NSG

Sjogren's syndrome (SS) is a complex systemic autoimmune disease. This study aims to elucidate a humanized NOD-Prkdcscid Il2rgem1 /Smoc (NSG) murine model to better clarify the pathogenesis of SS. NSG female mice were adoptively transferred with 10 million peripheral blood mononuclear cells (PBMCs) through the tail vein from healthy controls (HCs), primary Sjogren's syndrome (pSS), and systemic lupus erythematosus (SLE) patients on D0. The mice were subcutaneously injected with C57/B6j submandibular gland (SG) protein or phosphate-buffered saline on D3, D17 and D31, respectively...

Epstein-Barr virus (EBV) is an important cause of human lymphomas, including Burkitt lymphoma (BL). EBV+ BLs are driven by Myc translocation and have stringent forms of viral latency that do not express either of the two major EBV oncoproteins, EBNA2 (which mimics Notch signaling) and LMP1 (which activates NF-κB signaling). Suppression of Myc-induced apoptosis, often through mutation of the TP53 (p53) gene or inhibition of pro-apoptotic BCL2L11 (BIM) gene expression, is required for development of Myc-driven BLs...

Atractylodes macrocephala Koidz (AMK) is a traditional herbal medicine used for thousands of years in East Asia to improve a variety of illnesses and conditions, including cancers. This study explored the effect of AMK extract on apoptosis and tumor-grafted mice using AGS human gastric adenocarcinoma cells. We investigated the compounds, target genes, and associated diseases of AMK using the Traditional Chinese Medical Systems Pharmacy (TCMSP) database platform. Cell viability assay, cell cycle and mitochondrial depolarization analysis, caspase activity assay, reactive oxygen species (ROS) assay, and wound healing and spheroid formation assay were used to investigate the anti-cancer effects of AMK extract on AGS cells...

Cytokine release syndrome (CRS) is a frequently observed side effect of chimeric antigen receptor (CAR)-T cell therapy. Here, we report self-regulating T cells that reduce CRS severity by secreting inhibitors of cytokines associated with CRS. With a humanized NSG-SGM3 mouse model, we show reduced CRS-related toxicity in mice treated with CAR-T cells secreting tocilizumab-derived single-chain variable fragment (Toci), yielding a safety profile superior to that of single-dose systemic tocilizumab administration...

Lipid metabolic reprogramming is closely related to tumor progression with the mechanism not fully elucidated. Here, we report the immune-regulated role of lanosterol synthase (LSS), an essential enzyme in cholesterol synthesis. Database analysis and clinical sample experiments suggest that LSS was lowly expressed in colon and breast cancer tissues, which indicates poor prognosis. The biological activity of tumor cell lines and tumor progression in NOD scid gamma (NSG) mice were not affected after LSS knockdown, whereas LSS deficiency obviously aggravated tumor burden in fully immunized mice...

BACKGROUND: Despite recent advances in immunotherapy, a substantial population of late-stage melanoma patients still fail to achieve sustained clinical benefit. Lack of translational preclinical models continues to be a major challenge in the field of immunotherapy; thus, more optimized translational models could strongly influence clinical trial development. To address this unmet need, we designed a preclinical model reflecting the heterogeneity in melanoma patients' clinical responses that can be used to evaluate novel immunotherapies and synergistic combinatorial treatment strategies...

Ferroptosis has been demonstrated a promising way to counteract chemoresistance of multiple myeloma (MM), however, roles and mechanism of bone marrow stromal cells (BMSCs) in regulating ferroptosis of MM cells remain elusive. Here, we uncovered that MM cells were more susceptible to ferroptotic induction under the interaction of BMSCs using in vitro and in vivo models. Mechanistically, BMSCs elevated the iron level in MM cells, thereby activating the steroid biosynthesis pathway, especially the production of lanosterol, a major source of reactive oxygen species (ROS) in MM cells...

BACKGROUND: Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear. To find the co-regulators in erythroid and myeloid differentiation might help to find new target for therapy of myeloid leukemia. In hematopoiesis, ALA (alpha lipoic acid) is reported to inhibit neutrophil lineage determination by targeting transcription factor ELK1 in granulocyte-monocyte progenitors via splicing factor SF3B1...

When the scientific dataset evolves or is reused in workflows creating derived datasets, the integrity of the dataset with its metadata information, including provenance, needs to be securely preserved while providing assurances that they are not accidentally or maliciously altered during the process. Providing a secure method to efficiently share and verify the data as well as metadata is essential for the reuse of the scientific data. The National Science Foundation (NSF) funded Open Science Chain (OSC) utilizes consortium blockchain to provide a cyberinfrastructure solution to maintain integrity of the provenance metadata for published datasets and provides a way to perform independent verification of the dataset while promoting reuse and reproducibility...

BACKGROUND: In this diagnostic accuracy study, we examined the effectiveness of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) in predicting the need for surgical intervention in patients with anterior abdominal stab wounds (AASW) who exhibit unclear findings on physical examination yet remain hemodynamically stable. METHODS: Over a 7-year period, patients with AASW were retrospectively analyzed...

PURPOSE: In the pursuit of creating personalized and more effective treatment strategies for lung cancer patients, Patient-Derived Xenografts (PDXs) have been introduced as preclinical platforms that can recapitulate the specific patient's tumor in an in vivo model. We investigated how well PDX models can preserve the tumor's clinical and molecular characteristics across different generations. METHODS: A Non-Small Cell Lung Cancer (NSCLC) PDX model was established in NSG-SGM3 mice and clinical and preclinical factors were assessed throughout subsequent passages...

Immunodeficient NSG mice are reported to be less responsive to buprenorphine analgesia. Here, we used NSG mice to compare the efficacy of the commonly used dose of carprofen (5 mg/kg) with 5 and 10 times that dose (25 and 50 mg/kg) for attenuating postoperative mechanical and thermal hypersensitivity following an incisional pain model. Male and female NSG mice ( n = 45) were randomly assigned to one of 4 groups and received daily subcutaneous injections for 3 d: saline (5 mL/kg), 5 mg/kg carprofen (Carp5), 25 mg/kg carprofen (Carp25), and 50 mg/kg carprofen (Carp50)...

Stem cell gene therapy and hematopoietic stem cell transplantation (SCT) and stem cell gene therapy require conditioning to ablate the recipient's hematopoietic stem cells (HSC) and create a niche for gene-corrected/donor HSCs. Conventional conditioning agents are non-specific, leading to off-target toxicities, resulting in significant morbidity and mortality. We developed tissue-specific anti-human CD45 antibody-drug conjugates (ADCs), using rat IgG2b anti-human CD45 antibody clones YTH24.5 and YTH54.12, conjugated to cytotoxic pyrrolobenzodiazepine (PBD) dimer payloads with cleavable (SG3249) or non-cleavable (SG3376) linkers...

BACKGROUND: The modified Brain Injury Guidelines (mBIG) were developed to stratify traumatic brain injuries (TBI) and improve healthcare utilization by selectively requiring repeat imaging, ICU admission, and neurosurgical (NSG) consultation. The goal of this study is to assess safety and potential resource savings associated with the application of mBIG on interhospital patient transfers for TBI. METHODS: Adult patients with TBI transferred to our Level I trauma center from 01/2017 to 12/2022 meeting mBIG inclusion criteria were retrospectively stratified into mBIG1, mBIG2, and mBIG3 based on initial clinicoradiological factors...

Cytokine release syndrome (CRS) is a significant side-effect of conventional chimeric antigen receptor (CAR) T-cell therapy. To facilitate patient accessibility, short-term (st) CAR T cells, which are administered to patients only 24 h after vector exposure, are in focus of current investigations. Their impact on the incidence and severity of CRS has been poorly explored. Here, we evaluated CD19-specific stCAR T cells in preclinical models. In co-culture with tumor cells and monocytes, stCAR T cells exhibited anti-tumoral activity and potent release of CRS-related cytokines (IL-6, IFN-γ, TNF-α, GM-CSF, IL-2, IL-10)...

Tuberculosis (TB), caused by Mycobacterium tuberculosis ( Mtb ), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. Further, co-infections with HIV and Mtb have severe effects in the host, with people infected with HIV being fifteen to twenty-one times more likely to develop active TB. The use of an appropriate animal model for HIV/ Mtb co-infection that can recapitulate the diversity of the immune response in humans would be a useful tool for conducting basic and translational research in HIV/ Mtb infections...

Vγ9Vδ2 T cells represent a promising cancer therapy platform because the implementation of allogenic, off-the-shelf product candidates is possible. However, intravenous administration of human Vγ9Vδ2 T cells manufactured under good manufacturing practice (GMP)-compliant, serum-free conditions are not tested easily in most mouse models, mainly because they lack the ability to migrate from the blood to tissues or tumors. We demonstrate that these T cells do not migrate from the circulation to the mouse bone marrow (BM), the site of many malignancies...

BACKGROUND: Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some of these challenges are needed. Here, we describe the characterization of KTC1101, a novel pan-PI3K inhibitor that simultaneously targets tumor cell proliferation and the tumor microenvironment...

BACKGROUND: Liver metastasis is the major cause of colorectal cancer related death. Mesothelin (MSLN)-targeted chimeric antigen receptor (CAR) T-cell therapy has been illustrated effective and safe through regional delivery of breast cancer, ovarian cancer and malignant mesothelioma tumors. Herein, we investigated the safety, efficacy, and immune microenvironment of regional delivery of MSLN (CAR) T-cell in the treatment of colorectal carcinoma liver metastases (CRLM). METHODS: Second-generation MSLN CAR T-cells were administered by portal vein (PV) or caudal vein (CV, systemic administration) delivery in an orthotopic MSLN+ CRLM nonobese diabetic (NOD)/severe combined immunodeficient (SCID)/γc-/- (NSG) mouse model...

Background : The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to be explored. Methods : CLDN6 expression in primary human ovarian cancer, normal tissues and cell lines were detected by immunohistochemistry and western blot...