ABSTRACT
Boron has been suggested to enhance the biological effectiveness of proton beams in the Bragg peak region via the p + 11B â 3α nuclear capture reaction. However, a number of groups have observed no such enhancement in vitro or questioned its proposed mechanism recently. To help elucidate this phenomenon, we irradiated DU145 prostate cancer or U-87 MG glioblastoma cells by clinical 190 MeV proton beams in plateau or Bragg peak regions with or without 10B or 11B isotopes added as sodium mercaptododecaborate (BSH). The results demonstrate that 11B but not 10B or other components of the BSH molecule enhance cell killing by proton beams. The enhancement occurs selectively in the Bragg peak region, is present for boron concentrations as low as 40 ppm, and is not due to secondary neutrons. The enhancement is likely initiated by proton-boron capture reactions producing three alpha particles, which are rare events occurring in a few cells only, and their effects are amplified by intercellular communication to a population-level response. The observed up to 2-3-fold reductions in survival levels upon the presence of boron for the studied prostate cancer or glioblastoma cells suggest promising clinical applications for these tumour types.
Subject(s)
Boron Neutron Capture Therapy , Proton Therapy , Humans , Boron Neutron Capture Therapy/methods , Proton Therapy/methods , Cell Line, Tumor , Male , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/drug therapy , Glioblastoma/radiotherapy , Glioblastoma/drug therapy , Boron/chemistry , Cell Survival/drug effects , Cell Survival/radiation effects , ProtonsABSTRACT
Aim: Microbiomes influence the physiology and behavior of multicellular organisms and contribute to their adaptation to changing environmental conditions. However, yeast and bacterial microbiota have usually been studied separately; therefore, the interaction between bacterial and yeast communities in the gut of Drosophila melanogaster (D. melanogaster) is often overlooked. In this study, we investigate the correlation between bacterial and yeast communities in the gut of D. melanogaster. Methods: We studied the shifts in the joint microbiome of Drosophila melanogaster, encompassing both yeasts and bacteria, during adaptation to substrate with varying salt concentrations (0%, 2%, 4%, and 7%) using plating for both yeasts and bacteria and NGS-sequencing of variable 16S rRNA gene regions for bacteria. Results: The microbiome of flies and their substrates was gradually altered at moderate NaCl concentrations (2% and 4% compared with the 0% control) and completely transformed at high salt concentrations (7%). The relative abundance of Acetobacter, potentially beneficial to D. melanogaster, decreased as NaCl concentration increased, whereas the relative abundance of the more halotolerant lactobacilli first increased, peaking at 4% NaCl, and then declined dramatically at 7%. At this salinity level, potentially pathogenic bacteria of the genera Leuconostoc and Providencia were dominant. The yeast microbiome of D. melanogaster also undergoes significant changes with an increase in salt concentration in the substrate. The total yeast abundance undergoes nonlinear changes: it is lowest at 0% salt concentration and highest at 2%-4%. At a 7% concentration, the yeast abundance in flies and their substrate is lower than at 2%-4% but significantly higher than at 0%. Conclusions: The abundance and diversity of bacteria that are potentially beneficial to the flies decreased, while the proportion of potential pathogens, Leuconostoc and Providencia, increased with an increase in salt concentration in the substrate. In samples with a relatively high abundance and/or diversity of yeasts, the corresponding indicators for bacteria were often lowered, and vice versa. This may be due to the greater halotolerance of yeasts compared to bacteria and may also indicate antagonism between these groups of microorganisms.
ABSTRACT
Type 2 diabetes is characterized by hyperglycemia and a relative loss of ß-cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin-nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased α-amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of ß-cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes.
Subject(s)
Betulinic Acid , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Rats , Female , Animals , Antioxidants/therapeutic use , Niacinamide/pharmacology , Niacinamide/therapeutic use , Rats, Wistar , Streptozocin/adverse effects , Diabetes Mellitus, Experimental/chemically induced , Blood Glucose , Plant Extracts/pharmacology , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/adverse effects , Glucose/adverse effects , Biomarkers , alpha-AmylasesABSTRACT
Blood metabolomics profiling using mass spectrometry has emerged as a powerful approach for investigating non-cancer diseases and understanding their underlying metabolic alterations. Blood, as a readily accessible physiological fluid, contains a diverse repertoire of metabolites derived from various physiological systems. Mass spectrometry offers a universal and precise analytical platform for the comprehensive analysis of blood metabolites, encompassing proteins, lipids, peptides, glycans, and immunoglobulins. In this comprehensive review, we present an overview of the research landscape in mass spectrometry-based blood metabolomics profiling. While the field of metabolomics research is primarily focused on cancer, this review specifically highlights studies related to non-cancer diseases, aiming to bring attention to valuable research that often remains overshadowed. Employing natural language processing methods, we processed 507 articles to provide insights into the application of metabolomic studies for specific diseases and physiological systems. The review encompasses a wide range of non-cancer diseases, with emphasis on cardiovascular disease, reproductive disease, diabetes, inflammation, and immunodeficiency states. By analyzing blood samples, researchers gain valuable insights into the metabolic perturbations associated with these diseases, potentially leading to the identification of novel biomarkers and the development of personalized therapeutic approaches. Furthermore, we provide a comprehensive overview of various mass spectrometry approaches utilized in blood metabolomics research, including GC-MS, LC-MS, and others discussing their advantages and limitations. To enhance the scope, we propose including recent review articles supporting the applicability of GC×GC-MS for metabolomics-based studies. This addition will contribute to a more exhaustive understanding of the available analytical techniques. The Integration of mass spectrometry-based blood profiling into clinical practice holds promise for improving disease diagnosis, treatment monitoring, and patient outcomes. By unraveling the complex metabolic alterations associated with non-cancer diseases, researchers and healthcare professionals can pave the way for precision medicine and personalized therapeutic interventions. Continuous advancements in mass spectrometry technology and data analysis methods will further enhance the potential of blood metabolomics profiling in non-cancer diseases, facilitating its translation from the laboratory to routine clinical application.
ABSTRACT
Insulin-positive (+) cells (IPCs), detected in multiple organs, are of great interest as a probable alternative to ameliorate pancreatic beta-cells dysfunction and insulin deficiency in diabetes. Liver is a potential source of IPCs due to it common embryological origin with pancreas. We previously demonstrated the presence of IPCs in the liver of healthy and diabetic rats, but detailed description and analysis of the factors, which potentially can induced ectopic hepatic expression of insulin in type 1 (T1D) and type 2 diabetes (T2D), were not performed. In present study we evaluate mass of hepatic IPCs in the rat models of T1D and T2D and discuss factors, which may stimulate it generation: glycaemia, organ injury, involving of hepatic stem/progenitor cell compartment, expression of transcription factors and inflammation. Quantity of IPCs in the liver was up by 1.7-fold in rats with T1D and 10-fold in T2D compared to non-diabetic (ND) rats. We concluded that ectopic hepatic expression of insulin gene is activated by combined action of a number of factors, with inflammation playing a decision role.
Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Insulin-Secreting Cells , Rats , Animals , Insulin/metabolism , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Experimental/metabolism , Cell Differentiation/genetics , Insulin-Secreting Cells/metabolism , Insulin, Regular, Human/metabolism , Liver/metabolism , Inflammation/metabolismABSTRACT
Essential oils (EOs) are of commercial importance for medicine, food, cosmetics, the perfume industry, and agriculture. In plants, EOs, like the wax cover, serve as protection against abiotic stresses, such as high temperatures and water deficiency. The use of spraying with exogenous hormones of aromatic plants affects the accumulation and composition of volatile compounds, as well as tolerance to abiotic stress. As a result of cytokinin treatment with 6-BAP (6-benzylaminopurine) (200 mg L-l) of Anetum graveolens L. "Uzory" and "Rusich" varieties, several responses to its action were revealed: a change in the division of leaf blades, inhibition of flowering, an increase in the content of EO and its main components α-phellandrene and p-cymene in leaves, and limonene in umbels and fruits. It was revealed that the increased accumulation of EO in dill leaves was longer with sufficient moisture. In contrast, under conditions of heat and water deficiency, the effect of 6-BAP treatment on accumulations of the EO in leaves was short-lived and did not appear on umbels and fruits. The study of the cytokinin effect on a fine structure of a wax cover on the adaxial side of leaves by scanning electron microscopy revealed a change in its elements (from amorphous layers with scales to thin tubules), which probably increased the sensitivity of leaves to water deficiency and, consequently, led to a decrease in the biosynthetic activity of leaf tissue. Thus, 6-BAP had an impact on the adaptive properties of dill plants, prolonging the "youth" of vegetative organs and the ability to EO biosynthesis under conditions of sufficient moisture.
Subject(s)
Anethum graveolens , Oils, Volatile , Anethum graveolens/chemistry , Oils, Volatile/pharmacology , Plant Leaves , Fruit , Cytokinins , WaterABSTRACT
A series of bifunctional catalysts, MoS2/Al2O3 (70 wt.%), zeolite (30 wt.%) (zeolite-ZSM-5, ZSM-12, and ZSM-22), and silica aluminophosphate SAPO-11, were synthesized for hydroconversion of methyl palmitate (10 wt.% in dodecane) in a trickle-bed reactor. Mo loading was about 7 wt.%. Catalysts and supports were characterized by different physical-chemical methods (HRTEM-EDX, SEM-EDX, XRD, N2 physisorption, and FTIR spectroscopy). Hydroprocessing was performed at a temperature of 250-350 °C, hydrogen pressure of 3.0-5.0 MPa, liquid hourly space velocity (LHSV) of 36 h-1, and an H2/feed ratio of 600 Nm3/m3. Complete conversion of oxygen-containing compounds was achieved at 310 °C in the presence of MoS2/Al2O3-zeolite catalysts; the selectivity for the conversion of methyl palmitate via the 'direct' hydrodeoxygenation (HDO) route was over 85%. The yield of iso-alkanes gradually increases in order: MoS2/Al2O3 < MoS2/Al2O3-ZSM-12 < MoS2/Al2O3-ZSM-5 < MoS2/Al2O3-SAPO-11 < MoS2/Al2O3-ZSM-22. The sample MoS2/Al2O3-ZSM-22 demonstrated the highest yield of iso-alkanes (40%). The hydroisomerization activity of the catalysts was in good correlation with the concentration of Brønsted acid sites in the synthesized supports.
Subject(s)
Molybdenum , Zeolites , Zeolites/chemistry , Alkanes/chemistry , Silicon DioxideABSTRACT
OBJECTIVE: Previous studies highlighted a high prevalence of mental health issues among students during the COVID-19 pandemic, but there is no evidence from Russia. This study was aimed to examine the prevalence of somatic and psychological distress among Russian university students. METHOD: The cross-sectional study was conducted in March-April 2021. The participants were university students from several regions of Russia (N = 1236). The Patient Health Questionnaire-15 and Depression, Anxiety, and Stress Scales-21 were used to measure the somatic and psychological distress. RESULTS: The prevalence of somatic burden, depression, anxiety, and stress was 72.2%, 54.7%, 63.4%, and 55.4%, respectively. Somatic burden, anxiety, and stress were more frequently observed in females and students with experience of COVID-19 disease compared to males and students without experience of COVID-19 disease. CONCLUSIONS: These data illuminate the high prevalence and potential risk factors for somatic and psychological distress among Russian university students and determine the importance of psychoeducation and preventive measures in the Russian university environment.
Subject(s)
COVID-19 , Psychological Distress , Male , Female , Humans , COVID-19/epidemiology , Cross-Sectional Studies , Universities , Pandemics , Depression/psychology , Stress, Psychological/epidemiology , Stress, Psychological/psychology , Anxiety/epidemiology , Anxiety/psychology , StudentsABSTRACT
Isoflavones are secondary metabolites that represent the most abundant category of plant polyphenols. Dietary soy, kudzu, and red clover contain primarily genistein, daidzein, glycitein, puerarin, formononetin, and biochanin A. The structural similarity of these compounds to ß-estradiol has demonstrated protection against age-related and hormone-dependent diseases in both genders. Demonstrative shreds of evidence confirmed the fundamental health benefits of the consumption of these isoflavones. These relevant activities are complex and largely driven by the source, active ingredients, dose, and administration period of the bioactive compounds. However, the preclinical and clinical studies of these compounds are greatly variable, controversial, and still with no consensus due to the non-standardized research protocols. In addition, absorption, distribution, metabolism, and excretion studies, and the safety profile of isoflavones have been far limited. This highlights a major gap in understanding the potentially critical role of these isoflavones as prospective replacement therapy. Our general review exclusively focuses attention on the crucial role of isoflavones derived from these plant materials and critically highlights their bioavailability, possible anticancer, antiaging potentials, and microbiome modulation. Despite their fundamental health benefits, plant isoflavones reveal prospective therapeutic effects that worth further standardized analysis.
Subject(s)
Female , Male , HumansABSTRACT
The healthy lifestyle of people around the world has changed dramatically during the COVID-19 pandemic. The personality risk factors for these processes from around the world remain understudied. This study aimed to examine the associations of the Big Five traits with a healthy lifestyle during the COVID-19 pandemic. In a cross-sectional study, data from 1215 Russian university students were analyzed. Participants completed the Big Five Inventory-10 and Short Multidimensional Inventory Lifestyle Evaluation. The results showed that personality traits predicted many dimensions of a healthy lifestyle during the COVID-19 pandemic. Diet and nutrition were positively predicted by extraversion, agreeableness, and conscientiousness, and it was negatively predicted by neuroticism. Substance abuse was positively predicted by agreeableness and conscientiousness, and it was negatively predicted by extraversion. Physical activity was positively predicted by extraversion and conscientiousness, and it was negatively predicted by neuroticism. Stress management was positively predicted by extraversion and conscientiousness, and it was negatively predicted by neuroticism. Restorative sleep was positively predicted by extraversion and conscientiousness, and it was negatively predicted by neuroticism. Social support for healthy practices was positively predicted by extraversion, agreeableness, and conscientiousness. Environmental exposures were positively predicted by extraversion, and neuroticism was positively and negatively predicted by conscientiousness. Our findings may be useful for further exploration of personality risk factors for healthy practices in challenging life circumstances.
Subject(s)
COVID-19 , Personality , COVID-19/epidemiology , Cross-Sectional Studies , Healthy Lifestyle , Humans , Pandemics , Personality InventoryABSTRACT
Proton radiotherapy for the treatment of cancer offers an excellent dose distribution. Cellular experiments have shown that in terms of biological effects, the sharp dose distribution is further amplified, by as much as 75%, in the presence of boron. It is a matter of debate whether the underlying physical processes involve the nuclear reaction of 11B with protons or 10B with secondary neutrons, both producing densely ionizing short-ranged particles. Likewise, potential roles of intercellular communication or boron acting as a radiosensitizer are not clear. We present an ongoing research project based on a multiscale approach to elucidate the mechanism by which boron enhances the effectiveness of proton irradiation in the Bragg peak. It combines experimental with simulation tools to study the physics of proton-boron interactions, and to analyze intra- and inter-cellular boron biology upon proton irradiation.
Subject(s)
Boron Neutron Capture Therapy , Proton Therapy , Boron , Neutrons , ProtonsABSTRACT
Boron derivatives have great potential in cancer diagnostics and treatment. Borocaptates are used in boron neutron capture therapy and potentially in proton boron fusion therapy. This work examines modulation effects of two borocaptate compounds on radiation-induced DNA damage. Aqueous solutions of pBR322 plasmid containing increasing concentrations of borocaptates were irradiated with 60Co gamma rays or 30 MeV protons. Induction of single and double DNA strand breaks was investigated using agarose gel electrophoresis. In this model system, representing DNA without the intervention of cellular repair mechanisms, the boron derivatives acted as antioxidants. Clinically relevant boron concentrations of 40 ppm reduced the DNA single strand breakage seven-fold. Possible mechanisms of the observed effect are discussed.
Subject(s)
Boron Neutron Capture Therapy , Boron , DNA/radiation effects , DNA Damage , Plasmids/geneticsABSTRACT
ß-cells dysfunction plays an important role in the pathogenesis of type 2 diabetes (T2D), partially may be compensated by the generation of extra-islet insulin-producing cells (IPCs) in pancreatic acini and ducts. Pdx1 expression and inflammatory level are suggested to be involved in the generation of extra-islet IPCs, but the exact reasons and mechanisms of it are unclear. Macrophages are key inflammatory mediators in T2D. We studied changes in mass and characteristics of extra-islet IPCs in rats with a streptozotocin-nicotinamide model of T2D and after i.m. administration of 20 daily doses of 2 mg/kg b.w. sodium aminophthalhydrazide (APH). Previously, we found that APH modulates macrophage production and increases the proliferative activity of pancreatic ß-cells. Expressions of insulin and Pdx1, as well as F4/80 (macrophage marker), were detected at the protein level by immunohistochemistry analysis, the concentration of pro- and anti-inflammatory cytokines in blood and pancreas-by ELISA. Diabetic rats treated with APH showed an increasing mass of extra-islet IPCs and the content of insulin in them. The presence of Pdx1+ cells in the exocrine pancreas also increased. F4/80+ cell reduction was accompanied by increasing TGF-ß1 content. Interestingly, during the development of diabetes, the mass of ß-cells decreased faster than the mass of extra-islet IPCs, and extra-islet IPCs reacted to experimental T2D differently depending on their acinar or ductal location.
Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Insulin-Secreting Cells , Islets of Langerhans , Animals , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/metabolism , Insulin/metabolism , Insulin-Secreting Cells/metabolism , Islets of Langerhans/metabolism , Rats , Sodium/metabolismABSTRACT
Type 1 diabetes (T1D) leads to ischemic heart disease and diabetic cardiomyopathy. We tested the hypothesis that T1D differently affects the contractile function of the left and right ventricular free walls (LV, RV) and the interventricular septum (IS) using a rat model of alloxan-induced T1D. Single-myocyte mechanics and cytosolic Ca2+ concentration transients were studied on cardiomyocytes (CM) from LV, RV, and IS in the absence and presence of mechanical load. In addition, we analyzed the phosphorylation level of sarcomeric proteins and the characteristics of the actin-myosin interaction. T1D similarly affected the characteristics of actin-myosin interaction in all studied regions, decreasing the sliding velocity of native thin filaments over myosin in an in vitro motility assay and its Ca2+ sensitivity. A decrease in the thin-filament velocity was associated with increased expression of ß-myosin heavy-chain isoform. However, changes in the mechanical function of single ventricular CM induced by T1D were different. T1D depressed the contractility of CM from LV and RV; it decreased the auxotonic tension amplitude and the slope of the active tension-length relationship. Nevertheless, the contractile function of CM from IS was principally preserved.
Subject(s)
Calcium/metabolism , Diabetes Mellitus, Type 1/pathology , Myocytes, Cardiac/pathology , Ventricular Function , Animals , Male , Myocardial Contraction , Rats , Rats, WistarABSTRACT
Diabetes remains a major health emergency in our entire world, affecting hundreds of millions of people worldwide. In conjunction with its much-dreaded complications (e.g., nephropathy, neuropathy, retinopathy, cardiovascular diseases, etc.) it substantially reduces the quality of life, increases mortality as well as economic burden among patients. Over the years, oxidative stress and inflammation have been highlighted as key players in the development and progression of diabetes and its associated complications. Much research has been devoted, as such, to the role of antioxidants in diabetes. Astaxanthin is a powerful antioxidant found mostly in marine organisms. Over the past years, several studies have demonstrated that astaxanthin could be useful in the treatment and management of diabetes. It has been shown to protect ß-cells, neurons as well as several organs including the eyes, kidney, liver, etc. against oxidative injuries experienced during diabetes. Furthermore, it improves glucose and lipid metabolism along with cardiovascular health. Its beneficial effects are exerted through multiple actions on cellular functions. Considering these and the fact that foods and natural products with biological and pharmacological activities are of much interest in the 21st-century food and drug industry, astaxanthin has a bright prospect in the management of diabetes and its complications.
Subject(s)
Antioxidants , Diabetes Mellitus , Antioxidants/pharmacology , Antioxidants/therapeutic use , Diabetes Mellitus/drug therapy , Humans , Oxidative Stress , Quality of Life , Xanthophylls/pharmacology , Xanthophylls/therapeutic useABSTRACT
Pharmacotherapy of hepatobiliary disorders is an important issue due to the high prevalence of liver failure, toxic and viral hepatitis and cirrhosis. The number of stimuli that can potentially induce or accelerate liver recovery is limited; in our study we selected sodium phthalhydrazide, which has been found to promote liver regeneration after partial hepatectomy. We examined the effects of phthalhydrazide on liver morphometric, histological and biochemical parameters in rats intoxicated with CCl4. Accelerated liver recovery after CCl4 intoxication in phthalhydrazide-treated animals was evidenced by increased number of liver sinusoidal cells, reduced focal necrosis of hepatocytes and reduced perifocal leukocyte infiltration. Decreased plasma levels of pro-inflammatory cytokines TNF-α and IL-18 and decreased concentrations of IL-6 and IFN-γ in liver homogenates were associated with reduced severity of cholestasis and normalized hepatic protein synthesis in CCl4-intoxicated rats exposed to phthalhydrazide. Anti-inflammatory and immunomodulating properties of phthahlhydrazide can be an important factor contributing to accelerated liver recovery at early stages of acute CCl4-toxic liver impairment.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , Hydrazines/therapeutic use , Immunologic Factors/therapeutic use , Phthalazines/therapeutic use , Protective Agents/therapeutic use , Animals , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/immunology , Chemical and Drug Induced Liver Injury/pathology , Cytokines/blood , Liver/drug effects , Liver/pathology , Male , Rats, WistarABSTRACT
BACKGROUND: Urothelial bladder cancer (BLCA) is one of the most common internal malignancies worldwide with poor prognosis. This study aims to explore effective prognostic biomarkers and construct a prognostic risk score model for patients with BLCA. METHODS: Weighted gene co-expression network analysis (WGCNA) was used for identifying the co-expression module related to the pathological stage of BLCA based on the RNA-Seq data retrieved from The Cancer Genome Atlas database. Prognostic biomarkers screened by Cox proportional hazard regression model and random forest were used to construct a risk score model that can predict the prognosis of patients with BLCA. The GSE13507 dataset was used as the independent testing dataset to test the performance of the risk score model in predicting the prognosis of patients with BLCA. RESULTS: WGCNA identified seven co-expression modules, in which the brown module consisted of 77 genes was most significantly correlated with the pathological stage of BLCA. Cox proportional hazard regression model and random forest identified TPST1 and P3H4 as prognostic biomarkers. Elevated TPST1 and P3H4 expressions were associated with the high pathological stage and worse survival. The risk score model based on the expression level of TPST1 and P3H4 outperformed pathological stage indicators and previously proposed prognostic models. CONCLUSION: The gene co-expression network-based study could provide additional insight into the tumorigenesis and progression of BLCA, and our proposed risk score model may aid physicians in the assessment of the prognosis of patients with BLCA.
Subject(s)
Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/mortality , Algorithms , Computational Biology/methods , Female , Gene Expression Profiling , Gene Ontology , Humans , Male , Models, Theoretical , Prognosis , Protein Interaction Mapping , ROC Curve , Risk Assessment , Survival Analysis , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/metabolismABSTRACT
The use of mushrooms as functional foods and in the treatment of diseases has a long history. Inonotus obliquus is a mushroom belonging to the Hymenochaetaceae family and has possible anticancer, antiviral, and hypoglycemic properties. Chemical analysis of this mushroom has allowed the identification of various constituents such as melanins, phenolic compounds, and lanostane-type triterpenoids. A plethora of findings have highlighted the potential molecular mechanisms of actions of this mushroom such as its ability to scavenge reactive oxygen species, inhibit the growth of tumors, decrease inflammation and insulin resistance in type 2 diabetes, and stimulate the immune system. This review summarizes the relevant findings with reference to the therapeutic potential of this mushroom in countering the progression of cancers, diabetes mellitus, and antiviral activities, while highlighting its possible molecular mechanisms of action. The possible role of this mushroom as a therapeutic agent in addressing the pathogenesis of diabetes and cancer has also been suggested.
Subject(s)
Agaricales/chemistry , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Neoplasms/drug therapy , Animals , Humans , Hypoglycemic Agents/pharmacology , Mice , RatsABSTRACT
Pharmacological interventions which could be hepatoprotective, depending on bioavailability, anti-inflammatory and macrophage-targeting potential of drugs, are still at early preclinical stages. Existing evidence from many animal models of liver injury, as well as from human data, indicate that pharmacological and/or phytochemical interventions have limited impact on liver recovery. Recent studies on stem cell therapies focused on different cell subsets involved in tissue repair, including monocytes/macrophages and bone marrow cells migrating to the injured liver. Partial hepatectomy (PH) resulted in a rapid increase of monocytes/macrophages in bone marrow and liver, which could be further enhanced by prior treatment of animals with sodium phthalhydrazide. Increased number of proliferating Ki67+ hepatocytes, increased total protein and albumin content in regenerating liver, recruitment of CD172a+ macrophages and more differentiated CD45lowCD117+ bone marrow cells, could be further promoted by the treatment of animals with 2â¯mg/kg b.w. phthalhydrazide, considered immunomodulatory, antioxidant and macrophage-silencing. Phenotypic polarization of macrophages can possibly explain the macrophage reparative capacities, protective against liver injury. Enhanced macrophage cell recruitment from bone marrow to regenerating liver can be possibly one of important events in hepatic recovery.
Subject(s)
Antioxidants/pharmacology , Hydrazines/pharmacology , Liver Regeneration/physiology , Macrophages/metabolism , Mesenchymal Stem Cells/metabolism , Phthalazines/pharmacology , Animals , Hematopoietic Stem Cells/drug effects , Hematopoietic Stem Cells/metabolism , Liver Regeneration/drug effects , Macrophages/drug effects , Male , Mesenchymal Stem Cells/drug effects , Mice , Mice, Inbred CBA , RatsABSTRACT
AIM: To investigate the temporal sequence of pathological changes in the cellular structures of retina and choroidea in the early stages of diabetes in laboratory animals. METHODS: Experimental type 1 diabetes was modeled by three intraperitoneal injections of an alloxan solution into 30 male nonlinear rats at 16 wk of age. The 30th and 60th days from the final alloxan injection were chosen as the endpoints. Light and electron microscopy and morphometric and immunohistochemical studies were performed on histological slices of eyeballs from experimental animals. RESULTS: Diabetic disturbances progressed to 60 d of the experiment. Thus, in the retina, a partial destruction of photoreceptors accompanied by interstitial edema was observed. The morphometric analysis revealed a reduction in the thickness of the retina. A reduction in the number of blood vessels of the choroid with disturbances of the endothelial cells and the vascular walls and a persistent reduction in the number of melanocytes were observed. The number of proliferating Ki-67 positive cells decreased, and the number of macrophages increased with diabetes development. CONCLUSION: The starting point in the development of destructive changes involves early reduction in the number of melanocytes of the choroidea and alterations in the retinal pigment epithelium.