The inherent carbohydrate-binding specificities of human galectins can serve as recognition elements in both biotechnological and biomedical applications. The combination of the carbohydrate-recognition domain (CRD) of galectins fused to peptides or proteins for purification, immobilization, and imaging enables multifunctional utilization within a single protein. We present here a library of color-coded galectin fusion proteins that incorporate a His6-tag, a fluorescent protein, and a SpyCatcher or SpyTag unit to enable immobilization procedures. These galectin fusion proteins exhibit similar binding properties to the non-fused galectins with micromolar apparent binding affinities. N- and C-terminal fusion partners do not interfere with the SpyCatcher/SpyTag immobilization. By applying SpyCatcher/SpyTag-mediated SC-ST-Gal-3 conjugates, we show the stepwise formation of a three-layer ECM-like structure in vitro. Additionally, we demonstrate the SpyCatcher/SpyTag-mediated immobilization of galectins in microgels, which can serve as a transport platform for localized targeting applications. The proof of concept is provided by the galectin-mediated binding of microgels to colorectal cancer cells.

• MeSH
• barva MeSH
• biokompatibilní materiály chemie   MeSH
• galektiny * chemie   metabolismus   MeSH
• gely chemie   MeSH
• lidé MeSH
• rekombinantní fúzní proteiny * chemie   metabolismus   genetika   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cíl: Protože kardiovaskulární onemocnění jsou příčinou závažné morbidity a mortality, je třeba zjišťovat jejich přítomnost a začít je včas léčit. Proto byla pro stanovení rizika vypracována řada stupnic, v současnosti se však rutinně nepoužívá žádný biochemický marker pro stanovení kardiovaskulárního rizika. Ateroskleróza je nejzávažnější příčinou rozvoje kardiovaskulárních onemocnění a v patofyziologii aterosklerózy hraje jistou úlohu zánět cév. Řada studií prokázala, že mnoho kroků v procesu rozvoje tohoto zánětu ovlivňují hodnoty YKL-40 v séru. Evropská kardiologická společnost používá pro stanovení desetiletého kardiovaskulárního rizika skórovací systém SCORE2. V naší studii jsme zkoumali vztah mezi algoritmem pro toto riziko a hodnotou biochemického markeru YKL-40 v séru. Materiál a metody: Do studie bylo zařazeno 87 dobrovolníků ve věku 40–70 let, kteří se dostavili na naši kliniku, v minulosti neprodělali kardiovaskulární příhodu, měli však rizikové faktory pro rozvoj kardiovaskulárního onemocnění. Pomocí predikčního modelu SCORE2 bylo stanoveno jejich kardiovaskulární riziko a současně změřeny hodnoty YKL-40 v séru. Tyto hodnoty se mění s věkem bez ohledu na přítomnost či nepřítomnost nemoci, což platilo pro naši studii stejně jako pro jiné studie. Abychom eliminovali toto paradigma, hodnotili jsme hodnoty YKL-40 v séru pomocí statistického modelu společně s věkem. Výsledky: Naše základní analýza nezjistila významný vztah mezi hodnotami YKL-40 a všemi parametry v algoritmu predikčního modelu SCORE2. Nicméně po porovnání výsledku analýzy s výsledkem statistického modelu s použitím věku se ukázalo se, že hodnota YKL-40 představuje biochemický marker, který lze použít, podobně jako systém SCORE2, při stanovování kardiovaskulárního rizika (R2 : 0,72; p < 0,001).

Objective: Since cardiovascular diseases are a cause of serious morbidity and mortality, it is important to detect and treat them in advance. For this reason, many risk scales have been created, but there is currently no biochemical marker in routine use to estimate cardiovascular risk. Atherosclerosis is the most important reason for the development of cardiovascular disease, and vascular inflammation plays a role in the pathophysiology of atherosclerosis. It has been observed in many studies that the serum YKL-40 level has an effect on many steps in the development process of this inflammation. SCORE2 are used by the European Society of Cardiology to estimate 10-year cardiovascular risk. In our study, we investigated the relationship between this risk algorithm and the serum YKL-40 level, which is a biochemical marker. Material and methods: 87 volunteers between the ages of 40-70 who applied to our clinic, who had not yet experienced a cardiovascular event but had risk factors for cardiovascular diseases, were included in the study. SCORE2 cardiovascular disease risk was calculated for the patients and serum YKL-40 levels were gaged. Serum YKL-40 levels change with age, regardless of the disease, in our study as in many studies. In order to eliminate this paradigm, we examined serum YKL-40 levels with a statistical model that evaluates them jointly with age. Results: We could not detect a significant relationship with YKL-40 levels in the basal analysis performed by considering all parameters of SCORE2 algorithm. However, result of the statistical model that we evaluated with age, we found that the YKL-40 level is a biochemical parameter that can be used like SCORE2 in cardiovascular disease risk estimation (R2 : 0.72, p < 0.001).

• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• kardiovaskulární nemoci krev   prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• protein CHI3L1 * krev   MeSH
• rizikové faktory kardiovaskulárních chorob * MeSH
• senioři MeSH
• statistika jako téma MeSH
• ukazatele zdravotního stavu MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie MeSH

PURPOSE: The use of inotuzumab ozogamicin (InO), a conjugated anti-CD22 monoclonal antibody, is becoming a promising frontline treatment for older patients with ALL. PATIENTS AND METHODS: EWALL-INO is an open-label prospective multicenter phase II trial (ClinicalTrials.gov identifier: NCT03249870). Patients age 55 years and older with newly diagnosed CD22+ Philadelphia chromosome-negative (Ph-) B-cell precursor (BCP) ALL were eligible. After a prephase, a first induction consisting of vincristine, dexamethasone, and three injections of InO (0.8 mg/m2 day 1, 0.5 mg/m2 day 8/day 15) was followed by a second induction combining cyclophosphamide, dexamethasone, and two injections of InO (0.5 mg/m2 day 1/day 8). Responders received up to six cycles of chemotherapy consolidation and 18-month chemotherapy maintenance. Allotransplant was allowed after three consolidations. The primary end point was 1-year overall survival (OS). RESULTS: Between December 2017 and March 2022, 131 patients (median age 68 years) were included. Three patients died during induction 1 (n = 130), two from multiple organ failure and one from hemorrhage, and none during induction 2 (n = 120). After induction 2, 90% of the patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) and 80% had measurable residual disease (MRD2) <10-4. Among responders (n = 119), 47 relapsed and 14 died in CR/CRp. One-year OS, relapse-free survival (RFS), and cumulative incidence of relapse (CIR) rates were 73.2%, 66%, and 25%, respectively. High-risk cytogenetics and lower CD22 expression (<70%) were associated with worse OS, while both high-risk cytogenetics and MRD2 ≥10-4 were associated with lower RFS and higher CIR. The 10 allotransplanted patients had very favorable outcomes (90% 2-year OS/RFS and no relapse). Only one nonfatal sinusoidal obstructive syndrome was documented during the study. CONCLUSION: Our results support InO's use in first-line regimens for older patients with CD22+ Ph- BCP-ALL.

• MeSH
• antigeny CD22 * MeSH
• cyklofosfamid aplikace a dávkování   terapeutické užití   MeSH
• dexamethason aplikace a dávkování   terapeutické užití   MeSH
• filadelfský chromozom MeSH
• inotuzumab ozogamicin * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pre-B-buněčná leukemie * farmakoterapie   mortalita   genetika   MeSH
• prospektivní studie MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vinkristin aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH

The castor plant (Ricinus communis) is primarily known for its seeds, which contain a unique fatty acid called ricinoleic acid with several industrial and commercial applications. Castor seeds also contain ricin, a toxin considered a chemical and biological warfare agent. Despite years of investigation, there is still no effective antidote or vaccine available. However, some progress has been made, and the development of an effective treatment may be on the horizon. To provide an updated overview of this issue, we have conducted a comprehensive review of the literature on the current state of research in the fight against ricin. This review is based on the reported research and aims to address the challenges faced by researchers, as well as highlight the most successful cases achieved thus far. Our goal is to encourage the scientific community to continue their efforts in this critical search.

• MeSH
• antidota * chemie   farmakologie   MeSH
• chemické bojové látky chemie   MeSH
• lidé MeSH
• ricin * antagonisté a inhibitory   chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The mammalian Natural Killer Complex (NKC) harbors genes and gene families encoding a variety of C-type lectin-like proteins expressed on various immune cells. The NKC is a complex genomic region well-characterized in mice, humans and domestic animals. The major limitations of automatic annotation of the NKC in non-model animals include short-read based sequencing, methods of assembling highly homologous and repetitive sequences, orthologues missing from reference databases and weak expression. In this situation, manual annotations of complex genomic regions are necessary. METHODS: This study presents a manual annotation of the genomic structure of the NKC region in a high-quality reference genome of the domestic cat and compares it with other felid species and with representatives of other carnivore families. Reference genomes of Carnivora, irrespective of sequencing and assembly methods, were screened by BLAST to retrieve information on their killer cell lectin-like receptor (KLR) gene content. Phylogenetic analysis of in silico translated proteins of expanded subfamilies was carried out. RESULTS: The overall genomic structure of the NKC in Carnivora is rather conservative in terms of its C-type lectin receptor gene content. A novel KLRH-like gene subfamily (KLRL) was identified in all Carnivora and a novel KLRJ-like gene was annotated in the Mustelidae. In all six families studied, one subfamily (KLRC) expanded and experienced pseudogenization. The KLRH gene subfamily expanded in all carnivore families except the Canidae. The KLRL gene subfamily expanded in carnivore families except the Felidae and Canidae, and in the Canidae it eroded to fragments. CONCLUSIONS: Knowledge of the genomic structure and gene content of the NKC region is a prerequisite for accurate annotations of newly sequenced genomes, especially of endangered wildlife species. Identification of expressed genes, pseudogenes and gene fragments in the context of expanded gene families would allow the assessment of functionally important variability in particular species.

• MeSH
• anotace sekvence MeSH
• buňky NK * imunologie   metabolismus   MeSH
• Carnivora * genetika   MeSH
• fylogeneze * MeSH
• genom MeSH
• genomika * metody   MeSH
• kočky genetika   MeSH
• lektiny typu C genetika   MeSH
• zvířata MeSH
• Check Tag
• kočky genetika   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

AIMS: The aim of this study was to evaluate the association of serum neurofilament heavy chain (sNfH) and chitinase 3-like 1 (sCHI3L1) with treatment response and disease activity in multiple sclerosis (MS). METHODS: This single-center, prospective, observational cohort study was conducted at the MS Centre, University Hospital Ostrava, Czech Republic, from May 2020 to August 2023. sNfH and sCHI3L1 were determined using ELISA. A mixed-effects linear model with a log-transformed outcome variable was applied. RESULTS: We analyzed 459 samples from 57 people with MS. Patients were sampled an average of 8.05 times during 21.9 months of follow-up. Those experiencing a relapse at sampling had a sNfH concentration 50 % higher than those in remission (exp(β) 1.5, 95 % CI 1.15-1.96). A longer duration of treatment was associated with lower sNfH (exp(β) 0.95, 95 % CI 0.94-0.96). Patients switched from low- to high-efficacy disease-modifying therapies (DMTs) had higher sNfH than patients treated with low-efficacy DMTs only (exp(β) 1.95, 95 % CI 1.35-2.81). Higher sCHI3L1 was associated with older age (exp(β) 1.01, 95 % CI 1.00-1.02) and longer DMT use (exp(β) 1.01, 95 % CI 1.00-1.02). sCHI3L1 values were not associated with relapse at the time of sampling, renal function, sex, or type of DMT. CONCLUSION: In contrast to sCHI3L1, sNfH may be a potential biomarker for monitoring treatment response and confirming clinical relapse in MS. Further research is needed to determine the long-term dynamics of sNfH and develop related treatment strategies.

• MeSH
• biologické markery * krev   MeSH
• dospělí MeSH
• hodnocení výsledků zdravotní péče MeSH
• imunologické faktory aplikace a dávkování   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• neurofilamentové proteiny * krev   MeSH
• prospektivní studie MeSH
• protein CHI3L1 * krev   MeSH
• roztroušená skleróza krev   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

• MeSH
• čočka * MeSH
• fenoly farmakologie   MeSH
• funkční potraviny MeSH
• jedlá semena MeSH
• lektiny farmakologie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH

The detection of HPV infection and microbial colonization in cervical lesions is currently done through PCR-based viral or bacterial DNA amplification. Our objective was to develop a methodology to expand the metaproteomic landscape of cervical disease and determine if protein biomarkers from both human and microbes could be detected in distinct cervical samples. This would lead to the development of multi-species proteomics, which includes protein-based lateral flow diagnostics that can define patterns of microbes and/or human proteins relevant to disease status. In this study, we collected both non-frozen tissue biopsy and exfoliative non-fixed cytology samples to assess the consistency of detecting human proteomic signatures between the cytology and biopsy samples. Our results show that proteomics using biopsies or cytologies can detect both human and microbial organisms. Across patients, Lumican and Galectin-1 were most highly expressed human proteins in the tissue biopsy, whilst IL-36 and IL-1RA were most highly expressed human proteins in the cytology. We also used mass spectrometry to assess microbial proteomes known to reside based on prior 16S rRNA gene signatures. Lactobacillus spp. was the most highly expressed proteome in patient samples and specific abundant Lactobacillus proteins were identified. These methodological approaches can be used in future metaproteomic clinical studies to interrogate the vaginal human and microbiome structure and metabolic diversity in cytologies or biopsies from the same patients who have pre-invasive cervical intraepithelial neoplasia, invasive cervical cancer, as well as in healthy controls to assess how human and pathogenic proteins may correlate with disease presence and severity.

• MeSH
• biologické markery * analýza   metabolismus   MeSH
• biopsie MeSH
• cervix uteri * mikrobiologie   patologie   MeSH
• dospělí MeSH
• galektin 1 metabolismus   analýza   genetika   MeSH
• Lactobacillus MeSH
• lidé MeSH
• lumican MeSH
• mikrobiota MeSH
• nádory děložního čípku patologie   mikrobiologie   MeSH
• proteomika * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Pulmonary hypertension is a cardiovascular disease with a low survival rate. The protein galectin-3 (Gal-3) binding β-galactosides of cellular glycoproteins plays an important role in the onset and development of this disease. Carbohydrate-based drugs that target Gal-3 represent a new therapeutic strategy in the treatment of pulmonary hypertension. Here, we present the synthesis of novel hydrophilic glycopolymer inhibitors of Gal-3 based on a polyoxazoline chain decorated with carbohydrate ligands. Biolayer interferometry revealed a high binding affinity of these glycopolymers to Gal-3 in the subnanomolar range. In the cell cultures of cardiac fibroblasts and pulmonary artery smooth muscle cells, the most potent glycopolymer 18 (Lac-high) caused a decrease in the expression of markers of tissue remodeling in pulmonary hypertension. The glycopolymers were shown to penetrate into the cells. In a biodistribution and pharmacokinetics study in rats, the glycopolymers accumulated in heart and lung tissues, which are most affected by pulmonary hypertension.

• MeSH
• arteria pulmonalis účinky léků   metabolismus   MeSH
• biologické markery MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• galektin 3 * antagonisté a inhibitory   metabolismus   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• lidé MeSH
• plicní hypertenze * farmakoterapie   metabolismus   MeSH
• polymery chemie   farmakologie   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Mammalian spermatozoa have a surface covered with glycocalyx, consisting of heterogeneous glycoproteins and glycolipids. This complexity arises from diverse monosaccharides, distinct linkages, various isomeric glycans, branching levels, and saccharide sequences. The glycocalyx is synthesized by spermatozoa developing in the testis, and its subsequent alterations during their transit through the epididymis are a critical process for the sperm acquisition of fertilizing ability. In this study, we performed detailed analysis of the glycocalyx on the sperm surface of bull spermatozoa in relation to individual parts of the epididymis using a wide range (24) of lectins with specific carbohydrate binding preferences. Fluorescence analysis of intact sperm isolated from the bull epididymides was complemented by Western blot detection of protein extracts from the sperm plasma membrane fractions. Our experimental results revealed predominant sequential modification of bull sperm glycans with N-acetyllactosamine (LacNAc), followed by subsequent sialylation and fucosylation in a highly specific manner. Additionally, variations in the lectin detection on the sperm surface may indicate the acquisition or release of glycans or glycoproteins. Our study is the first to provide a complex analysis of the bull sperm glycocalyx modification during epididymal maturation.

• MeSH
• epididymis * metabolismus   cytologie   MeSH
• glykokalyx * metabolismus   MeSH
• glykoproteiny metabolismus   MeSH
• lektiny * metabolismus   MeSH
• polysacharidy metabolismus   MeSH
• skot MeSH
• spermie * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH