Exosomes in Colorectal Cancer: From Physiology to Clinical Applications.

Exosomes are nanosized vesicles that have been found to be involved in many diseases. Exosomes can mediate communication between cells in a variety of ways. Certain types of mediators derived from cancer cells can play a crucial role in the development of this pathology, promoting tumor growth, invasion, metastasis, angiogenesis, and immunomodulation. Exosomes in the bloodstream show promise as a future tool for detecting cancer at an early stage. The sensitivity and specificity of clinical exosome biomarkers need to be enhanced. Knowledge of exosomes is not only important for understanding the significance of cancer progression but also for providing clinicians with useful information for the diagnosis, treatment, and discovery of methods to prevent cancer from recurring. The widespread adoption of diagnostic tools based on exosomes may revolutionize cancer diagnosis and treatment. Tumor metastasis, chemoresistance, and immunity are all aided by exosomes. A potential new approach to cancer therapy involves preventing metastasis by inhibiting miRNA intracellular signaling and blocking the formation of pre-metastatic niches. For colorectal patients, exosomes represent a promising area of investigation for improving the diagnosis, treatment, and management. Reported data demonstrate that the serum expression level of certain exosomal miRNA is significantly higher in primary colorectal cancer patients. The present review discusses mechanisms and clinical implications of exosomes in colorectal cancer.

Inflammation and Psoriasis: A Comprehensive Review.

Psoriasis is an immune-mediated disease with a strong genetic component that brings many challenges to sick individuals, such as chronic illness, and which has multiple associated comorbidities like cardiovascular disease, metabolic syndrome, inflammatory bowel disease, and psychological disorders. Understanding the interplay between the innate and adaptative immune system has led to the discovery of specific cytokine circuits (Tumor Necrosis Factor-alpha (TNF-α), IL-23, IL-17), which has allowed scientists to discover new biomarkers that can be used as predictors of treatment response and pave the way for personalized treatments. In this review, we describe the footprint psoriasis leaves on the skin and beyond, key pathophysiological mechanisms, current available therapeutic options, and drawbacks faced by existing therapies, and we anticipate potential future perspectives that may improve the quality of life of affected individuals.

The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

Advanced cardiovascular multimodal imaging and aortic stenosis.

Aortic valve stenosis has become the most common valvular heart disease on account of aging population and increasing life expectancy. Echocardiography is the primary diagnosis tool for this, but it still has many flaws. Therefore, advanced cardiovascular multimodal imaging techniques are continuously being developed in order to overcome these limitations. Cardiac magnetic resonance imaging (CMR) allows a comprehensive morphological and functional evaluation of the aortic valve and provides important data for the diagnosis and risk stratification in patients with aortic stenosis. CMR can functionally assess the aortic flow using two-dimensional and time-resolved three-dimensional velocity-encoded phase-contrast techniques. Furthermore, by late gadolinium enhancement and T1-mapping, CMR can reveal the presence of both irreversible replacement and diffuse interstitial myocardial fibrosis. Moreover, its role in guiding aortic valve replacement procedures is beginning to take shape. Recent studies have rendered the importance of active and passive biomechanics in risk stratification and prognosis prediction in patients with aortic stenosis, but more work is required is just in its infancy, but data are promising. In addition, cardiac computed tomography is particularly useful for the diagnosis of aortic valve stenosis, and in preprocedural evaluation of the aorta, while positron emission tomography can be also used to assess valvular inflammation and active calcification. The purpose of this review is to provide a comprehensive overview of current available data regarding advanced cardiovascular multimodal imaging in aortic stenosis.

Cardiotoxicity in HER2-positive breast cancer patients.

Due to the recent advances in diagnosis and management of patients with HER2-positive breast cancer, especially through novel HER2-targeted agents, cardiotoxicity becomes an emerging problem. Although chemotherapy significantly increases survival, the risk of cardiovascular disease development is high and still underestimated and could imply treatment discontinuation. Frequently, due to lack of rigorous diagnosis strategies, cardiotoxicity assessment is delayed, and, moreover, the efficacy of current therapy options in restoring heart function is questionable. For a comprehensive risk assessment, it is vital to characterize the clinical spectrum of HER2-targeted agents and anthracyclines, as well as their pathogenic pathways involved in cardiotoxicity. Advanced cardiovascular multimodal imaging and circulating biomarkers plays primary roles in early assessing cardiotoxicity and also in guiding specific preventive measures. Even though the knowledge in this field is rapidly expanding, there are still questions that arise regarding the optimal approach in terms of timing and methods. The aim of the current review aims to providean overview of currently available data.

Automatic Detection of Colorectal Polyps Using Transfer Learning.

Colorectal cancer is the second leading cause of cancer death and ranks third worldwide in diagnosed malignant pathologies (1.36 million new cases annually). An increase in the diversity of treatment options as well as a rising population require novel diagnostic tools. Current diagnostics involve critical human thinking, but the decisional process loses accuracy due to the increased number of modulatory factors involved. The proposed computer-aided diagnosis system analyses each colonoscopy and provides predictions that will help the clinician to make the right decisions. Artificial intelligence is included in the system both offline and online image processing tools. Aiming to improve the diagnostic process of colon cancer patients, an application was built that allows the easiest and most intuitive interaction between medical staff and the proposed diagnosis system. The developed tool uses two networks. The first, a convolutional neural network, is capable of classifying eight classes of tissue with a sensitivity of 98.13% and an F1 score of 98.14%, while the second network, based on semantic segmentation, can identify the malignant areas with a Jaccard index of 75.18%. The results could have a direct impact on personalised medicine combining clinical knowledge with the computing power of intelligent algorithms.

Recent Advances in Nanoparticle-Mediated Diagnosis and the Treatment of Pancreatic Cancer.

Pancreatic cancer (PC), one of the most lethal solid tumors in humans, has a five-year survival rate of only 4%. Surgical treatment is the only accepted therapy with curative intent because the vast majority of these tumors are chemoresistant. Unfortunately, due to the aggressive nature of these tumors, fewer than 20% are resectable when the first symptoms occur. Novel therapies are required to overcome all these therapeutic issues, and the development of active nanocarriers represents an exciting opportunity to improve PC outcomes. The present review focuses on recent advances in the field of nanotechnology with application in PC treatment.

Carbon nanotubes as anti-bacterial agents.

Multidrug-resistant bacterial infections that have evolved via natural selection have increased alarmingly at a global level. Thus, there is a strong need for the development of novel antibiotics for the treatment of these infections. Functionalized carbon nanotubes through their unique properties hold great promise in the fight against multidrug-resistant bacterial infections. This new family of nanovectors for therapeutic delivery proved to be innovative and efficient for the transport and cellular translocation of therapeutic molecules. The current review examines the latest progress in the antibacterial activity of carbon nanotubes and their composites.

Assessing immunological surgical stress markers in patients undergoing digestive surgery for pancreatic, hepatic and gastric tumors.

PURPOSE: Cytokines like IL-6, IL-10 and other factors like CRP are involved in the postoperative inflammatory-stress response. The association between IL-6, IL-10, CRP, albumin and early postoperative complications and deaths was analyzed on a cohort of cancer patient. METHODS: The plasma levels of IL-6, IL-10 and serum levels of c-reactive protein (CRP) and albumin were measured in 85 patients undergoing surgical resection of pancreatic, hepatic and gastric tumors. The measurement of the studied biochemical parameters was made at three time points: before the operation, and on the 1st and 3rd day after the operation. RESULTS: Of the 85 patients, 28 suffered early postoperative complications (14 gastric cancer patients; 11 pancreatic cancer patients; 3 liver cancer patients) and 9 patients died in the early postoperative period (5 gastric cancer patients; 4 pancreatic cancer patients; 0 liver cancer patients). Patients with elevated levels of serum CRP on the 3rd postoperative day had a significant increased risk of death. Also, patients with higher levels of IL-10 on the 3rd postoperative day demonstrated a significantly increased risk of early postoperative complications. CONCLUSION: This study demonstrates that plasma IL-10 concentration is positively associated with postoperative complications.

Development of nanoparticle-based optical sensors for pathogenic bacterial detection.

BACKGROUND: Pathogenic bacteria contribute to various globally important diseases, killing millions of people each year. Various fields of medicine currently benefit from or may potentially benefit from the use of nanotechnology applications, in which there is growing interest. Disease-related biomarkers can be rapidly and directly detected by nanostructures, such as nanowires, nanotubes, nanoparticles, cantilevers, microarrays, and nanoarrays, as part of an accurate process characterized by lower sample consumption and considerably higher sensitivity. There is a need for accurate techniques for pathogenic bacteria identification and detection to allow the prevention and management of pathogenic diseases and to assure food safety. CONCLUSION: The focus of this review is on the current nanoparticle-based techniques for pathogenic bacterial identification and detection using these applications.

Harmonic Contrast-Enhanced Endoscopic Ultrasonography for the Guidance of Fine-Needle Aspiration in Solid Pancreatic Masses.

Purpose The global accuracy of fine-needle aspiration guided by endoscopic ultrasound (EUS-FNA) for pancreatic adenocarcinoma is about 85 %. The use of contrast agents during EUS to highlight vessels and the necrotic parts of pancreatic masses may improve biopsy guidance. Our aim was to assess whether the guidance of FNA by harmonic contrast-enhanced endoscopic ultrasound (CH-EUS) would increase diagnostic accuracy relative to conventional EUS-FNA in the same pancreatic masses. Patients and Methods In a prospective study, EUS-FNA was performed in patients with pancreatic masses on CT scan, followed by harmonic CH-EUS using SonoVue. A second cluster of CH-EUS-FNA was performed on contrast-enhanced images. The final diagnosis was based on the results of EUS-FNA and surgery, or the findings after 12 months' follow-up. Results The final diagnosis was adenocarcinoma (n = 35), chronic pancreatitis (n = 10), or other (n = 6). The diagnostic accuracy based on core histology was 78.4 % for EUS-FNA and 86.5 % for CH-EUS-FNA (p = 0.35). The accuracy increased to 94 % when the two methods' results were combined. The two false-negative EUS-FNA cases were correctly appreciated by CH-EUS. Neither core histology size nor the presence of necrosis was significant for the true-positive diagnosis of malignancy. Conclusion CH-EUS-FNA had an insignificant incremental effect on diagnostic accuracy compared with conventional EUS-FNA in our small group. The presence of necrosis did not influence the results of CEUS-FNA. Qualitative assessment of the contrast uptake within the lesion was useful in false-negative EUS-FNA cases.

Rational design of gold nanocarrier for the delivery of JAG-1 peptide.

BACKGROUND: Unique properties exhibited by nanoparticles makes them great candidates for applications in physics, chemistry, biology, material science and medicine. The biological applications of water-soluble gold nanoparticles range from contrast agents, delivery vehicles to therapeutics. Notch signaling is a complex network that orchestrates cell fate decisions, which involves proliferation, migration, differentiation and cell death in organisms ranging from insects to humans. Studies have showed that a correct orientation of the Jag-1 signalling protein on the substrates proves to be of great importance when promoting Jagged-1 Notch interactions, also the availability of the ligands, super cedes the importance of their concentration. RESULTS: The aim of the present study was to synthetize a Jag-1 functionalized nanocarrier, which would promote an efficient interaction between the Jag-1 peptide and the Notch receptor. To this end, two routes for gold nanoparticle-peptide assembly were investigated, and the synthetized bio-nanostructures were characterized and compared by means of UV-Vis, FT-IR, DLS and AFM techniques. CONCLUSIONS: We have obtained a stable, monodisperse, hetero-functionalized GNP-PEG-JAG-1 bio-nanostructure for Notch pathway activation applications.

Laparoscopic rectal resection versus conventional open approach for rectal cancer - a 4-year experience of a single center.

PURPOSE: This study was carried out to compare the therapeutic outcomes and complications of the laparoscopic and the conventional open surgery technique used for treating rectal cancer. Another goal was to find the fastest and most accurate method of treatment for rectal cancer, along with establishing the advantages and disadvantages of the two surgical techniques, depending on cancer location and its stage. METHODS: A total of 172 patients diagnosed with rectal cancer and hospitalized in the Department of Surgery III between January 1st 2008 and December 31st 2011 were studied. The laparoscopic approach was performed on 29 (16.8%) patients, and the remaining 143 (83.2%) underwent the conventional Miles/Lloyd-Davies abdominoperineal resection. A longitudinal study was conducted on patients with rectal resection, the used data being obtained from the database of the Department of Surgery III, hospital records, protocols and clinical charts of rectal cancer cases. RESULTS: There were no statistically significant differences regarding symptoms, gender, age, body mass index (BMI), tumor site, TNM stage, intraoperative accidents, operative time, and postoperative mortality between the two groups. The laparoscopic group presented advantages regarding antibiotic and analgesic therapy, early mobilization, hospital stay, intraoperative blood loss, resuming oral nutrition, bowel transit resumption, postoperative complications and wound complications. CONCLUSION: Laparoscopic abdominoperineal resection for rectal cancer is feasible, safe and effective. It can be safely performed by an experienced team, reducing the rate of postoperative complications, the need for blood transfusions, the adminstration of antibiotics and painkillers, allowing faster bowel transit resumption, shortening hospital stay and providing superior aesthetic results.

Right Atrium Volume Index in Patients with Secondary Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease.

BACKGROUND: Right atrium volume index has recently been described as a quantitative and highly reproducible echocardiographic parameter associated with right ventricle systolic dysfunction in patients with chronic systolic heart failure. The aim of the current study was to assess right atrium remodeling and to establish correlations with echocardiographic parameters of right ventricle systolic and diastolic dysfunction in patients with pulmonary hypertension due to chronic obstructive pulmonary disease (COPD). METHODS: The study was conducted on 40 patients with secondary pulmonary hypertension due to COPD and 40 healthy volunteers (mean age 59 ± 6 years) who submitted to detailed echocardiographic examinations. Plasma levels of the soluble interleukin-1 receptor family member, N-terminal pro-B type natriuretic peptide and galectin-3 were measured in both groups. RESULTS: The right atrium volume index was significantly higher in the test group (45.7 ± 15.3 vs. 25.4 ± 4.0 mL/m(2)) and showed strong correlations to tricuspid annular plane systolic excursion (r = -0.733, p < 0.0001), right ventricle fractional area change (r = -0.662, p < 0.0001), right ventricle ejection fraction (r = -0.741, p < 0.0001), and systolic pulmonary artery pressures (r = 0.721, p < 0.0001). Multivariate analysis facilitated the construction of a linear regression model which showed that right ventricle systolic dysfunction parameters (R(2)-adjusted = 0.62, p < 0.001), elevated systolic pulmonary artery pressure (R(2)-adjusted = 0.52, p < 0.001) and heart failure biomarkers (log-transformed sST2, galectin-3 and N-terminal pro-B type natriuretic peptide) (R(2)-adjusted = 0.41, p < 0.001) were independently associated with right atrium volume index. CONCLUSIONS: Right ventricle systolic dysfunction and elevated systolic pulmonary artery pressure are independently associated with right atrium volume index in patients with pulmonary hypertension due to COPD. KEY WORDS: Echocardiography; Right atrium volume index; Right ventricular diastolic function; Right ventricular systolic function.

The influence of a prophylactic dose of dexamethasone for postoperative nausea and vomiting on plasma interleukin concentrations after laparoscopic cholecystectomy: a randomised trial.

BACKGROUND: Little is known about the effects of small doses of dexamethasone used for the prophylaxis of postoperative nausea and vomiting on the innate host response. OBJECTIVES: We studied the influence of dexamethasone 4 mg on the perioperative plasma concentrations of interleukins after laparoscopic cholecystectomy. We hypothesised that there would be differences in pro-inflammatory interleukin concentrations in patients who received dexamethasone. DESIGN: A randomised controlled study. SETTING: University hospital. PATIENTS: Forty-six patients undergoing laparoscopic cholecystectomy under total intravenous anaesthesia were allocated randomly into one of two study groups; 42 patients completed the study. INTERVENTIONS: Patients in group 1 (dexamethasone, n = 22) received dexamethasone 4 mg and group 2 (n = 20) acted as controls. MAIN OUTCOME MEASURES: Plasma levels of tumour necrosis factor alpha and interleukins 1ß, 6, 8, 10 and 13 were measured before anaesthesia, before surgery and 2 and 24 h after surgery. The frequency and number of episodes of postoperative nausea and vomiting were recorded. RESULTS: Areas under the curve of the percentage variation of interleukins 6 and 8 were significantly lower in the dexamethasone group. There were no significant differences between groups in the areas under the curve for tumour necrosis factor alpha and interleukins 1ß, 10 and 13. The greatest variation in interleukin concentrations was 2 h postoperatively, when the concentration of interleukin 6 was greater in the control group, whereas the concentration of interleukin 10 was higher in the dexamethasone group. Twenty-four hours after surgery, only the concentration of interleukin 6 remained significantly increased in both groups (P = 0.001 and P = 0.002, respectively). There were no significant differences between groups in respect of postoperative nausea and vomiting. CONCLUSION: Prophylactic dexamethasone given before laparoscopic cholecystectomy produced a significant decrease in concentrations of interleukins 6 and 8. Further studies are needed to investigate the clinical implications of these findings.

In vitro photothermal therapy of pancreatic cancer mediated by immunoglobulin G-functionalized silver nanoparticles.

Pancreatic cancer is one of the most aggressive forms of cancer, and treatment options are limited. One therapeutic approach is to use nanoparticles to deliver the active agent directly to pancreatic cancer cells. Nanoparticles can be designed to specifically target cancer cells, minimizing damage to healthy tissues. Silver nanoparticles have the unique ability to absorb light, especially in the near-infrared (NIR) region. In this study, silver nanoparticles functionalized with IgG molecules were synthesized and administered to pancreatic cancer cell lines. Subsequently, the cells were photo-excited using a 2 W 808 nm laser and further examined in PANC-1 pancreatic cancer cell lines. Flow cytometry and confocal microscopy combined with immunochemical staining were used to examine the interaction between photo-excited silver nanoparticles and pancreatic cancer cells. The photothermal therapy based on IgG-functionalized silver nanoparticles in pancreatic cancer induces dysfunction in the Golgi apparatus, leading to the activation of the caspase-3 apoptotic pathway and ultimately resulting in cellular apoptosis. These findings suggest that our proposed IgG nanoparticle laser treatment could emerge as a novel approach for the therapy of pancreatic cancer.

Innovative prophylactic and therapeutic approaches in liver cirrhosis.

Liver cirrhosis is the consequence of chronicisation and of the evolution of untreated liver diseases. The complexity of the disease and the complications it can cause have been and are still intensively researched, aiming to discover new therapies or improve existing ones for the effective management of liver cirrhosis. Currently, the treatment used is directed against the cause that caused the disease, if it is known; in advanced cases, liver transplantation is the only valid therapeutic option. Hepatoprotectors that are currently on the market are numerous, having as common properties the antioxidant, anti-inflammatory, stabilizing properties of the hepatocytic membrane; A few examples: the ethanolic extract of Curcuma longa, the extract from the plant called Sophora flavescens, the extract of Glycyrrhiza glabra, silymarin (extracted from Sylibum marianum), the extract of Ganoderma lucidum, etc. Liver cirrhosis is accompanied by generalized hypovitaminosis, so supplementing the diet with hydro- and liposoluble vitamins is mandatory. Protein-caloric malnutrition can be prevented by a hyperprotein diet, especially beneficial being the supplementation with branched-chain amino acids, which are also applicable in the prophylaxis and treatment of hepatic encephalopathy. Nanoparticles are a state-of-the-art therapeutic option, proving increased bioavailability, for example polydopamine nanoparticles loaded with l-arginine have been tested as therapy in liver cirrhosis. Among the innovative treatment directions in liver cirrhosis are hybrid products (e.g. hybrid polymer nanoparticles loaded with caffeic acid), cell cultures and artificial or bioartificial liver support.

Biologic Therapies Decrease Disease Severity and Improve Depression and Anxiety Symptoms in Psoriasis Patients.

BACKGROUND: Psoriasis is an immune-mediated chronic skin disease that is associated with a significant psychological burden. A newer line of therapy is represented by biologic agents. Our study aimed to evaluate the effect of biologic therapies in the treatment of psoriasis concerning both disease severity and psychological comorbidity. MATERIAL AND METHODS: We performed a prospective case-control comparison to evaluate the prevalence of depression and anxiety in psoriasis patients and unaffected individuals. All patients were recruited between October 2017 and February 2021. Baseline depression (PHQ-9), anxiety (GAD-7), PASI, and DLQI scores were noted. Then, we evaluated the efficacy of biologic treatment in reducing these scores at 6 months of therapy. Patients were treated with either ixekizumab, secukinumab, guselkumab, certolizumab, ustekinumab, risankizumab, or adalimumab. RESULTS: 106 bio-naïve patients with psoriasis and 106 controls without the disease were included in this study. Depression and anxiety were significantly more common among psoriasis patients than in unaffected individuals (p < 0.0001). Female patients presented both depression and anxiety more frequently than men in both case and control groups. Disease severity was significantly associated with worsened depression and anxiety symptoms. Biologic therapy resulted in a significant decrease in all four scores at the 6-month mark for each patient (p < 0.0001). Only an improved PASI correlated significantly with lower depression and anxiety scores (p < 0.005), whereas a decreased DLQI did not (p > 0.955). None of the seven biologic agents used was discovered to be superior. CONCLUSION: biologic therapies are effective in decreasing both disease severity and alleviating depression and anxiety symptoms in psoriasis.

Effects of Tocilizumab on Inflammation and Iron Metabolism in Critically Ill Patients with COVID-19.

COVID-19 produces cytokine-mediated persistent inflammation and is associated with elevated iron stores and low circulating iron. It is believed that central to the pathophysiological mechanism is interleukin 6 and hepcidin. A state of iron overload, termed hyperferritinemia, and inflammatory anemia take place. Both conditions are linked to a worse result in critically ill patients. Blocking the interleukin 6-hepcidin pathway with Tocilizumab could present favorable outcomes. The aim of this study was to evaluate if Tocilizumab influences survival, the occurrence of sepsis, anemia and transfusions in critically ill patients suffering from COVID-19. This prospective observational study focused on levels of interleukin 6, hepcidin and blood iron parameters in patients treated with Tocilizumab. Data were compared before and after therapy as well as between treated and control groups. Results indicate that there is no difference in terms of survival nor in the rate of anemia or sepsis occurrence. Hepcidin was elevated and anemia ensued after treatment, which could indicate alternative pathways. In conclusion, when the classic interleukin 6-hepcidin pathway is blocked, inflammation seems to use alternative routes. Further understanding of these pathways is required and new pharmacological therapies need to be developed to treat persistent inflammation.

Recent Trends in Hydroxyapatite Supplementation for Osteoregenerative Purposes.

Bone regeneration has gained attention in the biomedical field, which has led to the development of materials and synthesis methods meant to improve osseointegration and cellular bone activity. The properties of hydroxyapatite, a type of calcium phosphate, have been researched to determine its advantages for bone tissue engineering, particularly its biocompatibility and ability to interact with bone cells. Recently, the advantages of utilizing nanomolecules of hydroxyapatite, combined with various substances, in order to enhance and combine their characteristics, have been reported in the literature. This review will outline the cellular and molecular roles of hydroxypatite, its interactions with bone cells, and its nano-combinations with various ions and natural products and their effects on bone growth, development, and bone repair.