Biomedicines最新文献

Background: Disorders of glucose and lipid metabolism, such as obesity, diabetes mellitus, or hypercholesterolemia, can cause serious complications, reduce quality of life, and lead to increased premature mortality. Olivetol, a natural compound, could be proposed as a promising therapeutic agent for preventing, treating, or alleviating metabolic complications of such pathological conditions.

Methods: In this study, the researchers conducted a broad parallel investigation of olivetol's effects on metabolic state and gut microbiota functionality in mouse models of alimentary obesity, diabetes mellitus type 1 and 2, and hypercholesterolemia.

Results: According to the results of the study, olivetol caused a lowering of body weight in C57Bl6 mice fed a high-fat diet and in ldlr(-/-) mice, decreased serum glucose levels in db/db mice, improved lipid metabolism in ldlr(-/-) mice, and prevented inflammatory infiltration of the pancreas and loss of insulin secretion in NOD mice. In addition, olivetol affected the composition and functional activity of gut microbiota communities, inducing an expansion of probiotic species such as Akkermansia muciniphila and Bacteroides acidifaciens and depleting the representation of pathobionts such as Prevotella, although olivetol supplementation did not influence the diversity or richness of the communities.

Conclusions: These results suggest that olivetol is a promising therapeutic agent for preventing, treating, or alleviating the metabolic complications of obesity, diabetes mellitus type 1 and 2, and hypercholesterolemia; however, more investigations are required in order to attain a full understanding of its physiological effects.

Background/Objectives: This systematic review and meta-analysis aimed to investigate the effect of prebiotics, alone or as part of synbiotics, on cardiometabolic parameters in polycystic ovary syndrome (PCOS) women. Methods: Databases, including PubMed, Scopus, ISI Web of Science, Embase, and the Cochrane Central Register of Controlled Trials, were searched for relevant randomized-controlled trials (RCTs) until 12 December 2024. Changes in mean ± standard deviations were extracted and combined using a random-effects model. Bias was assessed using Cochrane risk of bias and evidence quality with GRADE. Results: Twenty RCTs with 1271 participants were included. Results showed high-quality evidence supporting prebiotics' effects, alone or as part of synbiotics, in reducing body-mass index [n = 853; weighted-mean difference (WMD): -0.510, 95%CI: -0.669, -0.351 kg/m²] and diastolic blood pressure (WMD: -2.218, 95%CI: -4.425, -0.010 mmHg), moderate-quality evidence for weight, waist-to-hip ratio, and triglycerides improvements, and low or very-low-quality evidence for waist circumference (WC), fat mass, fasting plasma glucose, fasting insulin, low-density lipoprotein (LDL), total cholesterol (TC), high sensitive-C reactive protein, total testosterone, follicle-stimulating hormone and free androgen index improvements. Subgroup analyses revealed possible reduction in LDL with prebiotics, as well as possible decreases in WC, TC, and total testosterone with synbiotics. Dietary approaches to stop hypertension diet improved insulin sensitivity. Conclusions: This study suggests that prebiotics may beneficially affect several cardiometabolic parameters in PCOS women. Approximately one-third of the results were based on moderate-to-high-quality evidence. This study highlights the need for future well-designed, larger RCTs with longer treatment duration to strengthen the evidence base and guide clinical decision-making.

Background/Objectives: Cold atmospheric plasma (CAP) has been demonstrated as an adjustable device to generate various combinations of short-lived reactive oxygen and nitrogen species (RONS) and as a promising appliance for cancer therapy. This study investigated the effects of direct and indirect treatments of Argon-based CAP to cancer cells (A2058, A549, U2OS and BCC) and fibroblasts (NIH3T3 and L929) on cell viability. We also aimed to understand whether plasma-generated RONS were involved in this process using genetic evidence. Methods: The intensity of reactive species in the plasma gas and the concentrations of RONS in phosphate-buffered saline (PBS) and cell culture medium were measured. A viability assay was performed after the cells were treated by plasma in PBS and medium with various volumes to realize the lethal effects of plasma under different conditions. Diverse cells were treated in the same solution to compare the sensitivities of different cells to plasma treatments. The gene expression profiles of A2058 cells after the direct and indirect treatments were analyzed by next generation gene sequencing. Accordingly, we discovered the advantages of sequential treatments on cancer therapy. Results: The cumulative concentration of hydroxyterephthalic acid (HTA) revealed that the pre-existing OH radical (•OH) in PBS increased with the treatment durations. However, there was no significant increase in the concentration of HTA in culture medium. HTA was detected in the treatment interface of PBS but not medium, showing the penetration of •OH through PBS. The concentrations of H₂O₂ and NO₂^- increased with the treatment durations, but that of NO₃^- was low. The direct treatments caused stronger lethal effects on cancer cells under certain conditions. The fibroblasts showed higher tolerance to plasma treatments. From gene expression analysis, the initial observations showed that both treatments influenced transcription-related pathways and exhibited shared or unique cellular stress responses. The pre-treatments, especially of direct exposure, revealed better cancer inhibition. Conclusions: The anti-cancer efficiency of plasma could be enhanced by pre-treatments and by adjusting the liquid interfaces to avoid the rapid consumption of short-lived RONS in the medium. To achieve better therapeutic effects and selectivity, more evidence is necessary to find optional plasma treatments.

Background: Treprostinil, which is administered via continuous subcutaneous or intravenous infusion, is a medication applied in the treatment of pulmonary arterial hypertension (PAH). The dose of treprostinil is adjusted on an individual basis for each patient. A number of factors determine how well patients respond to treatment. Objectives: The aim of this study was to identify factors that may influence the clinical response to the dose of treprostinil at 3 months after the start of therapy. Methods: The factors influencing treatment response were analyzed in consecutive PAH patients who started receiving treprostinil treatment. The treatment efficacy was assessed as improvement in 6 min walk distance (6MWD) and WHO functional class (WHO FC), a reduction in N-terminal prohormone of brain natriuretic peptide (NTproBNP), and the percentage of patients achieving low-risk status after 12 months of treatment. Results: A total of 83 patients were included in this analysis. Classification of patients according to the tertiles of treprostinil dose achieved at 3 months after drug inclusion shows that after 12 months of follow-up, the median WHO FC in the highest dose group was lower than that in the intermediate dose group (WHO FC II vs. WHO FC III, p = 0.005), the median NTproBNP was lower (922 pg/mL, vs. 1686 pg/mL, p = 0.036) and 6MWD was longer (300 m vs. 510 m, p = 0.015). The French Noninvasive Criteria (NIFC) scale score was higher (2 vs. 0, p = 0.008), and the Reveal scale score was lower (5.0 vs. 8.5, p = 0.034). In the group of patients who exceeded a dose of 19.8 ng/kg/min within 3 months, an improvement in 6MWD was observed significantly more often after one year of therapy, and they were more likely to show an increase in NIFC scale scores after one year of therapy than the group of patients who received the lower dose (65% vs. 30%, p = 0.02). In the group of patients younger than 50 years of age, a statistically significant correlation was observed between the dose of treprostinil achieved after three months of treatment and the parameters assessed after 12 months of treatment, including WHO FC, 6MWD, and NIFC prognostic scale scores (all p < 0.05). Conclusions: The clinical effect of treatment is critically dependent on the rapid escalation of the treprostinil dose during the first three months of treatment.

Background: Conventional treatments for cancers of the head and neck region are often associated with high recurrence rates and impaired quality of life. Photodynamic therapy (PDT) has emerged as a promising alternative, leveraging photosensitizers such as hypericin to selectively target tumour cells with minimal damage to surrounding healthy tissues. Objectives: We aimed to evaluate the efficacy and underlying mechanisms of hypericin-mediated PDT (HY-PDT) in treating head and neck cancers. Methods: Adhering to PRISMA 2020 guidelines, a systematic search was conducted across PubMed/Medline, Embase, Scopus, and the Cochrane Library for studies published between January 2000 and December 2024. Inclusion criteria encompassed preclinical in vitro and in vivo studies and clinical trials focusing on HY-PDT for head and neck malignancies and its subtypes. Results: A total of 13 studies met the inclusion criteria, comprising both in vitro and in vivo investigations. HY-PDT consistently demonstrated significant cytotoxicity against squamous cell carcinoma cells through apoptotic and necrotic pathways, primarily mediated by ROS generation. Hypericin exhibited selective uptake in cancer cells over normal keratinocytes. Additionally, HY-PDT modulated the tumour microenvironment by altering cytokine profiles, such as by increasing IL-20 and sIL-6R levels, which may enhance antitumor immunity and reduce metastasis. Conclusions: HY-PDT emerges as a highly promising and minimally toxic treatment modality for head and neck cancers, demonstrating efficacy in inducing selective tumour cell death and modulating the immune microenvironment. Despite the encouraging preclinical evidence, significant methodological variability and limited clinical data necessitate further large-scale, standardized and randomized controlled trials.

Background/Objectives: It is unknown how early exercise therapy combined with acupuncture (AP) affects the speed of recovery in patients suffering from heart failure with reduced ejection fraction (HFrEF) who are hospitalized due to worsening HF. Methods: A prospective, sham-procedure-controlled, double-blind, randomized clinical trial with three patient groups was conducted. The study included patients with HFrEF who were hospitalized for worsening HF. After initial stabilization, patients were randomly assigned to three groups, the controls (C) treated with optimal drug therapy (ODT); E1 received ODT with kinesitherapy, and sham AP; E2 received ODT, kinesitherapy, and needle AP aiming to enhance compensation. Improvement in physical activity was measured by the modified Barthel index (A test), 2 or 6 min walking tests, an endurance walking test, and decrease of blood brain natriuretic peptide (BNP). Results: A total of 120 patients completed the study. The average age was 74 years, 73.3% were male, median EF was 32%, and 83.3% were New York Heart Association (NYHA) Class III. After the fifth day of therapy, the E2 group showed the greatest improvement in the A test compared to other groups (p = 0.022). After 5 days, 80%, 50%, and 10% achieved an A test score of 30 or higher, demonstrating functional independence, (p < 0.01) in the E2, E1, and C groups, respectively. At hospital discharge, the E2 group showed significantly better walking endurance compared to the E1 and C groups (p < 0.001). At discharge, BNP decreased significantly more in both E groups, compared to the C group. Conclusions: Short-term early rehabilitation with AP and kinesitherapy significantly improves the functional status of HFrEF decompensated patients when compared to kinesitherapy alone and ODT.

Background/Objectives: Periprosthetic osteolysis is the primary cause of arthroplasty failure in the majority of patients. Mechanistically, wear debris released from the articulating surfaces of a prosthesis initiates local inflammation and several modes of regulated cell death programs, such as ferroptosis, which represents a promising therapeutic target in various chronic inflammatory diseases. Thus, the current study aimed at exploring the therapeutic potential of targeting ferroptosis in a polyethylene-wear-debris-induced osteolysis model. Methods: Inverted cell culture model was used for stimulating the cells with wear debris in vitro, and calvarial osteolysis model was used for evaluating the therapeutic effects of inhibitors in vivo. Results: The immunostaining of periprosthetic bone tissues demonstrated a number of osteocytes expressing ferroptosis markers. Likewise, the expressions of ferroptosis markers were confirmed in polyethylene-wear-debris-stimulated osteocyte-like cells and primary osteoblasts in a direct stimulation model but not in an indirect stimulation model. Furthermore, polyethylene wear debris was implanted onto calvarial bone and mice were treated with the ferroptosis inhibitors DFO and Fer-1. These treatments alleviated the inflammatory and pathological bone resorption induced by the wear debris implantation. Conclusions: Our data broaden the knowledge of the pathogenesis of periprosthetic osteolysis and highlight ferroptosis as a promising therapeutic target.

Background: Prostate cancer remains one of the leading causes of cancer-related mortality in men worldwide. The treatment of it is currently based on surgical removal, radiotherapy, and hormone therapy. It is crucial to improve therapeutic prospects for the diagnosis and treatment of prostate cancer via drug target screening. Methods: We integrated eQTL data from the eQTLGen Consortium and pQTL data from UK Biobank Proteome Plasma Proteins (UKB-PPP) and deCODE health datasets. MR analyses (SMR, heterogeneity in dependent instruments (HEIDI), IVW, Wald ratio, weighted median, and MR-Egger) were used to screen candidate genes associated with prostate adenocarcinoma (PRAD) risk. Candidate genes were further verified through TCGA-based gene expression profile, survival analysis, and immune microenvironment evaluations. TIDE analysis was utilized to investigate gene immunotherapy response. Single-cell RNA sequencing data from the GSE176031 dataset were used to investigate the gene expression patterns. The Drug Bank, Therapeutic Target Database and Drug Signatures Database were utilized to predict targeted drugs for candidate genes. Results: MTHFD1 and LGALS4 were identified as promising therapeutic targets for PRAD, with evidence provided at multi-omics levels. LGALS4 was predominantly expressed in malignant cells and was correlated with enhanced immune checkpoint pathways, increased TIDE scores, and immunotherapy resistance. In contrast, MTHFD1was expressed in both tumor and microenvironmental cells and was associated with poor survival. Drug target prediction suggested that there are no currently approved drugs specifically targeting MTHFD1 and LGALS4. Conclusions: Our study identified MTHFD1 and LGALS4 as potential preventive targets for PRAD. However, future experiments are warranted to assess the utility and effectiveness of these candidate proteins.

Severe inflammation leading to organ dysfunction is the cornerstone of the pathophysiology of sepsis. Thus, from a theoretical point of view, rebalancing inflammation has the potential to improve patient outcomes.

Methods: To better understand the clinical effectiveness of hemoadsorption in managing inflammation, we conducted an updated meta-analysis on the effects of CytoSorb in critically ill septic patients. Ten studies containing 715 patients (355 in the interventional group and 360 in the control group) have been included in the final analysis.

Results: Statistical analysis demonstrated that the use of CytoSorb did not influence overall mortality (OR 0.95, 95% CI [0.58, 1.56], p = 0.85), but we observed a decreased mortality when comparing CytoSorb-treated patients with patients in the control group treated with continuous renal replacement therapy (CRRT) (OR 0.97, 95% CI [0.46, 0.98], p = 0.04). We also observed an increased mortality in patients in whom hemoadsorption was initiated earlier in the treatment course (OR 0.97, 95% CI [0.46, 0.98], p = 0.04). We did not observe any significant difference in either intensive care unit length of stay (p = 0.93) or between end-of-treatment severity scores in the two groups (p = 0.24).

Conclusions: Although it has a high risk of bias, current evidence does not support the routine use of CytoSorb in critically ill septic patients. The addition of CytoSorb to CRRT may be associated with decreased survival as compared to CRRT alone, but future studies are needed to draw a definitive conclusion.

Background/Objectives: A wide range of syphilis-related pregnancy complications are encountered in clinical practice. Active surveillance of the epidemiological situation in different countries and a series of retrospective data analyses allow for a comprehensive assessment of the feasible consequences of syphilis infection during pregnancy. The negative effects of infection on reproductive health are also described. Risk-increasing factors (inadequate or late treatment, partner coinfection) and protective factors (timely diagnostics and treatment) are distinguished. The importance of adequate and timely management as well as the accessibility of healthcare and socioeconomic status, which influence health outcomes, are stressed. This article presents a rare case of untreated syphilis infection during pregnancy. The infection was diagnosed during the first antenatal visit; how-ever, treatment was not initiated. At the 33rd week of gestation, the patient was admitted to the hospital because of sparse bloody vaginal discharge. Following sudden fetal hypoxia, an urgent cesarean section was performed at 33 weeks of gestation. A preterm newborn was delivered in critical condition, and congenital syphilis was diagnosed. Methods: We searched the PubMed, Cochrane, and MeSH databases using the key search terms "treponema pallidum", "sexually transmitted infections", "pregnancy", "congenital infection", "syphilis", and "congenital syphilis", as well as their combinations. A total of 28 papers published over a ten-year period were included in the literature review. A clinical case was analyzed. Results: The impact of syphilis on pregnancy is quite evident. Our case showcased one of the most common impacts, i.e., premature birth, of congenital infections with associated bacterial meningitis, respiratory distress syndrome, multiple organ damage, and insufficient weight. Such associations with many adverse pregnancy outcomes as well as congenital syphilis and neonatal defects are often avoidable. Conclusions: Considering the potential consequences of infections, the issue of sexually transmitted diseases remains relevant, and improving diagnostic and treatment opportunities becomes of paramount importance as cases increase.