Explor Target Antitumor Ther
December 2024
The emergence of immunotherapy has ushered in a new era in the management of non-small cell lung cancer (NSCLC). Various immune check point inhibitors have demonstrated significant benefit in the management of locally advanced NSCLC that are treated with either surgery or concurrent chemoradiation. We provide a comprehensive and up-to-date review of data from key studies, discuss the challenging clinical issue regarding the timing and duration of immunotherapy in patients undergoing surgery, and highlight the unmet needs and future directions of immunotherapy in NSCLC.
View Article and Find Full Text PDFUnlabelled: The persistence of HIV-1 reservoirs during combination anti-retroviral therapy (cART) leads to chronic immune activation and systemic inflammation in people with HIV (PWH), associating with a suboptimal immune reconstitution as well as an increased risk of non-AIDS events. This highlights the needs to develop novel therapy for HIV-1 related diseases in PWH. In this study, we assessed the therapeutic effect of CD24-Fc, a fusion protein with anti-inflammatory properties that interacts with danger-associated molecular patterns (DAMPs) and siglec-10, in chronic HIV-1 infection model using humanized mice undergoing suppressive cART.
View Article and Find Full Text PDFMany agents that show promise in preclinical cancer models lack efficacy in patients due to patient heterogeneity that is not captured in traditional assays. To address this problem, we have developed GENEVA, a platform that measures the molecular and phenotypic consequences of drug perturbations within diverse populations of cancer cells at single-cell resolution, both and . Here, we apply GENEVA to study the KRAS G12C inhibitors, recapitulating known properties of these drugs and uncovering a previously unknown role for mitochondrial activation in cell death induced by KRAS inhibition.
View Article and Find Full Text PDFSepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infections that is initiated by the body's innate immune system. Nearly a decade ago, we discovered that bacterial lipopolysaccharide (LPS) and serum amyloid A (SAA) upregulated Connexin 43 (Cx43) and Pannexin 1 (Panx1) hemichannels in macrophages. When overexpressed, these hemichannels contribute to sepsis pathogenesis by promoting ATP efflux, which intensifies the double-stranded RNA-activated protein kinase R (PKR)-dependent inflammasome activation, pyroptosis, and the release of pathogenic damage-associated molecular pattern (DAMP) molecules, such as HMGB1.
View Article and Find Full Text PDFBackground: Camels, known as the enduring "ships of the desert," host a complex gut microbiota that plays a crucial role in their survival in extreme environments. However, amidst the fascinating discoveries about the camel gut microbiota, concerns about antibiotic resistance have emerged as a significant global challenge affecting both human and animal populations. Indeed, the continued use of antibiotics in veterinary medicine has led to the widespread emergence of antibiotic-resistant bacteria, which has worsened through gene transfer.
View Article and Find Full Text PDFMol Ther Nucleic Acids
December 2024
Anti-gene oligonucleotides belong to a group of therapeutic compounds, which, in contrast to antisense oligonucleotides, bind to DNA. Clamp anti-gene oligonucleotides bind through a double-stranded invasion mechanism. With two arms connected by a linker, they hybridize to one of the DNA strands forming Watson-Crick and Hoogsteen hydrogen bonds.
View Article and Find Full Text PDFBackground: Metastasis is the primary cause of mortality in small cell lung cancer (SCLC), with the liver being a predominant site for distal metastasis. Despite this clinical significance, mechanisms underlying the interaction between SCLC and liver microenvironment, fostering metastasis, remain unclear.
Methods: SCLC patient tissue array, bioinformatics analysis were performed to demonstrate the role of periostin (POSTN) in SCLC progression, metastasis, and prognosis.
Niemann-Pick disease type C protein 1 (NPC1), classically associated with cholesterol transport and viral entry, has an emerging role in cancer biology. Here, we demonstrate that knockout of Npc1 in hepatocytes attenuates hepatocellular carcinoma (HCC) progression in both DEN (diethylnitrosamine)-CCl induced and MYC-driven HCC mouse models. Mechanistically, NPC1 significantly promotes HCC progression by modulating the TGF-β pathway, independent of its traditional role in cholesterol transport.
View Article and Find Full Text PDFLead-free halide double perovskites (DPs) have become a research hotspot in the field of photoelectrons due to their unique optical properties and flexible compositional tuning. However, the luminescence of DPs exhibits thermal quenching at high temperatures, which severely affects their further application. Herein, we synthesized the rare earth Dy and transition metal Mn codoped CsNaYCl rare earth DPs and characterized the optical properties using temperature-dependent photoluminescence spectra and time-resolved photoluminescence decay profiles at different temperatures.
View Article and Find Full Text PDFTo investigate the combined application of cytology, cell block histology and immunohistochemistry to improve the diagnostic accuracy of solid pancreatic lesions in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples. The pathological data of EUS-FNA in 311 cases of solid pancreatic lesions submitted to the Second Hospital of Hebei Medical University, Shijiazhuang, China from May 2019 to September 2023 were retrospectively analyzed. The cases included pancreatic ductal adenocarcinoma (PDAC, 172 cases), solid pseudopapillary neoplasm (SPN, 12 cases), neuroendocrine tumors (PNET, 14 cases) and chronic pancreatitis (113 cases).
View Article and Find Full Text PDFProstate cancer is a significant cause of cancer-related deaths in men. Poly (ADP-ribose) polymerase inhibitors (PARPi) have been shown to improve progression-free survival, especially in patients with BRCA1/2 mutations and deficiencies in homologous recombination repair (HRR). We conducted systematic reviews and meta-analyses and found that PARPi, combined with androgen receptor inhibitors, significantly improved overall survival (OS) and progression-free survival (PFS) in BRCA1/2-mutant and HRR-deficient patients.
View Article and Find Full Text PDFJ Biomed Mater Res B Appl Biomater
January 2025
Massive bleeding and bacterial infection of wounds may be life-threatening or even lead to death. Nowadays, gelatin-based hemostatic sponges have been widely used, but gelatin is not antibacterial and has poor structural stability. In this study, we mixed an antibacterial polypeptide, ε-poly-L-lysine (EPL), into gelatin.
View Article and Find Full Text PDFChinese pond turtle muscle peptide's molecular features, purification, structural characteristics, and antioxidant activity were investigated. The Flavourzyme hydrolysate demonstrated greater relative crystallinity (37.53%) than other hydrolysates using X-ray diffraction.
View Article and Find Full Text PDFPurpose: In the United States, there are disparities in access to care for patients with non-small cell lung cancer (NSCLC) on the basis of socioeconomic and racial/ethnic factors. This study investigates the association between race/ethnicity and the utilization of immune checkpoint inhibitor (ICI) therapy among older patients with advanced NSCLC (aNSCLC).
Methods: This retrospective study used data from the SEER-Medicare-linked database.
Glycosite-specific antibody-drug conjugates (gsADCs), which carry cytotoxic payloads at the conserved -glycosylation site, N297, of an IgG, have emerged as a promising ADC format with better therapeutic index. Conjugating the payloads aldehyde-based chemistry is more friendly to IgGs, and has been widely investigated. However, the efficiency of introducing an aldehyde tag at the N297 site is poor due to the complicated procedures required, such as the multiple-enzyme-catalyzed IgG glycoengineering process and the successive oxidation step, which always results in heterogeneous products and poor stability.
View Article and Find Full Text PDFTeucrifarides A-D (1-4), four previously unreported neo-clerodane-type diterpenoids, combined with sixteen known analogs (5-20), were purified from Teucrium quadrifarium. The absolute forma of compounds 1-4 were determined via spectroscopic and ECD calculation methods, together with X-ray crystallography experiments. Among them, compound 1 possessed a 5,20-epoxy ring featuring a unique cage-like 12-oxatricyclo [5.
View Article and Find Full Text PDFBackground: The relationship between dietary live microbe intake, non-dietary prebiotics/probiotics, and mortality in older adults remains unclear.
Methods: Participants from the National Health and Nutrition Examination Survey 2003-2018 were included. Participants were categorized into three groups based on estimated live microbe intake: low, medium, and high.
Chitosan is a kind of natural material with many unique physicochemical and biological properties related to antibacterial, antioxidant, and chelating. In recent years, chitosan-based nano gels (CS-NG) have been widely used in the field of cancer nanomedicine due to their excellent characteristics including biodegradability, biocompatibility, flexibility, large surface area, controllability, high loading capacity, and especially it can be engineered to become stimuli-responsive to tumor environments. In this review, we summarized the main synthesis approaches of CS-NGs including radical polymerization, self-assembly, microemulsion, and ionic gelation methods.
View Article and Find Full Text PDFThis study explores the association between serum chloride concentrations and all-cause mortality among patients in the Surgical Intensive Care Unit (SICU). Employing a retrospective cohort design, the study utilized data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, specifically focusing on individuals admitted to the surgical/trauma ICUs. This dataset encompassed demographic profiles, laboratory findings, historical medical data, vital statistics, and variables pertinent to prognosis.
View Article and Find Full Text PDFObjective: To evaluate the added value of dynamic contrast-enhanced ultrasound (DCE-US) analysis in pre-operative differential diagnosis of small (≤20 mm) solid pancreatic lesions (SPLs).
Methods: In this retrospective study, patients with biopsy or surgerical resection and histopathologically confirmed small (≤20 mm) SPLs were included. One wk before biopsy/surgery, pre-operative B-mode ultrasound and contrast-enhanced ultrasound were performed.
High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.
View Article and Find Full Text PDFIn recent years, researchers have drawn inspiration from natural ion channels to develop various artificial nanopores/nanochannels, including solid-state and biological. Through imitating the precise selectivity and single molecule sensing exhibited by natural ion channels, nanopores/nanochannels have been widely used in many fields, such as analyte detection, gene sequencing and so on. In these applications, the surface functionalization of nanopores/nanochannels directly determines the effectiveness in quantitative analysis and single molecule detection.
View Article and Find Full Text PDFImatinib resistance is a major obstacle to the successful treatment of gastrointestinal stromal tumors (GIST). Long non-coding RNAs (LncRNAs) have been identified as important regulatory factors in chemotherapy resistance. This study aimed to identify key lncRNAs involved in imatinib resistance of GISTs.
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