Intercellular Medium Research Articles

The biological role of extracellular vesicles in gastric cancer metastasis

Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, and lipids. EVs play a crucial biological role in the process of GC metastasis. Through mechanisms such as remodeling the tumor microenvironment (TME), immune suppression, promoting angiogenesis, and facilitating epithelial–mesenchymal transition (EMT) and mesothelial–mesenchymal transition (MMT), EVs promote invasion and metastasis in GC. Further exploration of the biological roles of EVs will contribute to our understanding of the mechanisms underlying GC metastasis and may provide novel targets and strategies for the diagnosis and treatment of GC. In this review, we summarize the mechanisms by which EVs influence GC metastasis from four aspects: remodeling the TME, modulating the immune system, influencing angiogenesis, and modulating the processes of EMT and MMT. Finally, we briefly summarized the organotropism of GC metastasis as well as the potential and limitations of EVs in GC.

Exosomal lncCRLA is predictive for the evolvement and development of lung adenocarcinoma

Lung adenocarcinoma, the most common histological subtype of non-small cell lung cancer, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Our team uncovers that lncRNA related to chemotherapy resistance in lung adenocarcinoma (lncCRLA) is preferentially expressed in lung adenocarcinoma cells with the mesenchymal phenotype. lncCRLA can not enhance chemotherapy resistance in lung adenocarcinoma due to its binding to RIPK1 in exosomes, which is released into intercellular media and transferred by exosomes from mesenchymal-like to epithelial-like cells. However, plasmatic lncCRLA corresponding to tissue lncCRLA functions as a preferred biomarker to reflect the response to chemotherapy and disease progression of lung adenocarcinoma. Through single-cell sequencing, RNA-Mutect technique and spatial transcriptomics, a handful of hybrid EMT cells with elevated lncCRLA are characterized as the origin of lung adenocarcinoma, which are indiscriminated from hybrid EMT cells by the in-depth sequencing. Plasmatic lncCRLA is properly predictive for the preinvasive lesion of lung adenocarcinoma that would evolve to invasive lesion. That notion is confirmed by a brand-new transgenic mouse model in which EMT is tracked by Cre and Dre system. Dasatinib is potential to hinder the spontaneous progression from preinvasive to invasive lesion of lung adenocarcinoma. Together, plasmatic lncCRLA is defined as a brand-new circulating biomarker to predict the occurrence and evolvement of lung adenocarcinoma, a light for early detection of lung adenocarcinoma.

Silica-exposed macrophages-secreted exosomal miR125a-5p induces Th1/Th2 and Treg/Th17 cell imbalance and promotes fibroblast transdifferentiation

Until now, the specific pathogenesis of silicosis is not clear. Exosomal miRNAs, as a newly discovered intercellular communication medium, play an important role in many diseases. Our previous research found that serum exosomal miR125a-5p was increased in silicosis patients by miRNAs high-throughput sequencing. TRAF6, is a target gene of miR125a-5p, which is involved in T-cell differentiation. Furthermore, results from animal study indicate that knockdown of miR-125a-5p can regulate T lymphocyte subsets and significantly reduce pulmonary fibrosis by targeting TRAF6. However, the level of serum exosomal miR125a-5p in silicosis patients has not been reported, the role of macrophages-secreted exosomal miR-125a-5p in regulating T cell differentiation to promote fibroblast transdifferentiation (FMT) remains unknown. In this study, the levels of serum exosomal miR125a-5p and serum TGF-β1, IL-17A, IL-4 cytokines in silicosis patients were elevated, with the progression of silicosis, the level of serum exosomal miR125a-5p and serum IL-4 were increased; thus, the serum level of IFN-γ was negatively correlated with the progression of silicosis. In vitro, the levels of miR125a-5p in macrophages, exosomes, and T cells stimulated by silica were significantly increased. When the mimic was transfected into T cells, which directly suppressed TRAF6 and caused the imbalance of T cells differentiation, induced FMT. To sum up, these results indicate that exosomal miR-125a-5p may by targeting TRAF6 of T cells, induces the activation and apoptosis of T cells and the remodeling of Th1/Th2 and Th17/Tregs distribution, ultimately promotes FMT. Suggesting that exosomal miR-125a-5p may be a potential therapeutic target for silicosis.

METHOD OF DISCRETE SINGULARITIES FOR ACCOUNTING FOR CONVECTION WHEN MODELING DYNAMICS OF INFECTIOUS DISEASE UNDER DIFFUSION PERTURBATIONS AND CONCENTRATED INFLUENCES

A wide range of various mathematical models have been developed to predict the dynamics of an infectious disease. As a rule, such models do not take into account spatial effects, which are associated with both the uneven distribution of active factors and their convective transfer by the intercellular fluid. The paper proposes a variant of taking into account convection when modeling the process of an infectious disease under conditions of diffusion perturbations and concentrated influences. Based on the reduction of original singularly perturbed model problem with delay to a sequence of problems without delay, an effective step-by-step procedure for numerically asymptotically approximating the solution as a perturbation of the solution of the corresponding degenerate problems is synthesized. To find the velocity field, it is proposed to model the movement of fluid in the intercellular medium as a potential flow in the source-drain system. It is emphasized that this approach can be used for a wide range of configurations of model areas with sufficient variability of boundary conditions. The results of computer modeling are presented, which illustrate the influence of diffusion scattering and convection on the development of a viral disease under the conditions of injections of immunological drugs. It is shown that as a result of diffusion scattering and convective transfer of viral elements, their concentration in the epicenter of infection decreases over time, which leads to a corresponding decrease in the "severity" of the disease. It is also shown that with an uneven field of movement speed of the intercellular fluid, there will be zones with a less intense influx of both own and donor antibodies. As a result, the amount of antibodies available in these zones may be insufficient to neutralize antigens, which may lead to the emergence of new epicenters of infection here. The importance of taking such effects into account, in particular, when forming effective treatment programs, is indicated.

Emulgel: An Effective Drug Delivery System

When emulgel comes to administering hydrophobic medications, many of the benefits of gels are also severe disadvantages. An emulsion-based strategy is adapted to bypass barriers, giving even a hydrophobic medicinal component to take advantage of the special features of gels. Emulgel is a dosage form that combines gels and emulsions. The utilization of novel polymers has sparked a lot of curiosity in recent years. The direct convenience of the skin as a target organ for diagnostic and therapeutic objectives distinguishes dermatological pharmacology. Both hydrophilic and hydrophobic chemicals are blocked by this barrier is created by combining hydrophilic horn cells with a hydrophobic intercellular medium. Within the primary group of semi-solid preparations, the use of opaque gels in cosmetics and pharmaceutical preparations has grown. By lowering surface and interfacial tensions while raising aqueous phase viscosity, these chemicals allow the formation of stable emulsions and creams. An emulgel is created by adding a gelling ingredient to a conventional emulsion's aqueous phase. In various ways, these emulsifiers exceed both novel vesicular systems and traditional systems. Using various permeation enhancers, emulsifiers could be used as better topical medication delivery systems than they are today. The use of emulsifiers can be expanded to include analgesics and antifungals. Analgesics and antifungals can both benefit from emulsifiers. We discuss the types, advantages, marked emulgel, formulation of emulgel, emulgel preparation, and characterization.

Microcapsule-Based Dose-Dependent Regulation of the Lifespan and Behavior of Adipose-Derived MSCs as a Cell-Mediated Delivery System: In Vitro Study.

The development of “biohybrid” drug delivery systems (DDS) based on mesenchymal stem/stromal cells (MSCs) is an important focus of current biotechnology research, particularly in the areas of oncotheranostics, regenerative medicine, and tissue bioengineering. However, the behavior of MSCs at sites of inflammation and tumor growth is relevant to potential tumor transformation, immunosuppression, the inhibition or stimulation of tumor growth, metastasis, and angiogenesis. Therefore, the concept was formulated to control the lifespan of MSCs for a specific time sufficient for drug delivery to the target tissue by varying the number of internalized microcontainers. The current study addressed the time-dependent in vitro assessment of the viability, migration, and division of human adipose-derived MSCs (hAMSCs) as a function of the dose of internalized polyelectrolyte microcapsules prepared using a layer-by-layer technique. Polystyrene sulfonate (PSS)—poly(allylamine hydrochloride) (PAH)-coated spherical micrometer-sized (diameter ~2−3 µm) vaterite (CaCO3) microcapsules (PAH-PSS)6 with the capping PSS layer were prepared after dissolution of the CaCO3 core template. The Cell-IQ phase contrast imaging results showed that hAMSCs internalized all (PAH-PSS)6 microcapsules saturating the intercellular medium (5−90 particles per cell). A strong (r > 0.7) linear dose-dependent and time-dependent (up to 8 days) regression was observed between the in vitro decrease in cell viability and the number of internalized microvesicles. The approximate time-to-complete-death of hAMSCs at different concentrations of microcapsules in culture was 428 h (1:5 ratio), 339 h (1:10), 252 h (1:20), 247 h (1:45), and 170 h (1:90 ratio). By varying the number of microcontainers loaded into the cells (from 1:10 to 1:90), a dose-dependent exponential decrease in both the movement rate and division rate of hAMSCs was observed. A real-time cell analysis (RTCA) of the effect of (PAH-PSS)6 microcapsules (from 1:5 to 1:20) on hAMSCs also showed a dose- and time-dependent decrease in cell longevity after a 50h study at ratios of 1:10 and 1:20. The incorporation of microcapsules (1:5, 1:20, and 1:45) resulted in a dose-dependent increase in 24−48 h secretion of GRO-α (CXCL1), MIF, and SDF-1α (CXCL12) chemokines in hAMSC culture. In turn, the normalization or inhibition of chemokine secretion occurred after 72 h, except for MIF levels below 5−20 microcapsules, which were internalized by MSCs. Thus, the proposed concept of controlling the lifespan of MSC-based DDS using a dose of internalized PAH-PSS microcapsules could be useful for biomedical applications. (PAH-PSS)6 microcapsule ratios of 1:5 and 1:10 have little effect on the lifespan of hAMSCs for a long time (up to 14−18 days), which can be recommended for regenerative therapy and tissue bioengineering associated with low oncological risk. The microcapsule ratios of 1:20 and 1:45 did not significantly restrict the migratory activity of hAMSCs-based DDS during the time interval required for tissue delivery (up to 4−5 days), followed by cell death after 10 days. Therefore, such doses of microcapsules can be used for hAMSC-based DDS in oncotheranostics.

Feasibility of the Skin Electrodynamic Introscopy to Assess 2D Acid-Base Balance Dynamics

Synchronization is a universal phenomenon that occurs at all levels of the existence of living and inanimate matter. Shortly after enabling monitoring of the electrical impedance landscape of the skin, such phenomena were detected as dynamic clusters with in-phase and anti-phase dynamics. The behavior of these clusters turned out to be very sensitive to various endogenous and exogenous factors and was especially pronounced, for example, at the melanoma areas. Hypothesis of the acid-base balance fluctuations have been put forward as one of the most likely mechanisms for this phenomenon, since hydrogen ions are one of the main factors that determine tissue electrical conductivity. The purpose of this study was to obtain experimental evidence for this hypothesis. The 2D dynamics of glycolysis metabolism was studied on a yeast model as an adequate model of cancer cells. The image sequences reflected the dynamics of processes occurring at the intercellular and intracellular levels, in the form of current values of the 2D active and capacitive components of the impedance in the range of 2 kHz and 1 MHz. As a test factor, a single drop of glucose was used. The revealed effects of clusterization were found similar to those obtained earlier in human experiments. Specifically, these effects were also clearly manifested in the affected region. At the same time, the intercellular medium turned out to be the most rapidly responsive, while the intracellular response occurred with a significant delay but without so marked manifestations of anti-phase behavior. The observed effects are presumably a macroscopic manifestations of quorum sensing mechanisms and cooperative wave processes. We believe that the developed technology can be used as an inexpensive and non-invasive tool for both In vivo and In vitro real-time pH monitoring.

Development of the poly(l-histidine) grafted carbon nanotube as a possible smart drug delivery vehicle

Polyhistidine is among the cell-penetrating peptides that in an acidic environment can facilitate membrane transition. Keeping in mind that the pH of the tumor intercellular medium is ∼5.5, in this paper, we examined the functionalization of a convenient drug delivery vehicle with cell-penetrating poly(l-histidine) to provide a smart drug delivery system. Classical molecular dynamics and metadynamics simulations are used to investigate the interactions between doxorubicin, carbon nanotube, poly(l-histidine), and the cell membrane. Metadynamics simulation revealed that not only the global minimum of FES reduced in an acidic environment but also the difference between the free energy of Doxorubicin as being adsorbed on poly(l-histidine) compared to when being freely dissolved in the aqueous medium show a dramatic reduction.MD simulations showed that functionalization of carbon nanotube with poly(l-histidine) groups has no detriment effect in the adsorption of Doxorubicin. The L-J interaction between Doxorubicin and carrier at the equilibrium states reached around −600 kJ/mol, both for the pristine and functionalized carbon nanotube. The coulombic interactions for both complexes were negligible in the neutral environment. At the acidic environment, the L-J interactions retained the same values as the neutral, while the coulombic interactions showed positive values, which suggested its participation in the detachments. At the vicinity of the membrane, the complexes retain their integrity both in neutral and acidic environments. In the present work, we performed metadynamics simulation to investigate the effects of poly(l-histidine) on the adsorption capacity of the carbon nanotubes, and explore the adsorption/desorption processed of Doxorubicin on pristine and poly(l-histidine)-grafted carbon nanotube. The resulted complexes were then subjected to interact with the POPC membrane model in both acidic and neutral environments via molecular dynamic simulations. The results provided here will hopefully help in a better understanding of future drug delivery systems and be helpful in designing more efficient and smart drug delivery systems.

Influence of ultraviolet radiation on kinetic characteristics in erythrocytes

Erythrocytes were irradiated with an ultraviolet lamp of the VMT type (λ = 253.7 nm). The kinetic characteristics in irradiated and non-irradiated blood samples were compared by the acid (chemical) erythrogram method and by the counter transport method. Obtained:
 - by the method of acidic erythrograms it was found that in ultraviolet-irradiated blood samples there is a decrease in the time of half hemolysis.
 - ultraviolet radiation increases the speed of counter movement of ions through erythrocyte membranes.
 - a decrease in the time of half hemolysis and an increase in the rate of counter transfer of ions, irradiated blood samples, is due to a decrease in the "effective" thickness of the near-membrane diffusion layer - an immiscible layer of water adjacent to the erythrocyte membrane.
 A decrease in the "effective thickness" of the near-membrane water layer changes the rate of metabolic processes in the "cell - intercellular medium" system, changing the mode of cell functioning. The altered mode of functioning is a biological response to light radiation. Red blood cells with an altered mode of functioning are stimulus signals that force the body to mobilize resources to fight pathology. These circumstances can predict the creation of a universal phototherapeutic equipment for extracorporeal blood irradiation based on LEDs with certain exposure parameters. Figs.: 4. Tabl.: 3. Refs.: 12 titles.

Interspecies evolutionary dynamics mediated by public goods in bacterial quorum sensing.

Bacterial quorum sensing is the communication that takes place between bacteria as they secrete certain molecules into the intercellular medium that later get absorbed by the secreting cells themselves and by others. Depending on cell density, this uptake has the potential to alter gene expression and thereby affect global properties of the community. We consider the case of multiple bacterial species coexisting, referring to each one of them as a genotype and adopting the usual denomination of the molecules they collectively secrete as public goods. A crucial problem in this setting is characterizing the coevolution of genotypes as some of them secrete public goods (and pay the associated metabolic costs) while others do not but may nevertheless benefit from the available public goods. We introduce a network model to describe genotype interaction and evolution when genotype fitness depends on the production and uptake of public goods. The model comprises a random graph to summarize the possible evolutionary pathways the genotypes may take as they interact genetically with one another, and a system of coupled differential equations to characterize the behavior of genotype abundance in time. We study some simple variations of the model analytically and more complex variations computationally. Our results point to a simple trade-off affecting the long-term survival of those genotypes that do produce public goods. This trade-off involves, on the producer side, the impact of producing and that of absorbing the public good. On the nonproducer side, it involves the impact of absorbing the public good as well, now compounded by the molecular compatibility between the producer and the nonproducer. Depending on how these factors turn out, producers may or may not survive.

Therapeutic potential of adipose-derived mesenchymal stem cell exosomes in tissue-engineered bladders

Mesenchymal stem cells (MSCs) are a therapeutic tool for tissue engineering. However, many studies have recently shown that the therapeutic effects of MSCs are mediated by paracrine signaling and their secretory factors rather than their multidirectional differentiation ability. Exosomes isolated from the conditioned medium of MSCs are considered the main intercellular communication medium between MSCs and their target cells. Exosomes have been utilized in a novel cell-free therapy strategy that has attracted much attention. In this study, we evaluated the effects of a new cell-free tissue-engineered bladder (bladder acellular matrix combined with adipose-derived mesenchymal stem cell exosomes (AMEs)) in vivo and in vitro to prove that AMEs promoted tissue regeneration and functional recovery in a rat bladder replacement model.

CAUSES OF THE DEVELOPMENT OF CORONARY SYNDROME X IN WOMEN

The work considers the causes of the coronary X syndrome development in women by assessing the experimental group and the control group with typical angina pectoris with angiographically altered vessels. Each group included 30 patients. When studingy medical records of the patients in the study group, we found out that in the reproductive period all of them had hyperestrogenemia, confirmed by the laboratory data, with the corresponding consequences in the form of various gynecological diseases, while the patients of the control group had unburdened gynaecological history. In terms of the lipid spectrum, the results turned out to be opposite. In the experimental group, the rates were within the normal range, and the control level of LDL-C significantly exceeded the required values. Despite the fact that estrogens increase the concentration of high density lipoprotein (HDL) in the blood and lower the content of low density lipoprotein (LDL) that are atherogenic, their surplus has a less negative effect than their lack, as the risk of developing atherosclerosis increases with decreasing concentration, and with an increase there is a risk of developing endothelial dysfunction, which provokes the development of coronary syndrome X. These date confirm the development of endothelial dysfunction in the patients of the experimental group with hyperestrogenemia in the history resulted from the impairment of the process of proliferation of endothelial cells with subsequent imbalance of secretion of biologically active substances. Among them, there is nitric oxide, which causes the relaxation of smooth myocytes, thus resulting in vasodilatation, and endothelins, providing the opposite, vasodilating effect. Prostacyclines and thrombomodulins secreted by the vascular endothelium in physiological conditions, counteract platelet aggregation. In the case of damage to the vascular wall, the production of prostacyclin and thrombomodulin is suppressed, but the release of thromboplastin, platelet activation factor and von Willerband factor activates that promote platelet aggregation and blood clotting. Under the participation of other physiologically active substances, selectins, endothelial cells promote adhesion to their surface and further penetration into the site of inflammation of neutrophils, blood acidophils. Selectin is accumulated in the cytoplasm of the endothelial cells in the form of specific electron-cellular inclusions, the so-called bodies of Weibel-Palade. Normally, vascular endothelium is impervious to blood components. However, being affected by a number of factors, and in particular histamine, endothelial cells lose contact with each other and decrease in number. This leads to the release of water and plasma proteins into the intercellular medium causing oedema. Due to the ability of the inner layer of vessels to produce a large number of biologically active substances, such changes can hardly be corrected by therapy.

A modified technique of the finite-difference method calculations to mimic the four-terminal method measurements of electrical impedance and admittance of skeletal muscles

A modified technique of the finite-difference method (FDM) calculations was developed to mimic the measurements of the electrical impedance, Z, and admittance, Y, of skeletal muscles using the four-terminal method. The elements in this technique contained bundled plural tubular muscle cells. The electrical currents in the transversal direction were formulated based on a theory for two-dimensional suspensions, and those in the longitudinal direction were formulated based on the discretized cable-line theory. Using the relations for the currents, simultaneous linear relations with respect to electrical potentials in the intercellular medium and cell interior at the center of the elements were constructed. The effects of the T-tubules and surface membrane folding were included using the equivalent complex conductivity for the surface membrane. The current-supply electrodes were characterized as regions of fixed potentials. At each potential-pickup electrode, the summation of the electrical current was made to be null. Z and Y were obtained from the current into the current-supply electrodes and the difference between the potentials at the potential-pickup electrodes. The validity of the modified technique was demonstrated by the good agreement between the results of the calculations using the modified and conventional techniques. The FDM calculations revealed that changes reported in the Z value of the gastrocnemius muscle of mice due to amyotrophic lateral sclerosis were attributable to the decrease in the diameter of the muscle cells, and those due to growth were attributable to the increase in the diameter of the muscle cells and size of the whole muscle. The α-relaxation observed in the dissected samples of the muscles could be explained by the deviation of the direction of the external electrical fields from the ideal longitudinal and transversal directions.

Когерентне та монохроматичне випромінювання змінює час гемолізу еритроцитів, а також швидкість зустрічного переміщення іонів крізь еритроцитарну мембрану

The erythrocytes of human blood were sequentially irradiated with a low-intensity laser (λ = 640 nm), a violet LED (λ = 400 nm), a green LED (λ = 540 nm), and a yellow LED (λ = 592 nm). The method of acid (chemical) erythrograms and the method of counter ion transport compared the kinetic characteristics in irradiated and unirradiated blood samples. Received: - by the method of acid erythrograms it was found that in the irradiated blood samples there is a decrease in the time of hemolysis; - low intensity laser radiation, as well as the emission of LEDs, increase the rate of counter ion transport through red blood cells. - a decrease in the time of hemolysis and an increase in the rate of counter ion transport of irradiated blood samples is due to a decrease in the "effective" thickness of the near-membrane diffusion layer - an immiscible layer of water adjoined to the erythrocyte membrane. A decrease in the "effective” thickness of the near-membrane water layer (minimal in the wavelength range of 570-590 nm and 630-640 nm) changes the rate of metabolic processes in the "cell - intercellular medium" system, changing the mode of cell functioning. The altered mode of functioning is a biological response to light radiation. Red blood cells with an altered mode of functioning are signals - stimuli that cause the body to mobilize resources to fight pathology. These circumstances can predict the creation of a universal phototherapeutic equipment for extracorporeal blood irradiation based on light-emitting diodes with certain exposure parameters.

Long-range mechanical coupling of cells in 3D fibrin gels.

When seeded in fibrous gels, pairs of cells or cell aggregates can induce bands of deformed gel, extending to surprisingly long distances in the intercellular medium. The formation of bands has been previously shown and studied in collagen systems. In this study, we strive to further our understanding of this fundamental mechanical mechanism in fibrin, a key element in wound healing and angiogenesis processes. We embedded fibroblast cells in 3D fibrin gels, and monitored band formation by real-time confocal microscopy. Quantitative dynamic analysis of band formation revealed a gradual increase in fiber density and alignment between pairs of cells. Such intercellular bands extended into a large-scale network of mechanically connected cells, in which the connected cells exhibited a more spread morphology than the isolated cells. Moreover, computational modeling demonstrated that the direction of cell-induced force triggering band formation can be applied in a wide range of angles relative to a neighboring cell. Our findings indicate that long-range mechanical coupling between cells is an important mechanism in regulating multicellular processes in reconstituted fibrin gels. As such, it should motivate exploration of this mechanism in studies in vivo, in wound healing or angiogenesis, in which fibrin is contracted by fibroblast cells.

Surface roughness-induced absorption acts as an ovarian cancer cells growth sensor-monitor

Uncontrolled growth of ovarian cancer cells is the fifth leading cause of female cancer deaths since most ovarian cancer patients are diagnosed at an advanced stage of metastatic disease. Here, we report on the sensor for monitoring the cancer treatment efficiency in real-time. We measure the optical interaction between the evanescent fields of microfiber and ovarian cancer inter-cellular medium at different treatment stages. Spectral absorption signatures are correlated with optical micrographs and western blot tests. We found that the treatment of tumor cells with induces both cells growth arrest and alter the spectral lines in a dose-dependent manner. These observations are mediated by surface roughness out of silica glass material, form an essential step toward the development of early detection of response to cancer therapy.

Coupling of cell fate selection model enhances DNA damage response and may underlie BE phenomenon.

Double-strand break-induced (DSB) cells send signal that induces DSBs in neighbour cells, resulting in the interaction among cells sharing the same medium. Since p53 network gives oscillatory response to DSBs, such interaction among cells could be modelled as an excitatory coupling of p53 network oscillators. This study proposes a plausible coupling model of three-mode two-dimensional oscillators, which models the p53-mediated cell fate selection in globally coupled DSB-induced cells. The coupled model consists of ATM and Wip1 proteins as variables. The coupling mechanism is realised through ATM variable via a mean-field modelling the bystander signal in the intercellular medium. Investigation of the model reveals that the coupling generates more sensitive DNA damage response by affecting cell fate selection. Additionally, the authors search for the cause-effect relationship between coupled p53 network oscillators and bystander effect (BE) endpoints. For this, they search for the possible values of uncertain parameters that may replicate BE experiments' results. At certain parametric regions, there is a correlation between the outcomes of cell fate and endpoints of BE, suggesting that the intercellular coupling of p53 network may manifest itself as the form of observed BEs.

Extracellular vesicle-based Nanotherapeutics: Emerging frontiers in anti-inflammatory therapy.

Dysregulated inflammation is a complicated pathological process involved in various diseases, and the treatment of inflammation-linked disorders currently represents an enormous global burden. Extracellular vesicles (EVs) are nanosized, lipid membrane-enclosed vesicles secreted by virtually all types of cells, which act as an important intercellular communicative medium. Considering their capacity to transfer bioactive substances, both unmodified and engineered EVs are increasingly being explored as potential therapeutic agents or therapeutic vehicles. Moreover, as the nature's own delivery tool, EVs possess many desirable advantages, such as stability, biocompatibility, low immunogenicity, low toxicity, and biological barrier permeability. The application of EV-based therapy to combat inflammation, though still in an early stage of development, has profound transformative potential. In this review, we highlight the recent progress in EV engineering for inflammation targeting and modulation, summarize their preclinical applications in the treatment of inflammatory disorders, and present our views on the anti-inflammatory applications of EV-based nanotherapeutics.

Scattering-Induced Absorption Acts as a Cancer Treatment Monitor

Uncontrolled growth of ovarian cancer cells is the fifth leading cause of female cancer deaths. Here, we describe the role of scattering-induced absorption in monitoring the cancer treatment efficiency in real-time. We measure the optical interaction between the evanescent fields of microfiber and ovarian cancer inter-cellular medium at different treatment stages. By introducing the roughness of silica glass, we demonstrate that the treatment of tumor cells with GDC0032, a beta-sparing PI3K, induces both cells growth arrest and alter the spectral lines in a dose-dependent manner. The data support observed affected tumor cells with decrease in proliferation and their spatial distribution. Spectral absorption signatures are correlated with optical micrographs and western blot tests. These observations are mediated by surface scatterers out of silica glass material, form an essential step toward the development of early detection of response to cancer therapy.

Biochemistry of Direct Cell-Cell Interactions. Signaling Factors Regulating Orchestration of Cell Populations.

Biochemical mechanisms for the orchestration of cell populations are discussed in view of direct cell-cell interactions and composition of the intercellular medium. In our works of the last 20 years, we used circahoralian (ultradian) rhythm of protein synthesis as a marker of cell interactions. Experiments in cell cultures are described; some influences on the organism native medium were performed. Information is presented on the signaling membrane factors that trigger a cascade of processes in the cytoplasm and lead to the orchestration of cell activity in vitro and in vivo. Among these factors are blood serum neurotransmitters, gangliosides, and some hormones. Studying protein synthesis kinetics allowed us to understand the importance of maintaining the constant levels of signaling factors in mammalian blood. The literature on protein phosphorylation as a key process of cell organization is reviewed. The persistence of the organizing signal for several days is described as a type of cell "memory". It seems promising to extend the area for application of direct cell-cell interactions (respiration of cells, proliferation, etc.) to study possibilities of epigenetic regulation. It is important to continue the studies on the mechanisms of biochemical action of the known drugs as signaling factors.