Gut Microbiome Changes After Neoadjuvant Chemotherapy and Surgery in Patients with Gastric Cancer.

Background/objectives: Neoadjuvant chemotherapy (NAC) followed by radical gastrectomy is the current standard approach for locally advanced gastric cancer (GC) in the West. Both NAC and gastrectomy can significantly influence the gut microbiome, potentially leading to clinically significant changes. However, no longitudinal studies to date support this hypothesis.

The microplastic-crisis: Role of bacteria in fighting microplastic-effects in the digestive system.

Plastic particles smaller than 5 mm, referred to as Microplastics, pose health risks, like metabolic, immunological, neurological, reproductive, and carcinogenic effects, after being ingested. Smaller plastic particles are more likely to be absorbed by human cells, with nanoplastics showing higher potential for cellular damage, including DNA fragmentation and altered protein functions. Micro- and nanoplastics (MNPs) affect the gastrointestinal tract by altering the microbial composition, they could influence digestive enzymes, and possibly disrupt mucus layers.

Dual specific STAT3/5 degraders effectively block acute myeloid leukemia and natural killer/T cell lymphoma.

The transcription factors STAT3, STAT5A, and STAT5B steer hematopoiesis and immunity, but their enhanced expression and activation promote acute myeloid leukemia (AML) or natural killer/T cell lymphoma (NKCL). Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, but these kinase blockers are not selective against STAT3/5 activation and frequent resistance causes relapse, emphasizing the need for targeted drugs. We evaluated the efficacy of JPX-0700 and JPX-0750 as dual STAT3/5 binding inhibitors promoting protein degradation.

Probiotic Therapy of Gastrointestinal Symptoms During COVID-19 Infection: A Randomized, Double-Blind, Placebo-Controlled, Remote Study.

Background: The novel coronavirus (SARS-CoV-2) led to gastrointestinal manifestations in up to 50% of cases, with diarrhea being common, and probiotics have been suggested as a potential treatment.

Aim: This study aimed to assess changes in the microbiome and the effects of a multispecies probiotic in patients with COVID-19 in home quarantine through a fully remote telemedical approach.

Methods: Thirty patients were randomized to receive either the Ecologic AAD probiotic (Winclove Probiotics, Amsterdam, The Netherlands), on the market as OMNi-BiOTiC 10 (Allergosan, Austria), or a placebo for 30 days in a 2:1 ratio.

Alteration of the Gut-Lung Axis After Severe COVID-19 Infection and Modulation Through Probiotics: A Randomized, Controlled Pilot Study.

Background: The gut-lung axis could be a potential therapeutic target for improving post-acute COVID-19 symptoms, and probiotics have been proposed as possible modulators.

Aim: We conducted a pilot study to understand alterations in the gut-lung axis and to explore the effects of a probiotic in post-acute COVID-19 disease.

Methods: We included patients after severe COVID-19 disease (sCOV, n = 21) in a randomized, placebo-controlled trial to test the effect of a probiotic (Pro-Vi 5, Institute Allergosan, Graz, Austria) in a six-month intervention and used patients after mild disease (mCOV, n = 10) as controls, to compare the intestinal microbiome, metabolome, and patient-reported outcomes and biomarkers along the gut-lung axis at baseline and throughout probiotic intervention.

Advanced single-cell and spatial analysis with high-multiplex characterization of circulating tumor cells and tumor tissue in prostate cancer: Unveiling resistance mechanisms with the CoDuCo in situ assay.

Background: Metastatic prostate cancer is a highly heterogeneous and dynamic disease and practicable tools for patient stratification and resistance monitoring are urgently needed. Liquid biopsy analysis of circulating tumor cells (CTCs) and circulating tumor DNA are promising, however, comprehensive testing is essential due to diverse mechanisms of resistance. Previously, we demonstrated the utility of mRNA-based in situ padlock probe hybridization for characterizing CTCs.

The adsorption of drugs on nanoplastics has severe biological impact.

Micro- and nanoplastics can interact with various biologically active compounds forming aggregates of which the effects have yet to be understood. To this end, it is vital to characterize these aggregates of key compounds and micro- and nanoplastics. In this study, we examined the adsorption of the antibiotic tetracycline on four different nanoplastics, made of polyethylene (PE), polypropylene (PP), polystyrene (PS), and nylon 6,6 (N66) through chemical computation.

Targeting Androgen, Thyroid Hormone, and Vitamin A and D Receptors to Treat Prostate Cancer.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR), upon ligand binding and homodimerization, shuttles from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors (TRs), retinoic acid receptors (RARs), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXRs) and repress gene expression.

Cellular and Microbial In Vitro Modelling of Gastrointestinal Cancer.

Human diseases are multifaceted, starting with alterations at the cellular level, damaging organs and their functions, and disturbing interactions and immune responses. In vitro systems offer clarity and standardisation, which are crucial for effectively modelling disease. These models aim not to replicate every disease aspect but to dissect specific ones with precision.

Screening for oncogenic AF1q expression predicts disease recurrence in gastric cancer patients.

AF1q associates with tumor progression and metastases upon WNT signaling. The downstream WNT target CD44 has demonstrated prognostic significance in gastric cancer (GC). This study evaluates the impact of AF1q on tumor stage and survival in GC patients.

Characterization of Inflammatory Mediators and Metabolome in Interstitial Fluid Collected with Dermal Open Flow Microperfusion before and at the End of Dupilumab Treatment in Atopic Dermatitis.

Dupilumab is a monoclonal antibody approved for the treatment of atopic dermatitis (AD); however, its effects on molecular, cellular, and immunological levels remain to be elucidated. In this study, blood and dermal interstitial fluid (ISF) from nonlesional (NL) and lesional (L) skin were collected from eight patients with moderate to severe AD, before (visit 2-v2) and at the end of a 16-week treatment with dupilumab (visit 10-v10). Clinical treatment effect was demonstrated by significantly decreased AD severity scores at the end of treatment.

JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression.

Background: Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood.

Methods: We analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in a Pten-deficient mouse model.

Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma.

Targeting Anaplastic lymphoma kinase (ALK) is a promising therapeutic strategy for aberrant ALK-expressing malignancies including neuroblastoma, but resistance to ALK tyrosine kinase inhibitors (ALK TKI) is a distinct possibility necessitating drug combination therapeutic approaches. Using high-throughput, genome-wide CRISPR-Cas9 knockout screens, we identify miR-1304-5p loss as a desensitizer to ALK TKIs in aberrant ALK-expressing neuroblastoma; inhibition of miR-1304-5p decreases, while mimics of this miRNA increase the sensitivity of neuroblastoma cells to ALK TKIs. We show that miR-1304-5p targets NRAS, decreasing cell viability via induction of apoptosis.

Corrigendum: Application of a multispecies probiotic reduces gastro-intestinal discomfort and induces microbial changes after colonoscopy.

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

Primary sarcopenia is associated with elevated spontaneous NET formation.

Sarcopenia is a frequent complication of liver cirrhosis, but it can also occur independently as a result of any underlying cause. The immune system plays an important role in the pathogenesis of both liver cirrhosis and sarcopenia. Neutrophil function, including neutrophil extracellular trap (NET) formation, is linked to chronic inflammation; however, it has not been extensively studied in patients with sarcopenia.

Circulating neutrophil anti-pathogen dysfunction in cirrhosis.

Neutrophils are the largest population of leucocytes and are among the first cells of the innate immune system to fight against intruding pathogens. In patients with cirrhosis, neutrophils exhibit altered functionality, including changes in phagocytic ability, bacterial killing, chemotaxis, degranulation, reactive oxygen species production and NET (neutrophil extracellular trap) formation. This results in their inability to mount an adequate antibacterial response and protect the individual from infection.

Human gut microbiome: Therapeutic opportunities for metabolic syndrome-Hype or hope?

Shifts in gut microbiome composition and metabolic disorders are associated with one another. Clinical studies and experimental data suggest a causal relationship, making the gut microbiome an attractive therapeutic goal. Diet, intake of probiotics or prebiotics and faecal microbiome transplantation (FMT) are methods to alter a person's microbiome composition.

Maternal COVID-19 causing intrauterine foetal demise with microthrombotic placental insufficiency: a case report.

Background: Pregnant women have an increased risk of getting infected with SARS-CoV-2 and are more prone to severe illness. Data on foetal demise in affected pregnancies and its underlying aetiology is scarce and pathomechanisms remain largely unclear.

Case: Herein we present the case of a pregnant woman with COVID-19 and intrauterine foetal demise.

Fluid shear stress induces a shift from glycolytic to amino acid pathway in human trophoblasts.

Background: The human placenta, a tissue with a lifespan limited to the period of pregnancy, is exposed to varying shear rates by maternal blood perfusion depending on the stage of development. In this study, we aimed to investigate the effects of fluidic shear stress on the human trophoblast transcriptome and metabolism.

Results: Based on a trophoblast cell line cultured in a fluidic flow system, changes caused by shear stress were analyzed and compared to static conditions.

Spatial tumour gene signature discriminates neoplastic from non-neoplastic compartments in colon cancer: unravelling predictive biomarkers for relapse.

Background: Opting for or against the administration of adjuvant chemotherapy in therapeutic management of stage II colon cancer remains challenging. Several studies report few survival benefits for patients treated with adjuvant therapy and additionally revealing potential side effects of overtreatment, including unnecessary exposure to chemotherapy-induced toxicities and reduced quality of life. Predictive biomarkers are urgently needed.