Genome-wide CRISPR screening identifies tyrosylprotein sulfotransferase-2 as a target for augmenting anti-PD1 efficacy.

Background: Immune checkpoint therapy (ICT) provides durable responses in select cancer patients, yet resistance remains a significant challenge, prompting the exploration of underlying molecular mechanisms. Tyrosylprotein sulfotransferase-2 (TPST2), known for its role in protein tyrosine O-sulfation, has been suggested to modulate the extracellular protein-protein interactions, but its specific role in cancer immunity remains largely unexplored.

Methods: To explore tumor cell-intrinsic factors influencing anti-PD1 responsiveness, we conducted a pooled loss-of-function genetic screen in humanized mice engrafted with human immune cells.

Targeting the mA RNA methyltransferase METTL3 attenuates the development of kidney fibrosis.

Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N-methyladenosine (mA) RNA methylation is associated with organ fibrosis. We investigated mA profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-β-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model).

Gut bacteria-derived 3-phenylpropionylglycine mitigates adipocyte differentiation of 3T3-L1 cells by inhibiting adiponectin-PPAR pathway.

Background: Gut microbiota provide numerous types of metabolites that humans cannot produce and have a huge influence on the host metabolism. Accordingly, gut bacteria-derived metabolites can be employed as a resource to develop anti-obesity and metabolism-modulating drugs.

Objective: This study aimed to examine the anti-adipogenic effect of 3-phenylpropionylglycine (PPG), which is a glycine conjugate of bacteria-derived 3-phenylpropionic acid (PPA).

Augmentation of the RNA m6A reader signature is associated with poor survival by enhancing cell proliferation and EMT across cancer types.

N-Methyladenosine (m6A) RNA modification plays a critical role in the posttranscriptional regulation of gene expression. Alterations in cellular m6A levels and m6A-related genes have been reported in many cancers, but whether they play oncogenic or tumor-suppressive roles is inconsistent across cancer types. We investigated common features of alterations in m6A modification and m6A-related genes during carcinogenesis by analyzing transcriptome data of 11 solid tumors from The Cancer Genome Atlas database and our in-house gastric cancer cohort.

CRISPR screens identify a novel combination treatment targeting BCL-X and WNT signaling for KRAS/BRAF-mutated colorectal cancers.

Metastatic or recurrent colorectal cancer (CRC) patients require systemic chemotherapy, but the therapeutic options of targeted agents remain limited. CRC patients with KRAS or BRAF gene mutations exhibit a worse prognosis and are resistant to anti-EGFR treatment. Previous studies have shown that the expression of anti-apoptotic protein BCL-X is increased in CRC patients with KRAS/BRAF mutations, suggesting BCL-X as a therapeutic target for this subgroup.

Targeting antioxidant enzymes enhances the therapeutic efficacy of the BCL-X inhibitor ABT-263 in KRAS-mutant colorectal cancers.

Cancer chemotherapeutic drugs exert cytotoxic effects by modulating intracellular reactive oxygen species (ROS) levels. However, whether ROS modulates the efficacy of targeted therapeutics remains poorly understood. Previously, we reported that upregulation of the anti-apoptotic protein, BCL-X, by KRAS activating mutations was a potential target for KRAS-mutant colorectal cancer (CRC) treatment.

Gene signature for prediction of radiosensitivity in human papillomavirus-negative head and neck squamous cell carcinoma.

Purpose: The probability of recurrence of cancer after adjuvant or definitive radiotherapy in patients with human papillomavirus-negative (HPV(-)) head and neck squamous cell carcinoma (HNSCC) varies for each patient. This study aimed to identify and validate radiation sensitivity signature (RSS) of patients with HPV(-) HNSCC to predict the recurrence of cancer after radiotherapy.

Materials And Methods: Clonogenic survival assays were performed to assess radiosensitivity in 14 HNSCC cell lines.

Correlation of Nasal Fluid Biomarkers and Symptoms in Patients with Persistent Allergic Rhinitis.

Objectives: This study investigated whether the biomarkers present in nasal fluid reflect the severity of symptoms in patients with persistent allergic rhinitis (PAR).

Methods: We enrolled 29 PAR patients complaining of nasal symptoms and testing positive to skin prick test. Patients' total nasal symptom score (TNSS) was measured and their nasal lavage fluid (NALF) was collected.

CD56CD57 infiltrates as the most predominant subset of intragraft natural killer cells in renal transplant biopsies with antibody-mediated rejection.

Little is known about the characteristics and clinical implications of specific subsets of intragraft natural killer (NK) cells in kidney transplant recipients. We analyzed 39 for-cause renal transplant biopsies performed at our center from May 2015 to July 2017. According to histopathologic reports, 8 patients (20.

Urinary transglutaminase 2 as a potent biomarker to predict interstitial fibrosis and tubular atrophy of kidney allograft during early posttransplant period in deceased donor kidney transplantation.

Purpose: Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. We tested whether quantification of urinary TG2 may represent a noninvasive method to estimate the severity of kidney allograft fibrosis.

Methods: We prospectively collected urine specimens from 18 deceased donor kidney transplant recipients at 1-day, 7-day, 1-month, 3-month, and 6-month posttransplant.

Tissue-resident natural killer cells exacerbate tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in a model of aristolochic acid-induced nephropathy.

Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis.

Antioxidant activity and contents of leaf extracts obtained from LEV are dependent on the collecting season and extraction conditions.

This study compared the antioxidant activity of extracts from () Levillis leaves. The concentrations of flavonoids and polyphenols were measured in extracts of leaves. The antioxidant activities were examined by ABTS and DPPH radical scavenging activity and ferric reducing antioxidant power (FRAP).

A composite of urinary biomarkers for differentiating between tubulointerstitial inflammation and interstitial fibrosis/tubular atrophy in kidney allografts.

Backgrounds/aims: Compared with a single urinary biomarker, a composite of multiple urinary biomarkers may be more helpful for differentiating tubulointerstitial inflammation from interstitial fibrosis/tubular atrophy (IFTA) in kidney allografts.

Methods: In this cross-sectional cohort study, we collected urine samples from 115 patients with for-cause biopsy, 53 patients with stable allografts, and 50 living kidney donors. We measured the urinary levels of transglutaminase 2 (TG2), syndecan-4 (SDC4), alpha 1 microglobulin (A1M), interferon-inducible protein 10 (IP-10), interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1).

SOX2 activation predicts prognosis in patients with head and neck squamous cell carcinoma.

SOX2 copy number and mRNA expression were analysed to examine the clinical significance of SOX2 activation in HNSCC. Gene expression signatures reflecting SOX2 activation were identified in an HNSCC cohort. Patients with HNSCC were classified into two subgroups according to the gene expression signature: SOX2-high and SOX2-low.

Determination of origin and intended use of plutonium metal using nuclear forensic techniques.

Nuclear forensics techniques, including micro-XRF, gamma spectrometry, trace elemental analysis and isotopic/chronometric characterization were used to interrogate two, potentially related plutonium metal foils. These samples were submitted for analysis with only limited production information, and a comprehensive suite of forensic analyses were performed. Resulting analytical data was paired with available reactor model and historical information to provide insight into the materials' properties, origins, and likely intended uses.

Improving gastric cancer preclinical studies using diverse in vitro and in vivo model systems.

Background: "Biomarker-driven targeted therapy," the practice of tailoring patients' treatment to the expression/activity levels of disease-specific genes/proteins, remains challenging. For example, while the anti-ERBB2 monoclonal antibody, trastuzumab, was first developed using well-characterized, diverse in vitro breast cancer models (and is now a standard adjuvant therapy for ERBB2-positive breast cancer patients), trastuzumab approval for ERBB2-positive gastric cancer was largely based on preclinical studies of a single cell line, NCI-N87. Ensuing clinical trials revealed only modest patient efficacy, and many ERBB2-positive gastric cancer (GC) patients failed to respond at all (i.

HNF4α is a therapeutic target that links AMPK to WNT signalling in early-stage gastric cancer.

Background: Worldwide, gastric cancer (GC) is the fourth most common malignancy and the most common cancer in East Asia. Development of targeted therapies for this disease has focused on a few known oncogenes but has had limited effects.

Objective: To determine oncogenic mechanisms and novel therapeutic targets specific for GC by identifying commonly dysregulated genes from the tumours of both Asian-Pacific and Caucasian patients.

Differential subcellular localization of DNA topoisomerase-1 isoforms and their roles during Caenorhabditis elegans development.

DNA topoisomerase-1 (TOP-1) resolves the topological problems associated with DNA replication, transcription and recombination by introducing temporary single-strand breaks in the DNA. Caenorhabditis elegans TOP-1 has two isoforms, TOP-1α and TOP-1β. TOP-1β is broadly localized to the nuclei of many cells at all developmental stages and concentrated in nucleoli in embryo gut and oogenic cells.

Overfilling of calcium hydroxide-based paste Calcipex II produced a foreign body granuloma without acute inflammatory reaction.

A patient, a 62-year-old man, received endodontic treatment of the lower left canine complicated by apical overfilling of Calcipex II. At the second day after the root canal filling, the 14th day after placement of Calcipex II intracanal medication, he complained of a gingival swelling in the treated area. The incisional biopsy of the gingival swelling revealed a foreign body granuloma infiltrated with macrophages engulfing the fine Calcipex II granules but with polymorphonuclear leukocytes (PMNs).

The atopic dog as a model of peanut and tree nut food allergy.

Background: Animal models are needed that mimic human IgE-mediated peanut and tree nut allergy. Atopic dogs have been previously used in a model of food allergy to cow's milk, beef, wheat, and soy, with the demonstration of specific IgE production and positive oral challenges similar to those seen in human subjects.

Objective: We sought to sensitize dogs to peanut, walnut, and Brazil nut and to assess whether sensitization is accompanied by clinical reactions and whether there is cross-reactivity among the different preparations.