Exploring In Vivo Pulmonary and Splenic Toxicity Profiles of Silicon Quantum Dots in Mice.

Silicon-based quantum dots (SiQDs) represent a special class of nanoparticles due to their low toxicity and easily modifiable surface properties. For this reason, they are used in applications such as bioimaging, fluorescent labeling, drug delivery, protein detection techniques, and tissue engineering despite a serious lack of information on possible in vivo effects. The present study aimed to characterize and evaluate the in vivo toxicity of SiQDs obtained by laser ablation in the lung and spleen of mice. The particles were administered in three different doses (1, 10, and 100 mg QDs/kg of body weight) by intravenous injection into the caudal vein of Swiss mice. After 1, 6, 24, and 72 h, the animals were euthanized, and the lung and spleen tissues were harvested for the evaluation of antioxidant enzyme activity, lipid peroxidation, protein expression, and epigenetic and morphological changes. The obtained results highlighted a low toxicity in pulmonary and splenic tissues for concentrations up to 10 mg SiQDs/kg body, demonstrated by biochemical and histopathological analysis. Therefore, our study brings new experimental evidence on the biocompatibility of this type of QD, suggesting the possibility of expanding research on the biomedical applications of SiQDs.

Paraneoplastic Syndromes in Hepatocellular Carcinoma, Epidemiology, and Survival: A Retrospective Seven Years Study.

Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS's impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association (p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia (p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.

The Anti-Leukemic Activity of Natural Compounds.

The use of biologically active compounds has become a realistic option for the treatment of malignant tumors due to their cost-effectiveness and safety. In this review, we aimed to highlight the main natural biocompounds that target leukemic cells, assessed by in vitro and in vivo experiments or clinical studies, in order to explore their therapeutic potential in the treatment of leukemia: acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL). It provides a basis for researchers and hematologists in improving basic and clinical research on the development of new alternative therapies in the fight against leukemia, a harmful hematological cancer and the leading cause of death among patients.

Nano Selenium-Enriched Probiotics as Functional Food Products against Cadmium Liver Toxicity.

Since cadmium is a toxic metal that can cause serious health problems for humans, it is necessary to find bioremediation solutions to reduce its harmful effects. The main goal of our work was to develop a functional food based on elemental selenium nanoparticles (SeNPs) obtained by green synthesis using Lactobacillus casei and to validate their ability to annihilate the hepatic toxic effects induced by cadmium. The characterization of SeNPs was assessed by UV-Vis spectroscopy, FTIR, XRD, DLS and TEM. In order to investigate the dose-dependent protective effects of SeNPs on Cd liver toxicity, mice were assigned to eight experimental groups and fed by gavage, with 5 mg/kg b.w. cadmium, respectively, with co-administration with SeNPs or lacto-SeNPs (LSeNPs) in 3 doses (0.1, 0.2 and 0.4 mg/kg b.w.) for 30 days. The protective effect was demonstrated by the restoration of blood hepatic markers (AST, ALT, GGT and total bilirubin) and antioxidant enzymes, such as catalase (CAT) and glutathione peroxidase (GPx). Moreover, the antioxidant capacity of mice plasma by the FRAP assay, revealed the highest antioxidant capacity for the 0.2 mg/kg LSeNPs group. Histopathological analysis demonstrated the morphological alteration in the group that received only cadmium and was restored after the administration of SeNPs or LSeNPs, while the immunohistochemical analysis of the bcl family revealed anti-apoptotic effects; the Q-PCR analysis showed an upregulation of hepatic inflammatory markers for the group exposed to Cd and a decreased value for the groups receiving oral SeNPs/ LSeNPs in a dose-dependent manner. The best protective effects were obtained for LSeNPs. A functional food that includes both probiotic bacteria and elemental SeNPs could be successfully used to annihilate Cd-induced liver toxicity, and to improve both nutritional values and health benefits.

The morphological changes of the colonic goblet cells and mucin profile in oncohematological patients under Epirubicin-based chemotherapy.

Changes in the lining of the small intestine following chemotherapy have been extensively studied, although also occurs in the large intestine. The aim of this study was to assess the consequences of Epirubicin-based therapy on goblet cells (GCs) and mucus production on colonic mucosa, immediately and after short-time of chemotherapy administration to oncohematological patients, by clinical and histopathological analysis. We assessed the mucus production, composition, and distribution by Alcian Blue (pH 2.5)-Periodic Acid-Schiff (PAS) staining, alongside with the immunoexpression of mucin (MUC)2, MUC4 and inflammatory markers in a series of oncohematological patients, immediately and after short-time of Epirubicin-based chemotherapy cumulative therapy cessation. We showed that GCs number decrease slightly at 48 hours, while mucous secretion became mixed (with a few neutral) after three weeks. Overall, the secretion was increased immediately after the Epirubicin administration, due to the activation of inflammatory pathways, assessed by increased immunostaining of tumor necrosis factor-alpha (TNF-α) at 48 hours. The MUC2 and MUC4 showed a decreased immunoexpression at 48 hours after the Epirubicin administration compared to controls and partially restored three weeks after the cessation. Overall, it is highly plausible that all these key players revolve around the chemotherapy-induced mucositis in oncohematological patients and highlights the morphofunctional particularities of the GCs, which further modulates the clinical outcome of the patient.

Diagnosis reliability of combined flexible sigmoidoscopy and fecal-immunochemical test in colorectal neoplasia screening.

BACKGROUND: Employing colonoscopy, the gold standard in colorectal cancer (CRC) diagnosis testing, for CRC screening presents a significant risk of complications. Alternative methods with a lower invasive-level and fewer risks are proposed in combination, though each with lower diagnosis performance when applied separately. The main objective of this cross-sectional pilot study was to evaluate the feasibility of a CRC screening program using combined flexible sigmoidoscopy and fecal-immunochemical test (FIT). METHODS: The patient population consisted of 2,201 consecutive-case symptomatic patients attending the gastroenterology outpatient clinic with mild complaints between 2012 and 2014. They were referred for FIT. A sample of 252 individuals underwent a subsequent colonoscopy, blind to FIT results, and theoretical sigmoidoscopy was simulated. On a subsample of 57 patients, real sigmoidoscopy was additionally performed. Prior probabilities in terms of patients' compliance and CRC prevalence were estimated, together with predictive ability of FIT and sigmoidoscopy in screening population. We assessed the merit of a screening strategy employing two-stage serial multiple testing: a) first stage by combining two parallel tests, that is, flexible sigmoidoscopy and FIT and b) colonoscopy as the second diagnosis test. The scheme was validated using the actual predictive values derived from the study population. RESULTS: Colonoscopy found 75 (29.76%) individuals with advanced neoplasia. FIT was positive in 30.3% of advanced neoplasia cases, while between 23.73% and 28.28% met the theoretical sigmoidoscopy simulation criteria, with good concordance between real and theoretical sigmoidoscopy. The colonoscopy referral compliance rate was 52% among FIT-positives. Sensitivity and specificity of the first-stage test combination were better than sigmoidoscopy alone (McNemar test: P<0.001). Negative predictive values for low prevalence levels were between 81.5% and 90.12%. CONCLUSION: Combining less resource challenging and less invasive testing procedures is worthwhile in colorectal neoplasia detection, improving sensitivity and specificity of either test alone, and leading to better posterior probabilities in usual screening scenarios.

Protective effects of silymarin on epirubicin-induced mucosal barrier injury of the gastrointestinal tract.

Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the protective effects of silymarin on epirubicin-induced mucosal barrier injury in CD-1 mice. Immunohistochemical activity of both pro-apoptotic Bax and anti-apoptotic Bcl-2 markers, together with p53, cyt-P450 expression and DNA damage analysis on stomach, small intestine and colon were evaluated. Our results indicated stronger expression for cyt P450 in all analyzed gastrointestinal tissues of Epi group, which demonstrate intense drug detoxification. Bax immunopositivity was intense in the absorptive enterocytes and lamina connective cells of the small intestine, surface epithelial cells of the stomach and also in the colonic epithelium and lamina concomitant with a decreased Bcl-2 expression in all analyzed tissues. Epirubicin-induced gastrointestinal damage was verified by a goblet cell count and morphology analysis on histopathological sections stained for mucins. In all analyzed tissues, Bax immunopositivity has been withdrawn by highest dose of silymarin concomitant with reversal of Bcl-2 intensity at a level comparable with control. p53 expression was found in all analyzed tissues and decreased by high dose of silymarin. Also, DNA internucleosomal fragmentation was observed in the Epi groups for all analyzed tissues was almost suppressed at 100 mg/kg Sy co-treatment. Histological aspect and goblet cell count were restored at a highest dose of Sy for both small and large intestine. In conclusion, our findings suggest that silymarin may prevent cellular damage of epirubicin-induced toxicity and was effective in reducing the severity indicators of gastrointestinal mucositis in mice.

Results of faecal immunochemical test for colorectal cancer screening, in average risk population, in a cohort of 1389 subjects.

AIM: The aim of this study is to evaluate the usefulness of the fecal immunochemical test (FIT) in colorectal cancer screening, detection of precancerous lesions and early colorectal cancer. MATERIAL AND METHODS: The study evaluated asymptomatic patients with average risk (no personal or family antecedents of polyps or colorectal cancer), aged between 50 and 74 years. The presence of the occult haemorrhage was tested with the immunochemical faecal test Hem Check 1 (Veda Lab, France). The subjects were not requested to have any dietary or drug restrictions. Colonoscopy was recommended in all subjects that tested positive. RESULTS: In our study, we had a total of 1389 participants who met the inclusion criteria, with a mean age of 61.2 ± 12.8 years, 565 (40.7%) men and 824 (59.3%) women. FIT was positive in 87 individuals (6.3%). In 57/87 subjects (65.5%) with positive FIT, colonoscopy was performed, while the rest of the subjects refused or delayed the investigation. A number of 5 (8.8%) patients were not able to have a complete colonoscopy, due to neoplastic stenosis. The colonoscopies revealed in 10 cases (0.7%) cancer, in 29 cases (2.1%) advanced adenomas and in 15 cases (1.1%) non advanced adenomas from the total participants in the study. The colonoscopies performed revealed a greater percentage of advanced adenomas in the left colon compared to the right colon, 74.1% vs. 28.6% (p<0.001). CONCLUSIONS: In our study, FIT had a positivity rate of 6.3%. The detection rate for advanced neoplasia was 2.8% (0.7% for cancer, 2.1% for advanced adenomas) in our study group. Adherence to colonoscopy for FIT-positive subjects was 65.5%.

The survey on the practice of gastroenterology in Romania.

AIM OF THE STUDY: To get data on the current practice of Gastroenterology in Romania. MATERIAL AND METHOD: We obtained data regarding the number of gastroenterologists in Romania from the Centre of Statistics of the Ministry of Health and Family (CSMHF) and the National Centre of Training for Medical Personnel (NCTMP). We sent a questionnaire to all the Centers of Gastroenterology in Romania inquiring about the number of gastroenterologists and fellows, and about the gastroenterological procedures performed. We compared these data to that of 17 European countries. RESULTS: The total number of gastroenterologists in Romania on January 1, 2005 was 175 (123 specialists and 52 senior consultants), and the total number of fellows in training was 133. Romania has a small number of gastroenterologists - 0.83/100,000 inhabitants, expected to reach approximately 1.4/100,000 inhabitants in 2010. Regarding the abilities in gastroenterological procedures, we obtained data from 98 gastroenterologists. They have good performances in diagnostic gastroscopy (97%), colonoscopy (81.6%), abdominal ultrasound (79.6%), but a poor performance in ERCP (10.2%). Less than half of the gastroenterologists (46.9%) perform proctologic procedures. Data regarding the training program of the Romanian fellows are disappointing: only 69.1% of them perform gastroscopy, 33.8% colonoscopy, 2.9% ERCP, 64.7% abdominal ultrasound and 14.7% proctology. CONCLUSIONS: The number of gastroenterologists in Romania seems low compared with most European countries. They do not acquire a uniform satisfactory mastering of gastroenterological procedures during their training program. This should be improved according to the guidelines of the European Diploma of Gastroenterology.

The prevalence of coeliac disease at endoscopy units in Romania: routine biopsies during gastroscopy are mandatory (a multicentre study).

UNLABELLED: The incidence and prevalence of coeliac disease vary internationally. In Eastern Europe little is known about the prevalence of coeliac disease. THE AIM: of this study was to evaluate the prevalence and the clinical features of coeliac disease in adults biopsied during upper endoscopy in Romania. This is the first incidence study of the coeliac disease in Romania. METHODS: The study was initiated by the Romanian Society of Digestive Endoscopy for the period 1 January 2002 - 31 May 2002. It was carried out in 9 Academic Centres in Romania, which ensured an even geographical distribution and therefore significant statistical results at a national level. The study included 2436 patients according to following criteria: age over 16 years, with no known history of coeliac disease, visiting the participating upper endoscopy units or patients with documented coeliac disease presenting for follow-up check or recurrence of clinical symptoms. At least two bioptic samples were obtained from the distal duodenum, as distally as possible, which were submitted to histopathological examination and scored according to the modified UEGW Marsh criteria (2001). A database was set up to include all the patients with data regarding sex, age, urban or rural background, full clinical diagnosis, clinical symptoms, history of the coeliac disease. RESULTS: Of the 2436 patients studied, 54 (2.22%) were diagnosed with coeliac disease. Their demographic features: 48.15% men, 51.85% women, 68.52% living in urban areas, 31.48% in rural ones, mean age 42 +/-17.0 years. The most frequent reasons for performing upper digestive endoscopy were: dyspeptic syndrome - 15.93%, anemia - 24.07%, and chronic diarrhoea - 22.22%. The most frequently recorded clinical manifestations were: chronic diarrhoea in 46.3%, asthenia in 29.63%, anemia in 24.07%, aphthae in 24.07%. Histopathological results according to Marsh classification were: Marsh III- 64.81 %, Marsh II-35.19%. CONCLUSIONS: The prevalence of the coeliac disease in Romania is 2.22%: its sex distribution is fairly equal, the age distribution includes two peaks, at 30-40 and 50-60 years respectively, and patients from urban areas predominate. The most frequent (over 50% of the cases) histological type was M III. The most common clinical symptoms were diarrhoea, asthenia, anemia, aphthae, while the most frequent associated diseases were diabetes mellitus and Duhring-Brocq dermatiti

[Probiotics in gastrointestinal pathology]. / Probioticele si patologia gastrointestinala.

There are a variety of conditions in which the use of pro-biotics has proven effective:diarrhoea with its various causes, inflammatory bowel diseases, irritable bowel disease, colon cancer chemoprevention and hepato-portal encefalopathy. The pro-biotics have shown to be a promising therapeutical alternative for the future due to their lack of side effects and convenient mode of administration. Further, the potential of other pro-biotics is awaiting validation by clinical trials.