Search Results (2,747)

The novel data show that the Hsp70 protein is a potent activator of the immune system. Using limited trypsinolisis, we have identified the epitopes of Hsp70 responsible for TREM-1-dependent and TREM-1-independent cytotoxicity. The 11aa N9 peptide (AMTKDNNLLGR) contains nine amino acids that correspond to the amino acid sequence of the known TKD peptide. Also, like TKD, this peptide does not interact with the TREM-1 receptor but activates CD94+ NK cells that kill tumor cells by secreting granzymes and inducing apoptosis. The 16aa peptide N7 (SDNQPGVLIQVYEGEK) interacts with the TREM-1 receptor and induces the activation of NK cells and cytotoxic T lymphocytes at different time points. T-lymphocytes activated by this peptide induce two alternative processes of cell death in HLA-negative tumor cells, apoptosis and necroptosis, through the interaction of the FasL lymphocyte with the Fas receptor of the tumor cell. A shortened fragment of this peptide, N7.1 (SDNQPGVL), has been identified that inhibits the interaction of TREM-1 with its ligands. This peptide has shown protective effects in the development of sepsis in mice. The results obtained can be used in antitumor and anti-inflammation therapy. Full article

Background: Anastomotic leakage (AL) is a major complication after esophago-gastric surgery, with incidence rates of 11–21% and mortality up to 14%. Early intervention is essential to reduce morbidity. Endoscopic treatments have advanced, with self-expandable metal stents (SEMSs) as the traditional standard (success ~90%), but they carry risks like migration, stenosis, and need for drainage. Endoscopic vacuum therapy (EVT), applying negative pressure to drain secretions and promote healing, has shown success rates of 66–100%. Limited comparative data exists from small retrospective studies. This study compares SEMS and EVT for safety and efficacy in AL management. Methods: A retrospective case–control study from a prospective database at our institution was performed (March 2012–2025). We included patients with AL post-esophageal/gastric surgery treated endoscopically (SEMS or EVT). We excluded patients treated with conservative or surgical management. Demographics, comorbidities, oncology, surgery type, leak details, treatments, and outcomes were collected. Primary outcome was complete healing of the leak, while secondary outcomes were time to success, number of procedures needed, hospital stay, complications, mortality. Results: From 592 resections, we extracted 68 AL (11.5%), 45 of which met the inclusion criteria (22 SEMS, 23 EVT). Groups were similar demographically, but SEMS had more respiratory issues (43% vs. 8.7%, p = 0.018). SEMS were used more after esophagectomy (86.4% vs. 56.5%, p = 0.004); EVT was performed mostly after gastrectomy (34.7% vs. 9.1%, p = 0.009). Success rate was 86.4% for SEMS vs. 95.6% for EVT (p = 1.000). Complications were significantly lower in EVT (8.3% vs. 50%, p = 0.001; SEMS: 36.4% migrations, 18.2% stenoses). Leak onset time, modality of diagnosis, and leak size were comparable among the groups. Need for jejunostomy was higher in EVT (43.5% vs. 9.1%, p = 0.015), while chest drains in SEMS (63.7% vs. 13.1%, p < 0.001). Hospital stays (33–38 days, p = 0.864) and mortality (22.7% vs. 8.7%, p = 0.225) were similar. No differences were observed in terms of long-term mortality (log-rank p = 0.815). Conclusions: SEMS and EVT are both effective for AL after esophago-gastric surgery. EVT offers fewer complications and shorter treatment, so it is favored especially for esophago-jejunal leaks. Full article

Background: MicroRNA-379 (miR-379) has been reported to play a tumour-suppressing role in several cancer types. Our previous work demonstrated that miR-379 overexpression attenuates the metastatic spread of prostate cancer (PCa) both in vitro and in vivo. However, the underlying mechanisms remain poorly understood. Methods: To elucidate the mechanisms by which miR-379 affects metastases, we performed a cytokine array to identify secreted proteins modulated by miR-379 dysregulation in a bone microenvironment model. We then assessed the levels of the key candidate, and performed functional studies, including reporter assays, of the transcriptional regulation. Results: Prostate-specific antigen (PSA)—the clinically widely used blood biomarker for PCa—emerged as the most significantly affected secreted protein. We observed that PSA secretion increased following miR-379 inhibition and decreased with miR-379 overexpression, with parallel changes in intracellular PSA levels. However, our data suggests that miR-379 does not directly regulate PSA expression. Instead, miR-379 appears to downregulate androgen receptor (AR) expression by targeting its 3′-untranslated region (3′-UTR), thereby indirectly reducing PSA transcription through diminished AR-mediated promoter activation. Supporting this indirect mechanism, analysis of clinical samples from prostate cancer patients revealed an inverse correlation between expression of miR-379 in prostatic tissue and serum PSA levels. Furthermore, reduced miR-379 expression was associated with increased levels of AR immunostaining in malignant tissues. Conclusions: Taken together, these findings suggest that miR-379 negatively regulates PSA secretion indirectly via suppression of AR, and that the interplay between miR-379, AR, and PSA may contribute to the metastatic progression of PCa to bone. Full article

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder connected with insulin resistance (IR), low-grade inflammation, dyslipidemia, and altered adipokine secretion. We evaluated serum levels of leptin, adiponectin, visfatin, resistin, IL-6, and TNF-α in 150 women with PCOS, stratified by IR status (IR, n = 76; non-IR, n = 74), and examined their associations with anthropometric, metabolic, hormonal, inflammatory, and atherogenic parameters. Anthropometric data included body weight, height, BMI, waist circumference, and waist-to-height ratio (WHtR), while IR was assessed using HOMA-IR and the Matsuda index. Serum adipokines were measured using ELISA, and lipid parameters and atherogenic indices—including non-HDL cholesterol, AIP, leptin/adiponectin, and adiponectin/resistin ratios—were calculated. Women with IR had higher levels of leptin, visfatin, resistin, and TNF-α, and lower levels of adiponectin. Leptin correlated positively with weight, WHtR, HOMA-IR, and atherogenic indices. Adiponectin showed the strongest and most consistent associations with anthropometric indices, HOMA-IR, and the Matsuda index. Resistin was linked to IR indices and IL-6, and visfatin correlated negatively with HDL-C and insulin sensitivity. In a multivariate general linear model, WHtR, but not HOMA-IR, remained independently associated with higher leptin levels and with atherogenic indices. These findings suggest that in PCOS, central adiposity rather than IR explains a substantial part of the adverse adipokine and inflammatory profile, thereby contributing to elevated cardiometabolic risk and highlighting the need for targeted treatment strategies. Full article

Chicoric and chlorogenic acids (CRA and CGA), two caffeic acid derivatives found in a large variety of plants, particularly in Asteraceae, are known to modulate glucose-6-phosphatase (G6Pase) in hepatic and muscle cells. The aim of the present study is to use CRA/CGA to explore the modulation role and molecular mechanism of endocrine pancreatic beta-cells’ insulin secretion. The G6Pase enzyme activity influenced by caffeic and derivatives alone or in combination was assessed on microsomal fractions of INS1-beta-cells and hepatocytes. Overall, our results show inverse effects of CGA/CRA, allowing us to investigate the G6Pase activity modulation under low and high glucose concentrations. Our data strongly suggests the existence of two putative forms of the G6Pase enzyme. Based on these observations, we formulate the hypothesis of an adaptative bi-conformational model of G6Pase enzyme activity modulation depending on the level of the beta-cell glucose exposure. Full article

Acute lung injury (ALI) is a severe pulmonary disorder characterized by the disruption of the alveolar–capillary barrier, leading to impaired oxygenation and pulmonary edema. Current pharmacological interventions primarily involve the use of steroid drugs, oxygen radical scavengers, and bronchodilators. However, the therapeutic efficacy of these interventions remains inconsistent. Canthin-6-ones, a class of tryptophan-derived alkaloids, exhibit anti-inflammatory, antioxidant, and immunomodulatory properties. In this study, we synthesized a novel Canthin-6-one derivative, namely HCX3, and evaluated its potential beneficial effects and underlying mechanisms on ALI. Prior to the experimental study, network pharmacology analysis revealed that HCX3 may exert anti-inflammatory effects in the context of ALI through the regulation of multiple signaling pathways, including the NF-κB pathways. To validate these findings, Lipopolysaccharide (LPS) was employed to stimulate RAW 264.7 macrophages and bone marrow-derived macrophages (BMDMs) to construct cellular models of inflammatory response associated with ALI. Our data demonstrated that exposure to HCX3 significantly inhibited the transcription and the secretion of multiple pro-inflammatory mediators, including IL-1β, IL-6, and TNF-α, in a dose-dependent manner. Additionally, HCX3 reduced LPS-induced phosphorylation levels of p65 and IκB-α in macrophages, indicating an inhibitory effect of the compound on the activation of NF-κB signaling pathway. Collectively, our data suggest that HCX3 exhibits significant anti-inflammatory effects by inhibiting NF-κB-related signaling pathways, providing new insights for ALI treatment. Full article

Periprosthetic joint infection (PJI) remains a major complication in orthopedic surgery, with accurate and timely diagnosis being essential for optimal patient management. Traditional culture-based diagnostics are often limited by suboptimal sensitivity, especially in biofilm-associated and low-virulence infections. In recent years, non-culture-based methodologies have gained prominence. Molecular techniques, such as polymerase chain reaction (PCR) and next-generation sequencing (NGS), offer enhanced detection of microbial DNA, even in culture-negative cases, and enable precise pathogen identification. In parallel, extensive research has focused on biomarkers, including systemic (e.g., C-reactive protein, fibrinogen, D-dimer), synovial (e.g., alpha-defensin, calprotectin, interleukins), and pathogen-derived markers (e.g., D-lactate), the latter reflecting metabolic products secreted by microorganisms during infection. The development of multiplex platforms now allows for the simultaneous measurement of multiple synovial biomarkers, improving diagnostic accuracy and turnaround time. Furthermore, the integration of artificial intelligence (AI) and machine learning algorithms into diagnostic workflows has opened new avenues for combining clinical, molecular, and biochemical data. These models can generate probability scores for PJI diagnosis with high accuracy, supporting clinical decision-making. While these technologies are still being validated for routine use, their convergence marks a significant step toward precision diagnostics in PJI, potentially improving early detection, reducing diagnostic uncertainty, and guiding targeted therapy. Full article

Obesity is a multifactorial disease with endocrine, metabolic, and inflammatory underpinnings, leading to numerous comorbidities and increased mortality. This has driven research into adipose tissue’s role as an endocrine organ that secretes adipokines. This review critically analyzes three of these adipokines: chemerin, omentin-1, and visfatin. Chemerin and omentin-1 have well-defined roles as pro- and anti-inflammatory mediators, respectively. However, the function of visfatin remains controversial, with conflicting data regarding its role in glucose metabolism and inflammation. This conflicting evidence highlights an urgent need for standardized assays and population-specific studies to clarify its true function. We conclude that while chemerin and omentin-1 represent promising targets, the ambiguity surrounding visfatin limits its current clinical utility, and resolving these knowledge gaps is essential for developing effective biomarkers and therapies for obesity and its comorbidities. Full article

Fragaria vesca L. is a common plant species in Slovenia. It flowers from May to July. Our study was conducted throughout the 2024 season in two locations at which we sampled nectar in F. vesca flowers. To take the nectar samples, we used microcapillaries. We studied Fragaria vesca nectar production and its composition (sugars, amino acids, and phenolic compounds) throughout the day. We had some problems with sampling nectar in the afternoon, which affected our research, since there were times during which we could not obtain any samples. F. vesca on average secreted 0.02 μL nectar per one flower sample. Our data show that nectar production is highest in the morning, nectar is hexose-dominant, and the time of day affects the sugar concentration, which reaches a maximum at noon. The most common amino acid in F. vesca nectar is proline, and the amino acid concentration is highest in the morning. Quercetin and rutin are common phenolic compounds in the nectar of F. vesca, and the concentration of phenolic acids is highest at noon, as bees are the most active in the spring when mornings are colder. Full article

This submission is focused on the implementation of a system that acquires data from various types of sensors and securely stores them after encryption on a chip with a reconfigurable architecture. The system has the unique capability of encrypting the input data with a single secret cryptographic key, which is stored only inside the hardware of the system itself, so the key remains unrecognizable upon completion of the system synthesis for any unauthorized user. Being stored as a part of the whole system architecture, the cryptographic key cannot be attained. It is not stored separately on the system RAM or any other supported memory, making the collected data fully protected. The reported work shows a data acquisition system which measures temperature with a high level of precision, transforms it to degrees Celsius, stores the collected data, and transfers them via serial interface when requested. Before storage, the data are encrypted with a 256-bit key, applying the AES algorithm. The data which are stored in the system memory and sent as UART packets towards the main computer do not include the cryptographic key in the data stream, so it is impossible for it to be retrieved from them. We show the flexibility of such kinds of data acquisition systems for sensing different types of signals, emphasizing secure storage and transferring, including data from meteorological sensors or highly confidential or biometrical data. Full article

The widespread use of advanced imaging techniques has led to a rising incidence of adrenal incidentalomas (AIs), asymptomatic adrenal masses discovered during imaging for non-adrenal-related conditions. AIs represent a diagnostic and therapeutic challenge due to their varied etiology, secretory potential, and potential for malignancy. This review aims to provide a comprehensive overview of the current knowledge on adrenal incidentalomas, focusing on their pathogenesis, diagnostic work-up, imaging features, hormonal evaluation, and evidence-based management, with a special emphasis on autonomous cortisol secretion (ACS). A thorough narrative review of the literature from the past two decades was conducted, synthesizing data from key international guidelines (ESE/ENSAT), observational studies, meta-analyses, and case series regarding the evaluation and treatment of AI. AI represents an increasingly relevant clinical condition requiring a multidisciplinary, personalized approach. Prompt endocrine and radiological evaluation is essential to identify hormonally active or potentially malignant tumors. The complexity of the natural history of AI and the evolving understanding of ACS underline the need for tailored follow-up and management strategies. Full article

An emerging area of microbial biology focuses on oligonucleotides excised from functional RNAs and subsequently fulfilling an independent cellular role. Some of these products are subjected to modifications that may expand their functional inventory. Here, we applied a differential analysis of intra- and extracellular RNA fragments produced by wild-type Escherichia coli and its dps-null mutant and discovered leucine tRNA fragments with random 3′-terminal extensions among oligonucleotides with Dps-dependent secretion. We observed an exclusive intracellular enrichment of modified LeuT(VPQ) tRNA fragments compared to secretomes, with abundance level dependent on growth medium and the presence of competing bacteria. To assess the pervasiveness of this phenomenon, we developed a custom computational pipeline for detecting variable RNA termini in RNA-seq data. Beyond LeuT(VPQ) tRNA fragments, several other genomic loci yielded oligos with highly heterogeneous ends, indicating that terminal elongation, most prevalent in LeuT(VPQ), is not exclusive to these fragments. Ex vivo testing using synthetic LeuT(VPQ) analogs revealed their stimulatory effect on the persistence of multiple taxa in an artificial microbiome, which was attenuated by 3′-end elongation. We propose that non-template extensions may serve to broaden the spectrum of target molecules for elimination of unused mRNAs by an interference-like mechanism or to generate sequences absent from the E. coli genome as part of a primitive defense system. Full article

It is estimated that one in four people worldwide carries Mycobacterium tuberculosis bacteria. MPT64 is a protein exclusively secreted by Mycobacterium tuberculosis complex (MTC) bacteria. It serves as a crucial diagnostic marker and plays a role in the bacterium’s survival by modulating the host immune response. Consequently, the development of innovative diagnostic tools based on MPT64, as well as the production of high-purity MPT64 protein to support research on tuberculosis pathogenesis and the advancement of novel therapeutic strategies, is of great importance. In this study, optimization experiments were conducted to produce this protein in E. coli with high yield and purity. First, a gBlock was designed by codon optimization and then cloned into a plasmid vector using the LIC method. For more efficient production, E. coli BL21(DE3)-R3-pRARE2 strain, which carries rare tRNAs for rare codons, was used as the host. Five different culture media were tested to maximize protein production, with the highest yield obtained in eBHI medium. The resulting protein yield was 4.9 mg/L. To the best of our knowledge, this study provides the most detailed information on the recombinant production and characterization of MPT64 to date. Therefore, these results contribute important data for future studies on the MPT64 protein. Full article

The NBS-LRR genes constitute the largest class of resistance (R) proteins in plants, capable of recognizing pathogen-secreted effectors to trigger immune responses. However, systematic studies of NBS-LRR genes in medicinal plants have not yet been reported. In this study, we performed a comprehensive genome-wide identification and analysis of the NBS-LRR gene family in the medicinal plant Salvia miltiorrhiza. A total of 196 NBS-LRR genes were identified, among which 62 possessed complete N-terminal and LRR domains. Multiple NBS-LRR proteins extracted from other model plants can be classified and distinguished on the phylogenetic tree according to subfamilies CNL, TNL, and RNL. Comparative analysis revealed a marked reduction in the number of TNL and RNL subfamily members within the Salvia species. Analysis of the expression patterns of SmNBS-LRR genes with transcriptomes data revealed a close association between SmNBS-LRRs and secondary metabolism. Promoter analysis demonstrated an abundance of cis-acting elements in SmNBS genes related to plant hormones and abiotic stress. Our study enhances the understanding of the NBS-LRR gene family in medicinal plants and provides a foundation for future functional characterization of the NBS-LRR genes in S. miltiorrhiza and its potential application in disease-resistance breeding. Full article

This study explores the direct effects of amphibian skin secretions on human cells involved in joint diseases, aiming to identify species with potential for inflammatory modulation. Secretions were obtained from sixteen species distributed across Brazilian biomes and one European species. Following biochemical characterization, human chondrocytes, synoviocytes, and macrophages were treated with secretions for 24 h. The cytotoxicity and modulation of the IL-6, IL-8, TNF-α, and IL-1β release were assessed. Synoviocytes showed the greatest resistance to cytotoxic effects, though sensitivity varied by species. Secretions from Trachycephalus mesophaeus, Pipa carvalhoi, and Phyllomedusa bahiana exhibited the highest cytotoxicity. At non-cytotoxic concentrations, P. carvalhoi and Leptodactylus fuscus strongly induced IL-6 and IL-8 in chondrocytes and synoviocytes, with P. carvalhoi also stimulating IL-1β and TNF-α release in macrophages. Among Bufonidae species, particularly Rhinella jimi and Bufo bufo, were potent inducers of TNF-α and IL-1β in macrophages. Secretions lacking pro-inflammatory effects were further tested for anti-inflammatory activity. P. bahiana reduced TNF-α production in stimulated macrophages and IL-6 in synoviocytes, while Siphonops annulatus and T. mesophaeus reduced LPS-induced TNF-α in macrophages. Our data underscore the rich biodiversity of amphibians, supporting the bioprospecting of their cutaneous secretions. These data reveal substantial potential for uncovering bioactive compounds with pharmacological applications. Full article