The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.

Background As an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients. Method Forty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively. Result Our primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant ( P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant ( P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin. Conclusion Nano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.

In the course of the coronavirus disease 2019 (COVID‐19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID‐19 patients compared with the control group. Forty COVID‐19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real‐time polymerase chain reaction, and enzyme‐linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR‐related orphan receptor gamma [RORγt], IL‐17, and IL‐23), and the secretion levels of IL‐17 and IL‐23 cytokines in COVID‐19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor‐β [TGF‐β], and IL‐10), and cytokine secretion levels (TGF‐β and IL‐10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL‐17/IL‐10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019‐n‐CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID‐19‐dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.

Multiple sclerosis (MS) is a common degenerative disorder of the central nervous system. The decreased frequency and dysfunction of Treg cells cause inflammation and disease progression. Ozone autohemotherapy can be used as a potential therapeutic approach to regulate the immune system responses and inflammation in MS. For this purpose, 20 relapsing‐remitting multiple sclerosis patients were under treatment with ozone twice weekly for 6 months. The frequency of Treg cell, the expression levels of the Treg cell‐related factors (FoxP3, IL‐10, TGF‐β, miR‐17, miR‐27, and miR‐146A), and the secretion levels of IL‐10 and TGF‐β were assessed. We found a significant increase in the number of Treg cells, expression levels of FoxP3, miRNAs (miR‐17 and miR‐27), IL‐10, and TGF‐β factors in patients after oxygen–ozone (O2‐O3) therapy compared to before treatment. In contrast, oxygen–ozone therapy notably decreased the expression level of miR‐146a in treated patients. Interestingly, the secretion levels of both IL‐10 and TGF‐β cytokines were considerably increased in both serum and supernatant of cultured peripheral blood mononuclear cells in posttreatment condition compared to pretreatment condition. According to results, oxygen–ozone therapy raised the frequency of Treg cell and its relevant factors in treated MS patients. Oxygen–ozone therapy would contribute to improving the MS patients by elevating the Treg cell responses.

Bioprinting offers tremendous potential in the fabrication of functional tissue constructs for replacement of damaged or diseased tissues. Among other fabrication methods used in tissue engineering, bioprinting provides accurate control over the construct's geometric and compositional attributes using an automated approach. Bioinks are composed of the hydrogel material and living cells that are critical process variables in the fabrication of functional, mechanically robust constructs. Appropriate cells can be encapsulated in bioinks to create functional tissue structures. Ideal bioinks are required to undergo a sol–gel transition consuming minimal processing time, and a plethora of chemical and physical crosslinking mechanisms are generally exploited to achieve high shape fidelity and construct stability. In contrast, crosslinking of hydrogel material at rapid rates can cause nozzle clogging, and hence, optimization of the bioink is often necessary. Bioinks can be formulated using natural or synthetic biomaterials, alone or in combination of these biomaterials. Herein, the various bioprinting methods are discussed; the natural, synthetic, or hybrid materials used as bioinks are analyzed; and the challenges, limitations, and future directions concerning the bioprinting technique are appraised.

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In Coronavirus disease 2019 (COVID-19), a decreased number of regulatory T (Treg) cells and their mediated factors lead to a hyperinflammatory state due to overactivation of the inflammatory cells and factors during the infection. In the current study, we evaluated the Nanocurcumin effects on the Treg cell population and corresponding factors in mild and severe COVID-19 patients. To investigate the Nanocurcumin effects, 80 COVID-19 patients (40 at the severe stage and 40 at the mild stage) were selected and classified into Nanocurcumin and placebo arms. In both the Nanocurcumin and placebo groups, the Treg cell frequency, the gene expression of Treg transcription factor forkhead box P3 (FoxP3), and cytokines (IL-10, IL-35, and TGF-β), as well as the serum levels of cytokines were measured before and after treatment. In both mild and severe COVID-19 patients, Nanocurcumin could considerably upregulate the frequency of Treg cells, the expression levels of FoxP3, IL-10, IL-35, and TGF-β, as well as the serum secretion levels of cytokines in the Nanocurcumin-treated group compared to the placebo group. The abovementioned factors were remarkably increased in the post-treatment with Nanocurcumin before pre-treatment conditions. By contrast, it has been observed no notable alterations in the placebo group. Our findings revealed the SinaCurcumin® effective function in a significant increase in the number of Treg cells and their mediated factors in the Nanocurcumin group than in the placebo group in both mild and severe patients. Hence, it would be an efficient therapeutic agent in rehabilitating COVID-19 infected patients.

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