The exact pathophysiology of severe COVID-19 is not entirely elucidated, but it has been established that hyperinflammatory responses and cytokine storms play important roles. The aim of this study was to examine CMV status, select chemokines, and complement components in COVID-19, and how concentrations of given molecules differ over time at both molecular and proteomic levels. A total of 210 COVID-19 patients (50 ICU and 160 non-ICU patients) and 80 healthy controls were enrolled in this study. Concentrations of select chemokines (CXCL8, CXCL10, CCL2, CCL3, CCR1) and complement factors (C2, C9, CFD, C4BPA, C5AR1, CR1) were examined at mRNA and protein levels with regard to a COVID-19 course (ICU vs. non-ICU group) and CMV status at different time intervals. We detected several significant differences in chemokines and complement profiles between ICU and non-ICU groups. Pro-inflammatory chemokines and the complement system appeared to greatly contribute to the pathogenesis and development of severe COVID-19. Higher concentrations of CXCL8 and CCL2 in the plasma, with reduced mRNA expression presumably through negative feedback mechanisms, as well as CMV-positive status, correlated with more severe courses of COVID-19. Therefore, CXCL8, CCL2, and CMV seropositivity should be considered as new prognostic factors for severe COVID-19 courses. However, more in-depth research is needed.

Purpose: Esthetic medicine is a rapidly developing field of medicine that is not only beneficial in terms of external appearance, but also significantly improves overall quality of life. Currently, pigmented and vascular skin lesions are more prevalent due to multiple environmental factors and are a characteristic manifestation of skin aging. The development of modern laser therapy has contributed to the successful management of multiple skin conditions. The aim of our study was to show the effect of concomitant reduction of both vascular and hyperpigmented skin lesions located on the facial area after repetitive 532 nm laser therapy and to emphasize that the detection of such observation was possible due to the implementation of System of Skin Analysis and Assessment. Patients and Methods: We retrospectively analyzed 100 patients’ records with “VISIA” Skin Analysis System after 532nm laser therapy. Results: Laser therapy significantly decreased VISIA scores for all tested lesions, ie, macules, pigmented and vascular lesions (p< 0.0001 for all). The efficacy of laser treatment was not significantly different regarding skin phototype (p> 0.05) and did not correlate with age of participants (p> 0.05). The more laser sessions were performed, the higher improvement in vascular lesion VISIA scores was observed (r=0.26, p=0.0097). Conclusion: 532 nm laser therapy is effective regarding vascular and hyperpigmented skin lesions located on the facial area. The System of Skin Analysis and Assessment is a good tool to test the treatment efficacy during regular follow-up procedure.

Multiple myeloma (MM) is the second most common hematologic malignancy, accounting for approximately 1% of all cancers. Despite the initial poor prognosis for MM patients, their life expectancy has improved significantly with the development of novel agents. Immunomodulatory drugs (IMiDs) are widely used in MM therapy. Their implementation has been a milestone in improving the clinical outcomes of patients. The first molecule belonging to the IMiDs was thalidomide. Subsequently, its novel derivatives, lenalidomide (LEN) and pomalidomide (POM), were implemented. Almost all MM patients are exposed to LEN, which is the most commonly used IMiD. Despite the potent anti-MM activity of LEN, some patients eventually relapse and become LEN-resistant. Drug resistance is one of the greatest challenges of modern oncology and has become the main cause of cancer treatment failures. The number of patients receiving LEN is increasing, hence the problem of LEN resistance has become a great obstacle for hematologists worldwide. In this review, we intended to shed more light on the pathophysiology of LEN resistance in MM, with particular emphasis on the molecular background. Moreover, we have briefly summarized strategies to overcome LEN resistance and we have outlined future directions.

Bortezomib-induced peripheral neuropathy (BiPN) occurs in approximately 40% of patients with multiple myeloma. The induction of severe neuropathy entails the dose reduction or complete elimination of bortezomib (BTZ). Interestingly, discontinuation of BTZ mostly results in a reduction or complete resolution of peripheral neuropathy (PN) symptoms. Therefore, it is likely that the BiPN mechanisms are based on temporary/reversible changes such as epigenetic alterations. In this study, we examined the effect of treating nerve cells, differentiated from the Lund human mesencephalic (dLUHMES) cell line, with several low-dose BTZ (0.15 nM) applications. We showed a significant decrease in global histone H3 acetylation as well as histone H3 lysine 9 acetylation. Moreover, analysis of the genetic microarray showed changes mainly in epigenetic processes related to chromatin rearrangement, chromatin silencing, and gene silencing. GSEA analysis revealed three interesting signaling pathways (SIRT1, B-WICH and, b-Catenin) that may play a pivotal role in PN development. We also performed an analysis of the miRNA microarray which showed the interactions of miR-6810-5p with the genes MSN, FOXM1, TSPAN9, and SLC1A5, which are directly involved in neuroprotective processes, neuronal differentiation, and signal transduction. The study confirmed the existence of BTZ-induced complex epigenetic alterations in nerve cells. However, further studies are necessary to assess the reversibility of epigenetic changes and their potential impact on the induction/resolution of PN.

Multiple myeloma (MM) remains an incurable hematological malignancy. Bortezomib (BTZ) is a proteasome inhibitor widely used in MM therapy whose potent activity is often hampered by the development of resistance. The immune system is vital in the pathophysiology of BTZ resistance. Vitamins D (VD) and K (VK) modulate the immune system; therefore, they are potentially beneficial in MM. The aim of the study was to evaluate the effect of BTZ therapy and VD and VK supplementation on the proliferation potential and gene expression profiles of MM cells in terms of the development of BTZ resistance. The U266 MM cell line was incubated three times with BTZ, VD and VK at different timepoints. Then, proliferation assays, RNA sequencing and bioinformatics analysis were performed. We showed BTZ resistance to be mediated by processes related to ATP metabolism and oxidative phosphorylation. The upregulation of genes from the SNORDs family suggests the involvement of epigenetic mechanisms. Supplementation with VD and VK reduced the proliferation of MM cells in both the non-BTZ-resistant and BTZ-resistant phenotypes. VD and VK, by restoring proper metabolism, may have overcome resistance to BTZ in vitro. This observation forms the basis for further clinical trials evaluating VD and VK as potential adjuvant therapies for MM patients.

The launch of novel chemotherapeutic agents—in particular, proteasome inhibitors and immunomodulatory drugs—dramatically changed multiple myeloma (MM) therapy, improving the response rate and prolonging progression-free survival. However, none of the anti-MM drugs are deprived of side effects. Peripheral neuropathy (PN) seems to be one of the most pressing problems. Despite extensive research in this area, the pathogenesis of drug-induced peripheral neuropathy (DiPN) has not yet been fully elucidated. In the present study, we aimed to assess the potential relationship between proinflammatory factors and the development of PN in MM patients with particular emphasis on the application of VTD (bortezomib, thalidomide, dexamethasone) regimen. Our analysis identified increased concentrations of CCL2, IL-1β, and IFN-γ in plasma of MM patients during treatment, both with and without symptoms of PN, compared with untreated neuropathy-free MM patients. At the same time, the plasma concentration of IL-1β in patients with neuropathy was significantly increased compared with patients without PN before and during treatment. Moreover, the results were enhanced at the transcript level by performing global mRNA expression analysis using microarray technology. The most significant changes were observed in the expression of genes responsible for regulating immunological and apoptotic processes. An in-depth understanding of the mechanisms responsible for the development of DiPN might in the future reduce the incidence of PN and accelerate diagnosis, allowing the choice of neuropathy-free treatment strategies for MM.