A rapid method to assess the multi-functionality of adoptively transferred engineered TCR T cells.

Introduction: The clinical efficacy of chimeric antigen and T cell receptor (TCR) T cell immunotherapies is attributed to their ability to proliferate and persist . Since the interaction of the engineered T cells with the targeted tumour or its environment might suppress their function, their functionality should be characterized not only before but also after adoptive transfer.

Materials And Methods: We sought to achieve this by adapting a recently developed Severe acute respiratory syndrome (SARS-CoV-2) rapid whole blood T cell assay to stimulate engineered TCR T cells in small volumes of whole blood (<1 ml) without cellular purification.

A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer.

Chromones are promising for anticancer drug development. 12 chromone-based compounds were synthesized and tested against cancer cell lines. Compound showed the highest cytotoxicity (LC 3.

G-quadruplex ligands as therapeutic agents against cancer, neurological disorders and viral infections.

G-quadruplexes (G4s) within the human genome have undergone extensive molecular investigation, with a strong focus on telomeres, gene promoters and repetitive regulatory sequences. G4s play central roles in regulating essential biological processes, including telomere maintenance, replication, transcription and translation. Targeting these molecular processes with G4-binding ligands holds substantial therapeutic potential in anticancer treatments and has also shown promise in treating neurological, skeletal and muscular disorders.

Lytic efficiency of immunosuppressive drug-resistant armoured T cells against circulating HBV-related HCC in whole blood.

Recurrence of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after liver transplant (LT) is mediated by circulating tumour cells (CTCs) and exacerbated by the immunosuppressants required to prevent graft rejection. To circumvent the effects of immunosuppressants, we developed immunosuppressive drug-resistant armoured HBV-specific T-cell receptor-redirected T cells (IDRA HBV-TCR). However, their ability to eliminate HBV-HCC circulating in the whole blood has never been tested, and whether their lytic efficacy is compatible with the number of adoptively transferred T cells has never been measured.

Messenger RNA electroporated hepatitis B virus (HBV) antigen-specific T cell receptor (TCR) redirected T cell therapy is well-tolerated in patients with recurrent HBV-related hepatocellular carcinoma post-liver transplantation: results from a phase I trial.

Background And Aims: Liver transplantation (LT) is the primary curative option for cirrhotic patients with early-stage hepatocellular carcinoma (HCC). However, tumor recurrence occurs in 15-20% of cases with unfavorable prognosis. We have developed a library of T cell receptors (TCRs) specific for different hepatitis B virus (HBV) antigens, restricted by different molecules of human leucocyte antigen (HLA)-class I, to redirect T cells against HBV antigens (Banu in Sci Rep 4:4166, 2014).

The impact of cycleanine in cancer research: a computational study.

Cancer is imposing a global health burden because of the steady increase in new cases. Moreover, current anticancer therapeutics are associated with many drawbacks, mainly the emergence of resistance and the severe adverse effects. Therefore, there is a continuous need for developing new anticancer agents with novel mechanisms of action and lower side effects.

Open versus laparoscopic intraperitoneal on-lay mesh repair: A comparison of outcomes in small ventral hernia.

Purpose: The ideal surgical treatment of small ventral hernias (defect less than 4 cm) is still debatable. In our study, we sought to compare the outcomes of open versus laparoscopic intraperitoneal on-lay mesh (IPOM) repair in small ventral hernias.

Methods: Patients with a single ventral hernia defect of less than 4 cm undergoing surgical mesh repair between January 2016 and September 2018 were prospectively registered for this study.

Immunological alterations after immunotherapy with short lived HBV-TCR T cells associates with long-term treatment response in HBV-HCC.

The application of hepatitis B virus (HBV)-T-cell receptor (TCR) T-cell immunotherapy in patients with HBV-related hepatocellular carcinoma (HBV-HCC) has been apathetic, as the expression of HBV antigens by both normal HBV-infected hepatocytes and HCC cells with HBV-DNA integration increases the risk of on-target off-tumor severe liver inflammatory events. To increase the safety of this immunotherapeutic approach, we developed messenger RNA (mRNA) HBV-TCR-redirected T cells that-due to the transient nature of mRNA-are functionally short lived and can be infused in escalating doses. The safety of this approach and its clinical potential against primary HBV-HCC have never been analyzed in human trials; thus, we studied the clinical and immunological parameters of 8 patients with chronic HBV infection and diffuse nonoperable HBV-HCC treated at weekly intervals with escalating doses (1 × 10 , 1 × 10 , 1 × 10 , and 5 × 10 TCR+ T cells/kg body weight) of T cells modified with HBV-TCR encoding mRNA.

Novel local anesthesia technique 'NATURE ' (Nerves And Transversalis-fascia Using RopivacainE) to improve outcomes during endo-laparoscopic inguinal hernia repair.

Background: The use of local anaesthesia infiltration techniques may attenuate pain following endo-laparoscopic inguinal hernia surgery. We aim to reduce post-operative pain and the subsequent need for analgesia using a novel technique of local anaesthesia infiltration 'NATURE' (Nerves And Transversalis-fascia Using RopivacainE).

Methods: This is a retrospective study of patients who underwent endo-laparoscopic inguinal hernia repair in two institutions in Singapore.

Feasibility of modified-TEP technique for large inguinoscrotal and large femoral hernia and its advantages.

Purpose: To describe the feasibility of modified-TEP technique in reducing dead space in large inguinoscrotal and large femoral hernia to prevent seroma, reduce recurrence and complications.

Methods: This is a case series of patients who have completed a minimum of 9 months follow-up after undergoing elective endo-laparoscopic inguinal hernia repair with modified-TEP technique for large inguinoscrotal and large femoral hernia in a single institution from June to October 2020.

Results: 14 large inguinoscrotal hernia and 4 large femoral hernia were repaired using the modified-TEP technique in 15 patients.

Biomimetic amphiphilic chitosan nanoparticles: Synthesis, characterization and antimicrobial activity.

Naturally derived antimicrobial peptides (AMPs) are an attractive source of new antimicrobial agents. However, clinical application of AMPs is associated with poor bioavailability and toxicity. In this study, we address these limitations by designing a new series of chitosan derivatives to mimic the amphiphilic topology of AMPs.

Immunosuppressive Drug-Resistant Armored T-Cell Receptor T Cells for Immune Therapy of HCC in Liver Transplant Patients.

Background And Aims: HBV-specific T-cell receptor (HBV-TCR) engineered T cells have the potential for treating HCC relapses after liver transplantation, but their efficacy can be hampered by the concomitant immunosuppressive treatment required to prevent graft rejection. Our aim is to molecularly engineer TCR-T cells that could retain their polyfunctionality in such patients while minimizing the associated risk of organ rejection.

Approach And Results: We first analyzed how immunosuppressive drugs can interfere with the in vivo function of TCR-T cells in liver transplanted patients with HBV-HCC recurrence receiving HBV-TCR T cells and in vitro in the presence of clinically relevant concentrations of immunosuppressive tacrolimus (TAC) and mycophenolate mofetil (MMF).

In silico studies, nitric oxide, and cholinesterases inhibition activities of pyrazole and pyrazoline analogs of diarylpentanoids.

A new series of pyrazole, phenylpyrazole, and pyrazoline analogs of diarylpentanoids (excluding compounds 3a, 4a, 5a, and 5b) was pan-assay interference compounds-filtered and synthesized via the reaction of diarylpentanoids with hydrazine monohydrate and phenylhydrazine. Each analog was evaluated for its anti-inflammatory ability via the suppression of nitric oxide (NO) on IFN-γ/LPS-activated RAW264.7 macrophage cells.

Liver fibrosis and CD206 macrophage accumulation are suppressed by anti-GM-CSF therapy.

Background & Aims: Chronic liver inflammation leads to fibrosis and cirrhosis and is associated with an accumulation of intrahepatic TNFα-secreting CD206 macrophages, which may participate in maintaining chronic liver disease in a GM-CSF-dependent manner. We aimed to elucidate the exact role of GM-CSF in the development and progression of chronic liver disease.

Methods: Liver immunohistochemistry and serum quantification were performed in patients with viral and non-viral-related liver disease to compare CD206 monocyte/macrophages, fibrosis and GM-CSF.

Fragility fractures and imminent fracture risk in Hong Kong: one of the cities with longest life expectancies.

Introduction: Imminent fracture risk, or fractures within 2 years of an initial fracture, is a pressing issue worldwide. Hong Kong is a city with one of the longest life expectancies. The concern of fragility fractures and the imminent risk of a subsequent fracture is becoming a top priority.

Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy.

Background & Aims: Hepatocellular carcinoma (HCC) is often associated with hepatitis B virus (HBV) infection. Cells of most HBV-related HCCs contain HBV-DNA fragments that do not encode entire HBV antigens. We investigated whether these integrated HBV-DNA fragments encode epitopes that are recognized by T cells and whether their presence in HCCs can be used to select HBV-specific T-cell receptors (TCRs) for immunotherapy.

Oestrogenic activity of mimosine on MCF-7 breast cancer cell line through the ERα-mediated pathway.

Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model.

Mixed adenoneuroendocrine carcinoma: A review of pathologic characteristics.

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare pathologic entity defined as a tumor exhibiting both adenocarcinoma and neuroendocrine carcinoma components. Though uncommon, these tumors show aggressive behavior and generally portend a poor prognosis. This study seeks to further define clinicopathological characteristics of MANEC to aid in accurate diagnosis and properly direct clinical management.

Coenzyme Q10-Loaded Fish Oil-Based Bigel System: Probing the Delivery Across Porcine Skin and Possible Interaction with Fish Oil Fatty Acids.

Coenzyme Q10 (CoQ10) is a vitamin-like oil-soluble molecule that has anti-oxidant and anti-ageing effects. To determine the most optimal CoQ10 delivery vehicle, CoQ10 was solubilised in both water and fish oil, and formulated into hydrogel, oleogel and bigel. Permeability of CoQ10 from each formulation across porcine ear skin was then evaluated.

Molecular Docking Analysis of Phytic Acid and 4-hydroxyisoleucine as Cyclooxygenase-2, Microsomal Prostaglandin E Synthase-2, Tyrosinase, Human Neutrophil Elastase, Matrix Metalloproteinase-2 and -9, Xanthine Oxidase, Squalene Synthase, Nitric Oxide Synthase, Human Aldose Reductase, and Lipoxygenase Inhibitors.

Background: The phytoconstituents phytic acid and 4-hydroxyisoleucine have been reported to posses various biological properties.

Objective: This prompted us to carry out the docking study on these two ligands (phytic acid & 4-hydroxyisoleucine) against eleven targeted enzymes.

Materials And Methods: Phytic acid & 4-hydroxyisoleucine were evaluated on the docking behaviour of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-2 (mPGES-2), tyrosinase, human neutrophil elastase (HNE), matrix metalloproteinase (MMP 2 and 9), xanthine oxidase (XO), squalene synthase (SQS), nitric oxide synthase (NOS), human aldose reductase (HAR) and lipoxygenase (LOX) using Discovery Studio Version 3.

Cyclopia: isolated and with agnathia-otocephaly complex.

Cyclopia is a rare form of lethal holoprosencephaly (HPE) due to incomplete cleavage of prosencephalon during embryogenesis, leading to failure of the orbits of the eye to divide into two cavities. We report two cases, one with cyclopia and another case of cyclopia with agnathia-otocephaly complex (AOC). AOC (also known as agnathia-microstomia-synotia syndrome) is a rare lethal congenital malformation of the first branchial arch characterised by the association of agnathia (agenesis of mandible) or mandibular hypoplasia, melotia (anteromedial malposition of ears), microstomia (small mouth), aglossia or microglossia (absent or rudimentary tongue).

Intrahepatic CD206 macrophages contribute to inflammation in advanced viral-related liver disease.

Background & Aims: Liver inflammation is key in the progression of chronic viral hepatitis to cirrhosis and hepatocellular carcinoma. The magnitude of viral replication and the specific anti-viral immune responses should govern the degree of inflammation, but a direct correlation is not consistently found in chronic viral hepatitis patients. We aim to better define the mechanisms that contribute to chronic liver inflammation.

Cholesterol modulates bitter taste receptor function.

Bitter taste perception in humans is believed to act as a defense mechanism against ingestion of potential toxic substances. Bitter taste is perceived by 25 distinct bitter taste receptors (T2Rs) which belong to the family of G protein-coupled receptors (GPCRs). In the overall context of the role of membrane lipids in GPCR function, we show here that T2R4, a representative member of the bitter taste receptor family, displays cholesterol sensitivity in its signaling function.