Biomedicines最新文献

Background/objectives: Micropulse laser trabeculoplasty (MLT) is gaining attention as a non-invasive treatment option for primary open-angle glaucoma (POAG), offering an alternative to traditional surgeries and medications. This systematic review evaluates the effectiveness, safety, and potential of MLT in glaucoma management.

Methods: This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, following the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) recommendations.

Results: We identified 79 articles, and after removing duplicates and screening abstracts, 56 articles were eligible for further review. A detailed full-text analysis was conducted on 26 articles, of which 15 met the predefined inclusion criteria.

Conclusions: MLT shows promise as a primary or adjunctive treatment for reducing intraocular pressure (IOP) in glaucoma and ocular hypertension patients. Current evidence supports its efficacy and safety; however, additional long-term studies are needed to confirm its durability and compare its effectiveness with traditional surgical and pharmacological approaches. Standardizing treatment protocols and refining patient selection criteria could enhance MLT's clinical value and support its broader adoption in glaucoma care.

Background: Brain cancers represent a formidable oncological challenge characterized by their aggressive nature and resistance to conventional therapeutic interventions. The tumor microenvironment has emerged as a critical determinant of tumor progression and treatment efficacy. Within this complex ecosystem, microglia and macrophages play fundamental roles, forming intricate networks with peripheral immune cell populations, particularly T cells. The precise mechanisms underlying microglial interactions with T cells and their contributions to immunosuppression remain incompletely understood. Methods: This review comprehensively examines the complex cellular dialogue between microglia and T cells in two prominent brain malignancies: primary glioblastoma and secondary brain metastases. Results: Through a comprehensive review of the current scientific literature, we explore the nuanced mechanisms through which microglial-T cell interactions modulate tumor growth and immune responses. Conclusions: Our analysis seeks to unravel the cellular communication pathways that potentially underpin tumor progression, with the ultimate goal of illuminating novel therapeutic strategies for brain cancer intervention.

Background/Objectives: Colorectal cancer (CRC) is one of the most common oncological disorders. Its fundamental treatments include surgery and chemotherapy, predominantly utilizing 5-fluorouracil (5-FU). Despite medical advances, CRC continues to present a high risk of recurrence, metastasis and low survival rates. Consequently, significant emphasis has been directed towards exploring novel types of cell death, particularly ferroptosis. Ferroptosis is characterized by iron imbalance and the accumulation of lipid peroxides and reactive oxygen species (ROS), leading to cellular damage and death. Thus, the discovery of safe inducers of ferroptosis, offering new hope in the struggle against CRC, remains crucial. In this study, we applied the concept of drug repositioning, selecting mesalazine (MES), a non-steroidal anti-inflammatory drug (NSAID), for investigation. Methods: The study was conducted on the colon cancer cell line DLD-1 and normal intestinal epithelial cells from the CCD 841 CoN cell line. Both cell lines were treated with MES solutions at concentrations of 10, 20, 30, 40, and 50 mM. Cytotoxicity was assessed using the MTT assay, while ferroptosis-related gene expression analysis was performed using oligonucleotide microarrays, with RT-qPCR used for validation. Results: MES effectively reduces the viability of DLD-1 cells while minimally affecting normal intestinal cells. Subsequent oligonucleotide microarray analysis revealed that MES significantly alters the expression of 56 genes associated with ferroptosis. Conclusions: Our results suggest that MES may induce ferroptosis in CRC, providing a foundation for further research in this area.

Poor ovarian response (POR) remains a significant challenge in the field of assisted reproductive technology (ART), as the quantity and quality of oocytes retrieved directly influence embryo implantation, clinical pregnancy, and live birth rates. Metabolomics has become a valuable tool for elucidating the molecular mechanisms underlying diminished ovarian reserve (DOR) and POR. This review aims to synthesize findings from metabolomic studies examining metabolite expression patterns in serum and follicular fluid samples from women with POR. A literature search was performed using the Medline/PubMed and Scopus databases, employing keywords related to metabolomics and POR. In total, nine studies met the inclusion criteria for this review. These studies identified several metabolites with differential expression in serum and follicular fluid samples between women with normal ovarian response and those with POR. Although the metabolomic profiles varied significantly among studies, consistent alterations in prostaglandin related metabolites were observed in two of the nine studies reviewed. These findings suggest that, pending further validation, these metabolites may serve as potential biomarkers for ovarian response. Metabolomics has significantly advanced our understanding of the mechanisms underlying ovarian function and holds promise for identifying effective biomarkers that could improve the prediction and management of POR.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and affects nearly 30% of the adult population and 10% of the pediatric population. It is estimated that this number will double by 2030. MASLD is one of the leading causes of hepatocellular carcinoma, cirrhosis, and liver transplantation, as well as a significant risk factor for cardiovascular disease and mortality. Due to the ever-increasing number of patients, the long-term asymptomatic course of the disease, serious complications, and lack of preventive programs, as well as insufficient awareness of the disease among patients and doctors themselves, MASLD is a growing interdisciplinary problem and a real challenge for modern medicine. The main cause of MASLD is an inappropriate lifestyle-inadequate nutrition and insufficient physical activity, which lead to various components of metabolic syndrome. Lifestyle changes-appropriate diet, weight reduction, and systematic physical activity-are also the basis for the prevention and treatment of MASLD. Hence, in recent years, so much importance has been attached to lifestyle medicine, to non-pharmacological treatment as prevention of lifestyle diseases. The narrative review presents possible therapeutic options for non-pharmacological management in the prevention and treatment of MASLD. The best documented and available diets used in MASLD were discussed, focusing on the benefits and drawbacks of the Mediterranean, high-protein, ketogenic, and intermittent fasting diets. In addition, the most recent recommendations regarding physical activity are summarized.

Background/objectives: Autoimmune inflammation enhances the electrical instability of the atrial myocardium in patients with systemic sclerosis (SSc); thus, atrial arrhythmia risk is increased, which might be predicted by evaluating the P wave interval and dispersion of a 12-lead surface electrocardiogram (ECG).

Methods: We examined 26 SSc patients and 36 healthy controls and measured the P wave interval and P wave dispersion of the 12-lead surface ECG in each patient. Furthermore, echocardiography and 24-h Holter ECG were performed and levels of inflammatory laboratory parameters, including serum progranulin (PGRN), sVCAM-1, sICAM-1, leptin and C-reactive protein (CRP), were determined. Lipid parameters, such as Apo A-I, LDL-cholesterol (LDL-C), oxidized LDL (oxLDL) and the LDL and HDL subfractions were also evaluated.

Results: The P wave interval showed a significant positive correlation with the levels of Apo A-I, LDL-C, CRP, sVCAM-1, sICAM-1 and leptin. The oxLDL level correlated positively with P wave dispersion. Of note, significant positive correlation was also found between the large HDL percentage and the P wave interval.

Conclusions: Our results suggest that PGRN, sVCAM-1, sICAM-1, leptin, CRP, LDL-C and oxLDL, along with LDL and HDL subfractions, might have a role in atrial arrhythmogenesis in patients with SSc.

Background: Hypertriglyceridemia has serious health risks such as cardiovascular disease, type 2 diabetes mellitus, nephropathy, and others. Fenofibrate is an effective hypolipidemic drug, but its benefits for ameliorating disorders associated with hypertriglyceridemia failed to be proven in clinical trials. Methods: To search for possible causes of this situation and possibilities of their favorable influence, we tested the effect of FF monotherapy and the combination of fenofibrate with silymarin on metabolic disorders in a unique model of hereditary hypertriglyceridemic rats (HHTg). Results: Fenofibrate treatment (100 mg/kg BW/day for four weeks) significantly decreased serum levels of triglyceride, (-77%) and free fatty acids (-29%), the hepatic accumulation of triglycerides, and the expression of genes encoding transcription factors involved in lipid metabolism (Srebf2, Nr1h4. Rxrα, and Slco1a1). In contrast, the hypertriglyceridemia-induced ectopic storage of lipids in muscles, the heart, and kidneys reduced glucose utilization in muscles and was not affected. In addition, fenofibrate reduced the activity of the antioxidant system, including Nrf2 expression (-35%) and increased lipoperoxidation in the liver and, to a lesser extent, in the kidneys and heart. Adding silymarin (micronized form, 600 mg/kg BW/day) to fenofibrate therapy increased the synthesis of glycogen in muscles, (+36%) and reduced hyperinsulinemia (-34%). In the liver, it increased the activity of the antioxidant system, including PON-1 activity and Nrf2 expression, and reduced the formation of lipoperoxides. The beneficial effect of combination therapy on the parameters of oxidative stress and lipoperoxidation was also observed, to a lesser extent, in the heart and kidneys. Conclusions: Our results suggest the potential beneficial use of the combination of FF with SLM in the treatment of hypertriglyceridemia-induced metabolic disorders.

Reprogramming energy metabolism is pivotal to tumor development. Ketone bodies (KBs), which are generated during lipid metabolism, are fundamental bioactive molecules that can be modulated to satisfy the escalating metabolic needs of cancer cells. At present, a burgeoning body of research is concentrating on the metabolism of KBs within tumors, investigating their roles as signaling mediators, drivers of post-translational modifications, and regulators of inflammation and oxidative stress. The ketogenic diet (KD) may enhance the sensitivity of various cancers to standard therapies, such as chemotherapy and radiotherapy, by exploiting the reprogrammed metabolism of cancer cells and shifting the metabolic state from glucose reliance to KB utilization, rendering it a promising candidate for adjunct cancer therapy. Nonetheless, numerous questions remain regarding the expression of key metabolic genes across different tumors, the regulation of their activities, and the impact of individual KBs on various tumor types. Further investigation is imperative to resolve the conflicting data concerning KB synthesis and functionality within tumors. This review aims to encapsulate the intricate roles of KBs in cancer metabolism, elucidating a comprehensive grasp of their mechanisms and highlighting emerging clinical applications, thereby setting the stage for future investigations into their therapeutic potential.

Background/Objectives: Traumatic brain injury (TBI) occurs after a sudden mechanical force to the skull and represents a significant public health problem. Initial brain trauma triggers secondary pathophysiological processes that induce structural and functional impairment of the central nervous system, even in the regions distant to the lesion site. Later in life, these changes can be manifested as neurodegenerative sequalae that commonly involve proteinopathies, such as transactive DNA-binding protein 43 (TDP-43). The progression of pathophysiological changes to the spinal cord motor neurons has been detected after repetitive TBI, while such changes have been less investigated after single TBI. Methods: Single TBI was applied over the left parietal cortex of mice by using the lateral fluid percussion injury apparatus and a separate cohort of animals received repetitive mild TBI by weight drop apparatus, with two mild injuries daily, for five days in a row. Mice were sacrificed after single moderate or last mild TBI and their spinal cords were prepared for the analyses. For both types of injury, sham-injured mice were used as a control group. Results: Here, we found an early formation of toxic phosphorylated TDP-43 species on the 3rdday post-injury which, together with TDP-43 cytoplasmic translocation, remained present in the subacute period of 14 days after repetitive mild but not single moderate TBI. During the subacute period following a repetitive brain trauma, we found an increased choline acetyltransferase protein expression and significant microgliosis in the cervical part of the spinal cord, which was not detected after single TBI. Astrogliosis presented similarly after both experimental procedures. Conclusions: This study demonstrates the differences in the spinal cord TDP-43 pathology and inflammation, depending on the brain trauma type, and may contribute to the development of targeted therapeutic strategies.

Background/Objectives: Tannic acid (TA) is a well-known natural phenolic acid composed of ten gallic acids linked to each other with ester bonding possessing excellent antioxidant properties in addition to antimicrobial and anticancer characteristics. Arginine (ARG) is a positively charged amino acid at physiological pH because of nitrogen-rich side chain. Method: Here, poly(tannic acid-co-arginine) (p(TA-co-ARG)) particles at three mole ratios, TA:ARG = 1:1, 1:2, and 1:3, were prepared via a Mannich condensation reaction between TA and ARG by utilizing formaldehyde as a linking agent. Results: The p(TA-co-ARG) particles in 300-1000 nm size range with smooth surfaces visualized via SEM analysis were attained. Abundant numbers of functional groups, -OH, -NH₂, and -COOH stemming from TA and ARG constituent confirmed by FT-IR analysis. The isoelectric point (IEP) of the particles increased from pH 4.98 to pH 7.30 by increasing the ARG ratios in p(TA-co-ARG) particles. The antioxidant capacity of p(TA-co-ARG) particles via gallic acid (GA) and rosmarinic acid (RA) equivalents tests revealed that particles possess concentration-dependent antioxidant potency and increased by TA content. The α-glucosidase inhibition of p(TA-co-ARG) particles (2 mg/mL) 1:1 and 1:2 mole ratios revealed significant enzyme inhibition ability, e.g., 91.3 ± 3.1% and 77.6 ± 12.0%. Interestingly, p(TA-co-ARG) (1:3 ratio) possessed significant antibacterial effectiveness against Escherichia coli (ATCC 8739) and Staphylococcus aureus (ATCC 6538) bacteria. Furthermore, all p(TA-co-ARG) particles at 1000 mg/mL concentration showed >80% toxicity on L929 fibroblast cells and increased as ARG content of p(TA-co-ARG) particles is increased. Conclusions: p(TA-co-ARG) showed significant potential as natural biomaterials for biomedical use.