Diminishing acetyl-CoA carboxylase 1 attenuates CCA migration via AMPK-NF-κB-snail axis.

Cholangiocarcinoma (CCA), a cancer of the biliary tract, is a significant health problem in Thailand. Reprogramming of cellular metabolism and upregulation of lipogenic enzymes have been revealed in CCA, but the mechanism is unclear. The current study highlighted the importance of acetyl-CoA carboxylase 1 (ACC1), a rate-limiting enzyme in de novo lipogenesis, on CCA migration.

Dense GM-CSFR-expressing immune infiltration is allied with longer survival of intrahepatic cholangiocarcinoma patients.

Background: Intrahepatic cholangiocarcinoma (iCCA) is a cancer arising from intrahepatic bile duct epithelium. An iCCA incidence is increasing worldwide; however, the outcome of the disease is dismal. The linkage between chronic inflammation and iCCA progression is well established, but the roles of granulocyte-macrophage colony-stimulating factor (GM-CSF) remain unrevealed.

Anti-ganglionic acetylcholine receptor antibodies in functional neurological symptom disorder/conversion disorder.

Objective: Autoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by autonomic failure associated with the presence of anti-ganglionic acetylcholine receptor (gAChR) antibodies; however, several studies have reported that individuals with anti-gAChR antibodies present with central nervous system (CNS) symptoms such as impaired consciousness and seizures. In the present study, we investigated whether the presence of serum anti-gAChR antibodies correlated with autonomic symptoms in patients with functional neurological symptom disorder/conversion disorder (FNSD/CD).

Methods: Clinical data were collected for 59 patients presenting with neurologically unexplained motor and sensory symptoms at the Department of Neurology and Geriatrics between January 2013 and October 2017 and who were ultimately diagnosed with FNSD/CD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition.

Dihydroartemisinin Induced Apoptosis and Synergized With Chemotherapy in Pleural Effusion Lymphoma Cells.

Background/aim: Primary effusion lymphoma (PEL) is a rare aggressive B-cell lymphoma associated with HHV-8. With a median survival of fewer than six months, the prognosis of the disease with current standard therapies is usually dismal. Dihydroartemisinin (DHA) is a derivative of artemisinin, originally designed as an antimalarial drug.

Prognostic analysis of smoldering ATLL with skin eruptions based on genomic aberrations.

Background: Patients with smoldering ATLL often present with a skin eruption due to skin infiltration of ATLL cells. Although skin eruption type is known to be associated with prognosis based on its pattern, it is unknown why different types of skin eruptions are associated with different prognoses.

Objective: Genomic analysis of patients with skin eruptions of smoldering ATLL will be performed to determine the mechanism of ATLL development and its association with prognosis.

HIV virologic response, patterns of drug resistance mutations and correlates among adolescents and young adults: A cross-sectional study in Tanzania.

Background: The emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania.

Methods: Data of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design.

Pharmacokinetics of Bictegravir in Older Japanese People Living with HIV-1.

Bictegravir (BIC) is an integrase strand transfer inhibitor widely used in the treatment of HIV-1. Although its potency and safety have been demonstrated in older patients, pharmacokinetics (PK) data remain limited in this patient population. Ten male patients aged 50 years or older with suppressed HIV RNA on other antiretroviral regimens were switched to a single-tablet regimen of BIC, emtricitabine, and tenofovir alafenamide (BIC+FTC+TAF).

Riceberry Rice Germination and UVB Radiation Enhance Protocatechuic Acid and Vanillic Acid to Reduce Cellular Oxidative Stress and Suppress B16F10 Melanogenesis Relating to F-Actin Rearrangement.

Ultraviolet type B (UVB) radiation plays an important role in hyperpigmentation disorder, which induces cellular oxidative stress and causes abnormal melanin production and secretion. The stress condition plays an essential role in actin polymerization relating to F-actin rearrangement and forms dendrite to send melanin pigment to the uppermost layer of the skin. Phenolic compounds are secondary metabolites that mainly synthesize under stress conditions to protect plants from harmful environments and have been reported as effective agents in anti-oxidant and anti-melanogenesis.

Multimodal single-cell analyses of peripheral blood mononuclear cells of COVID-19 patients in Japan.

SARS-CoV-2 continues to spread worldwide. Patients with COVID-19 show distinct clinical symptoms. Although many studies have reported various causes for the diversity of symptoms, the underlying mechanisms are not fully understood.

Neutralizing antibodies after three doses of the BNT162b2 vaccine, breakthrough infection, and symptoms during the Omicron-predominant wave.

Objectives: To investigate the role of immunogenicity after the third vaccine dose against Omicron infection and COVID-19-compatible symptoms of infection.

Methods: First, we examined vaccine effectiveness (VE) of the third dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of third vaccine recipients, we compared the preinfection live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls who had close contact with patients with COVID-19.

Corrigendum: Combining the SMAC mimetic LCL161 with Gemcitabine plus Cisplatin therapy inhibits and prevents the emergence of multidrug resistance in cholangiocarcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.

Emerging integrase strand transfer inhibitor drug resistance mutations among children and adults on ART in Tanzania: findings from a national representative HIV drug resistance survey.

Background: Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients.

Objectives: To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania.

Synthesis of Selenoesters via Aldol Condensation and/or Conjugate Reduction and Their Antiviral Activities.

A variety of unsaturated selenoesters (including phenolic ones) were produced in good to high yields and with high / ratios using TiCl-promoted aldol condensation between -phenyl selenoacetate and their respective aldehydes without aqueous workup. A representative phenolic unsaturated selenoester was applied to acylation of tyrosine methyl ester without protection of the phenolic hydroxy groups to furnish the corresponding amino acid conjugate. The conjugate reduction of the unsaturated selenoesters including phenolic ones and selenocoumarin with HSiEt was catalyzed by B(CF) to afford the corresponding saturated selenoesters in good to high yields.

Preserved SARS-CoV-2 neutralizing IgG activity of in-house manufactured COVID-19 convalescent plasma.

Purpose: In the current study, we aimed to evaluate the neutralizing IgG activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the coagulation factors of convalescent plasmas which we manufactured in-house without a fast-freezing technique.

Methods: We collected plasmas from eligible participants who had confirmed certain titers of neutralizing antibodies. The plasmas were frozen and stored in the ordinary biofreezer without a fast-freezing function.

Cepharanthine inhibits dengue virus production and cytokine secretion.

Dengue virus (DENV) infection is a public health problem in tropical and subtropical regions. It can cause a spectrum of clinical manifestations ranging from mild dengue fever (DF) to severe dengue haemorrhagic fever (DHF) and potentially life-threatening disease including dengue shock syndrome (DSS). Severe DENV infection is caused by high viral load and cytokine storm in dengue-infected patients.

[SARS-CoV-2-specific T cell recognition toward emerging variants].

Cytotoxic T lymphocytes (CTLs) play an important role in the control of various viral infection. CTLs recognize a complex of HLA (human leukocyte antigen) class I molecule and epitope peptide derived from viral protein on the cell surface via T cell receptors and can destroy virally infected cells. It is becoming evident that SARS-CoV-2 specific T cells play a crucial role in the control of COVID-19.

Sensitivity to a CD4 mimic of a consensus clone of monkey-adapted CCR5-tropic SHIV-MK38C.

By acclimatizing CCR5-tropic tier 1B SHIV-MK1 to rhesus monkeys, a tier 2 SHIV-MK38 strain with neutralization resistance and high replication ability was generated. In this study, we generated SHIV-MK38C, a monkey-infectious consensus molecular clone of SHIV-MK38. Analysis using pseudotype viruses showed that MK38C was tier 1C because it lacked the N169D mutation, which is the most important mutation for neutralization resistance.

A novel cDNA-uPA/SCID/Rag2 /Jak3 mouse model for hepatitis virus infection and reconstruction of human immune system.

Although human hepatocyte-transplanted immunodeficient mice support infection with hepatitis viruses, these mice fail to develop viral hepatitis due to the lack of an adaptive immune system. In this study, we generated new immunodeficiency cDNA-urokinase-type plasminogen activator (uPA)/SCID/Rag2 /Jak3 mice and established a mouse model with both a humanized liver and immune system. Transplantation of human hepatocytes with human leukocyte antigen (HLA)-A24 resulted in establishment of a highly replaced liver in cDNA-uPA/SCID/Rag2 /Jak3 mice.

A novel tdTomato transgenic mouse model to visualize FAP-positive cancer-associated fibroblasts.

Fibroblast activation protein (FAP) generally shows low or undetectable expression in most normal tissues but is highly expressed in fibroblasts in almost all carcinomas. FAP is one of the potential molecules to detect activated fibroblasts and has multiple roles in tumour progression. We generated transgenic mice that specifically expressed tdTomato along with FAP promoter activity.

Structural Insight into the Resistance of the SARS-CoV-2 Omicron BA.4 and BA.5 Variants to Cilgavimab.

We have recently revealed that the new SARS-CoV-2 Omicron sublineages BA.4 and BA.5 exhibit increased resistance to cilgavimab, a therapeutic monoclonal antibody, and the resistance to cilgavimab is attributed to the spike L452R substitution.

Efficacy of l-Arginine treatment in patients with HTLV-1-associated neurological disease.

Objective: HTLV-1 infection causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), resulting in loss of motor function. In this Phase 2 trial, we assessed the efficacy and safety of l-arginine in patients with HAM/TSP.

Methods: This open-label, single-arm, Phase 2 study enrolled patients diagnosed with HAM/TSP.