Search Results (13)

Human West Nile virus (WNV) infection is usually asymptomatic. Less than 1% of patients develop neuroinvasive disease (WNND) which may result in permanent neurological impairment. The aim of this study was to assess the functional and cognitive status of patients with WNND approximately one year after the onset of symptoms. This prospective observational cohort study involved patients with WNND. Patients’ functional and cognitive abilities one year post-infection were assessed by telephone interviews using the Modified Rankin Scale (mRS), Barthel Index, and Telephone Interview for Cognitive Status. Sixty-two participants were analyzed. All patients had encephalitis, and 7 (11.3%) also had acute flaccid paresis/paralysis (AFP). At discharge, 40 (64.5%) patients had no or minimal neurological deficit (mRS 0–1), and 14 (22.6%) were functionally dependent (mRS 3–5). One year later, 52 (83.9%) patients were functionally independent (mRS 0–2), none was severely dependent (Barthel index 0–60), and 50 (90.9%) had a Barthel index score of 91–100. Among 14 functionally dependent patients at discharge, 3 (21.4%) remained functionally dependent one year later. During the follow-up, 7 (11.3%) patients died. No significant difference was observed in the fatality rate between patients with and without AFP, mRS 3–5 at discharge, or age over 65. The most common persistent symptoms were muscle weakness, walking instability, and issues with focus and memory. Using TICS, it was found that 33/55 patients (60%) had unimpaired and 2 (3.6%) had moderately or severely impaired cognitive status. The long-term prognosis after WNV encephalitis is satisfying. The majority of patients reached functional independence and 60% had unimpaired cognitive status. Full article

The lemon flavonoid extract Eriomin^® (LE), which is rich in eriocitrin, has demonstrated antioxidant and anti-inflammatory properties in both animal and human studies. Given the established interplay among aging, oxidative stress, and inflammation, this study investigated the influences of LE on the pituitary–adrenal (PA) axis in aged rats and its potential to mitigate age-related physiological changes in this system. The effects of LE (40 mg/kg/day suspended in sunflower oil) on the morphofunctional properties of the PA axis were studied in 24-month-old male Wistar rats following four weeks of oral treatment. Control groups included vehicle-treated (sunflower oil; CON) and untreated intact controls (ICON). Stereological and imaging analyses revealed no significant changes in pituitary ACTH cells; however, Pomc gene expression was significantly downregulated in the LE group compared to both controls (p ≤ 0.05). LE treatment resulted in a significant reduction in adrenal gland weight (p ≤ 0.05), adrenal gland volume (p ≤ 0.01), zona fasciculata (ZF) volume (p ≤ 0.01) and ZF cell volume (p ≤ 0.05). These changes were accompanied by a significant decrease in serum corticosterone levels (p ≤ 0.05). In conclusion, LE downregulated PA axis activity in aged rats. Considering the association between age-related increases in PA activity and adverse health outcomes, citrus flavonoid extracts such as LE may hold promise as anti-aging supplements aimed at mitigating age-related stress dysregulation. Full article

Cancer stem cells (CSCs) significantly contribute to heterogeneity, malignancy, and therapy resistance in ovarian cancer. Recent studies emphasize the role of the vitamin D receptor (VDR) in regulating cell differentiation and stemness in various types of cancer. This study aims to determine the expression levels of CD44, CD133, and VDR in epithelial ovarian tumors (EOTs) and to compare these levels across different tumor types, including benign, atypical proliferative tumors, and five types of malignant phenotypes, in order to evaluate their potential as diagnostic tools for malignancy. Tissue samples from 218 patients diagnosed with EOT were analyzed. Clinical and histopathologic parameters were recorded. Quantitative immunohistochemical tissue microarray analysis was used to assess the expression levels of CD44, CD133, and VDR using two different scoring systems. Comparisons were made between benign tumors (n = 45), atypical proliferative tumors (n = 42), and ovarian carcinomas (n = 131), including high-grade serous (HGSC) and non-HGSC subtypes. Ovarian cancer, especially HGSC, showed a significantly higher expression of CD44 and VDR (p < 0.05) compared to atypical proliferative tumors and benign tumors. The expression of CD133 was highest in atypical proliferative tumors (p < 0.05). A moderate positive correlation was found between CD44, CD133, and VDR in all groups, with significant correlations with tumor grade and FIGO stage in ovarian cancer (p < 0.05). The increased expression of CD44 and VDR in aggressive ovarian cancer, along with elevated CD133 levels in atypical proliferative tumors, highlights the complexity of tumor biology. These markers may serve as valuable targets for the diagnosis of ovarian cancer. Full article

People who inject drugs (PWIDs) experience high rates of hepatitis C virus (HCV) infection, primarily due to needle sharing and limited healthcare access, resulting in a disproportionate disease burden within this population. This prospective study evaluated treatment outcomes in 432 adult patients with chronic hepatitis C (CHC) treated with direct-acting antivirals (DAAs) at the University Clinical Center of Serbia. Patients were categorized into two groups based on a history of drug addiction: PWIDs (163, 37.7%) and non-PWIDs (269, 62.3%). The PWID group was further categorized into subpopulations of problematic PWIDs (39, 23.9%), ex-PWIDs (124, 76.1%), and PWIDs on OST (96, 58.9%). The PWID group demonstrated significantly lower treatment adherence, with an intention-to-treat (ITT) rate of 82.8%, compared to 96.3% in the control group (p < 0.001). In contrast, no significant differences were observed in per-protocol (PP) outcomes between the two groups. Additionally, PWIDs were significantly younger (p < 0.001) and had higher rates of psychiatric disorders (p < 0.001), alcohol abuse (p < 0.001), and HCV genotype 1a (p < 0.001). Advanced fibrosis was predictor of PP treatment failure among PWIDs, while mood disorders and alcohol use disorder were associated with interruptions before the scheduled completion time. For non-PWIDs, older age and advanced fibrosis emerged as key predictors of PP treatment failure. The loss to follow-up was most commonly observed in the problematic PWID subgroup (p = 0.001). These findings highlight the importance of addressing barriers in PWIDs through integrated care strategies that concurrently manage addiction and HCV. Full article

Prenatal glucocorticoid overexposure alters the developmental program of fetal reproductive organs and results in numerous changes that can lead to various disorders later in life. Moderate fructose consumption during childhood and adolescence may impair the development and function of reproductive organs. The aim of this study was to investigate the effects of prenatal dexamethasone (Dx) exposure in combination with postnatal fructose overconsumption on testicular development and function in fetal and adult male rat offspring. Pregnant female rats were treated with a subcutaneous injection of Dx at a dose of 0.5 mg/kg/day on gestation days 16, 17, and 18, and the effects on fetal growth and testicular development were analyzed. Spontaneously born male offspring were fed 10% fructose in drinking water until the age of 3 months. Prenatal exposure to Dx led to a reduction in fetal weight and testicular volume. However, testicular development normalized by adulthood, with testosterone levels decreasing. After moderate fructose consumption, impaired redox homeostasis and structural changes in the testicles and decreased testosterone levels were observed, indicating reduced testicular function. The results suggest that the synergistic effect of prenatal Dx exposure and moderate postnatal fructose consumption leads to more deleterious changes in testicular tissue. Full article

This study, conducted at two university-based infectious disease clinics, included 216 patients with chronic hepatitis C. The primary objective was to assess the positive and negative predictive values, sensitivity, and specificity of achieving a sustained virological response (SVR) at 4 weeks compared to 12 weeks post-therapy. The results demonstrated a maximum sensitivity of 100% for achieving SVR at 12 weeks after reaching SVR at 4 weeks for all analyzed genotypes, except for genotype 1b treated with EBR/GZR therapy, where the specificity was 75%. Additionally, younger age and less advanced liver fibrosis were identified as independent predictors of achieving a sustained virological response at both 4 and 12 weeks. The significant normalization of various biochemical parameters was observed after treatment, indicating an overall improvement in liver function. This study suggests that shortening the monitoring period to 4 weeks might be effective for younger patients without significant fibrosis, potentially reducing loss to follow-up, which is a critical issue in HCV treatment. These findings align with the “test and treat” approach. Further research is needed to confirm these findings and incorporate them into official guidelines, which could simplify and enhance the effectiveness of HCV treatment protocols, aiding global efforts to eliminate HCV as a public health issue by 2030. Full article

Oxidative stress and inflammation are significant causes of aging. At the same time, citrus flavanones, naringenin (NAR), and hesperetin (HES) are bioactives with proven antioxidant and anti-inflammatory properties. Nevertheless, there are still no data about flavanone’s influence and its potential effects on the healthy aging process and improving pituitary functioning. Thus, using qPCR, immunoblot, histological techniques, and biochemical assays, our study aimed to elucidate how citrus flavanones (15 mg/kg b.m. per os) affect antioxidant defense, inflammation, and stress hormone output in the old rat model. Our results showed that HES restores the redox environment in the pituitary by down-regulating the nuclear factor erythroid 2-related factor 2 (Nrf2) protein while increasing kelch-like ECH-associated protein 1 (Keap1), thioredoxin reductase (TrxR1), and superoxide dismutase 2 (SOD2) protein expression. Immunofluorescent analysis confirmed Nrf2 and Keap1 down- and up-regulation, respectively. Supplementation with NAR increased Keap1, Trxr1, glutathione peroxidase (Gpx), and glutathione reductase (Gr) mRNA expression. Decreased oxidative stress aligned with NLRP3 decrement after both flavanones and glycogen synthase kinase-3 (GSK3) only after HES. The signal intensity of adrenocorticotropic hormone (ACTH) cells did not change, while corticosterone levels in serum decreased after both flavanones. HES showed higher potential than NAR in affecting a redox environment without increasing the inflammatory response, while a decrease in corticosterone level has a solid link to longevity. Our findings suggest that HES could improve and facilitate redox and inflammatory dysregulation in the rat’s old pituitary. Full article

This study aimed to assess the antioxidant capacity of lemon flavonoid extract Eriomin^® (LE) and its impact on cholesterol metabolism in the context of healthy aging. We orally treated 24-month-old male Wistar rats with an LE (40 mg/kg) suspended in 0.3 mL of sunflower oil. At the same time, control groups received an equal volume of sunflower oil (CON) or remained untreated (ICON) daily for 4 weeks. We examined LE’s effects on superoxide dismutase and catalase- and glutathione-related enzyme activities, the concentration of lipid peroxides and protein carbonyls, total oxidant status (TOS) and antioxidant status (TAS), and oxidative stress index (OSI) in the liver, jejunum, and ileum. We also measured total cholesterol, its biosynthetic precursors (lanosterol, lathosterol, desmosterol), its degradation products (bile acid precursors) in the serum, liver, jejunum, and ileum, and serum phytosterols (intestinal absorption markers). LE reduced TOS, TAS, and OSI (p < 0.05) compared with control values, indicating its consistent antioxidant action in all examined organs. LE lowered hepatic desmosterol (p < 0.05) while also reducing 7α- and 24-hydroxycholesterol levels in the liver and ileum (p < 0.01). Serum cholesterol, hepatic gene expression, and the immunostaining intensity of CYP7A1 were unchanged. In conclusion, LE exerted non-enzymatic antioxidant effects and reduced cholesterol degradation, reducing its biosynthesis products, thereby maintaining serum cholesterol levels. Full article

Age and sex influence serum cholesterol levels, but the underlying mechanisms remain unclear. To investigate further, we measured cholesterol, precursors (surrogate synthesis markers), degradation products (oxysterols and bile acid precursors) in serum, the liver, jejunum, and ileum, as well as serum plant sterols (intestinal absorption markers) in male and female Wistar rats (4 and 24 months old). The analysis of histomorphometric and oxidative stress parameters (superoxide dismutase, catalase, glutathione-related enzyme activities, lipid peroxide, and protein carbonyl concentrations) in the liver and jejunum offered further insights into the age- and sex-related differences. The hepatic gene expression analysis included AR, ERα, and sex-specific growth hormone-regulated (Cyp2c11 and Cyp2c12) and thyroid-responsive (Dio1, Tbg, and Spot 14) genes by qPCR. We observed age-related changes in both sexes, with greater prominence in females. Aged females had significantly higher serum cholesterol (p < 0.05), jejunum cholesterol (p < 0.05), and serum plant sterols (p < 0.05). They exhibited poorer hepato-intestinal health compared with males, which was characterized by mild liver dysfunction (hydropic degeneration, increased serum ALT, p < 0.05, and decreased activity of some antioxidant defense enzymes, p < 0.05), mononuclear inflammation in the jejunal lamina propria, and age-related decreases in jejunal catalase and glutathione peroxidase activity (p < 0.05). Aged females showed increased levels of 27-hydroxycholesterol (p < 0.05) and upregulated ERα gene expression (p < 0.05) in the liver. Our study suggests that the more significant age-related increase in serum cholesterol in females is associated with poorer hepato-intestinal health and increased jejunal cholesterol absorption. The local increase in 27-hydroxycholesterol during aging might reduce the hepatoprotective effects of endogenous estrogen in the female liver. Full article

As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a greater ability over the other to respond to and protect against possible maternal insults. Here, we characterized sex differences in the placenta’s morphological features and antioxidant status following dexamethasone (Dx) exposure. Pregnant rats were exposed to Dx or saline. The placenta was histologically and stereologically analyzed. The activity of the antioxidant enzymes, lipid peroxides (TBARS), superoxide anion and nitric oxide (NO) was measured. The decrease in placental zone volumes was more pronounced (p < 0.05) in female placentas. The volume density of PCNA-immunopositive nuclei was reduced (p < 0.05) in both sexes. The reduced (p < 0.05) antioxidant enzyme activities, enhanced TBARS and NO concentration indicate that Dx exposure triggered oxidative stress in the placenta of both fetal sexes, albeit stronger in the placenta of female fetuses. In conclusion, maternal Dx treatment reduced the size and volume of placental zones, altered placental histomorphology, decreased cell proliferation and triggered oxidative stress; however, the placentas of female fetuses exerted more significant responses to the treatment effects. The reduced placental size most probably reduced the transport of nutrients and oxygen, thus resulting in the reduced weight of fetuses, similar in both sexes. The lesser ability of the male placenta to detect and react to maternal exposure to environmental challenges may lead to long-standing health effects. Full article

Lakes in coastal lowland areas represent a critically vulnerable environment as a transitional space between freshwater and seawater environments. The paleoenvironmental reconstruction and anthropogenic impact are assessed through the lake sediment cores from Velo, Malo, and Kolanjsko Blato using multi-proxy analyses (sedimentological, mineralogical, geochemical, ¹³⁷Cs and ostracod analyses, and AMS ¹⁴C radiocarbon dating). The freshwater lake Velo Blato was formed at 8100 cal yr BP due to rising groundwater levels as a consequence of sea-level rise. The brackish conditions in Lake Velo Blato started at 7100 cal yr BP, giving the index point for the sea-level curve of 7-m lower than present. Lead concentrations showed slightly increased values in the last 1800 cal yr BP, while the spike in Malo Blato lake sediments probably derived from bird hunting with lead bullets. Kolanjsko Blato sediment core archives the sediment record of the last 2050 years, which represents a shallow brackish coastal wetland under marine influence. Enrichment factors showed the accumulation of Cu, Hg, P, Pb, S, and Zn in the sediments from Kolanjsko Blato in the last 650 cal yr BP, which coincides with the high organic carbon content, and in sediments from Malo Blato after the lake’s formation (from the depth of 20 cm upwards). Anthropogenic Cu introduced into the Kolanjsko Blato sediments is the highest in the surface sample. Surficial sediments from Velo Blato are characterized by the high organic carbon, S, P, and N content, indicating high productivity and eutrophication which led to occasional anoxic conditions on the lake bottom in the last 200 years. Full article

Vitamin D plays an essential role in prevention and treatment of osteoporosis. Thyroid hormones, in addition to vitamin D, significantly contribute to regulation of bone remodeling cycle and health. There is currently no data about a possible connection between vitamin D treatment and the thyroid in the context of osteoporosis. Middle-aged Wistar rats were divided into: sham operated (SO), orchidectomized (Orx), and cholecalciferol-treated orchidectomized (Orx + Vit. D₃; 5 µg/kg b.m./day during three weeks) groups (n = 6/group). Concentration of 25(OH)D in serum of the Orx + Vit. D₃ group increased 4 and 3.2 times (p < 0.0001) respectively, compared to Orx and SO group. T_4, TSH, and calcitonin in serum remained unaltered. Vit. D₃ treatment induced changes in thyroid functional morphology that indicate increased utilization of stored colloid and release of thyroid hormones in comparison with hormone synthesis, to maintain hormonal balance. Increased expression of nuclear VDR (p < 0.05) points to direct, TSH independent action of Vit. D on thyrocytes. Strong CYP24A1 immunostaining in C cells suggests its prominent expression in response to Vit. D in this cell subpopulation in orchidectomized rat model of osteoporosis. The indirect effect of Vit. D on bone, through fine regulation of thyroid function, is small. Full article

Estrogen signaling plays an important role in pituitary development and function. In sensitive rat or mice strains of both sexes, estrogen treatments promote lactotropic cell proliferation and induce the formation of pituitary adenomas (dominantly prolactin or growth-hormone-secreting ones). In male patients receiving estrogen, treatment does not necessarily result in pituitary hyperplasia, hyperprolactinemia or adenoma development. In this review, we comprehensively analyze the mechanisms of estrogen action upon their application in male animal models comparing it with available data in human subjects. Sex-specific molecular targets of estrogen action in lactotropic (PRL) cells are highlighted in the context of their proliferative and secretory activity. In addition, putative effects of estradiol on the cellular/tumor microenvironment and the contribution of postnatal pituitary progenitor/stem cells and transdifferentiation processes to prolactinoma development have been analyzed. Finally, estrogen-induced morphological and hormone-secreting changes in pituitary thyrotropic (TSH) and adrenocorticotropic (ACTH) cells are discussed, as well as the putative role of the thyroid and/or glucocorticoid hormones in prolactinoma development, based on the current scarce literature. Full article