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The Susceptible-Infected-Recovered (SIR) model for the spread of an infectious disease in a population of constant size is considered. In order to control the spread of infection, we propose the model with four bounded controls which describe vaccination of newborns, vaccination of the susceptible, treatment of infected, and indirect strategies aimed at a reduction of the incidence rate (e. g. quarantine). The optimal control problem of minimizing the total number of the infected individuals on a given time interval is stated and solved. The optimal solutions are obtained with the use of the Pontryagin Maximum Principle and investigated analytically. Numerical results are presented to illustrate the optimal solutions. [ABSTRACT FROM PUBLISHER]

Cancer-promoting proinflammatory microenvironment influences colorectal cancer (CRC) development. We examined the biomarkers of inflammation, intestinal differentiation, and DNA activity correlated with the clinical parameters to observe progression and prognosis in the adenocarcinoma subtype of CRC. Their immunohistology, immunoblotting, and RT-PCR analyses were performed in the adenocarcinoma and neighboring healthy tissues of 64 patients with CRC after routine colorectal surgery. Proinflammatory nuclear factor kappa B (NFκB) signaling as well as interleukin 6 (IL-6) and S100 protein levels were upregulated in adenocarcinoma compared with nearby healthy colon tissue. In contrast to nitrotyrosine expression, the oxidative stress marker 8-Hydroxy-2′-deoxyguanosine (8-OHdG) was increased in adenocarcinoma tissue. Biomarkers of intestinal differentiation β-catenin and mucin 2 (MUC2) were inversely regulated, with the former upregulated in adenocarcinoma tissue and positively correlated with tumor marker CA19-9. Downregulation of MUC2 expression correlated with the increased 2-year survival rate of patients with CRC. Proliferation-related mammalian target of rapamycin (mTOR) signaling was activated, and Ki67 frequency was three-fold augmented in positive correlation with metastasis and cancer stage, respectively. Conclusion: We demonstrated a parallel induction of oxidative stress and inflammation biomarkers in adenocarcinoma tissue that was not reflected in the neighboring healthy colon tissue of CRC. The expansiveness of colorectal adenocarcinoma was confirmed by irregular intestinal differentiation and elevated proliferation biomarkers, predominantly Ki67. The origin of the linked inflammatory factors was in adenocarcinoma tissue, with an accompanying systemic immune response. [ABSTRACT FROM AUTHOR]

This article considers the issues of ensuring operational performance and environmental sustainability of marine diesel engines by using biodiesel fuel. This research was conducted on 5S60ME-C8 MAN-B&W Diesel Group and 6DL-16 Daihatsu Diesel marine diesel engines, which are operated using RMG380 petroleum fuel and B10 and B30 biodiesel fuels. The efficiency of biofuel usage was assessed based on environmental (reduced nitrogen oxide concentration in exhaust gases) and economic (increased specific effective fuel consumption) criteria. It was found that the use of B10 and B30 biofuels provides a reduction in nitrogen oxide concentration in exhaust gases by 14.71–25.13% but at the same time increases specific effective fuel consumption by 1.55–6.01%. Optimum fuel injection advance angles were determined that ensure the best thermal energy, economic and environmental performance of diesel engines. The optimum angle of biofuel supply advance is determined experimentally and should correspond to the limits recommended by the diesel engine operating instructions. It has been proven experimentally that the use of biofuel increases the environmental sustainability of marine diesel engines by 13.75–29.42%. It increases the diesel engines environmental safety in case of emergency situations as well as accidental and short-term emissions of exhaust gases with an increased content of nitrogen oxides into the atmosphere phenomena that are possible in starting modes of diesel engine operation as well as in modes of sudden load changes. It is the increase in the environmental friendliness of marine diesel engines in the case of using biofuel that is the most positive criterion and contributes to the intensity of biofuel use in power plants of sea vessels. [ABSTRACT FROM AUTHOR]

Glucocorticoids are used during glioblastoma treatment to prevent the cerebral edema effect surrounding normal brain tissue. The aim of our study was to investigate the long-term effects of multiple administrations of glucocorticoids onto the glycosylated components (proteoglycans and glycosaminoglycans) of normal brain extracellular matrix and the glucocorticoid receptor (GR, Nr3c1) in an experimental model in vivo. Two-month-old male C57Bl/6 mice (n = 90) were injected intraperitoneally with various doses of dexamethasone (DXM) (1; 2.5 mg/kg) for 10 days. The mRNA levels of the GR, proteoglycans core proteins, and heparan sulfate metabolism-involved genes were determined at the 15th, 30th, 60th, and 90th days by a real-time RT–PCR. The glycosaminoglycans content was studied using dot blot and staining with Alcian blue. A DXM treatment increased total GAG content (2-fold), whereas the content of highly sulfated glycosaminoglycans decreased (1.5–2-fold). The mRNA level of the heparan sulfate metabolism-involved gene Hs3St2 increased 5-fold, the mRNA level of Hs6St2 increased6–7-fold, and the mRNA level of proteoglycan aggrecan increased 2-fold. A correlation analysis revealed an association between the mRNA level of the GR and the mRNA level of 8 of the 14 proteoglycans-coding and 4 of the 13 heparan sulfate metabolism-involved genes supporting GR involvement in the DXM regulation of the expression of these genes. In summary, multiple DXM administrations led to an increase in the total GAG content and reorganized the brain extracellular matrix in terms of its glycosylation pattern. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is the most common and aggressive brain tumor in adults. Despite surgery, radiation, and chemotherapy, survival rates remain low, which emphasizes the urgent need for improved therapies. Current preclinical models use untreated tumors, which do not reflect the clinical scenario where patients already receive initial treatments. This review examines the effects of current treatments on the properties of recurrent tumors and evaluates preclinical models that incorporate these standard treatments to better mimic real patient conditions. Improving these models could help to identify more effective treatments, potentially leading to better outcomes for glioblastoma patients. Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment—surgery, radiation, and chemotherapy—on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, with a bad prognosis and lack of targeted therapeutic options. Characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, TNBC is often associated with a significantly lower survival rate compared to other breast cancer subtypes. Our study aimed to explore the prognostic significance of 83 immune-related genes, by using transcriptomic data from the TCGA database. Our analysis identified the Poliovirus Receptor-Like 3 protein (PVRL3) as a critical negative prognostic marker in TNBC patients. Furthermore, we found that the Enhancer of Zeste Homolog 2 (EZH2), a well-known epigenetic regulator, plays a pivotal role in modulating PVRL3 levels in TNBC cancer cell lines expressing EZH2 along with high levels of PVRL3. The elucidation of the EZH2-PVRL3 regulatory axis provides valuable insights into the molecular mechanisms underlying TNBC aggressiveness and opens up potential pathways for personalized therapeutic intervention. [ABSTRACT FROM AUTHOR]

The local dynamics of a system of oscillators with a large number of elements and with diffusive- and advective-type couplings containing a large delay are studied. Critical cases in the problem of the stability of the zero equilibrium state are singled out, and it is shown that all of them have infinite dimensions. Applying special methods of infinite normalization, we construct quasinormal forms, namely, nonlinear boundary value problems of the parabolic type, whose nonlocal dynamics determine the behavior of the solutions of the initial system in a small neighborhood of the equilibrium state. These quasinormal forms contain either two or three spatial variables, which emphasizes the complexity of the dynamical properties of the original problem. [ABSTRACT FROM AUTHOR]

This study has reviewed the many roles of lumican as a biomarker of tissue pathology in health and disease. Lumican is a structure regulatory proteoglycan of collagen-rich tissues, with cell instructive properties through interactions with a number of cell surface receptors in tissue repair, thereby regulating cell proliferation, differentiation, inflammation and the innate and humoral immune systems to combat infection. The exponential increase in publications in the last decade dealing with lumican testify to its role as a pleiotropic biomarker regulatory protein. Recent findings show lumican has novel roles as a biomarker of the hypercoagulative state that occurs in SARS CoV-2 infections; thus, it may also prove useful in the delineation of the complex tissue changes that characterize COVID-19 disease. Lumican may be useful as a prognostic and diagnostic biomarker of long COVID disease and its sequelae. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer accounts for 11.4% of all cancer cases and 18.0% of all cancer deaths. Understanding the molecular mechanisms underlying lung adenocarcinoma (LUAD), one of the most common lung cancers, is imperative to enhance diagnostic accuracy, drug development, and prognostic evaluation. The present study explored the interaction between heparan sulfate (glucosamine) 3-O-sulfotransferase 1 (HS3ST1) and Glypican 4 (GPC4), as well as the influence of the hypoxia-derived exosomal lncRNA OIP5-AS1 on the glycolysis, proliferation, and metastasis ability in LUAD cell lines and their effects on the tumor growth in xenograft animal models. GPC4 promotes HS3ST1-mediated glycolysis, and the hypoxia-derived exosomal lncRNA OIP5-AS1 promotes glycolysis via the miR-200c-3p axis in LUAD cells. The hypoxia-derived exosomal lncRNA OIP5-AS1 enhances LUAD cell proliferation and metastasis in vitro and promotes LUAD tumor growth and metastasis via miR-200c-3p in vivo. These findings highlight that the hypoxia-derived exosomal lncRNA OIP5-AS1 may participate in LUAD progression. Objective: The diagnosis of lung adenocarcinoma (LUAD) is often delayed due to the typically asymptomatic nature of the early-stage disease, causing advanced-stage LUAD diagnosis in most patients. Hypoxia is widely recognized as a driving force in cancer progression. Exosomes originating from hypoxic tumor cells promote tumorigenesis by influencing glycolysis, migration, invasion, and immune infiltration. Given these insights, our study aimed to explore the role of hypoxia-derived exosomal long non-coding RNA (lncRNA) OIP5-AS1 in LUAD cell lines and mouse models. Materials and Methods: Exosomes were meticulously isolated and authenticated based on their morphology and biomarkers. The interaction between heparan sulfate (glucosamine) 3-O-sulfotransferase 1 (HS3ST1) and Glypican 4 (GPC4) was examined using immunoprecipitation. The influence of the hypoxia-derived exosomal lncRNA OIP5-AS1 on glycolysis was assessed in LUAD cell lines. The effect of the hypoxia-derived exosomal lncRNA OIP5-AS1 on cell proliferation and metastasis was evaluated using colony formation, cell viability, cell cycle, and apoptosis analyses. Its effects on tumor size were confirmed in xenograft animal models. Results: Our study revealed the mechanism of the hypoxia-derived exosomal lncRNA OIP5-AS1 in LUAD progression. We discovered that GPC4 promotes HS3ST1-mediated glycolysis and that the hypoxia-derived exosomal lncRNA OIP5-AS1 enhances glycolysis by regulating miR-200c-3p in LUAD cells. Notably, this lncRNA stimulates LUAD cell proliferation and metastasis and fosters LUAD tumor size via miR-200c-3p. Our findings underscore the potential role of the hypoxia-derived exosomal lncRNA OIP5-AS1 in LUAD progression. Conclusions: The hypoxia-derived exosomal lncRNA OIP5-AS1 promotes LUAD by regulating HS3ST1-GPC4-mediated glycolysis via miR-200c-3p. [ABSTRACT FROM AUTHOR]

Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect of EOC cells when they detach from the primary site of the ovary. However, the mechanism remains underexplored. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell–cell interactions. We examined the expression of CSPG4 in clinical samples and cell lines of EOC. The proliferation, migration, and invasion abilities of the CSPG4 knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in an in vivo model using sh-CSPG4 EOC cell lines. Of the clinical samples, 23 (44.2%) samples expressed CSPG4. CSPG4 was associated with a worse prognosis in patients with advanced EOC. Among the EOC cell lines, aggressive cell lines, including ES2, expressed CSPG4. When CSPG4 was knocked down using siRNA or shRNA, the cell proliferation, migration, and invasion abilities were significantly decreased compared to the control cells. Proteomic analyses showed changes in the expression of proteins related to the cell movement pathways. Spheroid formation was significantly inhibited when CSPG4 was inhibited. The number of nodules and the tumor burden of the omentum were significantly decreased in the sh-CSPG4 mouse models. In the peritoneal wash fluid from mice injected with sh-CSPG4 EOC cells, significantly fewer spheroids were present. Reduced CSPG4 expression was observed in lymphoid enhancer-binding factor 1-inhibited cells. CSPG4 is associated with aggressive features of EOC and poor prognosis. CSPG4 could be a new treatment target for blocking peritoneal metastasis by inhibiting spheroid formation. [ABSTRACT FROM AUTHOR]

Prostate cancer is among the top five cancer types according to incidence and mortality. One of the main obstacles in prostate cancer management is the inability to foresee its course, which ranges from slow growth throughout years that requires minimum or no intervention to highly aggressive disease that spreads quickly and resists treatment. Therefore, it is not surprising that numerous studies have attempted to find biomarkers of prostate cancer occurrence, risk stratification, therapy response, and patient outcome. However, only a few prostate cancer biomarkers are used in clinics, which shows how difficult it is to find a novel biomarker. Cell adhesion to the extracellular matrix (ECM) through integrins is among the essential processes that govern its fate. Upon activation and ligation, integrins form multi-protein intracellular structures called integrin adhesion complexes (IACs). In this review article, the focus is put on the biomarker potential of the ECM- and IAC-related molecules stemming from both body fluids and prostate cancer tissue. The processes that they are involved in, such as tumor stiffening, bone turnover, and communication via exosomes, and their biomarker potential are also reviewed. [ABSTRACT FROM AUTHOR]

The vacuum residue hydrocracker naphtha (VRHN) is a chemically unstable product that during storage changes its colour and forms sediments after two weeks. It cannot be directly exported from the refinery without improving its chemical stability. In this research, the hydrotreatment of H-Oil naphtha with straight run naphtha in a commercial hydrotreater, its co-processing with fluid catalytic cracking (FCC) gasoline in a commercial Prime-G+ post-treater, and its co-processing with vacuum gas oil (VGO) in a commercial FCC unit were discussed. The hydrotreatment improves the chemical stability of H-Oil naphtha and reduces its sulphur content to 3 ppm. The Prime-G+ co-hydrotreating increases the H-Oil naphtha blending research octane number (RON) by 6 points and motor octane number (MON) by 9 points. The FCC co-cracking with VGO enhances the blending RON by 11.5 points and blending MON by 17.6 points. H-Oil naphtha conversion to gaseous products (C1–C4 hydrocarbons) in the commercial FCC unit was found to be 50%. The use of ZSM 5 containing catalyst additive during processing H-Oil naphtha showed to lead to FCC gasoline blending octane enhancement by 2 points. This enabled an increment of low octane number naphtha in the commodity premium near zero sulphur automotive gasoline by 2.4 vol.% and substantial improvement of refinery margin. The processing of H-Oil naphtha in the FCC unit leads also to energy saving as a result of an equivalent lift steam substitution in the FCC riser. [ABSTRACT FROM AUTHOR]

This paper is devoted to the analysis of mathematical models of chemotherapy for malignant tumors growing according to the Gompertz law or the generalized logistic law. The influence of the therapeutic agent on the tumor dynamics is determined by a therapy function depending on the time-varying concentration of the drug in the patient's body. The case of a non-monotonic therapy function with two maxima is studied. It reflects the use of two different therapeutic agents. The state variables of the dynamics are the tumor volume and the amount of the therapeutic agent able to suppress malignant cells (concentration of the drug in the body). The treatment protocol (the rate of administration of the therapeutic agent) is the control in the dynamics. The optimal control problem for this models is considered. It is the problem of the construction of treatment protocols that provide the minimal tumor volume at the end of the treatment. The solution of this problem was obtained by the authors in previous works via the optimal control theory. The form of the considered therapy functions provides a specific structure for the optimal controls. The managerial insights of this structure are discussed. In this paper, the structure of the viability set is described for the model according to the generalized logistic law. It is the set of the initial states of the model for which one can find a treatment protocol that guarantees that the tumor volume remains within the prescribed limits throughout the treatment. The description of the viability set's structure is based on the optimal control theory and the theory of Hamilton–Jacobi equations. An inverse problem of therapy is also considered, namely the problem of reconstruction of the treatment protocol and identification of the unknown parameter of the intensity of the tumor growth. Reconstruction is carried out by processing information about the observations of the tumor volume dynamics and the measurements of the drug concentration in the body. A solution to this problem is obtained through the use of a method based on the calculus of variations. The results of the numerical simulations are presented herein. [ABSTRACT FROM AUTHOR]

Simple Summary: As recurrence in glioblastoma is locally generated around the resection cavity, surviving glioma stem-like cells may cause recurrence. Glioma stem-like cells expressing high levels of CD44 are highly invasive and are required to change to less invasive, more proliferative types to generate a recurrent tumor. CD44 promotes both the invasion and proliferation of tumor cells via various signaling pathways. Among these, paired pathways show reciprocal activation of invasion and proliferation under different conditions of oxygenation. Severe hypoxia activates genes related to cell invasion, whereas moderate hypoxia activates genes related to cell proliferation. CD44 is associated with both pathways and plays a critical role in regulating the balance between the promotion of cell invasion and cell proliferation. These results may indicate that CD44 is a key molecule for executing tumor recurrence in glioblastoma. High invasiveness is a characteristic of glioblastoma (GBM), making radical resection almost impossible, and thus, resulting in a tumor with inevitable recurrence. GBM recurrence may be caused by glioma stem-like cells (GSCs) that survive many kinds of therapy. GSCs with high expression levels of CD44 are highly invasive and resistant to radio-chemotherapy. CD44 is a multifunctional molecule that promotes the invasion and proliferation of tumor cells via various signaling pathways. Among these, paired pathways reciprocally activate invasion and proliferation under different hypoxic conditions. Severe hypoxia (0.5–2.5% O2) upregulates hypoxia-inducible factor (HIF)-1α, which then activates target genes, including CD44, TGF-β, and cMET, all of which are related to tumor migration and invasion. In contrast, moderate hypoxia (2.5–5% O2) upregulates HIF-2α, which activates target genes, such as vascular endothelial growth factor (VEGF)/VEGFR2, cMYC, and cyclin D1. All these genes are related to tumor proliferation. Oxygen environments around GBM can change before and after tumor resection. Before resection, the oxygen concentration at the tumor periphery is severely hypoxic. In the reparative stage after resection, the resection cavity shows moderate hypoxia. These observations suggest that upregulated CD44 under severe hypoxia may promote the migration and invasion of tumor cells. Conversely, when tumor resection leads to moderate hypoxia, upregulated HIF-2α activates HIF-2α target genes. The phenotypic transition regulated by CD44, leading to a dichotomy between invasion and proliferation according to hypoxic conditions, may play a crucial role in GBM recurrence. [ABSTRACT FROM AUTHOR]