Search Results (514)

Chronic heart failure (CHF) carries high morbidity and mortality. Circulating biomarkers of myocardial stretch, injury, and remodelling aids diagnosis and prognosis, but utility varies, especially in HFpEF, where natriuretic peptide (NP) values may be lower or normal in obesity. We systematically searched PubMed, Scopus, and Web of Science (2010–2025) for primary adult chronic-HF studies evaluating blood-based biomarkers: NPs, high-sensitivity troponins (hs-cTn), galectin-3, soluble ST2 (sST2), and microRNAs. Secondary sources (reviews/meta-analyses/guidelines) informed context only. Acute-HF studies were not pooled with chronic-HF analyses. Where appropriate, log hazard ratios were meta-analysed with random effects models. Twenty-nine studies met criteria. NT-proBNP remained the diagnostic/prognostic reference; across five prognostic cohorts, the pooled HR was 1.68 (95% CI 1.54–1.82; I² ≈ 55%). hs-cTn consistently improved risk stratification. Galectin-3 and sST2 were associated with adverse outcomes but typically provided modest incremental value beyond NPs/hs-cTn; galectin-3 is influenced by renal function, and sST2 is commonly interpreted around ~28–35 ng/mL. MicroRNAs (e.g., miR-21, miR-210-3p, miR-22-3p) showed promising yet heterogeneous signals across platforms and preanalytical workflows; therefore, findings were synthesised narratively without pooling. NT-proBNP and hs-cTn form the evidence-based backbone for biomarker-guided assessment in chronic HF. Galectin-3 and sST2 add adjunct prognostic information, while microRNAs remain investigational, pending standardised methods and external validation. Overall, evidence supports a multimarker, phenotype-tailored approach, with core NPs + hs-cTn and selective adjunct use of sST2/galectin-3 in context (HFrEF vs. HFpEF, obesity, renal function) to refine risk stratification and guide clinical decision-making. Full article

Studies in cervical and prostate cancer cells have reported that frequent consumption of foods rich in glycine betaine (GB) and choline have beneficial effects against some types of cancer. However, the role of GB against the human colorectal adenocarcinoma cell line HT-29 has not yet been elucidated. Therefore, this study aimed to evaluate the effect of GB on p53 and caspase-3 expression, which regulate cellular processes such as cell proliferation and apoptosis, respectively, on HT-29 cells. HT-29 cells were treated with GB at 5 mg/mL, 15.6 mg/mL, 31.2 mg/mL, and 62.5 mg/mL, after which RNA purification and cDNA synthesis were performed, followed by qPCR to detect the relative expression of p53 and caspase-3, using GAPDH as a reference gene, and protein levels were determined by ELISA. Results indicated that in HT-29 cells treated with GB at 62.5 mg/mL, the protein levels of p53 significantly (p < 0.05) increased to 45 U/mL, as compared with cells without GB (21 U/mL), whereas caspase-3 increased to 30 ng/mL, as compared with control cells (20.13 ng/mL). Therefore, we conclude that GB at high concentrations decreases cell proliferation and induces apoptosis in HT-29 cells. Full article

Background: The interaction between probiotics and the vitamin D/vitamin D receptor (VDR) pathway has been increasingly explored as a potential mechanism for immune modulation in inflammatory bowel disease (IBD). Lactobacillus rhamnosus GG (LGG) has shown promising results in ulcerative colitis (UC) patients, but its effect on the VDR pathway remains unexplored in humans. Aim: To test the hypothesis that LGG can stimulate the vitamin D/VDR pathway and modulate mucosal-adherent microbiota. Methods: In this study, we analyzed a subgroup of 13 patients from the LGGinUC trial, in which UC patients with mild-to-moderate disease activity received LGG monotherapy for four weeks. Colonic biopsy samples were collected before and after treatment to evaluate VDR expression via RT-qPCR and immunohistochemistry. Mucosal-adherent microbiota was also analyzed by DNA extraction and next-generation sequencing (NGS). Results: LGG administration significantly increased VDR mRNA expression in colonic mucosa (p < 0.05), with a corresponding rise in VDR protein levels in both epithelial and sub-epithelial compartments. Microbiota analysis revealed a reduction in α-diversity, primarily due to a decrease in commensal bacterial species, while β-diversity remained largely unchanged. Conclusions: Although the present results have to be considered preliminary, this is the first human study demonstrating that probiotic supplementation can upregulate VDR expression in colonic mucosa. We propose that LGG may exert its beneficial effects in UC by stimulating the VDR pathway, which in turn modulates mucosal immunity and microbiota composition. Further studies with larger sample sizes and longer treatment durations are needed to validate these findings and explore their therapeutic implications. Full article

Objectives: Meniscal integrity is crucial for knee joint stability and the prevention of osteoarthritis (OA) development. Recent studies suggested that mechanical overload and interleukin (IL)-17A may be important intertwined players in meniscal degeneration, but a direct impact of IL-17A on the meniscus has not been investigated. Therefore, the aim of this study was to analyze the effect of IL-17A on meniscal tissue with and without combined mechanical injury (MI). Methods: Meniscal explant disks (1 mm height, 3 mm diameter) were isolated from bovine menisci (preserving the native tibial superficial zone) and exposed to IL-17A [0–100 ng/mL] and/or MI (single compression, 50% strain, strain rate 1 mm/sec). After three days of incubation in a serum-free medium, the proteoglycan release (sGAG; DMMB assay), mRNA level of matrix-degrading enzymes (qRT-PCR), aggrecan degradation (NITEGE immunostaining), and cell death (histomorphometry of nuclear blebbing/apoptosis and condensed nuclei/unspecified cell death) were determined. Statistics: one- and two-way ANOVA with Tukey’s multiple comparisons or Kruskal–Wallis with post hoc testing. Results: IL-17A increased sGAG release in a dose-dependent significant manner. MI also induced the release of sGAG significantly, but the combination with IL-17A showed the highest levels. Both IL-17A and MI individually affected the mRNA levels for ADAMTS4 and MMP-13 slightly, but the combination of both particularly induced a significant increase in mRNA levels. Signals for the ADAMTS4-related aggrecan neoepitope NITEGE were elevated by IL-17A in superficial areas of the excised tissue and by MI in superficial and deeper areas. The combination of both stimuli intensified this signal further. MI increased the number of cells with condensed nuclei significantly and induced apoptosis in a small proportion of cells. IL-17A had no significant impact on the amount of condensed or apoptotic nuclei. Conclusions: Our findings emphasize an interaction between inflammatory cytokine IL-17A signaling and mechanical stress since IL-17A induced matrix degeneration in meniscal tissue, which intensified in combination with a trauma. The latter might create a post-traumatic environment that promotes meniscal degeneration and subsequently osteoarthritis progression. Full article

The diamondback moth, Plutella xylostella, is a major pest of brassica vegetables and oilseed crops, posing a serious threat to China’s grain and oil production. RNA interference (RNAi) has been developed as an efficient strategy to control pests. In this study, the effects of RNAi on P. xylostella were evaluated by injecting two doses of synthesized dsPxvATPasea. The transcripts of PxvATPasea were widely transcribed during different developmental stages from egg to adult. They were abundantly expressed in the hindgut and Malpighian tubules, compared with other tissue types. Introduction of 800 ng dsPxvATPasea in the fourth-instar larvae greatly reduced corresponding mRNA levels by 3.1 and 1.4 times on day 2 and 3, respectively, causing 66.6% mortality and 33.4% treated larvae pupated. Silencing PxvATPasea by injecting 1200 ng dsRNA significantly decreased the expression level by 5.0 and 2.0 times on the second and third day, leading to 79.2% larval lethality and 20.8% depleted larvae pupated. Moreover, introducing 800 ng or 1200 ng dsPxvATPasea finally reduced larval fresh weight by 22.1% and 28.8%, respectively. The results indicated that the silencing efficiency of PxvATPasea worked in a dose-dependent way. Consequently, PxvATPasea is a potential molecular target gene. Our findings will facilitate the application of RNAi technology to manage P. xylostella. Full article

Background/Objectives: Dyslipidemia is one of the major problems of long-term management in people living with human immunodeficiency virus (HIV) (PLH) as a risk factor for cardiovascular diseases. Lipoprotein lipase (LPL) is anchored on the surface of the capillary endothelial cells and plays a pivotal role in triglyceride metabolism by catabolizing dietary chylomicrons and very low-density lipoprotein synthesized in the liver. However, the details of the mechanisms in the era of integrase strand transfer inhibitor-based antiretroviral therapy have not yet been clarified. Methods: This study was a cross-sectional, single-center, non-interventional study evaluating the underlying factors associated with dyslipidemia, insulin resistance or secretion, and changes in the body composition of PLH. Results: Among PLH (n = 48), lower LPL (<60.8 ng/mL) and older age independently predicted antilipemic drug (ALD) necessity. A comparison of ALD-naïve PLH (n = 33) and age- and sex-matched non-HIV controls (n = 33) showed that PLH were significantly associated with lower high-density lipoprotein cholesterol (HDL-C) and higher HOMA-β. LPL was also the independent predictor of HDL-C < 40 mg/dL in PLH (adjusted odds ratio = 0.901, p = 0.044). Furthermore, LPL < 65.3 ng/mL predicted HDL-C < 40 mg/dL with 100% sensitivity and 60.9% specificity. Low levels of HIV-RNA were detected in the high HOMA-β group. Conclusions: In Japanese individuals, compared to non-HIV controls, PLH has low HDL-C and LPL. The measurement of LPL may confer the risk assessment and decision-making with relevance to ALD in PLH. Additionally, the effectiveness of HIV antiviral therapy and glucose tolerance may interact with each other. Full article

Dipeptidyl-peptidase IV (DPP4) inhibitors have shown potential anti-tumor properties. This study investigates the therapeutic potential of evogliptin, a DPP4 inhibitor, both as a single agent and in combination with temozolomide (TMZ), in glioma models. In vitro studies were performed using U87 and U373 glioma cell lines exposed to different concentrations of TMZ (250, 500 μM) and evogliptin (250, 500 ng/mL), either alone or together, for 24, 48, and 72 h. Cell viability was determined with the MTT assay. In vivo effectiveness was tested in a xenograft mouse model treated with intraperitoneal injections of evogliptin (60 mg/k g/day), TMZ (15 mg/kg/day), or their combination over 3 weeks. The combination of TMZ and evogliptin markedly reduced cell viability compared to single-agent treatments. DPP4 mRNA levels decreased more substantially with combination therapy. miRNA expression profiling with Affymetrix arrays indicated that certain miRNAs, such as miR-4440 and miR-6780b-5p, were upregulated after treatment with evogliptin or the combination regimen, whereas others were downregulated. These miRNAs could play a role in limiting glioma growth through DPP4 regulation. In the animal model, evogliptin alone did not provide a survival advantage. Analysis of TCGA data showed that glioma patients with decreased DPP4 expression had improved survival rates. The co-administration of evogliptin and temozolomide resulted in distinct miRNA profile changes. Nevertheless, both in vitro and in vivo, the added cytotoxicity from the combination was minimal. Full article

Addressing damage inflicted by environmental stress is difficult post-occurrence. The use of externally delivered gamma-aminobutyric acid (GABA) priming to healthy plants may serve as an effective preventive measure by stimulating plant defense pathways. A genome-wide transcriptional investigation was performed on tomato plants following GABA priming, with extended data about the stress memory of previously primed plants subjected to drought stress. GABA significantly stimulates starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, porphyrin metabolism, glycerolipid metabolism, biosynthesis of phenylalanine, tyrosine, and tryptophan, phenylalanine metabolism, ascorbate and aldarate metabolism, pantothenate and CoA biosynthesis, and plant hormone signal transduction pathways. The initial priming effect could be remembered when subsequent environmental stress arose, but its influence intensified in plants that had previously undergone priming. The application of GABA can establish a novel form of preventative defense against the detrimental effects of stresses. It can effectively enhance long-term plant defense by facilitating the development of plant stress memory. Full article

Background: Safe, microbiome-based interventions for autoimmune hyperthyroidism are lacking. We isolated the lactic acid bacterium NES-428 from kimchi and previously demonstrated that it shares 99% 16S-rRNA identity with Lactobacillus brevis reference strains, confirming NES-428 as a novel strain. Here we evaluated its immunomodulatory and anti-thyroid activity in cellular and murine models. Methods: Jurkat T cells (5 × 10⁶) were incubated with heat-killed NES-428 for 24 h and subsequently stimulated with phorbol 12-myristate 13-acetate/ionomycin (50 ng mL⁻¹/1 µg mL⁻¹) for 6 h; cytokine transcripts were quantified by qRT-PCR. Hyperthyroidism was induced in female BALB/c mice by three intramuscular injections of adenovirus-encoding human TSH receptor (Ad-TSHR). Mice received a daily oral dose of NES-428 (1 × 10⁹ CFU) for 15 weeks. Serum thyroxine (T₄) levels, splenocyte cytokine secretion, and thyroid histopathology were assessed. Statistical analyses employed one-way ANOVA with Tukey post hoc or log-rank tests (α = 0.05). Results: NES-428 pre-conditioning of Jurkat cells significantly down-regulated IL-2 and IFN-γ transcripts (−48% and –43%, respectively; p < 0.01) compared with stimulated controls while modestly increasing IL-4 (+26%). In Ad-TSHR mice, daily NES-428 reduced mean serum T₄ from 11.2 ± 2.1 to 5.8 ± 1.4 µg dL⁻¹ (p < 0.001), restored body weight gain, and normalized follicular architecture relative to untreated hyperthyroid animals. NES-428 supplementation also lowered splenocyte IFN-γ secretion by 58% and raised IL-4 by 41% (p < 0.05). Conclusions: The kimchi-derived strain NES-428 attenuates Th1-skewed cytokine responses and ameliorates experimental hyperthyroidism in vivo. These findings support further investigation of NES-428 as a probiotic candidate for immune modulation in Graves’ disease. Full article

Atherosclerosis as a multifactorial disease remains the first cause of death worldwide. Current oral lipid-lowering drugs (especially statins) reduce low-density lipoprotein cholesterol (LDLC) levels in the blood, but their clinical efficacy seems to be partially attributed to pleiotropic effects on different pathophysiologic factors of atherosclerosis extending beyond lipid-lowering properties such as anti-inflammatory, antithrombotic and antioxidative features. Novel drugs that interfere with proprotein convertase subtilisin/kexin type 9 (PCSK9) axis of LDL-C receptors (LDLRs) degradation, from the group of monoclonal antibodies (e.g., alirocumab, evolocumab) or small interfering RNA (siRNA), e.g., inclisiran, are effective in reducing LDLC as well. However, data depicting their antithrombotic and antiplatelet activity are scarce, whereas prothrombotic properties of PCSK9 are widely described. Thus, we performed a study to assess the effects of inclisiran on subclinical prothrombotic [fibrinogen, coagulation factor VIII (FVIII), plasminogen activator inhibitor-1 (PAI-1)] and platelet activation markers (platelet factor-4 (PF-4), soluble p-selectin (sCD62P)). Ten patients at high cardiovascular risk with concomitant heterozygous familial hypercholesterolemia (HeFH)—study group 1, and fourteen patients at very high cardiovascular risk without concomitant HeFH—study group 2, were recruited for the study. Lipid profile, subclinical prothrombotic and platelet activation markers were assessed at the beginning and after 3 months of therapy with inclisiran. During therapy, statistically significant reductions in both study groups were seen in total cholesterol levels (study group 1: from 287.6 ± 94.2 to 215.2 ± 89.1 (mg/dL), p = 0.022; study group 2: from 211.7 ± 52.7 to 147.6 ± 55.4 (mg/dL), p < 0.001) and LDL-c (study group 1: from 180.8 ± 73.3 to 114.7 ± 71.5 (mg/dL), p = 0.031; study group 2: from 129.6 ± 46.8 to 63.4 ± 43.6 (mg/dL), p < 0.001). Lipid profile changes were associated with significant decrease in the concentration of FVIII in both groups (study group 1: from 33.3 ± 22 to 22 ± 14.5 (ng/mL), p = 0.006; study group 2: from 37 ±16.9 to 29.3 ±16.4 (ng/mL), p = 0.002) and fibrinogen, but only in study group 2 (from 51.4 (33.2–72.7) to 42.6 (31.3–57.2) (µg/mL), p = 0.035). Among platelet activation markers, a significant decrease in PF-4 in study group 2 was noted (from 286 (272–295.5) to 272 (268–281.5) (ng/mL), p = 0.047). However, there were no statistically significant changes in PAI-1 and sCD62P throughout the study. In our study, inclisiran appeared to be an effective lipid-lowering drug in patients at high cardiovascular risk. Moreover, it was shown that beyond lipid-lowering properties, the drug may also partially affect thrombogenesis and platelet activation. Full article

CRISPR/Cas systems have made significant progress in the field of molecular diagnostics in recent years. To overcome the aerosol contamination problem brought on by amplicon transfer in the common two-step procedure, the “one-pot method” has become a major research hotspot in this field. However, these methods usually rely on specially designed devices or additional chemical modifications. In this study, a novel “one-pot” strategy was developed to detect the foodborne pathogen Cronobacter sakazakii (C. sakazakii). A specific sequence was screened out from the virulence gene ompA of C. sakazakii as the detection target. Combining with the recombinase polymerase amplification (RPA), a rapid detection platform for C. sakazakii based on the CRISPR/Cas12a system was established for the first time. The sensitivity of this method was determined from three different levels, which are 10⁻⁴ ng/μL for genomic DNA (gDNA), 1.43 copies/μL for target DNA, and 6 CFU/mL for pure bacterial culture. Without any microbial enrichment, the detection limits for artificially contaminated cow and goat milk powder samples were 4.65 CFU/mL and 4.35 CFU/mL, respectively. To address the problem brought on by aerosol contamination in the common RPA-CRISPR/Cas12a two-step method, a novel pipette tip-in-tube (PTIT) method for simple and sensitive one-pot nucleic acid detection was further developed under the inspiration of the capillary principle. The RPA and CRISPR/Cas systems were isolated from each other by the force balance of the solution in a pipette tip before amplification. The detection limits of the PTIT method in pure bacterial culture and the spiked samples were exactly the same as that of the two-step method, but with no false positive cases caused by aerosol contamination at all. Compared with other existing one-pot methods, the PTIT method requires no additional or specially designed devices, or any chemical modifications on crRNA and nucleic acid probes. Therefore, the PTIT method developed in this study provides a novel strategy for realizing one-pot CRISPR/Cas detection easily and holds significant potential for the rapid point-on-care testing (POCT) application. Full article

In bulk meningioma (MNG) tumors, a biomarker based on the expression of 34 transcripts (34HR-MNG) has recently been described to be able to predict their outcome, including recurrence. To better study the molecular mechanisms regulating the expression of the 34HR-MNG transcripts and predict their functional involvement in MNG recurrence, we built a competitive endogenous RNA (ceRNA) network through an in silico approach. MiRNAs targeting 34HR-MNG transcripts and corresponding sponging circRNAs were retrieved through MiRTarbase and ENCORI databases, respectively. The expression of candidate circRNA host genes belonging to the 34HR-MNG transcripts was correlated with specific molecular and clinical features of 89 and 20 WHO grade 1 and 2 MNGs, respectively, by querying the RNA-seq dataset GSE189672. The expression of candidate circRNAs and their host gene was validated through qRT-PCR. Among the 34HR-MNG transcripts, the Pim-1 proto-oncogene, serine/threonine kinase (PIM1) was significantly upregulated in (i) WHO grade 2 vs. grade 1 and (ii) recurrent vs. not recurrent WHO grade 2 MNGs. PIM1 expression positively and negatively correlated with that of Ki-67 and NF2, respectively, in recurrent WHO grade 2 MNGs. CircRNAs 0076215 and 0076216, both generated from the PIM1 host gene, were predicted to sponge miRNAs 16-5p and 195-5p, two tumor suppressors in MNG, in turn targeting PIM1. The expression of circRNAs 0076215 and 0076216, validated for the first time in a set of 19 physiological human tissues, positively correlated with that of their host gene (Rho value = 0.579 and 0.681, p-value = 0.026 and 0.013, respectively). Our data suggest that PIM1 is an oncogene involved in the recurrence of WHO grade 2 MNG and that the upstream ceRNA network, comprising circRNAs 0076215 and 0076216 and miRNAs 16-5p and 195-5p, is responsible for its upregulation through a feed-forward loop. Full article

The N-glycolylneuraminic acid (Neu5Gc), a major salivary acid molecule found on the cell surface of animals such as pigs, cows, and sheep, can be metabolically incorporated into the body through consumption of animal-derived foods like red meat. This leads to an immune response and chronic inflammation in individuals who do not naturally produce Neu5Gc, including humans and poultry, further increasing the risk of cancer. The trans-cleavage activity of Cas12a is activated by the recognition of the target aptamer by the crRNA, resulting in the cleavage of the dual-labeled probe. By combining this with immunochromatographic techniques, we established a chromatographic test strip assay that allows immediate on-site detection of Neu5Gc contamination in non-red meat samples devoid of Neu5Gc. Further optimization enabled specific detection within 25 min with a minimum detectable limit of 10 ng/mL. These analyses successfully detected the spiked samples and actual samples containing Neu5Gc. The developed lateral flow test strips based on aptamer-Cas12a can be utilized for detecting Neu5Gc contamination in non-red meat food products, animal bioproducts, and poultry feeds. Full article

Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article

Objective: To analyze the composition of the oral microbiome in periodontal pocket lesions and on the tongue dorsum of patients with Helicobacter pylori-associated gastric disease. Materials and Methods: Patients diagnosed with gastric disease and H. pylori (HP+) were evaluated in comparison to a control group of H. pylori-negative patients without gastric disease (HP−). Periodontal and oral health clinical parameters (PPD, BoP, PSE, plaque score and modified DMFT) were assessed for each patient. Microbiological samples were collected from the deepest periodontal pockets and tongue dorsum, followed by DNA extraction, 16S rRNA PCR amplification, and Next-Generation-Sequencing (NGS) analyses. Results: Sixty-seven patients (27F; 40M, aged 35–85 years) were enrolled. Of these, 52 were HP+ and 15 were HP−. HP+ patients exhibited a significantly higher presence of decayed teeth (p < 0.05) and slightly fewer missing teeth (p > 0.05). The plaque score was significantly higher in HP+ patients (p < 0.05), while PPD and BoP showed no significant differences (p > 0.05). NGS analysis revealed no presence of H. pylori in any samples of both periodontal and tongue sites. HP+ patients showed a distinct microbial composition, including higher prevalence of Capnocytophaga, Fusobacterium, and Peptostreptococcus genera in both locations (pockets and tongue dorsum). Conclusions: The study demonstrated that HP+ patients exhibit distinct oral microbial profiles compared to HP− patients, especially in areas with deeper periodontal pockets. H. pylori was not detected in the oral microbiomes of either group. Full article