LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver

Background: Nonalcoholic fatty liver disease(NAFLD) is one of the main liver diseases, and its pathologic profile includes nonalcoholic fatty liver(NAFL) and nonalcoholic steatohepatitis(NASH). However, there is no reliable non-invasive parameter in distinguishing NASH from NAFL in clinical practice. The present study was to find a non-invasive way to differentiate these two categories of NAFLD via lipidomic analysis. Methods: Lipidomic analysis was used to determine the changes of lipid moieties in blood from 20 NAFL and 10 NASH patients with liver biopsy. Liver histology was evaluated after hematoxylin and eosin staining and Masson’s trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflammation, hepatocellular necroptosis, fibrosis, and NAFLD activity score(NAS) was analyzed. Results: Compared with NAFL patients, NASH patients had higher degree of steatosis, ballooning degeneration, lobular inflammation. A total of 434 different lipid molecules were identified, which were mainly composed of various phospholipids and triacylglycerols. Many lipids, such as phosphatidylcholine(PC)(P-22:0/18:1), sphingomyelin(SM)(d14:0/18:0), SM(d14:0/24:0), SM(d14:0/22:0), phosphatidylethanolamine(PE)(18:0/22:5), PC(O-22:2/12:0), and PC(26:1/11:0) were elevated in the NASH group compared to those in the NAFL group. Specific analysis revealed an overall lipidomic profile shift from NAFL to NASH, and identified valuable lipid moieties, such as PCs [PC(14:0/18:2), PE(18:0/22:5) and PC(26:1/11:0)] or plasmalogens [PC(O-22:0/0:0), PC(O-18:0/0:0), PC(O-16:0/0:0)], which were significantly altered in NASH patients. In addition, PC(14:0/18:2), phosphatidic acid(18:2/24:4) were positively correlated with NAS;whereas PC(18:0/0:0) was correlated positively with fibrosis score. Conclusions: The present study revealed overall lipidomic profile shift from NAFL to NASH, identified valuable lipid moieties which may be non-invasive biomarkers in the categorization of NAFLD. The correlations between lipid moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.

Single-domain antibodies as therapeutics for solid tumor treatment

Single-domain antibodies(sdAbs),initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs,have emerged as a promising alternative to conventional therapeutic antibodies.These sdAbs have many superior physicochemical and pharmacological properties,including small size,good solubility and thermostability,easier accessible epitopes,and strong tissue penetration.However,the inherent challenges associated with the animal origin of sdAbs limit their clinical use.In recent years,various innovative humanization technologies,including complementarity-determining region(CDR)grafting or complete engineering of fully human sdAbs,have been developed to mitigate potential immunogenicity issues and enhance their compatibility.This review provides a comprehensive exploration of sdAbs,emphasizing their distinctive features and the progress in humanization methodologies.In addition,we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment,such as sdAbedrug conjugates,multispecific sdAbs,sdAb-based delivery systems,and sdAb-based cell therapy.

SARS-CoV-2 Omicron subvariant BA.2.86: limited potential for global spread

In recent studies published in Nature and Lancet Infectious Diseases,1,2 SARS-CoV-2 Omicron subvariant BA.2.86 exhibited a substantial antigenic drift,enhanced receptor affinity,and less immune evasion to sera of individuals upon XBB breakthrough infection or reinfection.These findings suggest that the potential for BA.2.86 to spread globally is limited,albeit the mutated BA.2.86 sequences were detected in wastewater in various public and commercial venues before the confirmed case of BA.2.86 infection in Thailand,which raised concerns about the spread of BA.2.86 through international travel.3.

Defining a highly conserved cryptic epitope for antibody recognition of SARS-CoV-2 variants

Dear Editor,In recent months,additional Omicron variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),including the BA.5 sublineage BF.7 and BQ.1.1 and the BA.2 linage recombination XBB,XBB.1.5 and XBB.1.16,have emerged following the BA.2 and BA.5 subvariants.Remarkably,BQ.1.1 and XBB showed substantial neutralization escape as compared with the previous variants,and have gradually become the dominant variants worldwide.1 These facts emphasize the urgency of identifying highly conserved SARS-CoV-2 epitopes,which would be essential for the design of universal vaccines and broadly neutralizing antibodies.

The impact of receptor-binding domain natural mutations on antibody recognition of SARS-CoV-2

Dear Editor,The ongoing COVID-19 pandemic has resulted in over 25.0 million confirmed cases and over 840,000 deaths globally.As the third severe respiratory disease outbreak caused by the coronavirus,COVID-19 has led to much larger infected populations and coverage of geographic areas than SARS and MERS.Such high prevalence of infection has raised significant concerns about the emergence and spread of escape variants,which may evade human immunity and eventually render candidate vaccines and antibody-based therapeutics ineffective.Indeed,some naturally mutated SARS-CoV or MERS-CoV strains from the sequential outbreaks were reported to resist neutralization by the antibodies isolated during the first outbreak1,2.

Recent advances in“universal”influenza virus antibodies:the rise of a hidden trimeric interface in hemagglutinin globular head

Influenza causes seasonal outbreaks yearly and unpredictable pandemics with high morbidity and mortality rates.Despite significant efforts to address influenza,it remains a major threat to human public health.This issue is partially due to the lack of antiviral drugs with potent antiviral activity and broad reactivity against all influenza virus strains and the rapid emergence of drug-resistant variants.Moreover,designing a universal influenza vaccine that is sufficiently immunogenic to induce universal antibodies is difficult.Some novel epitopes hidden in the hemagglutinin(HA)trimeric interface have been discovered recently,and a number of antibodies targeting these epitopes have been found to be capable of neutralizing a broad range of influenza isolates.These findings may have important implications for the development of universal influenza vaccines and antiviral drugs.In this review,we focused on the antibodies targeting these newly discovered epitopes in the HA domain of the influenza virus to promote the development of universal anti-influenza antibodies or vaccines and extend the discovery to other viruses with similar conformational changes in envelope proteins.

Inhalable antibodies for the treatment of COVID-19

By the end of July 2022,the SARS-CoV-2 pandemic had caused more than 6 million deaths worldwide.This viral infection results in a series of atypical respiratory diseases termed COVID-19,from asymptomatic infection to severe symptoms such as acute respiratory distress syndrome and pulmonary fibrosis.Development of vaccines and therapeutic measures that mitigate the sufferings caused by the pandemic has been achieved in a short period of time.Only 1 year after the emergence of the pandemic,COVID-19 vaccines have been approved in several countries.

Insights into biological therapeutic strategies for COVID-19

The worldwide pandemic of novel coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)that emerged in late December 2019 requires the urgent development of therapeutic options.So far,numerous studies have investigated and uncovered the underlying epidemiology and clinical characteristics of COVID-19 infections in order to develop effective drugs.Compared with antiviral small-molecule inhibitors,biotherapeutics have unique advantages such as fewer side effects by virtue of their high specificity,and thus can be rapidly developed for promising treatments of COVID-19.Here,we summarize potential biotherapeutics and their mechanisms of action,including convalescent plasma,therapeutic antibodies,peptides,engineered ACE2,interferons,cytokine inhibitors,and RNAi-based therapeutics,and discuss in depth the advancements and precautions for each type of biotherapeutics in the treatment of COVID-19.