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Frontiers in Immunology 2020The impact of anti-HLA donor-specific alloantibodies (DSA) which develop after long-term liver transplantation (LT) remains controversial and unclear. The aim of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The impact of anti-HLA donor-specific alloantibodies (DSA) which develop after long-term liver transplantation (LT) remains controversial and unclear. The aim of this study was to investigate the role of DSAs on the outcome in LT.
METHODS
We did a systematic review and meta-analysis of observational studies published until Dec 31, 2019, that reported DSA outcome data (≥1 year of follow-up) after liver transplant. A literature search in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus and Web of Science Core Collection databases was performed.
RESULTS
Of 5,325 studies identified, 15 fulfilled our inclusion criteria. The studies which reported 2016 liver transplant recipients with DSAs showed an increased complication risk, i.e. graft loss and chronic rejection (OR 3.61; 95% CI 1.94-6.71, < 0.001; I 58.19%), and allograft rejection alone (OR 6.43; 95% CI: 3.17-13.04; < 0.001; I 49.77%); they were compared to patients without DSAs. The association between DSAs and overall outcome failure was consistent across all subgroups and sensitivity analysis.
CONCLUSIONS
Our study suggested that DSAs had a significant deleterious impact on the liver transplant risk of rejection. The routine detection of DSAs may be beneficial as noninvasive biomarker-guided risk stratification.
Topics: Animals; Graft Rejection; Humans; Isoantibodies; Liver Transplantation; Observational Studies as Topic; Tissue Donors
PubMed: 33424868
DOI: 10.3389/fimmu.2020.613128 -
American Journal of Kidney Diseases :... Aug 1989De novo posttransplantation membranous glomerulonephropathy (MGN) is the most common form of de novo glomerulopathy in renal allografts. The clinical and pathological... (Review)
Review
De novo posttransplantation membranous glomerulonephropathy (MGN) is the most common form of de novo glomerulopathy in renal allografts. The clinical and pathological features of ten patients with de novo MGN were studied and the related literature was reviewed to assess the clinical features, morphologic characteristics, and natural course of this disease. De novo MGN may occur in both living related and cadaveric allografts at any time after transplantation. It presents clinically either as asymptomatic proteinuria or the nephrotic syndrome, a feature of poor prognostic implication. Morphologically, de novo MGN in most instances has distinct differences from idiopathic MGN in native kidneys and is accompanied by varying features of rejection. About 50% of grafts which develop de novo MGN eventually fail. This rather poor outcome may not represent the natural history of de novo MGN per se but rather the consequences of associated chronic rejection. Evidence is presented that many of the cases of so-called de novo MGN may be a complication of transplant glomerulopathy rather than being caused by mechanisms totally independent from rejection.
Topics: Cadaver; Female; Glomerulonephritis, Membranous; Graft Rejection; Humans; Kidney Glomerulus; Kidney Transplantation; Male; Microscopy, Electron; Prognosis
PubMed: 2667346
DOI: 10.1016/s0272-6386(89)80189-1 -
Proceedings of the National Academy of... Oct 2022De novo protein design enables the exploration of novel sequences and structures absent from the natural protein universe. De novo design also stands as a stringent test...
De novo protein design enables the exploration of novel sequences and structures absent from the natural protein universe. De novo design also stands as a stringent test for our understanding of the underlying physical principles of protein folding and may lead to the development of proteins with unmatched functional characteristics. The first fundamental challenge of de novo design is to devise "designable" structural templates leading to sequences that will adopt the predicted fold. Here, we built on the TopoBuilder (TB) de novo design method, to automatically assemble structural templates with native-like features starting from string descriptors that capture the overall topology of proteins. Our framework eliminates the dependency of hand-crafted and fold-specific rules through an iterative, data-driven approach that extracts geometrical parameters from structural tertiary motifs. We evaluated the TopoBuilder framework by designing sequences for a set of five protein folds and experimental characterization revealed that several sequences were folded and stable in solution. The TopoBuilder de novo design framework will be broadly useful to guide the generation of artificial proteins with customized geometries, enabling the exploration of the protein universe.
Topics: Models, Molecular; Protein Engineering; Protein Folding; Proteins
PubMed: 36252041
DOI: 10.1073/pnas.2206111119 -
World Journal of Gastroenterology May 2023Endoscopy has rapidly developed in recent years and has enabled further investigation into the origin and features of intestinal tumors. The small size and concealed...
BACKGROUND
Endoscopy has rapidly developed in recent years and has enabled further investigation into the origin and features of intestinal tumors. The small size and concealed position of these tumors make it difficult to distinguish them from nonneoplastic polyps and carcinoma in adenoma (CIA). The invasive depth and metastatic potential determine the operation regimen, which in turn affects the overall survival and distant prognosis. The previous studies have confirmed the malignant features and clinicopathological features of colorectal cancer (CRC).
AIM
To provide assistance for diagnosis and treatment, but the lack of a summary of endoscopic features and assessment of risk factors that differ from the CIA prompted us to conduct this retrospective study.
METHODS
In total, 167 patients with small-sized CRCs diagnosed by endoscopy were reviewed. The patients diagnosed as advanced CRCs and other malignant cancers or chronic diseases that could affect distant outcomes were excluded. After screening, 63 cases were excluded, including 33 and 30 CIA cases. Patient information, including their follow-up information, was obtained from an electronic His-system. The characteristics between two group and risk factors for invasion depth were analyzed with SPSS 25.0 software.
RESULTS
Nearly half of the CRCs were smaller than 1 cm ( = 16, 48.5%) and the majority were located in the distal colon ( = 26, 78.8%). The IIc type was the most common macroscopic type of CRC. In a Pearson analysis, the differential degree, Sano, JNET, and Kudo types, surrounding mucosa, and chicken skin mucosa (CSM) were correlated with the invasion depth ( < 0.001). CSM was a significant risk factor for deep invasion and disturbed judgment of endoscopic ultrasound. A high degree of tumor budding and tumor-infiltrating lymphocytes are accompanied by malignancy. Finally, CRCs have worse outcomes than CIA CRCs.
CONCLUSION
This is the first comprehensive study to analyze the features of CRCs to distinguish them from nonneoplastic polyps. It is also the first study paying attention to CSM invasive depth measurement. This study emphasizes the high metastatic potential of CRCs and highlights the need for more research on this tumor type.
Topics: Humans; Retrospective Studies; Colorectal Neoplasms; Endoscopy; Risk Factors; Adenoma
PubMed: 37274065
DOI: 10.3748/wjg.v29.i18.2836 -
F1000Research 2017Over the last few years, there has been an increasing amount of evidence for the emergence of protein-coding genes, i.e. out of non-coding DNA. Here, we review the... (Review)
Review
Over the last few years, there has been an increasing amount of evidence for the emergence of protein-coding genes, i.e. out of non-coding DNA. Here, we review the current literature and summarize the state of the field. We focus specifically on open questions and challenges in the study of protein-coding genes such as the identification and verification of -emerged genes. The greatest obstacle to date is the lack of high-quality genomic data with very short divergence times which could help precisely pin down the location of origin of a gene. We conclude that, while there is plenty of evidence from a genetics perspective, there is a lack of functional studies of bona fide genes and almost no knowledge about protein structures and how they come about during the emergence of protein-coding genes. We suggest that future studies should concentrate on the functional and structural characterization of protein-coding genes as well as the detailed study of the emergence of functional protein-coding genes.
PubMed: 28163910
DOI: 10.12688/f1000research.10079.1 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2015To substantiate the reasonability and duration of angiographic follow-up of patients operated on for cerebral aneurysms to rule out de novo aneurysm formation.
OBJECTIVE
To substantiate the reasonability and duration of angiographic follow-up of patients operated on for cerebral aneurysms to rule out de novo aneurysm formation.
MATERIAL AND METHODS
The results of angiographic examination (cerebral angiography and SCT angiography) of 43 patients with cerebral aneurysms operated on at the Burdenko Neurosurgical Institute in 1995-2012 are analyzed. The follow-up duration varied from 1 to 14 years after surgery (mean duration, 5 years). Patients' age ranged from 14 to 56 years.
RESULTS
Control angiographic examination showed that de novo aneurysms were formed in 7 (16.2%) patients. A total of 8 de novo aneurysms were detected (in one case there were two aneurysms formed). All aneurysms, both the previously operated and the de novo ones, were located in the anterior part of the circle of Willis. De novo aneurysms were clipped in 5 cases; the cavity of the de novo aneurysm was occluded with spirals in one case. One patient with a small aneurysm of the middle cerebral artery refused surgery. Neither lethal nor unfavorable outcomes were recorded.
CONCLUSIONS
The patient groups with the high risk of de novo aneurysm formation are as follows: 1) young smokers with hypertension; 2) patients who developed clinical signs of the disease when being young; 3) patients subjected to proximal exclusion of the main artery; and 4) patients with multiple and familial forms of the pathology. Dynamic angiographic follow-up (SCT angiography or magnetic resonance angiography) for 1-3 years is recommended for these patients.
Topics: Adolescent; Adult; Cerebral Angiography; Female; Humans; Hypertension; Intracranial Aneurysm; Magnetic Resonance Angiography; Male; Middle Aged; Recurrence; Smoking; Subarachnoid Hemorrhage; Tomography, Spiral Computed; Treatment Outcome; Young Adult
PubMed: 26146046
DOI: 10.17116/neiro201579275-81 -
Biopolymers Nov 2013Over the last 25 years, de novo design has proven to be a valid approach to generate novel, well-folded proteins, and most recently, functional proteins. In response to... (Review)
Review
Over the last 25 years, de novo design has proven to be a valid approach to generate novel, well-folded proteins, and most recently, functional proteins. In response to societal needs, this approach is been used increasingly to design functional proteins developed with an eye toward sustainable fuel production. This review surveys recent examples of bioinspired de novo designed peptide based catalysts, focusing in particular on artificial hydrogenases.
Topics: Catalysis; Hydrogenase; Iron; Peptides
PubMed: 24281721
DOI: 10.1002/bip.22420 -
Orvosi Hetilap May 2021Összefoglaló. A gyulladásos bélbetegség (inflammatory bowel disease, IBD) incidenciája folyamatosan nő, etiológiája egyelőre ismeretlen. Kezelésében gyakran...
Összefoglaló. A gyulladásos bélbetegség (inflammatory bowel disease, IBD) incidenciája folyamatosan nő, etiológiája egyelőre ismeretlen. Kezelésében gyakran alkalmazunk immunszuppresszív, illetve immunmoduláns szereket. Egyes esetekben azonban szolidszerv-transzplantációt követően, folyamatos immunszuppresszív kezelés mellett is megfigyelhető de novo IBD kialakulása. Célunk az volt, hogy Klinikánk beteganyagából összesítsük azon eseteket, amelyekben szolid szerv (máj, vese, tüdő) transzplantációját követően de novo IBD alakult ki. A transzplantációt megelőzően szklerotizáló cholangitis miatt gondozott betegeket kizártuk. A Klinikánkon gondozott, szolid szerv transzplantációján (179 máj, 197 vese, 29 tüdő) átesett betegek közül 4 (2 máj- és 2 vesetranszplantált) gyermeknél alakult ki de novo IBD. A transzplantációhoz vezető alapbetegségek biliaris atresia, polycystás vese és Denys-Drash-szindróma voltak. A transzplantációt követő immunszuppresszív terápia mind a 4 esetben tartalmazott szisztémásszteroid- és takrolimuszkezelést, emellett 3 esetben mikofenolát-mofetil (MMF)-terápiát is. A kivizsgálást indikáló főbb tünetek a haematochesia, hasmenés, fáradékonyság és fogyás voltak. A családi anamnézis 1 esetben volt pozitív. A de novo IBD diagnózisának felállítását követően mind a 4 betegnél az addigi immunszuppressziós terápia módosításra került. Összességében elmondható, hogy a szolidszerv-transzplantációt követő de novo IBD kialakulása ritka, etiológiája tisztázatlan. Az irodalom felveti az alkalmazott immunszuppresszív szerek (takrolimusz és MMF), illetve infekciók etiológiai szerepét, de az is felmerül, hogy a de novo IBD olyan önálló entitás, mely elkülönül a klasszikus IBD kategóriáitól. Klinikai szempontból fontos a tünetek hátterében álló betegség tisztázása, hiszen a prezentációs tüneteknek megfelelő, a differenciáldiagnosztika során felmerülő egyéb betegségek terápiája merőben eltér. A megfelelő terápia hozzájárulhat a transzplantált betegek morbiditásának és mortalitásának csökkentéséhez. Orv Hetil. 2021; 162(18): 720-726. Summary. The incidence of inflammatory bowel disease (IBD) is increasing, however, the aetiology is still unknown. The therapy consists of immunosuppressants and immunomodulators. In some cases, despite the continuous immunosuppressant therapy, de novo IBD develops. Our aim was to evaluate patients diagnosed with de novo IBD after solid organ (liver, kidney, or lung) transplantation. Patients treated with sclerosing cholangitis prior to liver transplantation were excluded. 4 patients (two kidney and two liver transplants) were diagnosed with de novo IBD. The underlying diseases leading to transplantation were biliary atresia, polycystic kidney, and Denys-Drash syndrome. All patients received systemic steroid and tacrolimus treatment, and 3 patients (2 kidney and 1 liver transplant) also received mycophenolate mofetil (MMF). The main symptoms indicative of de novo IBD were haematochezia, diarrhoea, fatigue, and weight loss. Family history for IBD was positive in 1 case. Following the diagnosis of IBD, immunosuppressive therapy was modified. Overall, the development of de novo IBD following solid organ transplantation is quite rare, and its aetiology is unknown. According to the literature, immunosuppressants (tacrolimus and MMF) and infections play a role in the pathomechanism, but it seems that de novo IBD is a separate entity from the classical IBD categories. From a clinical point of view, it is important to elucidate the underlying disease of the symptoms, as the treatment of other diseases that arise during differential diagnosis according to the presentation symptoms is very different. Appropriate therapy can help reduce morbidity and mortality in transplant patients. Orv Hetil. 2021; 162(18): 720-726.
Topics: Child; Humans; Inflammatory Bowel Diseases; Organ Transplantation
PubMed: 33934087
DOI: 10.1556/650.2021.32070 -
Protein Science : a Publication of the... Jun 2024De novo protein design expands the protein universe by creating new sequences to accomplish tailor-made enzymes in the future. A promising topology to implement diverse...
De novo protein design expands the protein universe by creating new sequences to accomplish tailor-made enzymes in the future. A promising topology to implement diverse enzyme functions is the ubiquitous TIM-barrel fold. Since the initial de novo design of an idealized four-fold symmetric TIM barrel, the family of de novo TIM barrels is expanding rapidly. Despite this and in contrast to natural TIM barrels, these novel proteins lack cavities and structural elements essential for the incorporation of binding sites or enzymatic functions. In this work, we diversified a de novo TIM barrel by extending multiple βα-loops using constrained hallucination. Experimentally tested designs were found to be soluble upon expression in Escherichia coli and well-behaved. Biochemical characterization and crystal structures revealed successful extensions with defined α-helical structures. These diversified de novo TIM barrels provide a framework to explore a broad spectrum of functions based on the potential of natural TIM barrels.
Topics: Models, Molecular; Escherichia coli; Crystallography, X-Ray; Protein Folding; Protein Engineering; Proteins
PubMed: 38723111
DOI: 10.1002/pro.5001 -
GigaScience May 2019In recent years, massively parallel complementary DNA sequencing (RNA sequencing [RNA-Seq]) has emerged as a fast, cost-effective, and robust technology to study entire... (Comparative Study)
Comparative Study
BACKGROUND
In recent years, massively parallel complementary DNA sequencing (RNA sequencing [RNA-Seq]) has emerged as a fast, cost-effective, and robust technology to study entire transcriptomes in various manners. In particular, for non-model organisms and in the absence of an appropriate reference genome, RNA-Seq is used to reconstruct the transcriptome de novo. Although the de novo transcriptome assembly of non-model organisms has been on the rise recently and new tools are frequently developing, there is still a knowledge gap about which assembly software should be used to build a comprehensive de novo assembly.
RESULTS
Here, we present a large-scale comparative study in which 10 de novo assembly tools are applied to 9 RNA-Seq data sets spanning different kingdoms of life. Overall, we built >200 single assemblies and evaluated their performance on a combination of 20 biological-based and reference-free metrics. Our study is accompanied by a comprehensive and extensible Electronic Supplement that summarizes all data sets, assembly execution instructions, and evaluation results. Trinity, SPAdes, and Trans-ABySS, followed by Bridger and SOAPdenovo-Trans, generally outperformed the other tools compared. Moreover, we observed species-specific differences in the performance of each assembler. No tool delivered the best results for all data sets.
CONCLUSIONS
We recommend a careful choice and normalization of evaluation metrics to select the best assembling results as a critical step in the reconstruction of a comprehensive de novo transcriptome assembly.
Topics: Animals; Arabidopsis; Contig Mapping; Escherichia coli; Humans; Mice; Sequence Analysis, RNA; Software; Transcriptome
PubMed: 31077315
DOI: 10.1093/gigascience/giz039