Rottlerin stimulates apoptosis in pancreatic cancer cells through interactions with proteins of the Bcl-2 family

Rottlerin is a polyphenolic compound derived from Mallotus philipinensis. In the present study, we show that rottlerin decreased tumor size and stimulated apoptosis in an orthotopic model of pancreatic cancer with no effect on normal tissues in vivo. Rottlerin also induced apoptosis in pancreatic cancer (PaCa) cell lines by interacting with mitochondria and stimulating cytochrome c release. Immunoprecipitation results indicated that rottlerin disrupts complexes of prosurvival Bcl-xL with Bim and Puma. Furthermore, siRNA knockdown showed that Bim and Puma are necessary for rottlerin to stimulate apoptosis. We also showed that rottlerin and Bcl-2 and Bcl-xL inhibitor BH3I-2' stimulate apoptosis through a common mechanism. They both directly interact with mitochondria, causing increased cytochrome c release and mitochondrial depolarization, and both decrease sequestration of BH3-only proteins by Bcl-xL. However, the effects of rottlerin and BH3I-2' on the complex formation between Bcl-xL and BH3-only proteins are different. BH3I-2' disrupts complexes of Bcl-xL with Bad but not with Bim or Puma, whereas rottlerin had no effect on the Bcl-xL interaction with Bad. Also BH3I-2', but not rottlerin, required Bad to stimulate apoptosis. In conclusion, our results demonstrate that rottlerin has a potent proapoptotic and antitumor activity in pancreatic cancer, which is mediated by disrupting the interaction between prosurvival Bcl-2 proteins and proapoptotic BH3-only proteins. Thus rottlerin represents a promising novel agent for pancreatic cancer treatment

Ways of Solving of Safety Problems of Single-Track Vehicles

This article describes the ways of solving essential problems regarding the safety of single-track vehicles (STV). All test procedures and STV research works were developed and approved by the authors

Composite sorbent for liquidation of oil pollution

A method of effective elimination and localization of oil spills using a composite sorbent has been developed. The resulting material consists of polymer waste, mineral filler and surfactant. Due to the peculiarities of the method, the resulting sorbent allows the utilization of polymer waste and has a high oil capacity. The size of the sorbent can vary depending on the specified parameters, what simplifies storage and application

Green synthesis of metal nanoparticles and application of nanoadditives in diesel fuel: bibliometric analysis

The problem of obtaining metal nanoparticles considering environmental risks in connection with the use of synthesis products in mixtures of new types of diesel fuel has been studied. An analysis of existing research on these topics was carried out. Based on the data sets obtained using the Dimensions and OpenAlex services, the characteristics of the studies were determined. To analyze the problem of green synthesis of nanoparticles, a dataset of 6,062 journal articles published from 2001 to October 2023 was used. The use of nanoparticles as diesel fuel components was investigated using a dataset of 540 journal articles published from 2005 to October 2023. The leading countries and organizations by the number of publications and citations have been identified. Based on the analysis of coauthorship, the issue of international cooperation is considered. The most significant publications were determined by the number of citations. Using methods of visual analysis of data on research keywords, their trends and prospects were determined. In addition, an assessment was made of the development of the problem of using “green” methods for obtaining nanoparticles used as components of diesel fuel

Traditional and green approaches to the synthesis of copper-containing nanoparticles using chemical reduction

The problem of obtaining copper-containing nanoparticles by chemical reduction has been studied. A comparison is made of traditional and “green” approaches to synthesis. The experimental data obtained during the synthesis of copper nanoparticles in the presence of a polymer stabilizer (polyvinylpyrrolidone) and a reducing agent (tert-butylamine-borane), as well as literature data on the synthesis of nanoparticles using plant and conditionally “green” substances (glucose, extracts of Ocimum sanctum and Celastrus paniculatus leaves, Sarcostemma acidum stem). The advantages and disadvantages of these approaches are identified and discussed. It is noted that the industrial applicability of “green” methods is limited due to the need to create completely new production of reagents for synthesis. In addition, the application of green synthesis is difficult due to scalability and standardization issues. Environmental pollution associated with the production of plant extracts also requires additional assessment. It has been established that traditional synthesis methods remain relevant for modern industry, and “green” methods have prospects for use in the distant future

The Effects of PK11195 and Protoporphyrin IX Can Modulate Chronic Alcohol Intoxication in Rat Liver Mitochondria under the Opening of the Mitochondrial Permeability Transition Pore

Decades of active research have shown that mitochondrial dysfunction, the associated oxidative stress, impaired anti-stress defense mechanisms, and the activation of the proapoptotic signaling pathways underlie pathological changes in organs and tissues. Pathologies caused by alcohol primarily affect the liver. Alcohol abuse is the cause of many liver diseases, such as steatosis, alcoholic steatohepatitis, fibrosis, cirrhosis, and, potentially, hepatocellular cancer. In this study, the effect of chronic alcohol exposure on rat liver mitochondria was investigated. We observed an ethanol-induced increase in sensitivity to calcium, changes in the level of protein kinase Akt and GSK-3β phosphorylation, an induction of the mitochondrial permeability transition pore (mPTP), and strong alterations in the expression of mPTP regulators. Moreover, we also showed an enhanced effect of PK11195 and PPIX, on the parameters of the mPTP opening in rat liver mitochondria (RLM) isolated from ethanol-treated rats compared to the RLM from control rats. We suggest that the results of this study could help elucidate the mechanisms of chronic ethanol action on the mitochondria and contribute to the development of new therapeutic strategies for treating the effects of ethanol-related diseases

Optimization design of the stick of an excavator under uncertain loading (in the conditions of the Syrian Arab Republic)

The article is devoted to the optimization design of the stick of a hydraulic excavator at the most frequent and greatest value loads. The uncertain loads acting on the working equipment of the excavator were obtained by the Monte Carlo method based on 3D analytical soil-tool interaction models. The results show that the adopted methodology can be used to optimize the design of elements of the excavator working equipment, since the design of stick was obtained with less weight and lower stress values than the original design

Astaxanthin Prevents Mitochondrial Impairment Induced by Isoproterenol in Isolated Rat Heart Mitochondria

Mitochondria are considered to be a power station of the cell. It is known that they play a major role in both normal and pathological heart function. Alterations in mitochondrial bioenergetics are one of the main causes of the origin and progression of heart failure since they have an inhibitory effect on the activity of respiratory complexes in the inner mitochondrial membrane. Astaxanthin (AST) is a xanthophyll carotenoid of mainly marine origin. It has both lipophilic and hydrophilic properties and may prevent mitochondrial dysfunction by permeating the cell membrane and co-localizing within mitochondria. The carotenoid suppresses oxidative stress-induced mitochondrial dysfunction and the development of diseases. In the present study, it was found that the preliminary oral administration of AST upregulated the activity of respiratory chain complexes and ATP synthase and the level of their main subunits, thereby improving the respiration of rat heart mitochondria (RHM) in the heart injured by isoproterenol (ISO). AST decreased the level of cyclophilin D (CyP-D) and increased the level of adenine nucleotide translocase (ANT) in this condition. It was concluded that AST could be considered as a potential mitochondrial-targeted agent in the therapy of pathological conditions associated with oxidative damage and mitochondrial dysfunction. AST, as a dietary supplement, has a potential in the prevention of cardiovascular diseases

The Identification of Prohibitin in the Rat Heart Mitochondria in Heart Failure

Mitochondria are considered the main organelles in the cell. They play an important role in both normal and abnormal heart function. There is a supramolecular organization between the complexes of the respiratory chain (supercomplexes (SCs)), which are involved in mitochondrial respiration. Prohibitins (PHBs) participate in the regulation of oxidative phosphorylation (OXPHOS) activity and interact with some subunits of the OXPHOS complexes. In this study, we identified a protein whose level was decreased in the mitochondria of the heart in rats with heart failure. This protein was PHB. Isoproterenol (ISO) has been used as a compound to induce heart failure in rats. We observed that astaxanthin (AX) increased the content of PHB in rat heart mitochondria isolated from ISO-injected rats. Since it is known that PHB forms complexes with some mitochondrial proteins and proteins that are part of the complexes of the respiratory chain, the change in the levels of these proteins was investigated under our experimental conditions. We hypothesized that PHB may be a target for the protective action of AX

The Effect of Astaxanthin on Mitochondrial Dynamics in Rat Heart Mitochondria under ISO-Induced Injury

Mitochondria are dynamic organelles that produce ATP in the cell and are sensitive to oxidative damage that impairs mitochondrial function in pathological conditions. Mitochondria are involved not only in a healthy heart but also in the development of heart disease. Therefore, attempts should be made to enhance the body’s defense response against oxidative stress with the help of various antioxidants in order to decrease mitochondrial damage and reduce mitochondrial dysfunction. Mitochondrial fission and fusion play an important role in the quality control and maintenance of mitochondria. The ketocarotenoid astaxanthin (AX) is an antioxidant able to maintain mitochondrial integrity and prevent oxidative stress. In the present study, we investigated the effect of the protective effect of AX on the functioning of rat heart mitochondria (RHM). Changes in the content of proteins responsible for mitochondrial dynamics, prohibitin 2 (PHB2) as a protein that performs the function of quality control of mitochondrial proteins and participates in the stabilization of mitophagy, and changes in the content of cardiolipin (CL) in rat heart mitochondria after isoproterenol (ISO)-induced damage were examined. AX improved the respiratory control index (RCI), enhanced mitochondrial fusion, and inhibited mitochondrial fission in RHM after ISO injury. Rat heart mitochondria (RHM) were more susceptible to Ca2+-induced mitochondrial permeability pore (mPTP) opening after ISO injection, while AX abolished the effect of ISO. AX is able to perform a protective function in mitochondria, improving their efficiency. Therefore, AX can be considered an important ingredient in the diet for the prevention of cardiovascular disease. Therefore, AX can be examined as an important component of the diet for the prevention of heart disease