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PloS One 2024Prostate stem cell antigen (PSCA) is associated with disease progression, promotion of angiogenesis, invasion, metastasis and immune evasion in cancer. However, its...
Prostate stem cell antigen (PSCA) is associated with disease progression, promotion of angiogenesis, invasion, metastasis and immune evasion in cancer. However, its expression pattern and diagnostic and prognostic potential have not been thoroughly analysed from a pan-cancer perspective. This study aimed to examine the effects of PSCA on the prognosis and inflammatory cell infiltration patterns of various cancer types. We analysed the relationship between PSCA expression and immunological subtypes in tumor microenvironment (TME) and the role of molecular subtypes, potentially promising immune biomarkers and tumour-infiltrating lymphocytes (TILs) in various cancer types, especially lung adenocarcinoma (LUAD). In addition, we investigated the prognostic significance of PSCA expression in LUAD. The co-expression network of PSCA was found to be mainly involved in the regulation of immune responses and antigen processing and expression and was significantly enriched in pathological and substance metabolism-related pathways in cancer. Altogether, this study reveals that PSCA is a promising target for immunotherapy in patients with cancer.
Topics: Humans; Antigens, Neoplasm; Prognosis; Tumor Microenvironment; Lymphocytes, Tumor-Infiltrating; Neoplasm Proteins; GPI-Linked Proteins; Biomarkers, Tumor; Neoplasms; Adenocarcinoma of Lung; Lung Neoplasms; Gene Expression Regulation, Neoplastic; Male
PubMed: 38917176
DOI: 10.1371/journal.pone.0298469 -
PloS One 2024Lu's approach for video-assisted thoracoscopic surgery (LVATS), which derives from UVATS, is a novel surgical approach for VATS and carries out micro-innovation for lung...
OBJECTIVES
Lu's approach for video-assisted thoracoscopic surgery (LVATS), which derives from UVATS, is a novel surgical approach for VATS and carries out micro-innovation for lung cancer resection. The objective of this study is to elucidate the safety, feasibility, and efficacy of this novel surgical approach.
METHODS
The clinical data of patients with non-small cell lung cancer (NSCLC) who underwent a curative thoracoscopic lobectomy between Mar. 2021 and Mar. 2022, were retrospectively collected, and analyzed. According to whether applied Lu's approach during the VATS operation, patients were divided into the LVATS group and the UVATS group. The propensity score (PS) matching method was used to reduce selection bias by creating two groups. After generating the PSs, 1:1 ratio and nearest-neighbor score matching was completed. Perioperative variables, including the operation time, intraoperative blood loss, lymph node stations dissected, total drainage volume, drainage duration, postoperative hospital stay, pain score (VAS, Visual Analogue Scale) on the postoperative first day (POD1) and third day (POD3), and incidence of postoperative complications, were compared between the two groups. The data were analyzed statistically with P<0.05 defined as statistically significant.
RESULTS
A total of 182 patients were identified, among whom 86 patients underwent LVATS and 96 UVATS. Propensity matching produced 62 pairs in this retrospective study. There were no deaths during perioperative period. Patients in the LVATS group experienced a shorter operation time (88 (75, 106) VS 122 (97, 144)min, P <0.001), less intraoperative blood loss(20 (20, 30) VS 25 (20, 50)ml, P = 0.021), shorten incision length (2.50 (2.50, 2.50) VS 3.00 (3.00, 3.50)cm, P <0.001), and more drainage volume (460 (310, 660) VS 345 (225, 600)ml, P = 0.041) than patients in the UVATS group. There was not significant difference in the lymph node stations dissected(5 (4, 5) VS 5 (4, 5), P = 0.436), drainage duration (3 (3, 4) VS 3 (3, 4)days, P = 0.743), length of postoperative hospital stay (4 (4, 5) VS 4 (4, 6)days, P = 0.608), VAS on the POD1(4 (4, 4) VS 4 (4, 4), P = 0.058)and POD3 (3 (3, 4) VS 4 (3, 4), P = 0.219), and incidence of postoperative complications (P = 0.521) between the two groups.
CONCLUSIONS
Lu's approach is a safe and feasible approach for video-assisted thoracoscopic surgery for the lobectomy of NSCLC. This approach can shorten surgical time, reduce incision length and intraoperative blood loss.
Topics: Humans; Thoracic Surgery, Video-Assisted; Male; Female; Middle Aged; Lung Neoplasms; Retrospective Studies; Carcinoma, Non-Small-Cell Lung; Aged; Postoperative Complications; Operative Time; Length of Stay; Pneumonectomy; Propensity Score; Treatment Outcome
PubMed: 38917144
DOI: 10.1371/journal.pone.0300632 -
PloS One 2024Neutrophil proteinase 3 (PR3) is an important drug target for inflammatory lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis. Drug...
Neutrophil proteinase 3 (PR3) is an important drug target for inflammatory lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis. Drug discovery efforts targeting PR3 require active enzyme for in vitro characterization, such as inhibitor screening, enzymatic assays, and structural studies. Recombinant expression of active PR3 overcomes the need for enzyme supplies from human blood and in addition allows studies on the influence of mutations on enzyme activity and ligand binding. Here, we report the expression of recombinant PR3 (rPR3) using a baculovirus expression system. The purification and activation process described resulted in highly pure and active PR3. The activity of rPR3 in the presence of commercially available inhibitors was compared with human PR3 by using a fluorescence-based enzymatic assay. Purified rPR3 had comparable activity to the native human enzyme, thus being a suitable alternative for enzymatic studies in vitro. Further, we established a surface plasmon resonance-based assay to determine binding affinities and kinetics of PR3 ligands. These methods provide valuable tools for early drug discovery aiming towards treatment of lung inflammation.
Topics: Humans; Myeloblastin; Ligands; Recombinant Proteins; Animals; Sf9 Cells; Surface Plasmon Resonance; Protein Binding; Baculoviridae; Kinetics; Gene Expression; Spodoptera
PubMed: 38917138
DOI: 10.1371/journal.pone.0294827 -
Journal of Medicinal Chemistry Jun 2024G protein-coupled receptor G2A was postulated to be a promising target for the development of new therapeutics in neuropathic pain, acute myeloid leukemia, and...
G protein-coupled receptor G2A was postulated to be a promising target for the development of new therapeutics in neuropathic pain, acute myeloid leukemia, and inflammation. However, there is still a lack of potent, selective, and drug-like G2A agonists to be used as a chemical tool or as the starting matter for the development of drugs. In this work, we present the discovery and structure-activity relationship elucidation of a new potent and selective G2A agonist scaffold. Systematic optimization resulted in (3-(pyridin-3-ylmethoxy)benzoyl)--phenylalanine (T-10418) exhibiting higher potency than the reference and natural ligand 9-HODE and high selectivity among G protein-coupled receptors. With its favorable activity, a clean selectivity profile, excellent solubility, and high metabolic stability, T-10418 qualifies as a pharmacological tool to investigate the effects of G2A activation.
PubMed: 38917049
DOI: 10.1021/acs.jmedchem.3c02164 -
Aging and Disease May 2024Non-small-cell lung carcinoma (NSCLC) often carries a dire prognosis. The advent of neoadjuvant chemoimmunotherapy (NCI) has become a promising approach in NSCLC...
Non-small-cell lung carcinoma (NSCLC) often carries a dire prognosis. The advent of neoadjuvant chemoimmunotherapy (NCI) has become a promising approach in NSCLC treatment, making the identification of reliable biomarkers for major pathological response (MPR) crucial. This study aimed to devise a deep learning (DL) model to estimate the MPR to NCI in lung squamous cell carcinoma (LUSC) patients and uncover its biological mechanism. We enrolled a cohort of 309 LUSC patients from various medical institutions. A ResNet50 model, trained on contrast-enhanced computed tomography images, was developed, and validated to predict MPR. We examined somatic mutations, genomic data, tumor-infiltrating immune cells, and intra-tumor microorganisms. Post-treatment, 149 (48.22%) patients exhibited MPR. The DL model demonstrated excellent predictive accuracy, evidenced by an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI: 0.98-1.00) and 0.90 (95% CI: 0.81-0.98) in the first and second validation sets, respectively. Multivariate logistic regression analysis identified the DL model score (low vs. high) as an independent predictor of MPR. The prediction of MPR (P-MPR) correlated with mutations in four genes, as well as gene ontology and pathways tied to immune response and antigen processing and presentation. Analysis also highlighted diversity in immune cells within the tumor microenvironment and in peripheral blood. Moreover, the presence of four distinct bacteria varied among intra-tumor microorganisms. Our DL model proved highly effective in predicting MPR in LUSC patients undergoing NCI, significantly advancing our understanding of the biological mechanisms involved.
PubMed: 38916736
DOI: 10.14336/AD.2024.0169 -
Emerging Infectious Diseases Jul 2024Few cases of hantavirus pulmonary syndrome have been reported in northeastern Argentina. However, neighboring areas show a higher incidence, suggesting underreporting....
Few cases of hantavirus pulmonary syndrome have been reported in northeastern Argentina. However, neighboring areas show a higher incidence, suggesting underreporting. We evaluated the presence of antibodies against orthohantavirus in small rodents throughout Misiones province. Infected Akodon affinis montensis and Oligoryzomys nigripes native rodents were found in protected areas of Misiones.
Topics: Animals; Argentina; Orthohantavirus; Antibodies, Viral; Hantavirus Infections; Rodentia; Rodent Diseases; Humans; Hantavirus Pulmonary Syndrome; Disease Reservoirs
PubMed: 38916725
DOI: 10.3201/eid3007.240183 -
Radiology Jun 2024
Topics: Humans; Tomography, X-Ray Computed; Biomarkers; Lung Diseases; Radiation Dosage; Bronchi
PubMed: 38916511
DOI: 10.1148/radiol.241381 -
International Journal of... Apr 2024Pharmacogenetic research has led to significant progress in understanding how genetic factors influence drug response in tuberculosis (TB) treatment. One ongoing...
BACKGROUND
Pharmacogenetic research has led to significant progress in understanding how genetic factors influence drug response in tuberculosis (TB) treatment. One ongoing challenge is the variable occurrence of adverse drug reactions in some TB patients. Previous studies have indicated that genetic variations in the N-acetyltransferase 2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) genes can impact the blood concentrations of the first-line anti-TB drugs isoniazid (INH) and rifampicin (RIF), respectively. This study aimed to investigate the influence of pharmacogenetic markers in the NAT2 and SLCO1B1 genes on TB treatment outcomes using whole-exome sequencing (WES) analysis.
METHODS
DNA samples were collected from 30 healthy Iranian adults aged 18-40 years. The allelic frequencies of single-nucleotide polymorphisms (SNPs) in the NAT2 and SLCO1B1 genes were determined through WES.
RESULTS
Seven frequent SNPs were identified in the NAT2 gene (rs1041983, rs1801280, rs1799929, rs1799930, rs1208, rs1799931, rs2552), along with 16 frequent SNPs in the SLCO1B1 gene (rs2306283, rs11045818, rs11045819, rs4149056, rs4149057, rs2291075, rs201722521, rs11045852, rs11045854, rs756393362, rs11045859, rs74064211, rs201556175, rs34671512, rs71581985, rs4149085).
CONCLUSION
Genetic variations in NAT2 and SLCO1B1 can affect the metabolism of INH and RIF, respectively. A better understanding of the pharmacogenetic profile in the study population may facilitate the design of more personalized and effective TB treatment strategies. Further research is needed to directly correlate these genetic markers with clinical outcomes in TB patients.
Topics: Humans; Arylamine N-Acetyltransferase; Liver-Specific Organic Anion Transporter 1; Adult; Antitubercular Agents; Male; Young Adult; Mycobacterium tuberculosis; Polymorphism, Single Nucleotide; Rifampin; Adolescent; Female; Isoniazid; Iran; Tuberculosis; Gene Frequency; Exome Sequencing; Pharmacogenomic Testing; Pharmacogenetics
PubMed: 38916393
DOI: 10.4103/ijmy.ijmy_106_24 -
International Journal of... Apr 2024Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), with a high global prevalence and mortality rate. To control the gruesome pathogen, a deep... (Comparative Study)
Comparative Study
BACKGROUND
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), with a high global prevalence and mortality rate. To control the gruesome pathogen, a deep understanding of pathophysiology and host-pathogen interaction is essential for early diagnosis and novel drug development. Cytokines play a crucial role in infection and susceptibility, and their expressions could serve as potential biomarkers to enhance our understanding of Mtb pathophysiology for improved therapeutic approaches. This cross-sectional study investigates the levels of four important T-cell immune-mediated cytokines: interleukins (IL-6 and IL-10), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha in 80 cohort samples, with 20 people in each group.
METHODS
Following proper ethics and patient consent, we collected blood samples and isolated serum from all four groups: TB, type 2 diabetes mellitus (T2DM), type 2 diabetes-TB comorbidity (T2DM + TB), and a healthy individual as a control group (C). Furthermore, cytokine expression was measured in individual serum samples through the enzyme-linked immunosorbent assay method using commercial kits (Diaclone, French). Statistical significance was observed by analyzing triplicate data using t-tests and the one-way ANOVA method with GraphPad Prism 10.
RESULTS
The results showed that all four cytokine levels were higher (P ≤ 0.0001) than the control, especially IL-6, IL-10, and IFN-γ, which were found to be upregulated in T2DM + TB samples (P ≤ 0.0001) than individual TB or T2DM samples.
CONCLUSION
The high levels of cytokines in comorbidity cases raise the risk of insulin resistance and the severity of TB infection. These levels of expression could be used to keep track of the Mtb infection status or severity, aid in early diagnosis as a possible biomarker, and suggest possible treatment plans.
Topics: Humans; Diabetes Mellitus, Type 2; Tuberculosis, Pulmonary; Cross-Sectional Studies; Male; Middle Aged; Female; Adult; Cytokines; Comorbidity; Mycobacterium tuberculosis; Interferon-gamma; Biomarkers; Interleukin-10; Tumor Necrosis Factor-alpha; Interleukin-6; Aged
PubMed: 38916387
DOI: 10.4103/ijmy.ijmy_40_24 -
Microbiology Spectrum Jun 2024The Platelia Aspergillus Antigen immunoassay is the "gold standard" for Aspergillus galactomannan (GLM) measurement in sera and bronchoalveolar lavage (BAL) for the...
Comparative performance of the Platelia Antigen and Galactomannan antigen Virclia Monotest immunoassays in serum and lower respiratory tract specimens: a "real-life" experience.
The Platelia Aspergillus Antigen immunoassay is the "gold standard" for Aspergillus galactomannan (GLM) measurement in sera and bronchoalveolar lavage (BAL) for the diagnosis of invasive pulmonary aspergillosis (IPA). We evaluated the performance of the Aspergillus GLM antigen Virclia Monotest compared to the Platelia assay. A total of 535 specimens [320 sera, 86 bronchial aspirates (BAs), 70 BAL, and 59 tracheal aspirates (TAs)] from 177 adult patients (72 hematological, 32 Intensive Care Unit, and 73 hospitalized in other wards) were processed for GLM testing upon clinical request. One patient had proven IPA, and 11 had probable disease. After excluding indeterminate Virclia results ( = 38), 396 specimens yielded concordant results (56 positive and 340 negative) and 101 discordant results (Virclia positive/Platelia negative, = 95). The overall agreement between immunoassays was higher for sera ( 0.56) than for BAL ( ≤ 0.24) or BAS and TA ( ≤ 0.22). When considering all specimen types in combination, the overall sensitivity and specificity of the Virclia assay for the diagnosis of proven/probable IPA were 100% and 65%, respectively, and for the Platelia immunoassay, sensitivity and specificity were 91.7% and 89.4%, respectively. The correlation between index values by both immunoassays was strong for serum/BAL ( = 0.73; < 0.001) and moderate for BAS/TA (Rho = 0.52; = 0.001). The conversion of Virclia index values into the Platelia index could be derived by the formula = (11.97 * )/3.62 + ). Data from GLM-positive serum/BAL clinical specimens fitted the regression model optimally ( = 0.94), whereas that of BAS and TA data did not ( = 0.11). Further studies are needed to determine whether the Virclia assay may be an alternative to the Platelia assay for GLM measurement in sera and lower respiratory tract specimens.IMPORTANCEGalactomannan detection in serum or bronchoalveolar fluid specimens is pivotal for the diagnosis of invasive pulmonary aspergillosis (IPA). The Platelia Aspergillus Antigen immunoassay has become the "gold standard" for Aspergillus GLM measurement. Here, we provide data suggesting that the Virclia Monotest assay, which displays several operational advantages compared with the Platelia assay, may become an alternative to the Platelia assay, although further studies are needed to validate this assumption. We also provide a formula allowing the conversion of Virclia index values into Platelia values. The study may contribute toward positioning the Virclia assay within the diagnostic algorithm of IPA.
PubMed: 38916338
DOI: 10.1128/spectrum.03910-23