheat disease in the world, threatening a large area of wheat production. Although major genes play an important role in the protection against Zymoseptoria tritici infection, the lifespan of their resistance unfortunately is very short in modern wheat production systems. Combinations of quantitative resistance with minor effects, therefore, are believed to have prolonged and more durable resistance to Z. tritici. In this study, new quantitative trait loci (QTLs) were identified that are responsible for seedling-stage resistance and adult-plant stage resistance (APR). More importantly was the characterisation of a previously unidentified QTL that can provide resistance during different stages of plant growth or multi-stage resistance (MSR). At the seedling stage, we discovered a new isolate-specific QTL, QSt.wai.1A.1. At the adult-plant stage, the new QTL QStb.wai.6A.2 provided stable and consistent APR in multiple sites and years, while the QTL QStb.wai.7A.2 was highlighted to have MSR. The stacking of multiple favourable MSR alleles was found to improve resistance to Z. tritici by up to 40%.