A donor PD-1CD8 T-like regulatory subset mobilized by G-CSF alleviates recipient acute graft-versus-host-disease.

Donor selection determines the occurrence of acute graft-versus-host-disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). To optimize the current clinical donor selection criteria and identify putative donor lymphocyte subsets associated with better recipient outcomes, we analyzed the peripheral CD4 and CD8 subsets in 80 granulocyte colony-stimulating factor (G-CSF) mobilized donors and examined the aGVHD incidence of the corresponding 80 haploidentical and identical allo-HSCT recipients. The G-CSF-induced expansion of subsets varied among donors.

CD8 T cells in patients with hypopharyngeal squamous cell carcinoma are susceptible to radiation-induced damage.

Radiotherapy (RT) is a commonly used clinical management for hypopharyngeal squamous cell carcinoma (HPSCC), which represents the most unfavorable prognosis among all subtypes of head and neck squamous cell carcinoma. However, radiation may cause lymphopenia, a significantly adverse event with detrimental prognostic implications for patients. While CD8 T cells are vital in tumor immunity, the specific effects of RT on CD8 T cells as well as the underlying mechanisms have not been clearly elucidated.

Trichosanthin elicits antitumor activity via MICU3 mediated mitochondria calcium influx.

Introduction: Trichosanthin (TK) is a glycoprotein extracted from the Chinese medicinal herb Trichosanthes kirilowi, which has anti-virus and anti-tumor activity. However, the target and detailed mechanism of TK remains elusive.

Objectives: We aimed to identify novel antitumor targets of TK in lung adenocarcinoma and study its anti-tumor mechanism.

Prolonged Survival of Neutrophils Induced by Tumor-Derived G-CSF/GM-CSF Promotes Immunosuppression and Progression in Laryngeal Squamous Cell Carcinoma.

Tumor-associated neutrophils (TANs) play a crucial role in tumor progression and exhibit prolonged survival. However, the mechanism underlying their extended lifespan and significance in laryngeal squamous cell carcinoma (LSCC) remains unclear. Herein, it is observed that apoptosis of TANs is significantly delayed owing to induction by tumor-derived G-CSF and GM-CSF through the activation of the PI3K-AKT signaling pathway, upregulation of anti-apoptotic Mcl-1 expression, and downregulation of activated Caspase-3 levels.

Transient inhibition of neutrophil functions enhances the antitumor effect of intravenously delivered oncolytic vaccinia virus.

Oncolytic viruses (OVs) possess the unique ability to selectively replicate within tumor cells, leading to their destruction, while also reversing the immunosuppression within the tumor microenvironment and triggering an antitumor immune response. As a result, OVs have emerged as one of the most promising approaches in cancer therapy. However, the effective delivery of intravenously administered OVs faces significant challenges imposed by various immune cells within the peripheral blood, hindering their access to tumor sites.

Trichosanthin alleviates streptozotocin-induced type 1 diabetes mellitus in mice by regulating the balance between bone marrow-derived IL6 and IL10 MDSCs.

Myeloid-derived suppressor cells (MDSCs) occupy a pivotal role in the intricate pathogenesis of the autoimmune disorder, Type 1 diabetes mellitus (T1DM). Since our previous work demonstrated that trichosanthin (TCS), an active compound of Chinese herb medicine Tian Hua Fen, regulated immune response, we aimed to clarify the efficacy and molecular mechanism of TCS in the treatment of T1DM. To this end, T1DM mouse model was established by streptozotocin (STZ) induction.

Trichosanthin-derived peptide Tk-PQ attenuates immune rejection in mouse tracheal allotransplant model by suppressing PI3K-Akt and inducing type II immune polarization.

Obliterative bronchiolitis (OB) is one of the main complications affecting long-term survival of post-lung transplantation patients. In this study, we evaluated the efficacy of Tk-PQ (a peptide derived from trichosanthin) in alleviating OB in a mouse ectopic tracheal transplant model. We found that post-transplantation treatment of Tk-PQ significant ameliorated OB symptoms including luminal occlusion, epithelial cells loss and fibrosis in the allograft.

High Expression of Tumor HLA-DR Predicts Better Prognosis and Response to Anti-PD-1 Therapy in Laryngeal Squamous Cell Carcinoma.

Background: HLA-DR is expressed in epithelial and several types of tumor cells. However, the correlation between tumor-expressed HLA-DR (teHLA-DR) and patient outcome as well as its regulation on the tumor microenvironment (TME) of laryngeal squamous cell carcinoma (LSCC) are yet to be elucidated.

Methods: Hematoxylin and eosin (HE) staining were performed to define the tumor nest and stroma of LSCC tissue microarrays.

CD206 tumor-associated macrophages interact with CD4 tumor-infiltrating lymphocytes and predict adverse patient outcome in human laryngeal squamous cell carcinoma.

Background: Tumor-associated macrophages (TAMs) are major component in the tumor microenvironment (TME) and play regulatory role in tumor progression. We aimed to investigate the infiltration and prognostic value of TAMs in laryngeal squamous cell carcinoma (LSCC) and to reveal the underlying mechanism of TAM subgroups in tumorigenesis.

Methods: Hematoxylin and eosin (HE) staining were performed to define the tumor nest and stroma of LSCC tissue microarrays.

Effect of renal function on the risk of thrombocytopaenia in patients receiving linezolid therapy: A systematic review and meta-analysis.

Aims: The association of renal function and linezolid-induced thrombocytopaenia (LIT) remains controversial. We performed a meta-analysis to determine whether impaired renal function is associated with an increased LIT risk.

Methods: We conducted a systematic search of PubMed, EMBASE and the Cochrane Library from inception to February 2021 for eligible studies evaluating the relationship between renal function and LIT.

lncRNA MRUL Suppressed Non-Small Cell Lung Cancer Cells Proliferation and Invasion by Targeting miR-17-5p/SRSF2 Axis.

The two broad histological subtypes of lung cancer are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which are the leading causes of cancer-related death in the world. Long noncoding RNAs (lncRNAs) have been verified to be critical in the regulation of cancer development. The present study identified and elucidated the regulatory roles of a novel lncRNA MRUL in NSCLC.

CXCL8 inflammatory B cells in the peripheral blood of patients with biliary atresia are involved in disease progression.

Biliary atresia (BA), the most common cause of pediatric end-stage liver disease, results from fibroinflammatory obstruction of the intrahepatic and extrahepatic bile ducts. The etiology of BA has been extensively studied, and inflammation and imbalanced immune system have been identified as the main pathogenesis of BA. B cells play roles in innate and adaptive immunity, but few studies have investigated the role of B cells in BA.

HAGLROS is overexpressed and promotes non-small cell lung cancer migration and invasion.

Introduction: Non-small cell lung cancer was one of the most common and deadly cancers worldwide. Long non-coding RNAs had been implicated in multiple human cancers, including non-small cell lung cancer. In this study, we focused on a novel long non-coding RNA, HAGLROS, in non-small cell lung cancer.

Peptide Tk-PQ induces immunosuppression in skin allogeneic transplantation via increasing Foxp3 Treg and impeding nuclear translocation of NF-κB.

Solid organ transplantation is used as the last resort for patients with end-stage disease, but allograft rejection is an unsolved problem. Here, we showed that Tk-PQ, a peptide derived from trichosanthin, had an immune-suppressive effect without obvious cytotoxicity in vitro and in a mouse skin allo-transplantation model. In vitro, treatment of Tk-PQ administrated type 2 T helper cell (Th2)/regulatory T-cell (Treg) cytokines, and increased the ratio of CD4CD25Foxp3 Treg by repressing the PI3K/mTOR pathway.

Interleukin-6 identified as an important factor in hypoxia- and aldehyde dehydrogenase-based gefitinib adaptive resistance in non-small cell lung cancer cells.

Gefitinib resistance and relapse of the disease were the greatest challenges facing clinical therapy of non-small-cell lung cancer (NSCLC). Of note, regarding the hypoxia condition in solid tumor tissues , roles of hypoxia in gefitinib adaptive resistance and its association with lung cancer stem cells (LCSCs) have not been fully elucidated. In the present study, the role of hypoxia in gefitinib adaptive resistance and its association with aldehyde dehydrogenase (ALDH)-based LCSC gefitinib resistance were comparatively studied using RNA-sequencing (RNA-seq) technology.

Role of α7-nicotinic acetylcholine receptor in nicotine-induced invasion and epithelial-to-mesenchymal transition in human non-small cell lung cancer cells.

Nicotine via nicotinic acetylcholine receptors (nAChRs) stimulates non-small cell lung cancer (NSCLC) cell invasion and epithelial to mesenchymal transition (EMT) which underpin the cancer metastasis. However, the receptor subtype-dependent effects of nAChRs on NSCLC cell invasion and EMT, and the signaling pathway underlying the effects remain not fully defined. We identified that nicotine induced NSCLC cell invasion, migration, and EMT; the effects were suppressed by pharmacological intervention using α7-nAChR selective antagonists or by genetic intervention using α7-nAChR knockdown via RNA inference.

Adrenergic DNA damage of embryonic pluripotent cells via β2 receptor signalling.

Embryonic pluripotent cells are sensitive to genotoxicity though they need more stringent genome integrity to avoid compromising multiple cell lineages and subsequent generations. However it remains unknown whether the cells are susceptible to adrenergic stress which can induce somatic cell genome lesion. We have revealed that adrenergic stress mediators cause DNA damage of the cells through the β2 adrenergic receptor/adenylate cyclase/cAMP/PKA signalling pathway involving an induction of intracellular reactive oxygen species (ROS) accumulation.

β2-Adrenoreceptor-Mediated Proliferation Inhibition of Embryonic Pluripotent Stem Cells.

Adrenoreceptors (ARs) are widely expressed and play essential roles throughout the body. Different subtype adrenoceptors elicit distinct effects on cell proliferation, but knowledge remains scarce about the subtype-specific effects of β2-ARs on the proliferation of embryonic pluripotent stem (PS) cells that represent different characteristics of proliferation and cell cycle regulation with the somatic cells. Herein, we identified a β2-AR/AC/cAMP/PKA signaling pathway in embryonic PS cells and found that the pathway stimulation inhibited proliferation and cell cycle progression involving modulating the stem cell growth and cycle regulatory machinery.

Simultaneous determination of the repertoire of classical neurotransmitters released from embryonal carcinoma stem cells using online microdialysis coupled with hydrophilic interaction chromatography-tandem mass spectrometry.

Dynamic, continuous, and simultaneous multi-analysis of transmitters is important for the delineation of the complex interactions between the neuronal and intercellular communications. But the analysis of the whole repertoire of classical transmitters of diverse structure is challenging due to their different physico-chemical properties and to their high polarity feature which leads to poor retention in traditional reversed-phase columns during LC-MS analysis. Here, an online microdialysis coupled with hydrophilic interaction chromatography-tandem mass spectrometry (online MD-HILIC-MS/MS) detection method was developed for the simultaneous measurement of the repertoire of classical transmitters (acetylcholine, serotonin, dopamine, norepinephrine, glutamate, GABA, and glycine).