Palmar-plantar erythrodysesthesia (PPE), also known as hand and foot syndrome, is a condition characterized by inflammation-mediated damage to the skin on the palms and soles of the hands and feet. PPE limits the successful therapeutic applications of anticancer drugs. However, identifying this toxicity during preclinical studies is challenging due to the lack of accurate in vitro and in vivo animal-based models. Therefore, there is a need for reliable models that would allow the detection of this toxicity early during the drug development process. Herein, we describe the use of an in vitro skin explant assay to assess traditional DXR, Doxil reference listed drug (RLD) and two generic PEGylated liposomal DXR formulations for their abilities to cause inflammation and skin damage. We demonstrate that the results obtained with the in vitro skin explant assay model for traditional DXR and Doxil correlate with the clinical data.

Desminopathy R350P is a human myopathy that is characterized by the progressive loss of muscle fiber organization. This results in the loss of muscle size, mobility, and strength. In desminopathy, inflammation affects muscle homeostasis and repair, and contributes to progressive muscle deterioration. Mitochondria morphology was also suggested to affect desminopathy progression. Epicatechin (Epi)-a natural compound found in cacao-has been proposed to regulate inflammatory signaling and mitochondria morphology in human and animal models. Hence, we hypothesize chronic Epi consumption to improve inflammatory pathway and mitochondria morphology in the peripheral blood mononuclear cells (PBMCs) of a desminopathy R350P patient. We found that 12 weeks of Epi consumption partially restored TRL4 signaling, indicative of inflammatory signaling and mitochondria morphology in the desminopathy patient. Moreover, Epi consumption improved blood health parameters, including reduced HOMA-IR and IL-6 levels in the desminopathy patient. This indicates that Epi consumption could be a useful tool to slow disease progression in desminopathy patients.

BACKGROUND: The risk of developing severe and even fatal coronavirus disease 2019 (COVID-19) increases with various factors such as advanced age and chronic diseases, especially those treated with immunosuppressive drugs. Viral ribonucleic acid (RNA) and viral load detection in extra-pulmonary specimens have been proposed to indicate disease severity.
METHODS: Here we describe a fatal COVID-19 case of an 83-year-old Caucasian male patient with various underlying comorbidities, including cardiovascular and autoimmune disorders, as well as immunosuppression due to lymphoma treatment. Upon admission, the patient was radiologically diagnosed with severe COVID-19. The patient was febrile and presented with diarrhea, continued dyspnea, tachypnea, and low blood oxygen saturation, treated with high-concentration oxygen supplementation and antibacterial therapy. Overall the patient was treated for COVID-19 for 19 days. Blood tests were performed upon admission, on the fifth, 10th, 13th, and 19th day. In addition, nasopharyngeal swab, blood, urine, and fecal samples were collected from the patient on the 14th day for virological and immunological investigations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detectable in all samples collected from this patient, including blood plasma and peripheral blood mononuclear cells (PBMC), with very high viral loads. However, neither virus-specific IgA, IgM, nor IgG antibodies were detectable.
CONCLUSIONS: The various cardiovascular, autoimmune, and oncological disorders, advanced age, and the high levels of inflammatory markers predisposed the patient to severe COVID-19 and determined the fatal outcome of the disease. We believe that the multiple specimen SARS-CoV-2 positivity and extremely high viral loads in nasopharyngeal swab and fecal samples to be the result of COVID-19 severity, the inability of viral clearance and weakened immune response due to advanced age, comorbidities, and the presence of non-Hodgkin\'s lymphoma and the immunosuppressive treatment for it, highlighting the risks of COVID-19 in such patients.

Crohn\'s disease (CD), as one of the principal form of inflammatory bowel disease (IBD), is characterized by the chronic and recurring inflammatory conditions in the intestine resulting from the over-activation of intestinal immunity. Hyposplenism is strongly associated with CD, while the effect of human spleen on the differentiation and development of immune cell subsets in CD patients remains unclear. Isolated congenital asplenia (ICA) is an extremely rare condition characterized by the absence of a spleen at birth without any other developmental defects. Here, we describe the first case of a patient with both ICA and CD, and follow the progression of CD from remission to active stage. Using cytometry by time of flight (CyTOF) analysis, we draw the first single-cell mapping of peripheral blood mononuclear cells (PBMC) from this unique patient, tracing back to the innate or adaptive immune cell subsets and cell surface markers affected by the spleen. Based on our analysis, it is speculated that the spleen contributes to maintaining immune homeostasis, alleviating intestinal inflammation and improving prognosis by influencing the differentiation and development of peripheral immune cell subsets and the expression of cell surface markers in patients with CD.

Repeated implantation failures are a constant challenge in reproductive medicine with a significant impact both on health providers and on infertile couples. Several approaches have been proposed so far as effective; however, accumulative data have clarified that most of the treatment options do not have the evidence base for a generalized application to be suggested by the relevant societies. Implantation failures are attributed to either poor quality embryos or to defected endometrial receptivity. The current review aims to summarize in a systematic way all the new trends in managing RIF via interference with endometrial receptivity. The authors focus mainly, but not exclusively, on endometrial injury prior to embryo transfer and endometrial priming with autologous cells or biological agents. To this direction, a systematic search of the Pubmed database has been conducted taking into account the emerged evidence of the last two decades. All the suggested interventions are herein presented and analyzed in terms of reproductive outcomes. It is evident that properly powered and designed randomized trials are needed to support a new standard approach in RIF treatment that will safely be incorporated in national and international guidelines.

Autism spectrum disorder (ASD) is a broad and heterogeneous group of neurological developmental disorders characterized by impaired social interaction and communication, restricted and repetitive behavioural patterns, and altered sensory processing. Currently, no reliable ASD molecular biomarkers are available. Since immune dysregulation has been supposed to be related with ASD onset and dyslipidaemia has been recognized as an early symptom of biological perturbation, lipid extracts from peripheral blood mononuclear cells (PBMCs), consisting primarily of lymphocytes (T cells, B cells, and NK cells) and monocytes, of 38 children with ASD and their non-autistic siblings were investigated by hydrophilic interaction liquid chromatography (HILIC) coupled with electrospray ionization and Fourier-transform mass spectrometry (ESI-FTMS). Performances of two freeware software for data extraction and processing were compared with acquired reliable data regardless of the used informatics. A reduction of variables from 1460 by the untargeted XCMS to 324 by the semi-untargeted Alex123 software was attained. All-ion fragmentation (AIF) MS scans along with Alex123 software were successfully applied to obtain information related to fatty acyl chain composition of six glycerophospholipid classes occurring in PBMC. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were explored to verify the occurrence of significant differences in the lipid pool composition of ASD children compared with 36 healthy siblings. After rigorous statistical validation, we conclude that phospholipids extracted from PBMC of children affected by ASD do not exhibit diagnostic biomarkers. Yet interindividual variability comes forth from this study as the dominant effect in keeping with the existing phenotypic and etiological heterogeneity among ASD individuals. Graphical abstract.