Ion channels research in hPSC-RPE cells: bridging benchwork to clinical applications.

Ion channels in retinal pigment epithelial (RPE) cells are crucial for retinal health and vision functions. Defects in such channels are intricately associated with the development of various retinopathies that cause blindness. Human pluripotent stem cells (hPSC)-derived RPE cells, including those from human-induced pluripotent stem cells (hiPSC) and human embryonic stem cells (hESC), have been used as in vitro models for investigating pathogenic mechanisms and screening potential therapeutic strategies for retinopathies.

Interleukin-6 in non-infectious uveitis: Biology, experimentalevidence and treatment strategies.

Uveitis is the leading cause of visual impairment worldwide. Interleukin-6 (IL-6), which is upregulated in response to inflammation, is one of the most important inflammatory cytokines associated with uveitis. Two major IL-6 receptors (IL-6R) mediate the pro-inflammatory and anti-inflammatory biological effects of IL-6.

CCL19-producing fibroblasts promote tertiary lymphoid structure formation enhancing anti-tumor IgG response in colorectal cancer liver metastasis.

Tertiary lymphoid structures (TLSs) are associated with enhanced immunity in tumors. However, their formation and functions in colorectal cancer liver metastasis (CRLM) remain unclear. Here, we reveal that intra- and peri-tumor mature TLSs (TLS+) are associated with improved clinical outcomes than TLS- tumors.

Simultaneous cholecystectomy for asymptomatic gallstones during elective colorectal cancer surgery.

Background: Asymptomatic gallstones are commonly detected using preoperative imaging in patients with colorectal cancer (CRC), but its management remains a topic of debate.

Methods: Clinicopathologic characteristics of patients who had asymptomatic gallstones presenting during the colorectal procedure were retrospectively reviewed. Medical records, including postoperative morbidity, mortality, and long-term gallstone-related diseases, were assessed.

Graves' disease and the risk of five autoimmune diseases: A Mendelian randomization and colocalization study.

Background: Epidemiological studies have consistently demonstrated a high prevalence of concurrent autoimmune diseases in individuals with Graves' disease (GD).

Objective: The objective of this study is to establish a causal association between GD and autoimmune diseases.

Methods: We employed a two-sample Mendelian randomization (MR) to infer a causal association between GD and five autoimmune diseases, namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS), in the East Asian and European population.

Wild-type IDH2 is a therapeutic target for triple-negative breast cancer.

Mutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo.

Coupling of nanostraws with diverse physicochemical perforation strategies for intracellular DNA delivery.

Effective intracellular DNA transfection is imperative for cell-based therapy and gene therapy. Conventional gene transfection methods, including biochemical carriers, physical electroporation and microinjection, face challenges such as cell type dependency, low efficiency, safety concerns, and technical complexity. Nanoneedle arrays have emerged as a promising avenue for improving cellular nucleic acid delivery through direct penetration of the cell membrane, bypassing endocytosis and endosome escape processes.

A novel DDIT3 activator dehydroevodiamine effectively inhibits tumor growth and tumor cell stemness in pancreatic cancer.

Background: The existence of pancreatic cancer stem cells (PCSCs) results in limited survival benefits from current treatment options. There is a scarcity of effective agents for treating pancreatic cancer patients. Dehydroevodiamine (DeHE), a quinazoline alkaloid isolated from the traditional Chinese herb Evodiae fructus, exhibited potent inhibition of pancreatic ductal adenocarcinoma (PDAC) cell proliferation and tumor growth both in vitro and in vivo.

[Preliminary study of PPARA regulate the ferroptosis of hepatocellular carcinoma to prevent disease deterioration].

To explore whether PPARA is involved in the process of ferroptosis in hepatoma cells, peroxisome proliferator activated receptor (PPARA) was comprehensively analyzed in hepatocellular carcinoma (HCC) through public database and experimental data, including the expression, the functions and the potential roles of tumor progression. The research design is experimental research,data analysis based on bioinformatics and cell experiment. From January 2022 to August 2022, relevant cell experiments were conducted in the Basic Medical Laboratory of the General Hospital of the Southern Theatre of the Chinese People's Liberation Army.

A TGF-β-dominant chemoresistant phenotype of hepatoblastoma associated with aflatoxin exposure in children.

Background And Aims: Hepatoblastoma (HB) is the most common liver cancer in children, posing a serious threat to children's health. Chemoresistance is the leading cause of mortality in patients with HB. A more explicit definition of the features of chemotherapy resistance in HB represents a fundamental urgent need.

Genetically predicted vitamin C levels significantly affect patient survival and immunotypes in multiple cancer types.

Background: Recent observational studies and meta-analyses have shown that vitamin C reduces cancer incidence and mortality, but the underlying mechanisms remain unclear. We conducted a comprehensive pan-cancer analysis and biological validation in clinical samples and animal tumor xenografts to understand its prognostic value and association with immune characteristics in various cancers.

Methods: We used the Cancer Genome Atlas gene expression data involving 5769 patients and 20 cancer types.

In Vivo and In Vitro Assay to Address Dendritic Cell Antigen Cross-Presenting Capacity.

Antigen cross-presentation by dendritic cells is an important pathway to prime CD8 T cells in infections, cancer, and other immune-mediated pathologies. Particularly in cancer, cross-presentation of tumor-associated antigens is crucial for an effective antitumor CTL response. The mostly accepted cross-presentation assay is to use chicken ovalbumin (OVA) as a model antigen and then utilize OVA-specific TCR transgenic CD8 T (OT-I) cells to measure the cross-presenting capacity.

Therapeutic effect of ustekinumab on patients with extra-intestinal manifestations of Crohn's disease.

Introduction: Ustekinumab serves as an important alternative option for patients with various extraintestinal manifestations (EIMs), which leads to poor quality of life and heavy burden of care. Therefore, a comprehensive review summarizing the efficacy and safety of ustekinumab in patients with CDassociated EIMs is needed to provide reference for clinical medication and help with the appliance of precision medicine.

Areas Covered: In this review, we collected and summarized the efficacy and paradoxical side effects of ustekinumab in patients with CDassociated EIMs including musculoskeletal, cutaneous, ocular, and hepatobiliary manifestations.

Umbilical cord blood-derived exosomes from healthy term pregnancies protect against hyperoxia-induced lung injury in mice.

Bronchopulmonary dysplasia (BPD) is a chronic, devastating disease primarily occurring in premature infants. To date, intervention strategies to prevent or treat BPD are limited. We aimed to determine the effects of umbilical cord blood-derived exosomes (UCB-EXOs) from healthy term pregnancies on hyperoxia-induced lung injury and to identify potential targets for BPD intervention.

ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation.

The process of oncogene-induced senescence (OIS) and the conversion between OIS and malignant transformation during carcinogenesis is poorly understood. Here, we show that following overactivation of oncogene Ras in lung epithelial cells, high-level transforming growth factor β1 (TGF-β1)-activated SMAD3, but not SMAD2 or SMAD4, plays a determinant role in inducing cellular senescence independent of the p53/p16/p15 senescence pathways. Importantly, SMAD3 binds a potential tumor suppressor ATOH8 to form a transcriptional complex that directly represses a series of cell cycle-promoting genes and consequently causes senescence in lung epithelial cells.

PKMYT1 inhibits lung adenocarcinoma progression by abrogating AKT1 activity.

Purpose: AKT hyperactivation drives malignant phenotypes in lung cancer via promoting tumor cell proliferation and survival. However, the relationship between dysregulation of cell cycle progression and AKT1 kinase activity is still not clear.

Methods: Following the expression level of PKMYT1 in lung cancer, we performed cell proliferation, migration, invasion, and xenograft assays to determine the function of PKMYT1.

Targeting tumour-intrinsic N-methylguanosine tRNA modification inhibits MDSC recruitment and improves anti-PD-1 efficacy.

Objective: Intrahepatic cholangiocarcinoma (ICC) exhibits very low response rate to immune checkpoint inhibitors (ICIs) and the underlying mechanism is largely unknown. We investigate the tumour immune microenvironment (TIME) of ICCs and the underlying regulatory mechanisms with the aim of developing new target to inhibit tumour growth and improve anti-programmed cell death protein-1 (PD-1) efficacy.

Design: Tumour tissues from patients with ICC together with hydrodynamic ICC mouse models were employed to identify the key cell population in TIME of ICCs.

Does a Healthy Lifestyle Lower the Elevated Risk of Obesity Caused by Caesarian Section Delivery in Children and Adolescents?

Background: Both caesarean section (CS) and lifestyle were linked with child adiposity. This study aimed to investigate whether CS delivery is linked with elevated risk of child adiposity regardless of a healthy lifestyle. Methods: All the subjects in this study came from a baseline survey of a national school-based program on healthy lifestyle interventions against adiposity among Chinese children and adolescents.

Cytoplasmic Clusterin Suppresses Lung Cancer Metastasis by Inhibiting the ROCK1-ERK Axis.

Clusterin (CLU) is a heterodimeric glycoprotein that has been detected in diverse human tissues and implicated in many cellular processes. Accumulating evidence indicates that the expression of secreted CLU correlates with the progression of cancers. However, the molecular mechanisms underlying its tumor-suppressive roles are incompletely uncovered.

Attenuated Toxoplasma gondii enhances the antitumor efficacy of anti-PD1 antibody by altering the tumor microenvironment in a pancreatic cancer mouse model.

Purpose: To investigate whether attenuated Toxoplasma is efficacious against solid tumors of pancreatic cancer and whether attenuated Toxoplasma improves the antitumor activity of αPD-1 antibody on pancreatic cancer.

Methods: The therapeutic effects of attenuated Toxoplasma NRTUA strain monotherapy and combination therapy of NRTUA with anti-PD-1 antibody on PDAC tumor volume and tumor weight of Pan02 tumor-bearing mice were investigated. We characterized the effects of combination therapy of NRTUA with anti-PD-1 antibody on tumor-infiltrating lymphocytes and tumor-specific IFN-γ by using immunohistochemistry, flow cytometry and ELISA.

Development of a Radiotracer for PET Imaging of the SNAP Tag.

Cell therapies have progressed to cures for hematopoietic disorders, neurodegenerative diseases, and cancer. However, only some patients can benefit from cell therapies even with prior screening. Due to the limited clinical methods to monitor the in vivo therapeutic functions of these transferred cells over time, the uncertain prognosis is hard to attenuate.

Delivery of CD47 blocker SIRPα-Fc by CAR-T cells enhances antitumor efficacy.

Background: Chimeric antigen receptor (CAR) T cell therapy has been successfully applied in treating lymphoma malignancies, but not in solid tumors. CD47 is highly expressed on tumor cells and its overexpression is believed to inhibit phagocytosis by macrophages and dendritic cells. Given the antitumor activity against preclinical model of CD47-blocking to induce the innate and adaptive immune system in the tumor microenvironment, here we developed a CAR-T cell secreting CD47 blocker signal regulatory protein α (SIRPα)-Fc fusion protein (Sirf CAR-T) to boost CAR-T cell therapeutic effect in solid tumor therapy.

Red blood cell distribution width and maximum left ventricular wall thickness predict poor outcomes in patients with hypertrophic cardiomyopathy.

Aim: To evaluate the prognostic utility of red blood cell distribution width (RDW) and maximum left ventricular wall thickness (MLVWT) in patients with hypertrophic cardiomyopathy (HCM).

Patients And Methods: This study is a retrospective cohort analysis. Patients diagnosed with HCM at the First Affiliated Hospital of Sun Yat-sen University from March 2014 to March 2019 were included.