Search Results (89)

This study evaluated the effect of irradiation of different energy densities in low-level laser therapy (LLLT) and exogenous nerve growth factor (NGF) on Schwann cells (SCs). SCs (SCL 4.1/F7) exposed to LLLT (4 or 80 J/cm²) and NGF (25 ng/mL) were evaluated on days 1, 3, and 7. Cell viability (MTT), proliferation (crystal violet) and morphology (SEM—Scanning Electron Microscopy) on the polyhydroxybutyrate (PHB) scaffold were compared among five study groups: Control; L4. 4 J/cm² LLLT; L80. 80 J/cm² LLLT; L4N. 4 J/cm² LLLT + NGF; and L80N. 80 J/cm² LLLT + NGF. Viability and proliferation increased over time in groups treated exclusively with LLLT, with 4 J/cm² reduced cell viability on the third day. The NGF exposition showed a reduction in cell viability and proliferation. The SCs remained attached to the PHB scaffold during the 7 days analyzed. The LLLT energy densities did not modify SC behavior, except for a reduction in cell viability after irradiation of 4 J/cm² on the third day. Consistently, SC exposure to exogenous NGF significantly reduced proliferation and viability in all periods analyzed. Morphological changes were observed, and NGF exposure appears to have helped cells intertwine with PHB scaffold fibers. Full article

As a fundamental information carrier in Industrial Internet of Things (IIoT), electromagnetic spectrum data presents critical challenges for efficient spectrum sensing and situational awareness in smart industrial cognitive radio systems. Addressing sparse sampling limitations caused by energy-constrained transceiver nodes in Unmanned Aerial Vehicle (UAV) spectrum monitoring, this paper proposes a compressive sensing-based 3D spectrum tensor completion framework for extrapolative reconstruction in obstructed areas (e.g., building occlusions). First, a Sparse Coding Neural Gas (SCNG) algorithm constructs an overcomplete dictionary adaptive to wide-range spectral fluctuations. Subsequently, a Bag of Pursuits-optimized Orthogonal Matching Pursuit (BoP-OOMP) framework enables adaptive key-point sampling through multi-path tree search and temporary orthogonal matrix dimensionality reduction. Finally, a Neural Gas competitive learning strategy leverages intermediate BoP solutions for gradient-weighted dictionary updates, eliminating computational redundancy. Benchmark results demonstrate 43.2% reconstruction error reduction at sampling ratios r ≤ 20% across full-space measurements, while achieving decoupling of highly correlated overlapping subspaces—validating superior estimation accuracy and computational efficiency. Full article

Objective: To evaluate five luteal support protocols in women with low serum progesterone (<10 ng/mL) undergoing HRT-FET. Methods: Randomized controlled trial at two centers including 200 women under 35 with unexplained infertility. Groups: (1) 600 mg vaginal, (2) 800 mg vaginal, (3) 600 mg vaginal + 50 mg IM, (4) 600 mg vaginal + 25 mg SC, (5) 600 mg vaginal + 30 mg oral. Results: Groups 3 and 4 achieved significantly higher serum progesterone (p < 0.001), higher clinical pregnancy (70%, 68%), and higher live birth (84%, 83%) compared to Groups 1, 2, and 5. Early pregnancy loss was lower in Groups 3 and 4. Conclusions: Combined vaginal and injectable progesterone improved outcomes compared to monotherapy. Full article

Type 1 Diabetes Mellitus (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells, predominantly manifesting in childhood or adolescence. The lack of clearly interpretable biological markers in the early stages, combined with the insidious onset of the disease, poses significant challenges to early diagnosis and the implementation of preventive strategies. The applicability of classic T1D biomarkers for understanding the mechanisms of the autoimmune process, preclinical diagnostics and treatment efficiency is limited. Despite advances in next-generation sequencing (NGS) technologies, which have enabled large-scale genome-wide association studies (GWASs) and the identification of polygenic risk scores (PRSs) associated with T1D predisposition, as well as progress in bioinformatics approaches for assessing dysregulated gene expression, no universally accepted risk assessment model or definitive predictive biomarker has been established. Until now, the use of new promising biomarkers for T1D diagnostics is limited by insufficient evidence base. However, they have great potential for the development of diagnostic methods on their basis, which has been shown in single or serial large-scale studies. This critical review covers both well-known biomarkers widely used in clinical practice, such as HLA-haplotype, non-HLA SNPs, islet antigen autoantibodies, C-peptide, and the promising ones, such as cytokines, cfDNA, microRNA, T1D-specific immune cells, islet-TCR, and T1D-specific vibrational bands. Additionally, we highlight new approaches that have been gaining popularity and have already demonstrated their potential: GWAS, single-cell transcriptomics, identification of antigen-specific T cells using scRNA-seq, and FTIR spectroscopy. Although some of the biomarkers, in our opinion, are still limited to a research context or are far from being implemented in clinical diagnostics of T1D, they have the greatest potential of being applied in clinical practice. When integrated with the monitoring of the classical autoimmune diabetes markers, they would increase the sensitivity and specificity during diagnostics of early and preclinical stages of the disease. This critical review aims to evaluate the current landscape of classical and emerging biomarkers in autoimmune diabetes, with a focus on those enabling early detection—prior to extensive destruction of pancreatic islets. Another goal of the review is to focus the attention of the scientific community on the gaps in early T1D diagnostics, and to help in the selection of markers, targets, and methods for scientific studies on creating novel diagnostic panels. Full article

Background/Objectives: MB09 is a denosumab biosimilar to the reference products (RPs) Xgeva and Prolia. A population pharmacokinetic (popPK) meta-analysis was conducted to characterize the denosumab PK profile and to support MB09 biosimilarity. Methods: Pooled denosumab PK data from one phase I study [255 healthy adult men receiving a single 35 mg subcutaneous (SC) dose] and one phase III study (555 postmenopausal women with osteoporosis receiving two 60 mg SC doses, one every six months) were used. A one-compartment model with first-order absorption and elimination and parallel non-linear saturable clearance was used. Body weight was included on clearance as a structural covariate and treatment was tested as a covariate on all PK parameters. PK biosimilarity was assessed at 35 mg dose. Results: For a 70 kg subject, the apparent clearance and central volume of distribution for denosumab were 0.123 L/day [95% confidence interval (CI): 0.114, 0.132] and 9.33 L (95% CI: 9.11, 9.55), respectively. The Michaelis constant was 0.124 ng/mL and the maximum rate for the non-linear clearance was 0.139 ng/day. Model-based bioequivalence criteria were met for RP Xgeva, European and US-sourced, versus MB09 for a dose of 60 mg SC. The mean area under the plasma concentration curve (AUC) resultant from the simulation of MB09 120 mg SC was similar to the published mean AUC observed for Xgeva 120 mg SC every four weeks. Conclusions: This analysis provides a valuable assessment of denosumab PK characteristics and elucidates in more detail how the MB09 PK profile compares to the denosumab RPs, supporting the totality of evidence on MB09 biosimilarity. Full article

Background: IgA vasculitis (IgAV) represents the most frequently seen form of vasculitis among children. Although it often resolves without intervention, renal involvement (IgAV nephritis) poses a risk for long-term complications. Although the lectin and alternative complement pathways are possible causes in its development, dependable serum biomarkers for the early identification of nephritis remain unavailable. Methods: In this prospective case-control study, we examined how the serum levels of a membrane attack complex (sC5b-9), complement factor H (CFH), mannose-binding lectin (MBL), and mannose-binding lectin-associated serine protease-1 (MASP-1) relate to renal involvement in IgAV. These complement proteins were measured in children diagnosed with IgAV and compared to levels in healthy controls (HCs) matched for age and sex. Results: The study cohort comprised 44 IgAV patients with a median age of 8 years and 34 HCs. The CFH levels were reduced significantly in the patient group (median: 357.31 ng/mL; IQR: 228.32) relative to the controls (median: 543.08 ng/mL; IQR: 504.05) (p < 0.001). This decrease was observed irrespective of the presence of nephritis. There were no significant differences in serum sC5b-9, MBL, or MASP-1 levels between the patients and controls. Furthermore, no correlation emerged between these complement components and renal involvement. Conclusion: The data suggest that lower CFH levels may signal systemic dysregulation of the alternative pathway in IgAV. In contrast, the serum levels of sC5b-9, MBL, and MASP-1 appear inadequate as markers for predicting renal involvement. Further research with larger cohorts that includes genetic analyses and examination of kidney tissue is needed to better define the contribution of complement activation in IgAV-related nephritis. Full article

Fibro-adipogenic progenitor cells (FAPs) support muscle tissue homeostasis, regulate muscle growth, injury repair, and fibrosis, and activate muscle progenitor cell differentiation to promote regeneration. We aimed to investigate the effects of co-culturing FAPs with muscle satellite cells (MuSCs) on myogenic differentiation. Proteomic profiling of co-culture supernatants identified significant DCX, IMP2A, NUDT16L1, SLC38A2, and IL-6 upregulation. Comparative transcriptomics of mono-cultured versus co-cultured MuSCs revealed differential expression of oxidative stress-related genes (HMOX1, ALOX5, GSTM3, TRPM2, PADI1, and CTSL). Pathway enrichment analyses highlighted cell cycle regulation, TNF signaling, and ferroptosis. Gene ontology analysis of MuSCs indicated significant gene enrichment in myosin-related components. Combined transcriptomic and proteomic analyses demonstrated HO-1 downregulation at the transcriptional and translational levels, with altered pathways being predominantly related to myosin filament, muscle system process, and muscle contraction cellular components. HO-1 knockdown reduced intracellular iron accumulation in MuSCs, suppressing iron-dependent autophagy. This alleviated oxidative stress and promoted myogenic differentiation. Exogenous IL-6 (0.1 ng/mL) downregulated HO-1 expression, initiating an identical regulatory cascade, while HO-1 overexpression reversed the IL-6-mediated reduction in the expression of the autophagy markers LC3 and ATG5, suppressing myogenic enhancement. This establishes the co-culture-induced IL-6/HO-1 axis as a core regulator of iron-dependent oxidative stress and autophagy during myogenic differentiation. Full article

Seed germination is recognized for enhancing the accumulation of bioactive compounds. Perilla frutescens (L.) Britt., commonly known as perilla seed, is rich in fatty acids that may be beneficial for anti-hair loss. This study investigated the hair regeneration potential of perilla seed extracts—non-germinated (NG-PS) and germinated in distilled water (0 ppm selenium; G0-PS), and germinated with 80 ppm selenium (G80-PS)—obtained from supercritical fluid extraction (SFE) and screw compression (SC). SFE extracts exhibited significantly higher levels of polyphenols, tocopherols, and fatty acids compared to SC extracts. Among the germinated groups, G0-PS showed the highest bioactive compound content and antioxidant capacity. Remarkably, treatment with SFE-G0-PS led to a significant increase in the proliferation and migration of hair follicle cells, reaching 147.21 ± 2.11% (p < 0.05), and resulted in complete wound closure. In addition, its antioxidant and anti-inflammatory properties were reflected by a marked scavenging effect on TBARS (59.62 ± 0.66% of control) and suppressed nitrite amounts (0.44 ± 0.01 µM). Moreover, SFE-G0-PS markedly suppressed SRD5A1-3 gene expression—key regulators in androgenetic alopecia—in both DU-145 and HFDPCs, with approximately 2-fold and 1.5-fold greater inhibition compared to finasteride and minoxidil, respectively. Simultaneously, it upregulated the expression of hair growth-related genes, including CTNNB1, SHH, SMO, GLI1, and VEGF, by approximately 1.5-fold, demonstrating stronger activation than minoxidil. These findings suggest the potential of SFE-G0-PS as a natural therapeutic agent for promoting hair growth and preventing hair loss. Full article

Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in the regulation of synaptic plasticity and metabolic processes, including glucose metabolism and insulin sensitivity. In patients with obstructive sleep apnea (OSA), recurrent episodes of intermittent hypoxia may stimulate BDNF expression as a compensatory neuroprotective response. OSA is associated with metabolic disturbances, such as increased insulin resistance and a higher risk of type 2 diabetes. Continuous positive airway pressure (CPAP) therapy may influence both BDNF levels and metabolic outcomes. The aim of this study was to evaluate changes in BDNF concentration and glucose metabolism in patients with OSA, with particular emphasis on the effect of long-term CPAP therapy. Sixty-six adult patients with OSA confirmed by polysomnography were enrolled and divided into severe (s-OSA) and non-severe (ns-OSA) groups. Fasting blood samples were collected to measure glucose, insulin, and BDNF concentrations. Patients with s-OSA were re-evaluated after 12 months of CPAP therapy and further classified as compliant (sc-OSA) or non-compliant (snc-OSA) based on recorded device usage. The same biochemical parameters were assessed after the 12-month follow-up. Baseline BDNF levels were significantly higher in the s-OSA group compared to the ns-OSA group (20.1 ng/mL vs. 8.1 ng/mL, p = 0.02) and correlated with the apnea–hypopnea index (AHI, r = 0.38, p = 0.02). In the nsc-OSA group, BDNF concentrations increased significantly after 12 months (16.2 ng/mL vs. 35.5 ng/mL, p < 0.001), while no significant change was observed in the sc-OSA group (24.4 ng/mL vs. 27.4 ng/mL, p = 0.33). Among sc-OSA patients, a significant improvement in insulin resistance was noted, although no significant changes were observed in fasting glucose or insulin levels. Increased BDNF levels were observed in patients with s-OSA compared to ns-OSA. Compliant CPAP therapy was associated with reduced insulin resistance and no further BDNF increase, in contrast to non-compliance, suggesting a beneficial effect of CPAP on glucose metabolism and BDNF regulation. These findings support the hypothesis that both neurotrophic and metabolic responses in OSA may be modulated by disease severity and therapy adherence. Full article

The objective of the present study was to examine the impact of dietary supplementation with probiotics and yeast cell wall prebiotics on the intestinal microbiota of common carp (Cyprinus carpio). A total of 96 carp, with an average body weight of 932 ± 161 g, were distributed into 12 fish tanks (800 L), with 8 fish/tank. The fish were fed a variety of experimental diets, including a basal diet only (CD) or a basal diet supplemented with the probiotic Pediococcus acidilactici (PA), the yeast probiotic Saccharomyces cerevisiae (SC), or the yeast cell wall prebiotic (YANG) at a concentration of 0.1% (1 g/kg) for a duration of 42 days. At the end of the trial, fish digesta were withdrawn, and the total bacterial community of the gut of common carp was analyzed using Illumina’s NGS targeting the 16S rRNA gene. A Krona phyla richness pie chart showed that 11 bacterial phyla were recorded in fish fed YANG, with the top three phyla being Fusobacteria, Firmicutes, and Proteobacteria. In addition, 10 phyla were identified in fecal samples from carp fed PA, with the top three phyla being Proteobacteria, Firmicutes, and Fusobacteria. Furthermore, nine phyla were recorded for carp fed SC, with the top three phyla being Fusobacteria, Firmicutes, and Proteobacteria. However, carp fed a basal diet exhibited 14 phyla, with the most abundant phyla being Fusobacteriota, Bacteroidota, and Proteobacteria. This study concluded that the tested feed supplements could cause considerable alterations in the composition of the gut microbiome of carps reared in recirculating systems. Full article

Next-generation sequencing (NGS) has been well applied to assess genetic abnormalities in various biological samples to investigate disease mechanisms. With the advent of high-throughput and automatic testing platforms, NGS can identify radiation-sensitive and dose-responsive biomarkers, contributing to triage patients and determining risk groups for treatment in a nuclear emergency. While bulk NGS provides a snapshot of the average gene expression or genomic changes within a group of cells after the radiation, it cannot provide information on individual cells within the population. On the other hand, single-cell sequencing involves isolating individual cells and sequencing the genetic material from each cell separately. This approach allows for the identification of gene expression and genomic changes in individual cells, providing a high-resolution view of cellular diversity and heterogeneity within a sample. Single-cell sequencing is particularly useful to identify cell-specific features of dose-response and organ-response genes. While single-cell RNA sequencing (scRNA-seq) technology is still emerging in radiation research, it holds significant promise for identifying biomarkers related to radiation exposure and tailoring post-radiation medical care. This review aims to focus on current methods of radiation dosimetry and recently identified biomarkers associated with radiation exposure. Additionally, it addresses the development of NGS techniques in the context of radiation situations, such as cancer treatment and emergency events, with a particular emphasis on single-cell sequencing technology. Full article

The glass–glass interfaces (GGIs) play an important role during the plastic deformation of metallic nano-glasses (NGs) such as Sc-Fe NGs. In this work, Co-P nano-glasses are synthesized by pulse electrodeposition. Their mechanical properties are characterized by micro-pillar compression and compared to those obtained by molecular dynamics (MD) simulation. The MD simulation reveals that the GGIs with a particular incline angle (about 50.0°) in the direction of applied uniaxial strain is preferable for the accommodation of localized plastic deformation in NGs. The results are consistent with those obtained by spherical aberration-corrected transmission electron microscopy, which reveals that most of shear bands form an angle of about 58.7° to the direction of compressive strain applied on the Co-P micro-pillar. The phenomena are explained with the differences in chemical composition and atom diffusion in the glassy grain interiors and in the GGI regions. This work sheds some light on the deformation mechanisms of NGs and provides guidelines for designing NGs with improved mechanical properties. Full article

Six novel green extraction techniques were evaluated and optimized to extract pyrethrin from dried Dalmatian pyrethrum (Tanacetum cinerariifolium (Trevir./Sch.Bip.). This approach offers a promising natural alternative to conventional chemotherapeutics. Four methods are presented for the first time in this study: microwave-assisted extraction (MAE), high-voltage electric discharge (HVED) extraction, subcritical water extraction (SWE), and deep eutectic solvent (DES) extraction, together with supercritical CO₂ extraction (SC-CO₂) and ultrasound-assisted extraction (UAE), for pyrethrin extraction from Dalmatian pyrethrum. The study revealed that supercritical CO₂ extraction was the most effective method for extracting all six pyrethrins, yielding the highest total amount of 124.37 ng/mg. This approach offers a “natural” insecticide produced with a clean, environmentally friendly technology that can contribute to the development of sustainable and effective insecticide strategies that are in line with environmental safety and organic production standards. In addition, this research highlights the potential application of pyrethrins as antiparasitic agents, emphasizing their role in environmentally friendly and ecological practices. Full article

Background/Objectives: Myeloid neoplasms are the most common secondary blood cancer in B-cell non-Hodgkin lymphoma (BNHL) patients treated with cytotoxic therapies. We aimed to characterize the genetic and clinicopathologic features of myeloid neoplasms arising after B-cell non-Hodgkin lymphoma (MN-BNHL) by comparing their features with myeloid neoplasms developing after solid cancer (MN-SC). Methods: We retrospectively analyzed the clinicopathologic and genetic data of myeloid neoplasm patients diagnosed between 2008 and 2023, categorized as MN-BNHL or MN-SC. Further NGS analysis was performed on available bone marrow samples with missing genetic data. The genetic profiles of myeloid neoplasms between BNHL and solid cancer groups were compared. Results: Sixteen patients developed MN-BNHL. Among the 11 MN-BNHL patients undergoing NGS, all harbored tier 1 mutations. PPM1D mutations (PPM1Dms) were most frequent (73%), followed by DNMT3A (46%) and TP53 (36%). PPM1Dms were significantly more prevalent than in MN-SC (n = 21), where TP53 mutations were most common (64%) (p < 0.001). PPM1Dms often co-occurred with DNMT3A. They were associated with prior radioimmunotherapy (relative risk (RR): 3.3 and RR 3.57). MN-BNHL patients with PPM1Dms exhibited improved survival compared to those without (p = 0.0376), but this benefit was negated by the presence of TP53 mutations (p = 0.0049). Conclusions: PPM1Dms are a prominent genetic feature in MN-BNHL, suggesting a distinct role in its development compared to MN-SC. Further investigation is needed to elucidate the precise contribution of PPM1D and its interaction with other mutations in BNHL-related myeloid neoplasm development and prognosis. Full article

Background/Objectives: COVID-19, caused by SARS-CoV-2, has emerged as a global pandemic since its outbreak in 2019. As an increasing number of variants have emerged, especially concerning variants such as Omicron BA.1, BA.2, XBB.1, EG.5, which can escape the immune system and cause repeated infections, they have exerted significant pressure on monoclonal antibodies and the treatment approaches for COVID-19. Broad spectrum antiviral medication was urgently needed. In this study, we developed several bispecific antibodies based on the IgG-scFv format and one trispecific antibody containing Fab fragments with different anti-virus mechanisms studied previously. The Fab fragments are from h11B11, S2P6, and S309 respectively. Method: all recombinant antibodies were expressed by HEK 293. The pseudoviruses’ neutralization assay and the virus challenge to BALB/c mice were deployed to assess the efficiency of recombinant antibodies in vitro and in vivo. Results: the bispecific antibodies exhibited a favorable pseudoviruses neutralization activity, with IC₅₀ values ranging from 8 to 591 ng/mL. The trispecific antibody performed even better, with IC₅₀ values ranging from 5 to 27 ng/mL. Furthermore, the virus challenge to mice confirmed that the bispecific antibodies, including the trispecific antibody, had decent therapeutic efficacy. Conclusions: our study provided several supplements to the therapeutic measures of COVID-19 based on multispecific antibodies, supporting the great potential of the multispecific antibodies strategy in dealing with emerging pathogens. Full article