Exploring In Vitro Immunomodulatory Properties of Moss Atrichum undulatum Extracts.

Bryophytes are rich sources of diverse secondary metabolites with a wide range of biological activities, including anti-inflammatory, antitumor and antimicrobial effects. The aim of this study was to investigate the chemical composition of extracts from two different genotypes (Serbian and Hungarian) of the axenic moss Atrichum undulatum and evaluate the immunomodulatory potential of the prepared extracts in vitro. Both genotypes of moss samples were cultivated in vitro and subsequently extracted in a Soxhlet apparatus with methanol or ethyl acetate. The highest concentration of total phenolic compounds was found in the methanolic extract of the Serbian genotype (54.25 mg GAE/g extract), while the ethyl acetate extract of the Hungarian genotype showed the highest concentration of phenolic acids (163.20 mg CAE/extract), flavonoids (35.57 mg QE/extract), and flavonols (2.25 mg QE/extract). The extracts showed anti-neuroinflammatory properties by reducing the production of reactive oxygen species, nitric oxide, and tumor necrosis factor alpha by lipopolysaccharide-stimulated microglial cells. Moreover, they mitigated the cytotoxic effects of the pro-inflammatory mediators produced by activated microglia on neurons. The data obtained suggest that extracts from A. undulatum moss have promising anti-neuroinflammatory and neuroprotective properties, making them interesting candidates for further research to combat neuroinflammation.

Emphysematous Pancreatitis as a Life-Threatening Condition: A Case Report and Review of the Literature.

Emphysematous pancreatitis represents the presence of gas within or around the pancreas on the ground of necrotizing pancreatitis due to superinfection with gas-forming bacteria. This entity is diagnosed on clinical grounds and on the basis of radiologic findings. Computed tomography is the preferred imaging modality used to detect this life-threating condition. The management of emphysematous pancreatitis consists of conservative measures, image-guided percutaneous catheter drainage or endoscopic therapy, and surgical intervention, which is delayed as long as possible and undertaken only in patients who continue to deteriorate despite conservative management. Due to its high mortality rate, early and prompt recognition and treatment of emphysematous pancreatitis are crucial and require individualized treatment with the involvement of a multidisciplinary team. Here, we present a case of emphysematous pancreatitis as an unusual occurrence and discuss disease features and treatment options in order to facilitate diagnostics and therapy.

Spontaneous coronary artery dissection in women in the generative period: clinical characteristics, treatment, and outcome-a systematic review and meta-analysis.

Introduction: Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic separation of the coronary arterial wall. Materials and methods: This systematic review and meta-analysis is reported following the PRISMA guidelines and is registered in the PROSPERO database. A literature search was focused on female patients in generative period (16-55 of age) with acute coronary syndrome (ACS) caused by SCAD, and comparison from that database NP-SCAD (spontaneous coronary artery dissection in non pregnant women) and P-SCAD (spontaneous coronary artery dissection in pregnant women). Results: 14 studies with 2,145 females in the generative period with ACS caused by SCAD were analyzed. The median age was 41 years (33.4-52.3 years). The most common risk factor was previous smoking history in 24.9% cases. The most common clinical presentation of ACS was STEMI in 47.4%. Conservative treatment was reported in 41.1%. PCI was performed in 32.7%, and 3.8% of patients had CABG surgery. LAD was the most frequently affected (50.5%). The prevalence of composite clinical outcomes including mortality, non-fatal MI and recurrent SCAD was 3.3% (95% CI: 1.4-5.1), 37.7% (95% CI: 1.9-73.4) and 15.2% (95% CI: 9.1-21.3) of patients. P-SCAD compared to NP-SCAD patients more frequently had STEMI (OR = 3.16; 95% CI: 2.30-4.34; I2 = 64%); with the left main and LAD more frequently affected [(OR = 14.34; 95% CI: 7.71-26.67; I2 = 54%) and (OR = 1.57; 95% CI: 1.06-2.32; I2 = 23%)]; P-SCAD patients more frequently underwent CABG surgery (OR = 6.29; 95% CI: 4.08-9.70; I2 = 0%). NP-SCAD compared to P-SCAD patients were more frequently treated conservatevly (OR = 0.61; 95% CI: 0.37-0.98; I2 = 0%). In P-SCAD compared to NP-SCAD mortality rates (OR = 1.13; 95% CI: 0.06-21.16; I2 = not applicable) and reccurence of coronary artery dissection (OR = 2.54; 95% CI: 0.97-6.61; I2 = 0%) were not more prevalent. Conclusion: The results of this meta-analysis indicated that patients with P-SCAD more frequently had STEMI, and events more frequently involved left main and LAD compared to NP-SCAD patients. Women with NP-SCAD were significantly more often treated conservatively compared to P-SCAD patients. P-SCAD compared to NP-SCAD patients did not have significantly higher mortality rates or recurrent coronary dissection.

Effect of Percutaneous Biliary Drainage on Enzyme Activity of Serum Matrix Metalloproteinase-9 in Patients with Malignant Hilar Obstructive Hyperbilirubinemia.

Background and Objectives. Cholestasis activates complex mechanisms of liver injury and as a result has an increased production of matrix metalloproteinases (MMP). Depending on the stage of liver disease, different matrix metalloproteinases expressions have been detected and could serve as indirect biomarkers as well as therapeutic targets. MMP-9 proteolytic activity has a proven role in both liver regeneration and neoplastic cell invasion in various malignancies. The purpose of this prospective cohort study was to evaluate the effect of external biliary drainage on enzyme activity of MMP-9 in the serum of patients with malignant hilar biliary obstruction. Materials and Methods. Between November 2020 and April 2021, 45 patients with malignant hilar biliary obstruction underwent percutaneous biliary drainage following determination of serum MMP-9 enzyme activity (before treatment and 4 weeks after the treatment) by gelatin zymography. Results. MMP-9 values decreased statistically significantly 4 weeks after percutaneous biliary drainage (p = 0.028) as well as the value of total bilirubin (p < 0.001), values of direct bilirubin (p < 0.001), aspartate aminotransferase (AST) (p < 0.001), alanine transaminase (ALT) (p < 0.001), and gamma-glutamyl transferase (GGT) (p < 0.001). Conclusions. In patients with malignant hilar biliary obstruction treated by external percutaneous biliary drainage for cholestasis resolution, a significant reduction in MMP-9 serum values was noted 4 weeks after the treatment.

CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer.

Cancer-associated fibroblasts (CAFs) are abundantly present in the microenvironment of virtually all tumors and strongly impact tumor progression. Despite increasing insight into their function and heterogeneity, little is known regarding the origin of CAFs. Understanding the origin of CAF heterogeneity is needed to develop successful CAF-based targeted therapies. Through various transplantation studies in mice, we show that CAFs in both invasive lobular breast cancer and triple-negative breast cancer originate from mammary tissue-resident normal fibroblasts (NFs). Single-cell transcriptomics, in vivo and in vitro studies reveal the transition of CD26+ and CD26- NF populations into inflammatory CAFs (iCAFs) and myofibroblastic CAFs (myCAFs), respectively. Functional co-culture experiments show that CD26+ NFs transition into pro-tumorigenic iCAFs which recruit myeloid cells in a CXCL12-dependent manner and enhance tumor cell invasion via matrix-metalloproteinase (MMP) activity. Together, our data suggest that CD26+ and CD26- NFs transform into distinct CAF subpopulations in mouse models of breast cancer.

Impact of the COVID-19 Pandemic on the Outcomes of Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma: A Single Center Experience from a Developing Country.

Background and Objectives: Treatment of cancer patients during the COVID-19 pandemic has been a challenge worldwide. In accordance with the current recommendations for hepatocellular carcinoma (HCC) management during the COVID-19 pandemic, loco-regional therapy such as transarterial chemoembolization (TACE) was proposed with the purpose of achieving local tumor control and improving overall survival. The aim of this prospective cohort study was to evaluate the outcomes of TACE treatment in patients with HCC during the COVID-19 pandemic in comparison with the outcomes of patients treated in the pre-pandemic period. Materials and Methods: Between September 2018 and December 2021, 154 patients were managed by serial TACE procedures for different liver tumors. Ninety-seven patients met the study criteria and were divided into two groups: the study group n = 49 (patients treated from May 2020 to December 2021); the control group n = 48 (patients treated from September 2018 to May 2020). Results: The mean waiting time for TACE was significantly longer in the study group compared to the control group (p < 0.001). No significant difference in survival between the groups is noted (log-rank test p = 0.823). In multivariate analysis, the MELD score (HR 1.329, 95% CI 1.140−1.548, p < 0.001) remained a significant predictor of mortality. Conclusions: COVID-19 pandemic did not affect the final outcome of TACE treatment.

Cancer of unknown primary - incidence, mortality trend, and mortality-to-incidence ratio is associated with human development index in Central Serbia, 1999-2018: Evidence from the national cancer registry.

OBJECTIVES: The aim was to estimate the trend of incidence, mortality and mortality-to-incidence ratio (MIR) in Central Serbia in 1999-2018 and its possible association with the human development index (HDI). METHODS: In this study, cancer of unknown primary (CUP) was included as C77-C80 codes. Trend analysis was performed in the Joinpoint Regression Programme version 4.8.0.1. HDI combines life expectancy, educational attainment and gross national income. HDI values for Serbia are extracted from the global bank site. RESULTS: Joinpoint regression analysis of the age-standardised incidence rate of CUP showed a significantly increasing trend with annual percent change (APC) of 8.5% (95% confidence interval [CI] 3.0-14.3%) in males and 7.8% (95%CI 2.7-13.2) in females. The age-standardised mortality rate of CUP showed a significantly decreasing trend with APC of -1.7% (95%CI -2.8 to -0.5%) in males and -1.4% (95%CI -2.7 to -0.1%) in females. MIR showed a significantly decreasing trend with APC of -9.3% (95%CI -14.6 - -3.6%) in males and -7.1% (95%CI -10.5% to -4.2%) in females. The linear regression showed significant inverse association among HDI and the MIR of CUP in males (r2 = 0.464, p = 0.002) and in females (r2 = 0.612, p < 0.001). CONCLUSIONS: Decline of MIR was associated with HDI, suggesting that CUP prognosis follows socio-economic status.

Total Fluoroscopy Time Reduction During Ultrasound- and Fluoroscopy-Guided Percutaneous Transhepatic Biliary Drainage Procedure: Importance of Adjusting the Puncture Angle.

BACKGROUND The purpose of this observational cohort study was to assess patient and operator-dependent factors which could have an impact on total fluoroscopy time during ultrasound and fluoroscopy-guided percutaneous transhepatic biliary drainage (PTBD). MATERIAL AND METHODS Between October 2016 and November 2020, 127 patients with malignant biliary obstruction underwent ultrasound- and fluoroscopy-guided PTBD with the right-sided intercostal approach. The initial bile duct puncture was ultrasound-guided in all patients, and the puncture angle was measured by ultrasound. Any subsequent steps of the procedure were performed under continuous fluoroscopy (15 fps). The patients were divided in 2 groups based on the puncture angle: ≤30° (group I) and >30° (group II). In a retrospective analysis, both groups were compared for inter- and intragroup variability, technical success, total fluoroscopy time, and complications. RESULTS In group II, the recorded total fluoroscopy time (232.20±140.94 s) was significantly longer than that in group I (83.44±52.61 s) (P<0.001). In both groups, total fluoroscopy time was significantly longer in cases with a lesser degree of bile duct dilatation, intrahepatic bile duct tortuosity, presence of liver metastases, and multiple intrahepatic bile duct strictures. CONCLUSIONS The initial bile duct puncture angle was identified as an operator-dependent factor with the possible impact on total fluoroscopy time. The puncture angle of less than 30° was positively correlated with overall procedure efficacy and total fluoroscopy time reduction.