Left Ventricular Wall Motion as an Additional Valuable Parameter in Diabetic Patients with Normal Myocardial Perfusion Imaging.

BACKGROUND: Gated SPECT is an established technique for assessment of left ventricular function in cardiovascular disease patients. However, there is little information about the influence of diabetes mellitus on gated SPECT parameters. This study was established to assess gated SPECT parameters in Diabetes Mellitus (DM) and non-diabetes mellitus (non-DM) patients with normal Myocardial Perfusion Imaging (MPI). METHODS: In this analytical cross-sectional study, 314 patients (157 DM, 157 non-DM) with normal MPI were enrolled. Prevalence of risk factors for CAD like hypertension (HTN), and dyslipidemia were found to be significantly higher (p <0.01) in DM patients compared to non-DM. RESULTS: No statistically significant difference was observed among the TID, ESV, EDV, PFR, TTPF, and Wall Thickness (WT) parameters between DM and non-DM patients. Wall motion (Wm) in DM patients was significantly higher compared to non-DM patients. (3.9 ± 0.51 vs. 2.69 ± 0.48 for DM and non-DM patients, respectively, p-value:0.01). Also, there was no significant difference in Wm in the two groups with and without HTN. This shows the independent effect of DM on the Wm. CONCLUSION: This study believes that the Wm parameter should be noted for the early diagnosis or prevention of heart disease in DM patients. These findings can indicate the gradual changes in the movements of the left ventricle and the beginning of the progression of diabetic cardiomyopathy.

Role of Non-coding RNAs on the Radiotherapy Sensitivity and Resistance in Cancer Cells.

Radiotherapy (RT) is an integral part of treatment management in cancer patients. However, one of the limitations of this treatment method is the resistance of cancer cells to radiotherapy. These restrictions necessitate the introduction of modalities for the radiosensitization of cancer cells. It has been shown that Noncoding RNAs (ncRNAs), along with modifiers, can act as radiosensitivity and radioresistant regulators in a variety of cancers by affecting double strand break (DSB), wnt signaling, glycolysis, irradiation induced apoptosis, ferroptosis and cell autophagy. This review will provide an overview of the latest research on the roles and regulatory mechanisms of ncRNA after RT in in vitro and preclinical research.

An In-depth Analysis of the Adverse Effects of Ionizing Radiation Exposure on Cardiac Catheterization Staffs.

Diagnostic and interventional angiograms are instrumental in the multidisciplinary approach to CAD management, enabling accurate diagnosis and effective targeted treatments that significantly enhance patient care and cardiovascular outcomes. However, cath lab staff, including interventional cardiologists, is consistently exposed to ionizing radiation, which poses inherent health risks. Radiation exposure in the cath lab primarily results from the use of fluoroscopy and cineangiography during diagnostic and interventional procedures. Understanding these risks and implementing effective radiation protection measurements are imperative to ensure the well-being of healthcare professionals while delivering high-quality cardiac care. Prolonged and repeated exposure can lead to both deterministic and stochastic effects. Deterministic effects, such as skin erythema and tissue damage, are more likely to occur at high radiation doses. Interventional cardiologists and staff may experience these effects when safety measures are not rigorously followed. In fact, while ionizing radiation is essential in the practice of radiation cardiology ward, cath lab staff faces inherent risks from radiation exposure. Stochastic effects, on the other hand, are characterized by a probabilistic relationship between radiation exposure and the likelihood of harm. These effects include the increased risk of cancer, particularly for those with long-term exposure. Interventional cardiologists, due to their frequent presence in the cath lab, face a higher lifetime cumulative radiation dose, potentially elevating their cancer risk. Protective measures, including the use of lead aprons, thyroid shields, and radiation monitoring devices, play a crucial role in reducing radiation exposure for cath lab personnel. Adherence to strict dose optimization protocols, such as minimizing fluoroscopy time and maximizing distance from the radiation source, is also essential in mitigating these risks. Ongoing research and advancements in radiation safety technology are essential in further for minimizing the adverse effects of ionizing radiation in the cath lab.

Nanotechnology Utilizing Ferroptosis Inducers in Cancer Treatment.

Current cancer treatment options have presented numerous challenges in terms of reaching high efficacy. As a result, an immediate step must be taken to create novel therapies that can achieve more than satisfying outcomes in the fight against tumors. Ferroptosis, an emerging form of regulated cell death (RCD) that is reliant on iron and reactive oxygen species, has garnered significant attention in the field of cancer therapy. Ferroptosis has been reported to be induced by a variety of small molecule compounds known as ferroptosis inducers (FINs), as well as several licensed chemotherapy medicines. These compounds' low solubility, systemic toxicity, and limited capacity to target tumors are some of the significant limitations that have hindered their clinical effectiveness. A novel cancer therapy paradigm has been created by the hypothesis that ferroptosis induced by nanoparticles has superior preclinical properties to that induced by small drugs and can overcome apoptosis resistance. Knowing the different ideas behind the preparation of nanomaterials that target ferroptosis can be very helpful in generating new ideas. Simultaneously, more improvement in nanomaterial design is needed to make them appropriate for therapeutic treatment. This paper first discusses the fundamentals of nanomedicine-based ferroptosis to highlight the potential and characteristics of ferroptosis in the context of cancer treatment. The latest study on nanomedicine applications for ferroptosis-based anticancer therapy is then highlighted.

Radioprotective Potency of Nanoceria.

Cancer presents a significant medical challenge that requires effective management. Current cancer treatment options, such as chemotherapy, targeted therapy, radiotherapy, and immunotherapy, have limitations in terms of their efficacy and the potential harm they can cause to normal tissues. In response, researchers have been focusing on developing adjuvants that can enhance tumor responses while minimizing damage to healthy tissues. Among the promising options, nanoceria (NC), a type of nanoparticle composed of cerium oxide, has garnered attention for its potential to improve various cancer treatment regimens. Nanoceria has demonstrated its ability to exhibit toxicity towards cancer cells, inhibit invasion, and sensitize cancer cells to both radiation therapy and chemotherapy. The remarkable aspect is that nanoceria show minimal toxicity to normal tissues while protecting against various forms of reactive oxygen species generation. Its capability to enhance the sensitivity of cancer cells to chemotherapy and radiotherapy has also been observed. This paper thoroughly reviews the current literature on nanoceria's applications within different cancer treatment modalities, with a specific focus on radiotherapy. The emphasis is on nanoceria's unique role in enhancing tumor radiosensitization and safeguarding normal tissues from radiation damage.

Ferroptosis Inducers as Promising Radiosensitizer Agents in Cancer Radiotherapy.

Radiotherapy (RT) failure has historically been mostly attributed to radioresistance. Ferroptosis is a type of controlled cell death that depends on iron and is caused by polyunsaturated fatty acid peroxidative damage. Utilizing a ferroptosis inducer may be a successful tactic for preventing tumor growth and radiotherapy-induced cell death. A regulated form of cell death known as ferroptosis is caused by the peroxidation of phospholipids containing polyunsaturated fatty acids in an iron-dependent manner (PUFA-PLs). The ferroptosis pathway has a number of important regulators. By regulating the formation of PUFA-PLs, the important lipid metabolism enzyme ACSL4 promotes ferroptosis, whereas SLC7A11 and (glutathione peroxidase 4) GPX4 prevent ferroptosis. In addition to introducing the ferroptosis inducer chemicals that have recently been demonstrated to have a radiosensitizer effect, this review highlights the function and methods by which ferroptosis contributes to RT-induced cell death and tumor suppression in vitro and in vivo.

Recent advances in synthesis of stilbene derivatives via cross-coupling reaction.

The stilbenes are undoubtedly some of the most significant moieties in various bioactive natural and synthetic structures, and they are considered privileged structures. In recent years, the preparation of these structures via cross-coupling reactions has attracted much attention. In the current review, we present a summary of the recent developments in the construction of stilbene and stilbene derivatives by carbon-carbon coupling reactions of organic compounds in the presence of transition metal catalysts or under metal-free conditions. In this context, we outline the features of the important reactions, some product yields, and challenging reaction mechanisms.

Promising Radiopharmaceutical Tracers for Detection of Cardiotoxicity in Cardio-oncology.

Cancer treatment has the potential to cause cardiovascular issues and can encourage the appearance of all aspects of cardiac disease, including coronary heart disease, myocardial disease, heart failure, structural heart disease, and rhythm problems. Imaging is required for both diagnostic workup and therapy monitoring for all possible cardiovascular side effects of cancer therapy. Echocardiography is the cardiac imaging gold standard in cardio-oncology. Despite advancements in its use, this method is often not sensitive to early-stage or subclinical impairment. The use of molecular imaging technologies for diagnosing, assessing, and tracking cardiovascular illness as well as for treating, it is fast growing. Molecular imaging techniques using biologically targeted markers are gradually replacing the traditional anatomical or physiological approaches. They offer unique insight into patho-biological processes at the molecular and cellular levels and enable the evaluation and treatment of cardiovascular disease. This review paper will describe molecularbased single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging techniques that are now available and in development to assess post-infarction cardiac remodeling. These methods could be used to evaluate important biological processes such as inflammation, angiogenesis, and scar formation.

Evaluation of the Effect of Chelating Arms and Carrier Agents on t he Radiotoxicity of TAT Agents.

Targeted Alpha Therapy (TAT) is considered an evolving therapeutic option for cancer cells, in which a carrier molecule labeling with an α-emitter radionuclide make the bond with a specific functional or molecular target. α-particles with high Linear Energy Transfer (LET) own an increased Relative Biological Effectiveness (RBE) over common ß-emitting radionuclides. Normal tissue toxicity due to non-specific uptake of mother and daughter α-emitter radionuclides seems to be the main conflict in clinical applications. The present survey reviews the available preclinical and clinical studies investigating healthy tissue toxicity of the applicable α -emitters and particular strategies proposed for optimizing targeted alpha therapy success in cancer patients.

Ferroptosis Inhibitors as New Therapeutic Insights into Radiation-Induced Heart Disease.

Radiation-induced heart disease (RIHD) is a significant cause of morbidity in breast and other mediastinal cancers. The many molecular and cellular patho-mechanisms that have a role in RIHD are not completely understood. Endothelial injury, oxidative stress, and inflammation, as well as endoplasmic reticulum and mitochondrial damage, are considered the primary causes of RIHD. Ferroptosis is a newly discovered type of cell death that results from irondependent lipid peroxide accumulation. As ferroptosis plays an important role in the pathogenesis of cardiovascular diseases, it seems that it has a significant effect on RIHD. It was recently shown that ionizing radiation (IR) generates severe ferroptosis, which is a critical component of Radiotherapy-mediated normal cell toxicity. These findings support the use of a ferroptosis inhibitor to reduce RIHD. In this perspective review, we summarize the role of ferroptosis in pathogens of cardiovascular disease and radiation toxicity, and we will introduce ferroptosis inhibitors as a new strategy to prevent or reduce RIHD.

A review of effects of atorvastatin in cancer therapy.

Cancer is one of the most challenging diseases to manage. A sizeable number of researches are done each year to find better diagnostic and therapeutic strategies. At the present time, a package of chemotherapy, targeted therapy, radiotherapy, and immunotherapy is available to cope with cancer cells. Regarding chemo-radiation therapy, low effectiveness and normal tissue toxicity are like barriers against optimal response. To remedy the situation, some agents have been proposed as adjuvants to improve tumor responses. Statins, the known substances for reducing lipid, have shown a considerable capability for cancer treatment. Among them, atorvastatin as a reductase (HMG-CoA) inhibitor might affect proliferation, migration, and survival of cancer cells. Since finding an appropriate adjutant is of great importance, numerous studies have been conducted to precisely unveil antitumor effects of atorvastatin and its associated pathways. In this review, we aim to comprehensively review the most highlighted studies which focus on the use of atorvastatin in cancer therapy.

Radioprotective effects of gliclazide against irradiation-induced cardiotoxicity and lung injury through inhibiting oxidative stress.

Radiotherapy is one of the main treatments for localized primary cancer in patients. Cardiotoxicity and lung injury are two of the main side effects of oxidative stress following radiotherapy in patients with thoracic region cancer. Gliclazide (GLZ) as an antihyperglycemic drug has antioxidant, anti-inflammatory, and anti-apoptotic activities. This study aimed to evaluate the effect of GLZ in cardiotoxicity and lung injury induced by irradiation (IR). In this experimental study, 64 mice were divided into eight groups: control, GLZ (5, 10, and 25 mg/kg), IR (6 Gy), and IR + GLZ (in three doses). GLZ was administrated for 8 consecutive successive days and mice were exposed with IR on the 9th day of study. On the 10th day of study, tissue biochemical assay and at 14th day of study, histopathological assay were performed to evaluate for cardiotoxicity and lung injury. The findings revealed that IR induces atypical features in heart and lung histostructure, and oxidative stress (an increase of MDA, PC levels, and decrease of GSH content) in these tissues. GLZ administration preserved heart and lung damages and improves oxidative stress markers in mice. Data have authenticated that GLZ could protect heart and lung histostructure against oxidative stress-induced injury through inhibiting oxidative stress.

Etodolac Enhances the Radiosensitivity of Irradiated HT-29 Human Colorectal Cancer Cells.

BACKGROUND: Radioresistance is found to be the main therapeutic restriction in colorectal radiation therapy. The aim of this study was to investigate the synergistic effect of Etodolac (ET) and ionizing radiation on human colorectal cancer cells. METHODS: Pretreated HT-29 cells with ET were exposed to ionizing radiation. The radiosensitizing effect of ET was evaluated using MTT, flow cytometry, and clonogenic assay. The amount of nitrite oxide (NO) in irradiated cells was also measured with the Griess reagent. RESULTS: The present study found that pretreatment of HT-29 cells with ET decreases their survival and colony formation. Higher concentrations of ET cause total apoptosis and an increase in NO levels in irradiated cells. CONCLUSION: Applying ET in a concentration-dependent manner had an incremental effect on the amount of apoptosis and cell death induced by radiation.

Ferroptosis Inhibitors as Potential New Therapeutic Targets for Cardiovascular Disease.

Ferroptosis is a novel form of programmed cell death that occurs due to an increase in iron levels. Ferroptosis is implicated in a number of cardiovascular diseases, including myocardial infarction (MI), reperfusion damage, and heart failure (HF). As cardiomyocyte depletion is the leading cause of patient morbidity and mortality, it is critical to thoroughly comprehend the regulatory mechanisms of ferroptosis activation. In fact, inhibiting cardiac ferroptosis can be a useful therapeutic method for cardiovascular disorders. The iron, lipid, amino acid, and glutathione metabolisms strictly govern the beginning and execution of ferroptosis. Therefore, ferroptosis can be inhibited by iron chelators, free radical-trapping antioxidants, GPX4 (Glutathione Peroxidase 4) activators, and lipid peroxidation (LPO) inhibitors. However, the search for new molecular targets for ferroptosis is becoming increasingly important in cardiovascular disease research. In this review, we address the importance of ferroptosis in various cardiovascular illnesses, provide an update on current information regarding the molecular mechanisms that drive ferroptosis, and discuss the role of ferroptosis inhibitors in cardiovascular disease.

Mefenamic acid as a promising therapeutic medicine against colon cancer in tumor-bearing mice.

Although radiotherapy is an effective strategy for cancer treatment, tumor resistance to ionizing radiation (IR) and its toxic effects on normal tissues are limiting its use. The aim of this study is to evaluate the anti-cancer effects of mefenamic acid (MEF), as an approved medicine, and its combination with IR against colon tumor cells in mice. Tumor-bearing mice were received MEF at a dose of 25 mg/kg for 6 successive days. The tumor size was measured. In the second experiment, after MEF treatment, tumor-bearing mice locally received an X-ray at dose 6 Gy. Tumor growth and biochemical, histological, and immunohistological assay (caspase-3) were performed. MEF significantly decreased tumor size in mice in comparison to the control group. IR and/or MEF treatment significantly reduced the tumor volume and inhibited tumor growth by 49%, 55%, and 67% by MEF, IR, and MEF + IR groups as compared with the control group. Administration of MEF in combination with radiation had a synergistic effect on enhanced histopathological changes in tumor tissues. MEF treatment in IR exposure mice showed a significant increase in the immunoreactivity of caspase-3 in the colon tumor tissue. MEF has an anti-tumor effect in colon tumor-bearing mice. MEF in combination with IR increased pathological changes and apoptosis in tumor tissues, suggesting that MEF might be clinically useful in the treatment of colon cancer.

The Radiosensitizing Effect of Olanzapine as an Antipsychotic Medication on Glioblastoma Cell.

BACKGROUND: Radiotherapy is used as one of the most effective regimens for cancer treatment, while radioresistance is a major drawback in cancer treatment. OBJECTIVES: This study aimed to evaluate the sensitizing effect of olanzapine (OLA) with X-ray on glioblastoma (U-87 MG) cells death. METHODS: The synergistic killing effect of OLA with ionizing radiation (IR) on glioma was evaluated by colony formation assay. The generations of reactive oxygen species (ROS) and protein carbonyl (PC) as oxidized proteins were determined in OLA-treated and irradiated cells. RESULTS: Results of this study showed that OLA reduced the number of colonies in irradiated glioma cells.OLA elevated ROS and PC levels in irradiated cells. The synergistic killing effect of OLA with IR in U-87 MG cells was observed at concentrations of 1 µM and 20 µM of OLA. The maximum radiosensitizing effect of OLA was observed at a concentration of 20 µM. CONCLUSION: The present study demonstrates that OLA has a radiosensitizing effect on cell death induced by IR in glioma cells.

Radioprotective Effect of Febuxostat Against Testicular Damage Induced by Ionizing Radiation in Mice.

BACKGROUND: The testis is one of the most radiosensitive tissues in pelvic radiotherapy, especially in prostate cancer. Febuxostat (FBX), as an inhibitor of xanthine oxidase, has anti-inflammatory, antioxidant, and anti-apoptosis properties. OBJECTIVES: The aim of this research was to survey the protective effect of FBX against irradiation (IR)-induced testis damage via the attenuation of oxidative stress. METHODS: Male adult mice were randomly assigned into eight groups: control, FBX with three doses of 5, 10, and 15 mg/kg, IR with 6 Gy, IR + FBX (IR + FBX in three doses), respectively. In the IR + FBX groups, FBX was administrated for 8 consecutive days, and then mice were exposed to IR at a dose of 6 Gy on the 9th day. One day after irradiation, biochemical parameters were evaluated in the testis of animals, while histopathological assessment had been performed on 14th day. RESULTS: Irradiation led to the induction of testicular toxicity. FBX significantly protected histopathological alterations and decreased oxidative stress parameters in irradiated testis. Besides, FBX increased the diameter and germinal epithelial thickness of seminiferous tubules and Johnson's score in irradiated mice. CONCLUSION: Data showed that FBX markedly protected testicular injury induced by IR by inhibiting oxidative stress and may be considered as an infertility inhibitor in cancer patients, especially prostate cancer.

Recent Achievements about Targeted Alpha Therapy-Based Targeting Vectors and Chelating Agents.

One of the most rapidly growing options in the management of cancer therapy is Targeted Alpha Therapy (TAT) through which lethal α-emitting radionuclides conjugated to tumor-targeting vectors selectively deliver high amount of radiation to cancer cells.225Ac, 212Bi, 211At, 213Bi, and 223Ra have been investigated by plenty of clinical trials and preclinical researches for the treatment of smaller tumor burdens, micro-metastatic disease, and post-surgery residual disease. In order to send maximum radiation to tumor cells while minimizing toxicity in normal cells, a high affinity of targeting vectors to cancer tissue is essential. Besides that, the stable and specific complex between chelating agent and α-emitters was found as a crucial parameter. The present review was planned to highlight recent achievements about TAT-based targeting vectors and chelating agents and provide further insight for future researches.

Febuxostat, an inhibitor of xanthine oxidase, ameliorates ionizing radiation-induced lung injury by suppressing caspase-3, oxidative stress and NF-κB.

Febuxostat (FBX), a selective inhibitor of xanthine oxidase, has several biological properties such as antioxidant, anti-inflammatory and anti-apoptosis activities. The purpose of this study was to evaluate the protective effect of FBX against ionizing radiation (IR)-induced lung injury through mitigation of oxidative stress, inflammation and apoptosis. Sixty-four mice were randomized into eight groups as control, FBX (5, 10, and 15 mg/kg), IR (6 Gy), and IR + FBX (IR + FBX in three doses). Mice were received FBX for 8 consecutive days and then were exposed to IR at a single dose (6 Gy) of X-ray. At 1 and 7 days after irradiation, the biochemical parameters were analyzed in lung tissue, while histological and immunohistochemical examinations were evaluated 1 week after irradiation. Irradiation led to elevate of oxidative stress parameters (an increase of MDA, PC, NO, and decrease of GSH), inflammation and apoptosis in lung of mice. Furthermore, IR resulted in histopathological changes in the lung tissues. These changes were significantly mitigated by FBX treatment. FBX also inhibited immunoreactivity of caspase-3, NF-κB, and reduced oxidative stress. This study showed that FBX is able to protect lung injury induced by IR through inhibiting apoptosis (caspase-3), oxidative stress and inflammation (NF-κB).

Current development of sigma-2 receptor radioligands as potential tumor imaging agents.

Sigma receptors are transmembrane proteins with two different subtypes: σ1 and σ2. Because of its overexpression in tumors, the σ2 receptor (σ2R) is a well-known biomarker for cancer cells. A large number of small-molecule ligands for the σ2Rs have been identified and tested for imaging the proliferative status of tumors using single photon emission computed tomography (SPECT) and positron emission tomography (PET). These small molecules include derivatives of bicyclic amines, indoles, cyclohexylpiperazines and tetrahydroisoquinolines. This review discusses various aspects of small molecule ligands, such as chemical composition, labeling strategy, affinity for σ2Rs, and in vitro/in vivo investigations. The recent studies described here could be useful for the development of σ2R radioligands as potential tumor imaging agents.