Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer(CRC).However,a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease,as such factors dictate the timing and drug regimen,which may affect treatment response and prognosis.In this study,we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local de-livery of the anticancer drug,oxaliplatin,to the lung.12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion(IVLP)with various doses of oxaliplatin(7.5,10,20,40,and 80 mg/L),which were administered to the perfusion circuit reservoir as a bolus.Biocompatible solid-phase microextraction(SPME)microprobes were combined with global metabolite profiling to obtain spatiotemporal infor-mation about the activity of the drug,determine toxic doses that exceed therapeutic efficacy,and conduct a mechanistic exploration of associated lung injury.Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin,and significant compromise of the hemodynamic lung function was found at 80 mg/L.This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate,resulting in a total of 139 discriminant compounds.Uncontrolled inflammatory response,abnormalities in energy metabolism,and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome.Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

The world has witnessed tremendous advancements in nano-base applications. Zinc oxide nanoparticles (ZON) are widely used in food industry and medicine. Although their application is of important value, they may cause toxicity to body tissues. Peripheral blood mononuclear cells (PBMCs) proved its efficacy in tissue regeneration especially when it is preconditioned by activated platelet supernatant (APS). The aim of this study is to evaluate the effect of ZON on the gastric mucosa and the therapeutic role of the PBMCs preconditioned by APS in rats. Ten rats were donors and fifty rats were recipients. The recipients were divided into; control group, ZON group (10 mg/kg/day orally for five days) and preconditioned PBMCs group (1×107 once intravenously 24 hours after ZON). Gastric specimens were processed for histological, immunohistochemical, biochemical and quantitative real-time polymerase chain reaction studies. ZON group showed marked structural changes in the gastric mucosa. There was desquamation or deep ulceration of the epithelium. Cytoplasmic vacuoles and pyknotic nuclei were in glandular cells. Reduced proliferating cell nuclear antigen and increased tumor necrosis factor-α were in epithelial cells. There were significant elevation in malondialdahyde and reduction in glutathione, superoxide dismutase, and catalase. Enhancement in mRNA expression of nuclear factor kappa-B and cyclooxygenase-2 was detected.The preconditioned PBMCs group showed significant improvement of all parameters. So, ZON had cytotoxic effects on the gastric mucosa and the preconditioned PBMCs had a therapeutic effect on gastric mucosal damage after ZON.

Development of a novel in vivo lung perfusion(IVLP)procedure allows localized delivery of high-dose doxorubicin(DOX)for targeting residual micrometastatic disease in the lungs.However,DOX delivery via IVLP requires careful monitoring of drug level to ensure tissue concentrations of this agent remain in the therapeutic window.A small dimension nitinol wire coated with a sorbent of biocompatible morphology(Bio-SPME)has been clinically evaluated for in vivo lung tissue extraction and determina-tion of DOX and its key metabolites.The in vivo Bio-SPME-IVLP experiments were performed on pig model over various(150 and 225 mg/m2)drug doses,and during human clinical trial.Two patients with metastatic osteosarcoma were treated with a single 5 and 7 μg/mL(respectively)dose of DOX during a 3-h IVLP.In both pig and human cases,DOX tissue levels presented similar trends during IVLP.Human lung tissue concentrations of drug ranged between 15 and 293 μg/g over the course of the IVLP procedure.In addition to DOX levels,Bio-SPME followed by liquid chromatography-mass spectrometry analysis generated 64 metabolic features during endogenous metabolite screening,providing information about lung status during drug administration.Real-time monitoring of DOX levels in the lungs can be per-formed effectively throughout the IVLP procedure by in vivo Bio-SPME chemical biopsy approach.Bio-SPME also extracted various endogenous molecules,thus providing a real-time snapshot of the physi-ology of the cells,which might assist in the tailoring of personalized treatment strategy.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.
Antioxidants ; Classification ; Clinical Protocols ; Diagnosis ; DNA ; Embryonic Structures ; Female ; Fertility ; Health Expenditures ; Humans ; Infertility ; Infertility, Male ; Male ; Membranes ; Ovum ; Oxidants ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species ; Reducing Agents ; Reproductive Health ; Semen ; Spermatozoa ; Subject Headings