Passive antibody therapy in emerging infectious diseases
AbstractThe epidemic of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome Coronavirus 2 and its variants of concern (VOCs) has been ongoing for over 3 years. Antibody therapies encompassing convalescent plasma, hyperimmunoglobulin, and neutralizing monoclonal antibodies (mAbs) applied in passive immunotherapy have yielded positive outcomes and played a crucial role in the early COVID-19 treatment. In this review, the development path, action mechanism, clinical research results, challenges, and safety profile associated with the use of COVID-19 convalescent plasma, hyperimmunoglobulin, and mA...
Source: Frontiers of Medicine - December 2, 2023 Category: General Medicine Source Type: research
Association between ICU quality and in-hospital mortality of V-V ECMO-supported patients —the ECMO quality improvement action (EQIA) study: a national cohort study in China from 2017 to 2019
AbstractThis cohort study was performed to explore the influence of intensive care unit (ICU) quality on in-hospital mortality of veno-venous (V-V) extracorporeal membrane oxygenation (ECMO)-supported patients in China. The study involved all V-V ECMO-supported patients in 318 of 1700 tertiary hospitals from 2017 to 2019, using data from the National Clinical Improvement System and China National Critical Care Quality Control Center. ICU quality was assessed by quality control indicators and capacity parameters. Among the 2563 V-V ECMO-supported patients in 318 hospitals, a significant correlation was found between ECMO-re...
Source: Frontiers of Medicine - November 22, 2023 Category: General Medicine Source Type: research
A pilot study on Paxlovid therapy for hemodialysis patients with severe acute respiratory syndrome coronavirus 2 infections
AbstractWe aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir (Paxlovid) therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thirteen hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30, 2022, were recruited. Laboratory parameters and chest CT (computed tomography) imaging were analyzed. The treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days, whereas the control group included seven patients who received basic treatment. No serious adverse r...
Source: Frontiers of Medicine - November 18, 2023 Category: General Medicine Source Type: research
Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell RNA-seq analysis
AbstractThe association of neurogenesis and gliogenesis with glioma remains unclear. By conducting single-cell RNA-seq analyses on 26 gliomas, we reported their classification into primitive oligodendrocyte precursor cell (pri-OPC)-like and radial glia (RG)-like tumors and validated it in a public cohort and TCGA glioma. The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carryEGFR mutations, and the pri-OPC-like ones were prone to carryingTP53 mutations. Tumor subclones only in pri-OPC-like tumors showed substantially down-regulatedMHC-I genes, suggesting their distinct immune evasion programs. F...
Source: Frontiers of Medicine - November 13, 2023 Category: General Medicine Source Type: research
Early-life famine exposure, adulthood obesity patterns, and risk of low-energy fracture
This study included 5323 community-dwelling subjects aged ⩾40 years from China. Early-life famine exposure was identified based on the participants’ birth dates. General obesity was assessed using the body mass index (BMI), and abdominal obesity was evaluated with the waist-to-hip ratio (WHR). Low-energy fracture was defined as fracture occurring after the age of ⩾40 typically caused by falls from standing height or lower. Compared to the nonexposed group, the group with fetal, childhood, and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios (ORs) and 95% confiden...
Source: Frontiers of Medicine - November 8, 2023 Category: General Medicine Source Type: research
Discovery of small molecule degraders for modulating cell cycle
AbstractThe cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize th...
Source: Frontiers of Medicine - November 8, 2023 Category: General Medicine Source Type: research
Phase separation in cGAS-STING signaling
AbstractBiomolecular condensates formed by phase separation are widespread and play critical roles in many physiological and pathological processes. cGAS-STING signaling functions to detect aberrant DNA signals to initiate anti-infection defense and antitumor immunity. At the same time, cGAS-STING signaling must be carefully regulated to maintain immune homeostasis. Interestingly, exciting recent studies have reported that biomolecular phase separation exists and plays important roles in different steps of cGAS-STING signaling, including cGAS condensates, STING condensates, and IRF3 condensates. In addition, several intrac...
Source: Frontiers of Medicine - October 31, 2023 Category: General Medicine Source Type: research
A randomized, controlled, open label non-inferiority trial of intravenous ferric carboxymaltose versus iron sucrose in patients with iron deficiency anemia in China
AbstractIron deficiency (ID) and ID anemia (IDA) pose significant public health concerns in China. Although iron sucrose (IS) treatment is well-established in the country, ferric carboxymaltose (FCM) offers the advantage of higher doses and fewer infusions. This open label, randomized, controlled, non-inferiority trial was conducted at multiple sites in China to compare the outcomes of FCM (maximum of 2 doses, 500 or 1000 mg iron) and IS (up to 11 infusions, 200 mg iron) treatments in subjects with IDA. The primary endpoint was the achievement of hemoglobin (Hb) response (an increase of ⩾2 g/dL from baseline) within 8 we...
Source: Frontiers of Medicine - October 28, 2023 Category: General Medicine Source Type: research
Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies
AbstractImmunotherapies based on immune checkpoint blockade (ICB) have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade. To date, immune checkpoint inhibitors (ICIs) of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy. Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers, however, a large subset of refractory patients presents poor responsiveness to ICB therapy; and the underlying mechanism remains elusive. Recently, numerous studies have revealed that metabolic reprogramming of tumor cells restrains immu...
Source: Frontiers of Medicine - October 28, 2023 Category: General Medicine Source Type: research
Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis
In conclusion, a novel JALS-associated gene calledTRMT2B was identified, thus broadening the clinical and genetic spectrum of ALS. (Source: Frontiers of Medicine)
Source: Frontiers of Medicine - October 24, 2023 Category: General Medicine Source Type: research
Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF- β signaling
AbstractTumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells...
Source: Frontiers of Medicine - October 23, 2023 Category: General Medicine Source Type: research
Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141, DDHD2, and LHFPL5
AbstractHighly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine. Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation. Here, a Pakistani family with parental consanguinity was presented, characterized with severe intellectual disability (ID), spastic paraplegia, and deafness. Homozygosity mapping, integrated single nucleotide polymorphism (SNP) array, whole-exome sequencing, and whole-genome sequencing were performed, and homozygous variants inTMEM141 (c.270G>A, p.Trp90*),DDH...
Source: Frontiers of Medicine - October 14, 2023 Category: General Medicine Source Type: research
Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1
AbstractLipin proteins including Lipin 1 –3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes, which play crucial roles in lipid metabolism. However, little is known about the function of Lipin3 in triglyceride (TG) metabolism. Here, we identified a novel mutation (NM_001301860: p.1835A>T/p.D612V) of Lipin3 in a large family with hypertriglyceridemia (HTG) and obesity through whole-exome sequencing and Sanger sequencing. Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein. Hence, we generated Lipin3 heterozygous knockout (Lipin3...
Source: Frontiers of Medicine - September 30, 2023 Category: General Medicine Source Type: research
BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models
AbstractOX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently und...
Source: Frontiers of Medicine - September 25, 2023 Category: General Medicine Source Type: research
Heterogeneity of the tumor immune microenvironment and clinical interventions
AbstractThe tumor immune microenvironment (TIME) is broadly composed of various immune cells, and its heterogeneity is characterized by both immune cells and stromal cells. During the course of tumor formation and progression and anti-tumor treatment, the composition of the TIME becomes heterogeneous. Such immunological heterogeneity is not only present between populations but also exists on temporal and spatial scales. Owing to the existence of TIME, clinical outcomes can differ when a similar treatment strategy is provided to patients. Therefore, a comprehensive assessment of TIME heterogeneity is essential for developin...
Source: Frontiers of Medicine - September 20, 2023 Category: General Medicine Source Type: research
