Exploring the impact of recent COVID-19 infection on perfusion and functional parameters derived from gated myocardial perfusion imaging in patients undergoing evaluation for coronary artery disease.

OBJECTIVE: This study seeks to evaluate how recent COVID-19 infection affects myocardial perfusion and functional parameters derived from gated myocardial perfusion imaging in patients undergoing evaluation for coronary artery disease. The goal is to enhance our understanding of COVID-19's influence on the cardiovascular system. METHOD: Conducted at Farshchian Heart Hospital from 2022 to 2023, this case-control study enrolled patients suspected of coronary artery disease, stratified into two groups: those with confirmed COVID-19 infection within the past 6 months (study group) and those without prior COVID-19 infection (control group). Employing a 2-day protocol, stress testing and gated SPECT MPI were performed. Statistical analysis included descriptive statistics, Chi-square test, Student's t test, and Mann-Whitney U test. RESULT: Among the 86 patients included, 43 were in each group. Significantly higher summed stress core and summed difference score values were observed in the study group compared to the control group (p < 0.05). In addition, the study group exhibited significantly altered global left ventricular ejection fraction, end-diastolic volume, and end-systolic volume (p < 0.05). Non-perfusion findings, including transient ischemic dilation and transient right ventricular visualization, were more prevalent in the study group. CONCLUSION: Recent COVID-19 infection is associated with impaired myocardial perfusion and altered functional parameters as detected by MPI. These findings underscore the intricate interplay between COVID-19 and cardiovascular health, emphasizing the importance of comprehensive evaluation and management strategies to address cardiac complications in affected individuals. Further research is warranted to elucidate the underlying mechanisms and optimize patient care in the context of COVID-19-associated cardiovascular manifestations.

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.

Investigating the Influence of Gut Microbiota-related Metabolites in Gastrointestinal Cancer.

Gastrointestinal (GI) cancer is a major health concern due to its prevalence, impact on well-being, high mortality rate, economic burden, and potential for prevention and early detection. GI cancer research has made remarkable strides in understanding biology, risk factors, and treatment options. An emerging area of research is the gut microbiome's role in GI cancer development and treatment response. The gut microbiome, vital for digestion, metabolism, and immune function, is increasingly linked to GI cancers. Dysbiosis and alterations in gut microbe composition may contribute to cancer development. Scientists study how specific bacteria or microbial metabolites influence cancer progression and treatment response. Modulating the gut microbiota shows promise in enhancing treatment efficacy and preventing GI cancers. Gut microbiota dysbiosis can impact GI cancer through inflammation, metabolite production, genotoxicity, and immune modulation. Microbes produce metabolites like short-chain fatty acids, bile acids, and secondary metabolites. These affect host cells, influencing processes like cell proliferation, apoptosis, DNA damage, and immune regulation, all implicated in cancer development. This review explores the latest research on gut microbiota metabolites and their molecular mechanisms in GI cancers. The hope is that this attempt will help in conducting other relevant research to unravel the precise mechanism involved, identify microbial signatures associated with GI cancer, and develop targets.

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.

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.

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.

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.

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.

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.

Transient ischemic dilation or transient RV visualization in patients with normal SPECT stress myocardial perfusion imaging: Correlation with CT coronary artery calcium scoring and coronary angiography.

BACKGROUND: Ancillary findings on MPI, such as transient ischemic dilation (TID) and transient right ventricular visualization (TRV), are recognized as markers of extensive CAD and predictive of adverse outcomes. They usually occur in association with stress-induced regional MPI abnormalities. However, the clinical significance of these ancillary markers in the presence of normal stress MPI is incompletely understood. METHODS: From a cohort of 564 consecutive patients referred for clinical SPECT stress MPI, 44 patients had normal stress SPECT MPI and either TID (n = 28) or TRV (n = 16). These imaging findings were correlated with CT coronary calcium (CAC), CT coronary angiography (CTA), and invasive coronary angiography (ICA) in patients with severe CAC ≥ 1000 HU. TID and TRV were quantified as stress/rest ratios. Severe CAD was defined as > 70% luminal stenosis on CTA or ICA. RESULTS: The median TID ratio was 1.23, with a range of 1.13-1.48; the median TRV ratio was 1.30, with a range of 1.20-1.48. Of 44 patients with TID or TRV, only 9 patients (20.5%) had severe obstructive > 70% CAD by angiography (6 of 28 patients (21.5%) with TID and 3 of 16 patients (19%) with TRV). Severe multi-vessel CAD occurred in only 2 of 44 patients (4.5%). In contrast, of 9 patients with CAC > 1000 HU, 6 (67%) had severe obstructive CAD. CONCLUSION: In patients with normal stress SPECT MPI and TID or TRV, the incidence of severe obstructive CAD was relatively low and predominantly single-vessel CAD. These findings do not support the concept that TID or TRV with normal stress MPI is predictive of high-risk CAD.

Human exposure to low dose ionizing radiation affects miR-21 and miR-625 expression levels.

BACKGROUND: Recently exposure to ionizing radiation driven by artificial radiation sources such as Medical X-rays and Nuclear medicine has increased hastily. Ionizing radiation-induced the DNA damage and activate the DNA damage response signaling pathways. The aim of this study was to evaluate the role of miR-21 and miR-625 in response to low-dose ionizing radiation. MATERIALS AND METHODS: In this study, the blood sample of 38 volunteer patients who underwent Cardiac scans before and after 99mTc-MIBI injection were used. The WBC of patients was used for RNA extraction and after cDNA synthesis by the poly-A method the expression level of miR-21 and miR-625 was evaluated by real-time PCR method. RESULTS: The results of this study indicated that miR-21 and miR- 625 were significantly upregulated under exposure to low-dose ionizing radiation. The expression level of these miRNAs was not significantly correlated with the age and BMI of patients. More ever the bioinformatics analysis indicated that SP1 was a common target of both miRNAs and had the highest degree between hub genes. CONCLUSION: In summary miR-21 and miR-625 can contribute to the response to acute low dose ionizing radiation by targeting the SP1. However further studies should be carried out on the molecular mechanism of effects of miR-21 and miR-625 in response to low dose ionizing radiation by targeting the SP1.

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.

Potential utility of peptides against damage induced by ionizing radiation.

Radioprotection is the process whereby biological systems are aided against undesirable radiation hazards. Primitive radioprotectors suffered from either having crucial side effects or low efficacy in clinical applications. Therefore, the search for less toxic but more capable radioprotectants has continued for decades. Peptides have been investigated as radioprotectants in a variety of preclinical models both in vitro and in vivo. Peptides exert their influence through scavenging free radicals, modifying cell signaling and inhibiting cell apoptosis. Demonstrating potential in vivo properties, peptide radiation countermeasures might find enough credit for use in humans in the future. This article reviews the potential therapeutic value of currently known radioprotective peptides and attempts to provide a comprehensive source for further scientific research in this area.

Effect of using different co-ligands during 99mTc-labeling of J18 peptide on SK-MES-1 cell binding and tumor targeting.

OBJECTIVES: Lung cancer is the main cause of cancer death, and its incidence is increasing worldwide. The goal of this study is to evaluate in vitro and in vivo tumor targeting behavior of [99mTc]Tc -HYNIC-(Ser)3-J18 in lung carcinoma (SK-MES-1)-bearing mice. MATERIALS AND METHODS: The J18 (RSLWSDFYASASRGP) peptide was conjugated with hydrazinonicotinamide (HYNIC) via three serine amino acids as a linker at the peptide's N-terminal and then labeled with technetium-99m using tricine and tricine/EDDA as the co-ligands. The radiolabeled peptides were assessed for in vitro receptor binding, specific binding, and saturation affinity. In vivo biodistribution studies were also performed for 99mTc-peptide 1 (tricine co-ligand) and 99mTc-peptide 2 (tricine/EDDA coligands) in nude mice bearing SK-MES-1 xenograft tumors. RESULTS: In vitro studies showed high specific binding for 99mTc-peptide 1 in SKMES-1 cells compared with 99mTc-peptide 2 (11.5 vs. 4.5). The KD values for 99mTc-peptide 1 and 99mTc-peptide 2 were reported to be 3.1±0.3 nM and 3.46 ± 0.8 nM, respectively. The biodistribution study also showed high significant tumor to muscle ratios of 5.1 and 6.18 for 99mTc-peptide 1 at 1 and 2 hr after injection, respectively, while these ratios were 3.81 and 5.18 for peptide 2, respectively. CONCLUSION: Overall, 99mTc-labeled J18 peptide in the presence of tricine as co-ligand has better in vitro and in vivo tumor targeting properties in SK-MES-1 cells than tricine/EDDA co-ligands. These findings show that the 99mTc-labeled J18 peptide is a good candidate for lung carcinoma targeting.

Applying Wells score to inconclusive perfusion only modified PIOPED II (Prospective Investigation of Pulmonary Embolism Diagnosis II) readings in order to optimize the lung scintigraphy diagnostic yield in acute pulmonary embolism detection.

OBJECTIVE: When using perfusion only modified PIOPED II criteria for PE detection, generated non-diagnostic scans are found to be the main diagnostic restriction. The objective of current study is to identify the role of Wells criteria added to inconclusive readings with the intent of enhancing the lung scintigraphy diagnostic yield. METHODS: CTPA was performed in 34 suspected PE patients with inconclusive lung scintigraphy. They also were evaluated by Wells score and classified as low, intermediate and high probability. Overall prevalence and the rate of PE for each probability were calculated. Furthermore, NPV for scores < 2 and PPV for scores > 6 were computed. RESULTS: Having a mean age of 59.75 ± 17.38 years, 7 (20.6%), 23 (67.6%) and 4 (11.8%) of cases had total criteria point count < 2, 2-6 and > 6, respectively. Using CTPA, 5 patients (14.7%) were diagnosed with PE. None of the patients with scores < 2 had PE with an associated NVP of 100%. Patients with scores 2-6 had a PE rate of 4.3% and 100% of patients with scores > 6 were diagnosed with PE, implying that the PPV of scores > 6 was 100%. CONCLUSION: Adding Wells score to non-diagnostic scans allowed identification of PE to be done reliably, and provided further insight into how lung scintigraphy in conjunction with clinical assessment is a practical strategy not only for the patients unfit for performing CTPA but also in all the patients referred for PE evaluation.

The evaluation of left ventricular dyssynchrony in hypertensive patients with a preserved systolic function undergoing gated SPECT myocardial perfusion imaging.

BACKGROUND: Hypertension as a known risk factor for cardiovascular diseases can result in left ventricular dyssynchrony (LVD) leading to uncoordinated contraction. The aim of our study was to evaluate whether systolic mechanical dyssynchrony measured by phase analysis of gated single-photon emission computed tomography (SPECT) imaging occurs in hypertensive patients with a low risk for coronary artery disease and a normal ejection fraction and its possible relationships with severity of hypertension and the influence of antihypertensive treatments. METHODS: A total of 466 patients (328 females and 138 males, with a mean age of 59.62 ± 10.27 years) who had a low risk factor for coronary artery disease, a normal perfusion study and, a normal ejection fraction were included of which 408 was hypertensive and 58 normotensive. Phase analysis parameters (derived using QGS software) were compared in patients with and without hypertension. Using different statistical methods, relationship between derived phase analysis indices (PSD, PHB) for LVD and amount of blood pressure and antihypertensive drugs consumption were evaluated. RESULTS: The prevalence of LVD in patients with hypertension was 63.2% (n = 258), while it was 6.9% in the normotensive group. The mean values of PSD and PHB were higher in hypertensive patients than normotensive ones (12.55 vs. 5.8 and 39.24 vs. 21.12), respectively, so that, statistically significant differences were found between the patients with and without hypertension (p < 0.001). Furthermore, there was a clear relationship between the severity of hypertension and the degree of LVD: by increasing 1 mmHg in systolic and diastolic blood pressure, PSD and PHB increase by (0.034, 0.108 and 0.035, 0.0311), respectively. The statistical results showed that the frequency of LVD in controlled hypertensive patients taking antihypertensive drugs was 55.2%, which significantly lower compared to the patient suffering from hypertension without taking any hypertensive drug (81.35%, p < 0.001). CONCLUSION: Our study findings are in favor of using phase analysis-gated SPECT imaging as a routine way for detection of LVD-known indicator of progression toward systolic dysfunction in the future-in hypertensive patients with a low risk for coronary artery diseases and a normal cardiac systolic function.