Search Results (2,291)

Glioblastoma (GBM) is a primary CNS tumor that is highly lethal in adults and has limited treatment options. Despite advancements in understanding the GBM biology, the standard treatment for GBM has remained unchanged for more than a decade. Only 6.8% of patients survive beyond five years. Telomerase, particularly the hTERT promoter mutations present in up to 80% of GBM cases, represents a promising therapeutic target due to its role in sustaining telomere length and cancer cell proliferation. This review examines the biology of telomerase in GBM and explores potential telomerase-targeted therapies. We conducted a systematic review following the PRISMA-P guidelines in the MEDLINE/PubMed and Scopus databases, from January 1995 to April 2024. We searched for suitable articles by utilizing the terms “GBM”, “high-grade gliomas”, “hTERT” and “telomerase”. We incorporated studies addressing telomerase-targeted therapies into GBM studies, excluding non-English articles, reviews, and meta-analyses. We evaluated a total of 777 records and 46 full texts, including 36 studies in the final review. Several compounds aimed at inhibiting hTERT transcription demonstrated promising preclinical outcomes; however, they were unsuccessful in clinical trials owing to intricate regulatory pathways and inadequate pharmacokinetics. Direct hTERT inhibitors encountered numerous obstacles, including a prolonged latency for telomere shortening and the activation of the alternative lengthening of telomeres (ALT). The G-quadruplex DNA stabilizers appeared to be potential indirect inhibitors, but further clinical studies are required. Imetelstat, the only telomerase inhibitor that has undergone clinical trials, has demonstrated efficacy in various cancers, but its efficacy in GBM has been limited. Telomerase-targeted therapies in GBM is challenging due to complex hTERT regulation and inadequate inhibitor pharmacokinetics. Our study demonstrates that, despite promising preclinical results, no Telomerase inhibitors have been approved for GBM, and clinical trials have been largely unsuccessful. Future strategies may include Telomerase-based vaccines and multi-target inhibitors, which may provide more effective treatments when combined with a better understanding of telomere dynamics and tumor biology. These treatments have the potential to be integrated with existing ones and to improve the outcomes for patients with GBM. Full article

Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response. Full article

Background: Central Venous Catheter (CVC)-related infections cannot always be solved by replacement, due to some vascular anomalies or an emergency status. This comprehensive, evidence-based review aimed to define the efficacy of antibacterial lock therapy (ALT) compared to the standard of care (SoC) in CVC-related infections. Methods: We performed a systematic search in PubMed, Embase, and Google Scholar, looking for randomized controlled trials (RCTs) and cohort or case-control observational studies. The eligible studies considered the subjects with a diagnosis of CVC-related infections treated with antibacterial lock therapy (ALT) compared to the standard of care (SoC). Results: Among 609 records at the end of the selection process, five articles, referring to observational studies, were included in this systematic review. In pooled analyses, including a total of 276 individuals, microbiological healing (OR 3.78; 95% CI; 2.03–7.03) showed significant differences between ALT and the SoC, with a follow-up varying from 2 weeks to 3 months. Conclusions: Our results suggested that ALT could improve the preservation of CVCs and could be considered when their replacement is not possible as a result of vascular problems. However, only observational studies were included and RCTs are needed to confirm these findings and to increase the level of evidence. Full article

Trans fatty acids are specific unsaturated fats found in processed foods that undergo hydrogenation, leading to hepatic disorders such as metabolic-associated fatty liver disease (MAFLD) and conditions like CVD and CKD. The effects of different food samples containing trans fatty acids (elaidic and oleic acid) on the liver, heart, and kidney through antioxidant enzyme activity were investigated in animal models. Liver function tests (ALT, ALP, AST, and LDH), heart biomarker levels (CPK, TC, HDL, LDL, and triglycerides), and kidney biomarker levels (serum creatinine, blood urea nitrogen, and serum uric acid) were examined in serum of rabbits and the histopathology of liver tissues. Results showed that these biomarkers were more elevated in the Mujahid Ghee group than in the normal control, oleic acid, and Kausar Ghee groups. The concentration of antioxidant markers such as peroxidase, glutathione, catalase, thiobarbituric acid reactive substances, and superoxide dismutase were lower in the Mujahid Ghee group. HPLC showed that Mujahid Ghee had the highest quantified value of elaidic acid among all selected samples. Overall, this study demonstrated that elaidic acid in its purest form aggravated MAFLD in rabbit livers and provoked CVK and CVD. Full article

Background: A few months after the COVID-19 pandemic onset, knowledge of SARS-CoV-2 infection and outcomes and treatments blew up. This paper aimed to evaluate the features of a Tuscany COVID-19 hospitalized cohort and to identify risk factors for COVID-19 severity. Methods: This retrospective observational COVID-19 cohort study (1 March 2020–1 March 2021) was conducted on patients ≥ 18 years old, admitted to Tuscany Hospital, and subjected to follow-up within 12 months after discharge. Patients were enrolled at Pisana, Senese and Careggi University Hospitals, and South East, North West, and Center Local Hospitals. Results: 2888 patients (M = 58.5%, mean age = 66.2 years) were enrolled, of whom 14.3% (N = 413) were admitted to an intensive care unit. Smokers were 25%, and overweight and obese 65%. The most used drugs were corticosteroids, antacids, antibiotics, and antithrombotics, all antiviral drugs, with slight differences between 2020 and 2021. A strong association was found between outcomes of evolution towards critical COVID-19 (non-invasive mechanical ventilation (NIV) and/or admission to intensive care) and smoking (RR = 4.91), ex-smoking (RR = 3.48), overweight (RR = 1.30), obese subjects (RR = 1.62), comorbidities (aRR = 1.38). The alteration of liver enzymes (aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyl transpeptidase) was associated with NIV (aOR = 2.28). Conclusions: Our cohort, characterized by patients with a mean age of 66.2 years, showed 65% of patients were overweight and obese. Smoking/ex-smoking, overweight/obesity, and other comorbidities were associated with COVID-19 adverse outcomes. The findings also demonstrated that alterations in liver enzymes were associated with worse outcomes. Full article

Background: Football, as the most popular sport worldwide, has long been under suspicion of causing varus knee alignment as early as adolescence. However, no causal relationship has yet been found. The first step to do so would be to determine the prevalence of lower leg malalignment among male junior football players depending on age, performance level and the number of active seasons played. Methods: Leg axis alignment in frontal plane was determined in male junior football players of different age levels between 7 and 18 years by measuring the intercondylar/intermalleolar distance (ICD/IMD) in an upright position. In addition to anthropometric data, multiple sport-specific data such as the start of their football career or training time per week were collected by means of questionnaires (clinical trial registration number: DRKS00020446). Results: 207 male junior football players were included in this survey. The mean age was 12.8 years. Within the group of 15 to 18 year olds, the prevalence of varus knee malalignment was highest at just under a third (32.1%). In the subpopulation that played actively for more than ten seasons, 28.9% showed varus leg axis. Regarding performance level, the highest IMD/ICD values and highest prevalence of varus alignment were found among football players who play on a semi-professional level (16.7%), compared to amateur (11.4%) and high-performance levels (2.8%). Conclusions: Further research is necessary to investigate if this high prevalence of varus knee in children of a higher age and higher playing levels is due to the selection bias of football players with varus knee or a real development of varus knee in individuals. Full article

Background: The serum levels of presepsin correlate with parameters indicating cholestasis in sepsis; however, the probability and significance of this association remain uncertain. We aimed to ascertain whether infection, as signaled by presepsin levels, is the primary determinant of elevated biliary parameters in sepsis. Methods: A unicenter, retrospective study included 396 COVID-free emergency-admitted patients, in which presepsin level was determined. Presepsin, neutrophil count, leukocyte count, C reactive protein, and fibrinogen evaluated the septic/inflammatory state. The statistically significant factors associated with cholestasis, ALT, and AST were analyzed by Fisher’s exact test and Spearman regression with Bonferroni’s correction. Results: Presepsin emerged as the most likely variable correlated with all cholestasis markers: alkaline phosphatase (p = 7 × 10⁻⁸), gamma-glutamyl transferase (p = 5 × 10⁻¹⁰), and conjugated bilirubin (p = 4 × 10⁻¹⁵). Thrombocyte count, C reactive protein, age, creatinine, urea, lactate, and blood pressure, were associated with only one or two of these markers. Conclusions: In a sepsis setting, the increase in cholestasis-related parameters is associated with presepsin with a higher probability than hemodynamic, inflammatory, or coagulation-related variables. Determining this robust link between sepsis and cholestasis could eliminate unnecessary imaging procedures in critically ill patients, enabling clinicians to focus efforts on addressing the primary infectious cause. Full article

Parenteral nutrition (PN) is a life-sustaining method to provide adequate nutrients to patients unable to receive oral or enteral nutrition. PN typically contains a mixture of macro- and micro-nutrients, although the lipid composition has been identified as a concern for liver disease. Therefore, the study of the intravenous lipid emulsion (ILE) prescribing practices in home-based PN (HPN) patients and whether differing lipid PN alters liver function tests (LFTs) is needed. Methods: A retrospective study of monthly LFTs from a random sample of 105 adult HPN patients in the U.S. over a 6-month period was conducted. Patients were receiving olive oil/soy oil (n = 53, Clinolipid), mixed ILE (n = 39, SMOF Lipid), soy oil (SO; n = 4, Intralipid), or none (n = 7). LFTs monitored were alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (T Bili). Results: No differences were observed in baseline LFTs across groups (all, p > 0.25, η² < 0.04), nor were there differences in age, body mass index, days of PN, or mean PN volume (all, p > 0.36, η² < 0.05). There were no significant interactions between ILE type and time (all p > 0.64, η_p² < 0.03), no effect of ILE type (all p > 0.60, η_p² < 0.03), and no effect of time (all p > 0.69, η_p² < 0.01) in terms of LFTs. Average LFTs over six months were also not different between ILE types (all p > 0.30, η² < 0.04). Conclusion: These findings suggested that patients were mostly prescribed mixed or ILE PN containing more than one lipid source and that differing ILEs in long-term HPN patients did not alter LFTs over a six-month period. Full article

During field surveys and culture procedures, large growth disparities in Anguilla japonica have been observed. However, the potential causes are unknown. This study explored differences in digestive ability, metabolic levels, and transcriptomic profiles of appetite-related genes between growth-retarded eel (GRE) and normal-growing eel (NGE) under the same rearing conditions. The results showed that growth hormone (gh) mRNA expression in GREs was considerably lower than NGEs. The levels of total protein (TP), total cholesterol (T-CHO), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood ammonia (BA), blood urea nitrogen (BUN), and alkaline phosphatase (ALP) in GREs were significantly lower than in NGEs. Conversely, levels of glucose (GLU), alanine aminotransferase (ALT), and aspartate transaminase (AST) were higher in GREs. The activities of SOD, CAT, and T-AOC levels were also significantly lower in GREs, as were the activities of glucose-related enzymes including hexokinase (HK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PASE). Additionally, orexigenic genes (npy and ghrelin) were dramatically downregulated, whereas anorexigenic genes (crh and pyy) were significantly upregulated in GREs. These findings suggested that variances in growth hormone, metabolic activities, and appetite level could be associated with the different growth rates of A. japonica. The present research not only revealed the characteristics of the growth, metabolism, and appetite of GREs but also offered new perspectives into the substantial growth discrepancies in A. japonica, providing novel ideas for enhancing fish growth. Full article

The growing demand for bio-pharmaceuticals necessitates improved methods for the characterization of stirred tank reactors (STRs) and their mixing heterogeneities. Traditional Eulerian measurement approaches fall short, culminating in the use of Lagrangian Sensor Particles (LSPs) to map large-scale STRs and track the lifelines of microorganisms such as Chinese Hamster Ovary cells. This study investigates the hydrodynamic characteristics of LSPs, specifically examining the effects that the size and position of the Center of Mass (CoM) have on their flow-following capabilities. Two Lagrangian Particle (LP) designs are evaluated, one with the CoM and a Geometric Center aligned, and another with a shifted CoM. The experimental study is conducted in a rectangular vessel filled with deionized water featuring a stationary circular flow. Off-center LPs exhibit higher velocities, an increased number of floor contacts, and moreover, a less homogeneous particle probability of presence within the vessel compared to LPs with CoM and Geometric Center aligned. Lattice Boltzmann Large Eddy Simulations provide complementary undisturbed fluid velocity data for the calculation of the Stokes number $St$. Building upon these findings, differences in the Stokes number $St$ between the two LP variants of $\Delta St$ = 0.01 (25 mm LP) and $\Delta St$ = 0.13 (40 mm LP) are calculated, highlighting the difference in flow behavior. Furthermore, this study offers a more representative calculation of particle response time approach, as the traditional Stokes number definition does not account for non-homogeneous particles, resulting in an alternative Stokes number ($\Delta {St}_{\mathrm{alt}}$ = 0.84 (25 mm LP) and $\Delta {St}_{\mathrm{alt}}$ = 2.72 (40 mm LP)). This study contributes to the improved characterization of STRs through the use of Lagrangian Sensor Particles. Results highlight the implications the internal mass distribution has on LSP design, offering crucial considerations for researchers in the field. Full article

Exposure to mercury (Hg) and lead (Pb), in combination with liver and kidney impairment, may result in adverse birth outcomes. From 408 women in the age range of 16 to 46 years, living in rural and urban areas in the interior of Suriname, we looked at the association between adverse birth outcomes and exposure to Hg and Pb in combination with liver and kidney function. This group of women represented a subcohort of pregnant women who participated in the Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH)—Meki Tamara study. Liver function was assessed by measuring aspartate amino transferase (AST), alanine amino transferase (ALT), and gamma-glutamyl transferase (GGT). Kidney function was assessed by measuring creatinine, urea, and cystatin C. We defined preterm births as birth before 37 weeks of gestation, low birthweight as birthweight < 2500 g, and low Apgar score as a score < 7 at 5 min, and these were used as indicators for adverse birth outcomes. Small size for gestational age was defined as gestational age < −2SD weight for GA. We found significant statistical associations between biomarkers for liver and kidney functions and adverse birth outcomes Apgar score and gestational age. No significant association was found between heavy metals Hg and lead and adverse birth outcomes. Full article

Background: Lipid metabolism disorder appears to be one of the early features of alcoholic liver disease (ALD), which can be speculated via omics analysis including liver transcriptomics and gut microbiota. A complex consisting of the roots of Pueraria lobata and dried fruits of Prunus mume (PPC), which possesses hepatoprotective effects, could serve as a drug or functional food. The lack of non-polysaccharide compounds in PPC with their moderation effects on gut microbiota suggests the necessity for a relevant study. Methods: Six groups of Kunming mice (control, Baijiu injury, silybin, low, medium, and high) were modelled by gavage with Baijiu (for 14 days) and PPC (equivalent to a maximum dose of 9 g/kg in humans). The liver transcriptome data were analyzed to predict gene annotation, followed by the verification of gut microbiota, serum, tissue staining, immunohistochemistry, and Western blotting. Liquid chromatography-mass spectrometry was used to detect the components. Results: PPC normalized serum ALT (40 U/L), down-regulated TLR4-NF-κB signaling pathway to inhibit the release of TNF-α (90 pg/mL), improved the expression of occludin, claudin-4, and ZO-1, and restored the abundance of Muribaculaceae, Bacteroides and Streptococcus. Conclusion: PPC can alleviate ALD by regulating the gut microbiota with an anti-inflammatory and intestinal barrier, and has an application value in developing functional foods. Full article

This study examines the complex interplay of genetic and environmental interactions that shape chronic illness risk. Evidence is mounting for the role of genetic expression and the immune response in the pathogenesis of chronic disease. In the Rio Grande Valley of south Texas, where 90% of the population is Mexican American, chronic illnesses (including obesity, diabetes, nonalcoholic liver disease, and depression) are reaching epidemic proportions. This study leverages an ongoing family study of the genetic determinants of risk for obesity, diabetes, hypertension, hyperlipidemia, and depression in a Mexican American population. Data collected included blood pressure, BMI, hepatic transaminases, HbA1c, depression (BDI-II), acculturation/marginalization (ARSMA-II), and liver health as assessed by elastography. Heritability and genotype-by-environment (G×E) interactions were analyzed, focusing on the marginalization/separation measure of the ARSMA-II. Significant heritabilities were found for traits such as HbA1c (h² = 0.52), marginalization (h² = 0.30), AST (h² = 0.25), ALT (h² = 0.41), and BMI (h² = 0.55). Genotype-by-environment interactions were significant for HbA1c, AST/ALT ratio, BDI-II, and CAP, indicating that genetic factors interact with marginalization to influence these traits. This study found that acculturation stress exacerbates the genetic response to chronic illness. These findings underscore the importance of considering G×E interactions in understanding disease susceptibility and may inform targeted interventions for at-risk populations. Further research is warranted to elucidate the underlying molecular pathways and replicate these findings in diverse populations. Full article

Background and Objectives: Gestational diabetes mellitus (GDM) may impact both maternal and fetal/neonatal health. The identification of prognostic indicators for GDM may improve risk assessment and selection of patient for intensive monitoring. The aim of this study was to find potential predictors of adverse pregnancy outcome in GDM and normoglycemic patients by comparing the levels of different biochemical parameters and the values of blood cell count (BCC) between GDM and normoglycemic patients and between patients with adverse and good outcome. Materials and Methods: Prospective clinical study included 49 patients with GDM (study group) and 44 healthy pregnant women (control group) who underwent oral glucose tolerance test (OGTT) at gestational age of 24–28 weeks. At the time of OGTT peripheral blood was taken for the determination of glucose levels, insulin, glycated hemoglobin, lipid status, homeostatic model assessment, BCC, iron and zinc metabolism, liver function, kidney function and inflammatory status. Each group was divided into two subgroups—normal and poor pregnancy outcome. Results: Higher RBC, hemoglobin concentration, hematocrit value, fasting glucose, uric acid and fibrinogen were found in GDM patients compared to control group. In GDM patients with poor pregnancy outcome values of fibrinogen, ALT, sedimentation rate, granulocyte and total leukocyte counts were elevated, while the serum level of zinc was significantly lower. Higher level of fibrinogen was found in normoglycemic patients with adverse pregnancy outcomes. ROC curve was constructed in order to assess fibrinogen’s biomarker potential. The established AUC value for diagnostic ROC was 0.816 (p < 0.001, 95% CI 0.691–0.941), while the AUC value for assessing fibrinogen’s potential to predict poor pregnancy outcome in GDM was 0.751 (p = 0.0096, 95% CI 0.561–0.941). Conclusions: The results of our study demonstrated that the best prognostic potential in GDM showed inflammation related parameters, identifying fibrinogen as a parameter with both diagnostic and prognostic ability. Full article

Background: The COVID-19 pandemic has brought about widespread effects on communities on a global scale, with impacts varying among different demographics. This study focuses on a unique cohort of COVID-19-positive patients from Arunachal Pradesh, a region in northeast India with a substantial indigenous population. This study aims to delve into the features and consequences of COVID-19 in this indigenous population within this distinct demographic region, with a special focus on assessing the effects on tribal communities. Out of a total of 1627 COVID-19 positive cases, 1392 belonged to various tribes of Arunachal Pradesh, categorized as the indigenous population of the region. Our research primarily focuses on examining the biochemical and inflammatory indicators that forecast the clinical results of COVID-19 patients, specifically within both indigenous and non-indigenous groups. Methods: Biochemical markers, including hematological parameters, liver and kidney function biomarkers, D-DIMER, and inflammatory markers, were assessed along with immune-inflammatory ratios: neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Differences in biomarker levels and ratios across disease severities were analyzed, and significant data were observed using descriptive statistics. Results: Elevated levels of Ferritin (CRP, IL-6, D-DIMER, Creatinine, Urea, AST/SGOT, and ALT/SGPT) were associated with increasing disease severity in COVID-19 cases, reflecting increased inflammation, multi-organ dysfunction, and coagulopathy in the severe COVID-19 category amongst the indigenous population. The data showed an aligned report with the non-indigenous population of India when compared with various other studies (using a Spearman rank correlation test). Similarly, an increase in the neutrophil-to-lymphocyte ratio (NLR) and a declining shift in the lymphocyte-to-monocyte ratio (LMR) indicated deregulated immune responses and systemic inflammation in the severe category of COVID-19. Conclusion: This population-based study from northeast India offers important perspectives into the pathophysiology of COVID-19 and its link with disease severity among indigenous and non-indigenous populations. Full article