Exploring the latest advances in 18F-FDG PET/CT and cardiac magnetic resonance for imaging for cardiac sarcoidosis diagnosis.

Sarcoidosis is a systemic inflammatory disease that affects multiple organs. Various clinical signs are associated with cardiac sarcoidosis (CS), and the diagnosis process is complicated because any organ could be involved. Despite the critical clinical importance of early and precise diagnosis of CS, there is currently no gold-standard method for CS evaluation. The non-invasive imaging modalities of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and cardiac magnetic resonance (CMR) imaging have demonstrated the potential for identifying various histological characteristics of CS. Recently, the development of hybrid FDG-PET/CMR scanners has enabled the simultaneous acquisition of these attributes. Compared to just one imaging modality, these scanners detect CS and stratify risk more accurately and with higher sensitivity. Analyzing the potential role of concurrent FDG-PET/CMR in enhancing the diagnosis of CS, the present review concentrates on the advantages of this technique in light of recent technological developments.

Advancing Novel Strategies against Post-surgical Tendon Adhesion Bands, Exploring New Frontiers.

Current interest in adhesion formation stems from its global impact on the function and quality of life, spanning a spectrum of subtle impairments to significant disabilities, based on the affected area and the extent of adhesion. Yet therapeutic agents are restricted to prophylactic anti-inflammatories, revision surgeries, and biological and physical techniques, none of which grant a decent outcome. Recent advancements in tissue- engineered biomaterials, drug delivery systems, and fabricating technologies such as nanoparticles, hydrogels, and weaving or braiding demonstrate potential for improved outcomes. However, none of the mentioned methods have reliable outcomes, thus this study aims to elucidate the mechanisms involved in the pathophysiology of tendon adhesion and post-surgical adhesion band formation (PSAB), with a closer look at inflammatory pathways stimulating the process. This article consolidates information on diverse therapeutic and prophylactic methods and cutting-edge technologies, aiming to provide a comprehensive update on this topic, and providing researchers an avenue for new and innovative ideas for further investigations.

cGAS-STING and PD1/PDL-1 pathway in breast cancer: a window to new therapies.

Breast cancer is a complex malignancy with diverse molecular and cellular subtypes and clinical outcomes. Despite advances in treatment, breast cancer remains a significant health challenge. However, recent advances in cancer immunotherapy have shown promising results in the treatment of breast cancer, particularly the use of inhibitors that target the immune checkpoint PD1/PDL1. Also, the cGAS-STING pathway, an important part of the innate immune response, has been considered as a major potential therapeutic target for breast cancer. In this narrative review, we provide an overview of the cGAS-STING and PD1/PDL-1 pathway in breast cancer, including their role in tumor development, progression, and response to treatment. We also discuss potential future directions for research.

Therapeutic potency of A1 adenosine receptor antagonists in the treatment of cardiovascular diseases, current status and perspectives.

BACKGROUND: Cardiomyocytes form, transport, and metabolize the omnipresent metabolite adenosine. Depending upon the adenosine concentrations and the pharmacological properties of receptor subtypes, adenosine exerts (patho)physiological responses in the cardiovascular system. The objective of this review is to present different protective mechanisms of A1-adenosine receptor inhibitors in cardiovascular diseases. METHODS AND RESULTS: Literature references were collected and sorted using relevant keywords and key phrases as search terms in scientific databases such as Web of Science, PubMed and Google Scholar. A1 adenosine receptor regulates free fatty acid metabolism, lipolysis, heart rate, blood pressure, and cardiovascular toxicity. The evidence clearly supporting the therapeutic potency of pharmacological A1 adenosine receptors agonists and antagonists in modulating cardiovascular risk factor parameters and treatment of cardiovascular diseases. CONCLUSION: This review summarizes the protective role of pharmacological A1-adenosine receptor regulators in the pathogenesis of cardiovascular diseases for a better management of cardiovascular diseases.

Pegylated nanoliposomal cisplatin ameliorates chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse effect of cisplatin. The current study aimed to determine whether PEGylated nanoliposomal cisplatin can limit CIPN in an animal model. METHODS: Cisplatin-loaded PEGylated liposome nanoparticles (Cis-PL) were produced as a combination of lecithin, cholesterol, and DSPE-mPEG2000 in a molar ratio of 50:45:5 and were characterized by polydispersity index (PDI), zeta potential, Field emission scanning electron microscopy (FESEM) analysis, as well as encapsulation efficiency (EE). Fifteen male rats were provided and randomly divided into 3 groups including Cis-PL group, cisplatin group, and control group. Behavioural tests (hot-plate test and acetone drop test) were used for evaluating CIPN. Moreover, oxidative stress markers and histopathological analysis were applied. Treatment-related toxicity was assessed by haematological analysis as well as liver and renal function tests. RESULTS: Cis-PL had an average particle size of 125.4, PDI of 0.127, and zeta potential of -40.9 mV. Moreover, the Cis-PL exhibited a high EE as well as low levels of leakage rate at 25 °C. In a hot-plate test, paw withdrawal latency was longer in Cis-PL group in comparison to rats treated with cisplatin. A lower number of withdrawal responses was detected during acetone drop test in Cis-PL group than in cisplatin-treated rats. Assessment of oxidative stress markers showed that Cis-PL could improve oxidative stress. Additionally, histopathological assessment demonstrated that the number of satellite cells was significantly reduced in the dorsal root ganglion (DRG) of Cis-PL-treated rats compared with those treated with cisplatin. The cisplatin group had elevated white blood cells counts, reduced platelet counts, and higher levels of bilirubin, ALT (alanine aminotransferase, and AST (aspartate aminotransferase), and creatinine compared with the control group, which was ameliorated in Cis-PL group. CONCLUSIONS: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice.

Classification and Diagnostic Prediction of Colorectal Cancer Mortality Based on Machine Learning Algorithms: A Multicenter National Study.

INTRODUCTION: Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths. This study aimed to predict survival outcomes of CRC patients using machine learning (ML) methods. MATERIAL AND METHODS: A retrospective analysis included 1853 CRC patients admitted to three prominent tertiary hospitals in Iran from October 2006 to July 2019. Six ML methods, namely logistic regression (LR), Naïve Bayes (NB), Support Vector Machine (SVM), Neural Network (NN), Decision Tree (DT), and Light Gradient Boosting Machine (LGBM), were developed with 10-fold cross-validation. Feature selection employed the Random Forest method based on mean decrease GINI criteria. Model performance was assessed using Area Under the Curve (AUC). RESULTS: Time from diagnosis, age, tumor size, metastatic status, lymph node involvement, and treatment type emerged as crucial predictors of survival based on mean decrease GINI. The NB (AUC = 0.70, 95% Confidence Interval [CI] 0.65-0.75) and LGBM (AUC = 0.70, 95% CI 0.65-0.75) models achieved the highest predictive AUC values for CRC patient survival. CONCLUSIONS: This study highlights the significance of variables including time from diagnosis, age, tumor size, metastatic status, lymph node involvement, and treatment type in predicting CRC survival. The NB model exhibited optimal efficacy in mortality prediction, maintaining a balanced sensitivity and specificity. Policy recommendations encompass early diagnosis and treatment initiation for CRC patients, improved data collection through digital health records and standardized protocols, support for predictive analytics integration in clinical decisions, and the inclusion of identified prognostic variables in treatment guidelines to enhance patient outcomes.

Targeting transforming growth factor beta (TGF-ß) using Pirfenidone, a potential repurposing therapeutic strategy in colorectal cancer.

The modulating factors within the tumor microenvironment, for example, transforming growth factor beta (TGF-ß), may limit the response to chemo and immunotherapy protocols in colorectal cancer (CRC). In the current study, the therapeutic potential of targeting the TGF-ß pathway using Pirfenidone (PFD), a TGF-ß inhibitor, either alone or in combination with five fluorouracil (5-FU) has been explored in preclinical models of CRC. The anti-proliferative and migratory effects of PFD were assessed by MTT and wound-healing assays respectively. Xenograft models were used to study the anti-tumor activity, histopathological, and side effects analysis. Targeting of TGF-ß resulted in suppression of cell proliferation and migration, associated with modulation of survivin and MMP9/E-cadherin. Moreover, the PFD inhibited TGF-ß induced tumor progression, fibrosis, and inflammatory response through perturbation of collagen and E-cadherin. Targeting the TGF-ß pathway using PFD may increase the anti-tumor effects of 5-FU and reduce tumor development, providing a new therapeutic approach to CRC treatment.

Introduce a novel post-biotic against Pseudomonas aeruginosa biofilm formation using Escherchia coli Nissle1917 outer membrane vesicles.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that can cause acute infections as well as chronic ones in humans. The expression of algD and PpyR genes involved in biofilm formation in clinical isolates of P. aeruginosa in the presence of Escherichia coli Nissle1917 outer membranes vesicles (EcN OMVs) was evaluated. All isolates were tested for biofilm formation. qPCR and disk diffusion were used to identify the expression of algD and PpyR genes, and antimicrobial resistance, respectively. EcN OMVs caused a more significant loss of algD and PpyR expression, compared with the control group. EcN OMVs contain a variety of biomolecules that are capable of influencing the biofilm formation genes. EcN OMVs treatment reduced P. aeruginosa biofilm formation significantly, which emphasizes their positive role in inhibiting biofilm formation. As a result, EcN OMVs can be used as new therapeutic strategies for inhibiting P. aeruginosa biofilm formation.

Therapeutic Potential of Targeting the Cytochrome P450 Enzymes Using Lopinavir/Ritonavir in Colorectal Cancer: A Study in Monolayers, Spheroids and In Vivo Models.

Cytochrome P450 (CYP450) enzyme has been shown to be expressed in colorectal cancer (CRC) and its dysregulation is linked to tumor progression and a poor prognosis. Here we investigated the therapeutic potential of targeting CYP450 using lopinavir/ritonavir in CRC. The integrative systems biology method and RNAseq were utilized to investigate the differential levels of genes associated with patients with colorectal cancer. The antiproliferative activity of lopinavir/ritonavir was evaluated in both monolayer and 3-dimensional (3D) models, followed by wound-healing assays. The effectiveness of targeting CYP450 was examined in a mouse model, followed by histopathological analysis, biochemical tests (MDA, SOD, thiol, and CAT), and RT-PCR. The data of dysregulation expressed genes (DEG) revealed 1268 upregulated and 1074 down-regulated genes in CRC. Among the top-score genes and dysregulated pathways, CYPs were detected and associated with poor prognosis of patients with CRC. Inhibition of CYP450 reduced cell proliferation via modulating survivin, Chop, CYP13a, and induction of cell death, as detected by AnnexinV/PI staining. This agent suppressed the migratory behaviors of cells by induction of E-cadherin. Moreover, lopinavir/ritonavir suppressed tumor growth and fibrosis, which correlated with a reduction in SOD/thiol levels and increased MDA levels. Our findings illustrated the therapeutic potential of targeting the CYP450 using lopinavir/ritonavir in colorectal cancer, supporting future investigations on this novel therapeutic approach for the treatment of CRC.

Nanoliposomal oxaliplatin ameliorates chemotherapy-induced neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is an important adverse effect of treatment with oxaliplatin (OXA). We have developed PEGylated nanoliposomal oxaliplatin (OXA-LIP) and tested its activity in an animal model of CIPN. OXA-LIPs were prepared using a combination of egg yolk lecithin, cholesterol, and DSPE-mPEG2000 (at ratios 400, 80, and 27 mg). These liposomes were characterized using several different methods (e.g., polydispersity index (PDI), and zeta potential, FESEM). The in vivo study was performed in 15 male rats comprising three groups: a negative control (normal saline) OXA, and OXA-LIP. These were injected intraperitoneally at a concentration of 4 mg/kg on two consecutive days every week, for 4 weeks. After that, CIPN was assessed using the hotplate and acetonedropmethods. Oxidative stress biomarkers such as SOD, catalase, MDA, and TTG were measured in the serum samples. The functional disturbances of the liver and kidney were assessed by measuring the serum levels of ALT, AST, creatinine, urea, and bilirubin. Furthermore, hematological parameters were determined in the three groups. The OXA-LIP had an average particle size, PDI, and zeta potential of 111.2 ± 1.35 nm, 0.15 ± 0.045, and -52.4 ± 17 mV, respectively. The encapsulation efficiency of OXA-LIP was 52% with low leakage rates at 25 °C.Thermal hyperalgesia changes showed OXA has significant effects in the induction of neuropathy on days 7, 14, and 21 compared to the control group. OXA had a significantly greater sensitivity than the OXA-LIP and control groups in the thermal allodynia test (P < 0.001). OXA-LIP administration did not show significant effects on the changes of oxidative stress, biochemical factors, and cell count. Our findings provide a proof of concept on the potential application of oxaliplatin encapsulated with PEGylated nanoliposome to ameliorate the severity of neuropathy, supporting further studies in clinical phases to explore the value of this agent for Chemotherapy-induced peripheral neuropathy.

Treatment options for infections caused by multidrug-resistant Gram-negative bacteria: a guide to good clinical practice.

The rapid emergence of multidrug-resistant Gram-negative bacterial infections necessitates the development of new treatments or the repurposing of available antibiotics. Here, treatment options for treatment of these infections, recent guidelines and evidence are reviewed. Studies that included treatment options for infections caused by multidrug-resistant Gram-negative bacteria (Enterobacterales and nonfermenters), as well as extended-spectrum ß-lactamase-producing and carbapenem-resistant bacteria, were considered. Potential agents for the treatment of these infections, considering type of microorganism, mechanism of resistant, source and severity of infection as well as pharmacotherapy considerations, are summarized.

Gram-negative bacteria (GNB) are one of the most important causes of infection in humans. GNB can evolve to neutralize the effects of antibiotics by producing proteins called enzymes that break down the antibiotics or through mechanisms that discharge antibiotics from bacteria. The antibiotic can therefore no longer kill the bacteria, so they are considered antibiotic-resistant. For the treatment of resistant GNB infections, smart consideration and selection of potential combinations of available antibiotics or the development of new drugs are needed. In this review, we summarized and collected the recent guidelines and literature reports and present the pharmacological considerations for treatment of resistant GNB infections.

Exploring new therapeutic potentials of curcumin against post-surgical adhesion bands.

BACKGROUND: Adhesion band formation is a common cause of morbidity for patients undergoing surgeries. Anti-inflammatory and anti-fibrotic properties of curcumin, a pharmacologically active component of Curcuma longa, have been investigated in several studies. The aim of this study is to explore the therapeutic potential of curcumin in attenuating post-operative adhesion band (PSAB) formation in both peritoneal and peritendinous surgeries in animal models. METHODS: Bio-mechanical, histological and quantitative evaluation of inflammation, and total fibrosis scores were graded and measured in the presence and absence of phytosomal curcumin. RESULTS: Results showed that phytosomal curcumin significantly decreased severity, length, density and tolerance of mobility of peritendinous adhesions as well as incidence and severity of abdominal fibrotic bands post-surgery. Curcumin may decrease inflammation by attenuating recruitment of inflammatory cells and regulating oxidant/anti-oxidant balance in post-operative tissue samples. Moreover, markedly lower fibrosis scores were obtained in the adhesive tissues of phytosomal curcumin-treated groups which correlated with a significant decrease in quantity, quality and grading of fibers, and collagen deposition in animal models. CONCLUSION: These results suggest that protective effects of phytosomal curcumin against PSAB formation is partially mediated by decreasing inflammation and fibrosis at site of surgery. Further studies are needed to investigate the therapeutic potential of this molecule in preventing PSAB.

Evaluating the HLA-G (rs1063320) genetic variant and risk of human papillomavirus infection: a meta-analysis of 953 cases and 877 controls.

Human leukocyte antigen-G (HLA-G) has immune-modulatory functions. Although the role of genetic variant HLA-G (rs1063320) in susceptibility to human papillomavirus (HPV) infection has been widely considered, it is still a matter of discussion. In order to shed light on the issue, we, therefore, conducted a meta-analysis to evaluate the common impact of the HLA-G (rs1063320) variant on susceptibility to HPV infection. Subsequently, the distribution of genotypes, genotyping techniques and ethnicity groups was collected, and general analyses were performed. A total number of five studies with 953 cases and 877 controls were found to meet our criteria. The polymorphism of HLA-G (rs1063320) was evaluated. This is the first meta-analysis to explore the connection between the HLA-G 3' UTR + 3142C/G (rs1063320) genetic variant and the risk of HPV infection. Our results showed no association between the variant of HLA-G 3' UTR + 3142C/G (rs1063320) and susceptibility to HPV infection in studied target populations.Impact StatementWhat is already known on this subject? Human papillomavirus (HPV) is the most widespread sexually transmitted infection in both men and women all over the world. It is correlated with prominent load of diseases and malignancies, including anogenital warts and anogenital and oropharyngeal cancers. In recent years, several studies manifested that different SNPs located on special genes seems to influence HPV infection risk.What the results of this study add? Our findings disclosed no relation between the variant of HLA-G 3' UTR + 3142C/G (rs1063320) and vulnerability to HPV infection in the target individuals.What are the implications of these findings for clinical practice and/or further research? The findings in current survey may offer a basis for further study on HLA-G variant in future investigation.

Preparation of PLA/chitosan nanoscaffolds containing cod liver oil and experimental diabetic wound healing in male rats study.

Diabetes mellitus is one of the most common metabolic disorders. One of the important metabolic complications in diabetes is diabetic foot ulcer syndrome, which causes delayed and abnormal healing of the wound. The formulation of nanoscaffolds containing cod liver oil by altering the hemodynamic balance toward the vasodilators state, increasing wound blood supply, and altering plasma membrane properties, namely altering the membrane phospholipids composition, can be effective in wound healing. In this study, electrospinning method was used to produce poly lactic acid/chitosan nanoscaffolds as a suitable bio-substitute. After preparing the nanoscaffolds, the products were characterized with dynamic light scattering (DLS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Also optical properties of polymer and comparison between adsorption between single polymer and polymer-drug calculated with UV-Vis spectra. The structure and functional groups of the final products were characterized by Fourier-transform infrared spectroscopy (FT-IR) and energy dispersive spectroscopy (EDAX) as elemental analysis. The results showed that the optimum formulation of cod liver oil was 30%, which formed a very thin fiber that rapidly absorbed to the wound and produced significant healing effects. According to the results, poly lactic acid/chitosan nanoscaffolds containing cod liver oil can be a suitable bio-product to be used in treating the diabetic foot ulcer syndrome.