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1.
Rev Esp Enferm Dig ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967269

RESUMO

Acute pancreatitis is a common condition in Gastroenterology. Among its possible etiologies are ampullary tumors, rare neoplasms whose growth can hinder pancreatic drainage. Although they are usually epithelial, adenomas and adenocarcinomas, less commonly other histological types have been reported, such as neuroendocrine tumors. They constitute a small percentage of both ampullary tumors and neuroendocrine tumors of the digestive tract, classified into three histological grades based on mitotic count and Ki-67. Although the diagnosis is usually incidental, its main form of presentation is clinical or analytical cholestasis, with acute pancreatitis being an exceptional initial presentation. Endoscopic resection is the treatment of choice for well-differentiated tumors without evidence of local infiltration of the duodenal wall or intraductal growth greater than 10mm, with endoscopic ultrasound playing a key role in this assessment. We present the case of a 45-year-old cholecystectomized woman who was admitted to our service with a condition compatible with acute pancreatitis, initially suspected to be of biliary origin. After several radiological and endoscopic studies, an enlargement of the duodenal papilla suggestive of ampulloma was detected. Histological examination demonstrated a well-differentiated neuroendocrine tumor of the duodenal papilla which, lacking evidence of local duodenal infiltration or intraductal growth, was successfully resected endoscopically.

2.
Kidney Int Rep ; 9(6): 1817-1835, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899167

RESUMO

Introduction: Current therapeutic management of lupus nephritis (LN) fails to induce long-term remission in over 50% of patients, highlighting the urgent need for additional options. Methods: We analyzed differentially expressed genes (DEGs) in peripheral blood from patients with active LN (n = 41) and active nonrenal lupus (n = 62) versus healthy controls (HCs) (n = 497) from the European PRECISESADS project (NTC02890121), and dysregulated gene modules in a discovery (n = 26) and a replication (n = 15) set of active LN cases. Results: Replicated gene modules qualified for correlation analyses with serologic markers, and regulatory network and druggability analysis. Unsupervised coexpression network analysis revealed 20 dysregulated gene modules and stratified the active LN population into 3 distinct subgroups. These subgroups were characterized by low, intermediate, and high interferon (IFN) signatures, with differential dysregulation of the "B cell" and "plasma cells/Ig" modules. Drugs annotated to the IFN network included CC-motif chemokine receptor 1 (CCR1) inhibitors, programmed death-ligand 1 (PD-L1) inhibitors, and irinotecan; whereas the anti-CD38 daratumumab and proteasome inhibitor bortezomib showed potential for counteracting the "plasma cells/Ig" signature. In silico analysis demonstrated the low-IFN subgroup to benefit from calcineurin inhibition and the intermediate-IFN subgroup from B-cell targeted therapies. High-IFN patients exhibited greater anticipated response to anifrolumab whereas daratumumab appeared beneficial to the intermediate-IFN and high-IFN subgroups. Conclusion: IFN upregulation and B and plasma cell gene dysregulation patterns revealed 3 subgroups of LN, which may not necessarily represent distinct disease phenotypes but rather phases of the inflammatory processes during a renal flare, providing a conceptual framework for precision medicine in LN.

3.
Int J Oncol ; 65(2)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38940351

RESUMO

Obesity is a chronic disease caused by the accumulation of excessive adipose tissue. This disorder is characterized by chronic low­grade inflammation, which promotes the release of proinflammatory mediators, including cytokines, chemokines and leptin. Simultaneously, chronic inflammation can predispose to cancer development, progression and metastasis. Proinflammatory molecules are involved in the recruitment of specific cell populations in the tumor microenvironment. These cell populations include myeloid­derived suppressor cells (MDSCs), a heterogeneous, immature myeloid population with immunosuppressive abilities. Obesity­associated MDSCs have been linked with tumor dissemination, progression and poor clinical outcomes. A comprehensive literature review was conducted to assess the impact of obesity­associated MDSCs on cancer in both preclinical models and oncological patients with obesity. A secondary objective was to examine the key role that leptin, the most important proinflammatory mediator released by adipocytes, plays in MDSC­driven immunosuppression Finally, an overview is provided of the different therapeutic approaches available to target MDSCs in the context of obesity­related cancer.


Assuntos
Progressão da Doença , Células Supressoras Mieloides , Neoplasias , Obesidade , Microambiente Tumoral , Humanos , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Obesidade/complicações , Obesidade/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/etiologia , Microambiente Tumoral/imunologia , Animais , Leptina/metabolismo , Inflamação/imunologia , Inflamação/patologia
4.
Mov Disord ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696306

RESUMO

BACKGROUND: Calcitriol, the active form of vitamin D (also known as 1,25-dihydroxycholecalciferol), improves the phenotype and increases frataxin levels in cell models of Friedreich ataxia (FRDA). OBJECTIVES: Based on these results, we aimed measuring the effects of a calcitriol dose of 0.25 mcg/24h in the neurological function and frataxin levels when administered to FRDA patients for a year. METHODS: 20 FRDA patients where recluted and 15 patients completed the treatment for a year. Evaluations of neurological function changes (SARA scale, 9-HPT, 8-MWT, PATA test) and quality of life (Barthel Scale and Short Form (36) Health Survey [SF-36] quality of life questionnaire) were performed. Frataxin amounts were measured in isolated platelets obtained from these FRDA patients, from heterozygous FRDA carriers (relatives of the FA patients) and from non-heterozygous sex and age matched controls. RESULTS: Although the patients did not experience any observable neurological improvement, there was a statistically significant increase in frataxin levels from initial values, 5.5 to 7.0 pg/µg after 12 months. Differences in frataxin levels referred to total protein levels were observed among sex- and age-matched controls (18.1 pg/µg), relative controls (10.1 pg/µg), and FRDA patients (5.7 pg/µg). The treatment was well tolerated by most patients, and only some of them experienced minor adverse effects at the beginning of the trial. CONCLUSIONS: Calcitriol dosage used (0.25 mcg/24 h) is safe for FRDA patients, and it increases frataxin levels. We cannot rule out that higher doses administered longer could yield neurological benefits. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

5.
Nat Commun ; 15(1): 3159, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605040

RESUMO

How RNA-binding proteins (RBPs) convey regulatory instructions to the core effectors of RNA processing is unclear. Here, we document the existence and functions of a multivalent RBP-effector interface. We show that the effector interface of a conserved RBP with an essential role in metazoan development, Unkempt, is mediated by a novel type of 'dual-purpose' peptide motifs that can contact two different surfaces of interacting proteins. Unexpectedly, we find that the multivalent contacts do not merely serve effector recruitment but are required for the accuracy of RNA recognition by Unkempt. Systems analyses reveal that multivalent RBP-effector contacts can repurpose the principal activity of an effector for a different function, as we demonstrate for the reuse of the central eukaryotic mRNA decay factor CCR4-NOT in translational control. Our study establishes the molecular assembly and functional principles of an RBP-effector interface.


Assuntos
Proteínas de Ligação a RNA , RNA , Animais , Proteínas de Ligação a RNA/metabolismo , RNA/metabolismo , Processamento Pós-Transcricional do RNA , Peptídeos/metabolismo
6.
Nucleic Acids Res ; 52(8): 4702-4722, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38572746

RESUMO

The SERF family of proteins were originally discovered for their ability to accelerate amyloid formation. Znf706 is an uncharacterized protein whose N-terminus is homologous to SERF proteins. We show here that human Znf706 can promote protein aggregation and amyloid formation. Unexpectedly, Znf706 specifically interacts with stable, non-canonical nucleic acid structures known as G-quadruplexes. G-quadruplexes can affect gene regulation and suppress protein aggregation; however, it is unknown if and how these two activities are linked. We find Znf706 binds preferentially to parallel G-quadruplexes with low micromolar affinity, primarily using its N-terminus, and upon interaction, its dynamics are constrained. G-quadruplex binding suppresses Znf706's ability to promote protein aggregation. Znf706 in conjunction with G-quadruplexes therefore may play a role in regulating protein folding. RNAseq analysis shows that Znf706 depletion specifically impacts the mRNA abundance of genes that are predicted to contain high G-quadruplex density. Our studies give insight into how proteins and G-quadruplexes interact, and how these interactions affect both partners and lead to the modulation of protein aggregation and cellular mRNA levels. These observations suggest that the SERF family of proteins, in conjunction with G-quadruplexes, may have a broader role in regulating protein folding and gene expression than previously appreciated.


Assuntos
Proteínas de Ligação a DNA , Quadruplex G , Agregados Proteicos , Humanos , Amiloide/metabolismo , Amiloide/química , Amiloide/genética , Transição de Fase , Ligação Proteica , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/química , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo
7.
Front Immunol ; 15: 1293931, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469299

RESUMO

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Biomarcadores , Linfócitos T CD8-Positivos/patologia , Células Matadoras Naturais/patologia , Lenalidomida/uso terapêutico , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/patologia , Resposta Patológica Completa
8.
bioRxiv ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38352439

RESUMO

While evolution is often considered from a DNA- and protein-centric view, RNA-based regulation can also impact gene expression and protein sequences. Here we examined interspecies differences in RNA-protein interactions using the conserved neuronal RNA binding protein, Unkempt (UNK) as model. We find that roughly half of mRNAs bound in human are also bound in mouse. Unexpectedly, even when transcript-level binding was conserved across species differential motif usage was prevalent. To understand the biochemical basis of UNK-RNA interactions, we reconstituted the human and mouse UNK-RNA interactomes using a high-throughput biochemical assay. We uncover detailed features driving binding, show that in vivo patterns are captured in vitro, find that highly conserved sites are the strongest bound, and associate binding strength with downstream regulation. Furthermore, subtle sequence differences surrounding motifs are key determinants of species-specific binding. We highlight the complex features driving protein-RNA interactions and how these evolve to confer species-specific regulation.

9.
Nano Lett ; 24(4): 1316-1323, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38227973

RESUMO

Color centers (CCs) in nanostructured diamond are promising for optically linked quantum technologies. Scaling to useful applications motivates architectures meeting the following criteria: C1 individual optical addressing of spin qubits; C2 frequency tuning of spin-dependent optical transitions; C3 coherent spin control; C4 active photon routing; C5 scalable manufacturability; and C6 low on-chip power dissipation for cryogenic operations. Here, we introduce an architecture that simultaneously achieves C1-C6. We realize piezoelectric strain control of diamond waveguide-coupled tin vacancy centers with ultralow power dissipation necessary. The DC response of our device allows emitter transition tuning by over 20 GHz, combined with low-power AC control. We show acoustic spin resonance of integrated tin vacancy spins and estimate single-phonon coupling rates over 1 kHz in the resolved sideband regime. Combined with high-speed optical routing, our work opens a path to scalable single-qubit control with optically mediated entangling gates.

10.
Rev Esp Enferm Dig ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38284905

RESUMO

Immunotherapy has revolutionized the management of oncological pathology, demonstrating effectiveness in treating various cancers by stimulating the immune system against tumor cells. Among the immunotherapy drugs are programmed cell death protein 1 (PD-1) inhibitors, such as Nivolumab, which, by blocking this receptor on the surface of T lymphocytes, enhance the immune response. Despite their significant benefits, these agents present specific adverse effects on healthy tissues that need to be understood. One of these effects is immune-mediated colitis, a potentially serious gastrointestinal disorder that may require the permanent discontinuation of the drug. Although it can occur with various immunotherapy regimens, it occurs more frequently with anti-CTLA4 agents like Ipilimumab, with its incidence much lower with anti-PD1 agents. We present the case of a 62-year-old male diagnosed with metastatic clear cell renal carcinoma treated with radical nephrectomy and subsequent palliative systemic treatment with Nivolumab. After the third cycle of immunotherapy, he developed abdominal pain and diarrhea. Colonoscopy revealed continuous mucosal inflammation up to the cecum, erosions, exudates, and loss of the vascular pattern. Biopsies showed signs of active colitis, cryptic abscesses, and focal cryptitis, all consistent with a case of immuno-mediated colitis induced by Nivolumab that mimics, both endoscopically and histologically, the findings found in ulcerative colitis.

11.
Int J Mol Sci ; 25(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38256268

RESUMO

Cancer is a complex disease that, despite advances in treatment and the greater understanding of the tumor biology until today, continues to be a prevalent and lethal disease. Chemotherapy, radiotherapy, and surgery are the conventional treatments, which have increased the survival for cancer patients. However, the complexity of this disease together with the persistent problems due to tumor progression and recurrence, drug resistance, or side effects of therapy make it necessary to explore new strategies that address the challenges to obtain a positive response. One important point is that tumor cells can interact with the microenvironment, promoting proliferation, dissemination, and immune evasion. Therefore, immunotherapy has emerged as a novel therapy based on the modulation of the immune system for combating cancer, as reflected in the promising results both in preclinical studies and clinical trials obtained. In order to enhance the immune response, the combination of immunotherapy with nanoparticles has been conducted, improving the access of immune cells to the tumor, antigen presentation, as well as the induction of persistent immune responses. Therefore, nanomedicine holds an enormous potential to enhance the efficacy of cancer immunotherapy. Here, we review the most recent advances in specific molecular and cellular immunotherapy and in nano-immunotherapy against cancer in the light of the latest published preclinical studies and clinical trials.


Assuntos
Imunoterapia , Neoplasias , Humanos , Neoplasias/terapia , Apresentação de Antígeno , Evasão da Resposta Imune , Nanomedicina , Microambiente Tumoral
12.
Res Sq ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38260685

RESUMO

Lupus nephritis (LN) represents one of the most severe complications of systemic lupus erythematosus, leading to end-stage kidney disease in worst cases. Current first-line therapies for LN, including mycophenolate mofetil (MMF) and azathioprine (AZA), fail to induce long-term remission in 60-70% of the patients, evidencing the urgent need to delve into the molecular knowledge-gap behind the non-response to these therapies. A longitudinal cohort of treated LN patients including clinical, cellular and transcriptomic data, was analyzed. Gene-expression signatures behind non-response to different drugs were revealed by differential expression analysis. Drug-specific non-response mechanisms and cell proportion differences were identified. Blood cell subsets mediating non-response were described using single-cell RNASeq data. We show that AZA and MMF non-response implicates different cells and regulatory functions. Mechanistic models were used to suggest add-on therapies to improve their current performance. Our results provide new insights into the molecular mechanisms associated with treatment failures in LN.

13.
Rev Esp Enferm Dig ; 116(3): 169-170, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37114397

RESUMO

The obesity pandemic is becoming one of the most prevalent diseases nowadays. There is a wide spectrum of treatment, ranging from hygienic-dietary measures to bariatric surgery. Endoscopic intragastric balloon placement is becoming increasingly more frequent, due to its technical simplicity, safety and short-term success(1). Although complications are rare some can be severe, so pre-endoscopic evaluation must be carried out carefully. A 43-year-old woman with a history of grade I obesity (BMI 32.7) had an Orbera® intragastric balloon implanted successfully. After the procedure she presented frequent nausea and vomiting, partially controlled with antiemetics. She attended the Emergency Department(ED) with a persistent emetic syndrome - oral intolerance and short-term loss of consciousness(syncope), for which she was admitted. Lab tests showed metabolic alkalosis with severe hypokalemia(K+ 1.8mmol/L), so fluid therapy was initiated for hydroelectrolytic replacement. During the patient's stay in the ED, two episodes of polymorphic ventricular tachychardia "Torsades de Pointes" (PVT-TDP) occurred, leading to cardiac arrest and requiring electrical cardioversion to restore sinus rhythm, in addition to a temporary pacemaker placement. Telemetry showed a corrected QT interval of >500ms, compatible with Long QT Syndrome(LQTS). Once the patient was hemodynamically stabilized a gastroscopy was performed. The intragastric balloon located in the fundus was removed using an extraction kit, puncturing and aspirating 500ml of saline solution, and extracting the collapsed balloon without any complications. The patient achieved an adequate oral intake afterwards, and no recurrence of emetic episodes were noticed. Previous ECGs revealed a prolonged QT interval and a genetic study confirmed a congenital type 1 LQTS. Treatment was initiated with beta-blockers and a bicameral automatic defibrillator was implanted in order to prevent recurrences. Intragastric balloon placement is generally a safe procedure, serious complications present in 0.70% of cases(2). It is essential to have a proper pre-endoscopic evaluation, including patient's medical history and comorbidities. Episodes of PVT-TDP may present precipitated by certain medications (eg. metoclopramide) or hydroelectrolytic imbalances (eg, hypokalemia)(3). A standardized evaluation of ECG before intragastric balloon placement may be useful to prevent these rare but serious complications.


Assuntos
Balão Gástrico , Hipopotassemia , Síndrome do QT Longo , Torsades de Pointes , Feminino , Humanos , Adulto , Torsades de Pointes/etiologia , Torsades de Pointes/terapia , Balão Gástrico/efeitos adversos , Eméticos , Hipopotassemia/complicações , Síndrome do QT Longo/terapia , Síndrome do QT Longo/complicações , Obesidade/complicações , Proteínas de Ligação a DNA
14.
bioRxiv ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-37790366

RESUMO

The SERF family of proteins were originally discovered for their ability to accelerate amyloid formation. Znf706 is an uncharacterized protein whose N-terminus is homologous to SERF proteins. We show here that human Znf706 can promote protein aggregation and amyloid formation. Unexpectedly, Znf706 specifically interacts with stable, non-canonical nucleic acid structures known as G-quadruplexes. G-quadruplexes can affect gene regulation and suppress protein aggregation; however, it is unknown if and how these two activities are linked. We find Znf706 binds preferentially to parallel G-quadruplexes with low micromolar affinity, primarily using its N-terminus, and upon interaction, its dynamics are constrained. G-quadruplex binding suppresses Znf706's ability to promote protein aggregation. Znf706 in conjunction with G-quadruplexes therefore may play a role in regulating protein folding. RNAseq analysis shows that Znf706 depletion specifically impacts the mRNA abundance of genes that are predicted to contain high G-quadruplex density. Our studies give insight into how proteins and G-quadruplexes interact, and how these interactions affect both partners and lead to the modulation of protein aggregation and cellular mRNA levels. These observations suggest that the SERF family of proteins, in conjunction with G-quadruplexes, may have a broader role in regulating protein folding and gene expression than previously appreciated.

15.
Rev. esp. enferm. dig ; 116(3): 169-170, 2024. ilus
Artigo em Inglês | IBECS | ID: ibc-231484

RESUMO

The obesity pandemic is becoming one of the most prevalent diseases nowadays. There is a wide spectrum of treatment, ranging from hygienic-dietary measures to bariatric surgery. Endoscopic intragastric balloon placement is becoming increasingly more frequent, due to its technical simplicity, safety and short-term success(1). Although complications are rare some can be severe, so pre-endoscopic evaluation must be carried out carefully. A 43-year-old woman with a history of grade I obesity (BMI 32.7) had an Orbera® intragastric balloon implanted successfully. After the procedure she presented frequent nausea and vomiting, partially controlled with antiemetics. She attended the Emergency Department(ED) with a persistent emetic syndrome - oral intolerance and short-term loss of consciousness(syncope), for which she was admitted. Lab tests showed metabolic alkalosis with severe hypokalemia(K+ 1.8mmol/L), so fluid therapy was initiated for hydroelectrolytic replacement. During the patient’s stay in the ED, two episodes of polymorphic ventricular tachychardia “Torsades de Pointes” (PVT-TDP) occurred, leading to cardiac arrest and requiring electrical cardioversion to restore sinus rhythm, in addition to a temporary pacemaker placement. Telemetry showed a corrected QT interval of >500ms, compatible with Long QT Syndrome(LQTS). Once the patient was hemodynamically stabilized a gastroscopy was performed. The intragastric balloon located in the fundus was removed using an extraction kit, puncturing and aspirating 500ml of saline solution, and extracting the collapsed balloon without any complications. The patient achieved an adequate oral intake afterwards, and no recurrence of emetic episodes were noticed. Previous ECGs revealed a prolonged QT interval and a genetic study confirmed a congenital type 1 LQTS. Treatment was initiated with beta-blockers and a bicameral automatic defibrillator was implanted in order to prevent recurrences. ... (AU)


Assuntos
Humanos , Feminino , Adulto , Balão Gástrico/efeitos adversos , Torsades de Pointes/diagnóstico , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/terapia
17.
Nat Commun ; 14(1): 7716, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001076

RESUMO

Programmable photonic integrated circuits (PICs) are emerging as powerful tools for control of light, with applications in quantum information processing, optical range finding, and artificial intelligence. Low-power implementations of these PICs involve micromechanical structures driven capacitively or piezoelectrically but are often limited in modulation bandwidth by mechanical resonances and high operating voltages. Here we introduce a synchronous, micromechanically resonant design architecture for programmable PICs and a proof-of-principle 1×8 photonic switch using piezoelectric optical phase shifters. Our design purposefully exploits high-frequency mechanical resonances and optically broadband components for larger modulation responses on the order of the mechanical quality factor Qm while maintaining fast switching speeds. We experimentally show switching cycles of all 8 channels spaced by approximately 11 ns and operating at 4.6 dB average modulation enhancement. Future advances in micromechanical devices with high Qm, which can exceed 10000, should enable an improved series of low-voltage and high-speed programmable PICs.

18.
Rev Esp Enferm Dig ; 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37882176

RESUMO

An increased risk of hematologic malignancies secondary to long-term immunomodulators and biologics has been described in patients with inflammatory bowel disease1. Here, we present a case of jejunal stricture after chemotherapy treatment in a patient with ileal Crohn´s disease (CD) and jejunal lymphoma. The patient was a 32-year-old male with ileal CD in remission presenting with abdominal pain and distension. Abdominal computed tomography (CT) showed a poorly defined mass in the proximal jejunum, and positron emission tomography (PET) - CT showed hypermetabolic activity at that level. An upper endoscopy evidenced an indurated, friable circumferential mass causing a significant reduction of the intestinal lumen. Histological and cytometry findings led to a diagnosis of large B cell lymphoma, for which the patient received standard treatment (R-CHOP and IPI), achieving complete response. Eight months later, the patient reported abdominal pain and distention. Abdominal CT showed a thickening of a short segment of the proximal jejunum. An upper endoscopy showed a punctiform stenosis, while multiple biopsies showed neither histological recurrence of lymphoma nor signs of IBD. The patient was diagnosed with a post-chemotherapy stricture and underwent progressive endoscopic balloon dilatation. He finally was scheduled for laparoscopic small bowel resection. An histological analysis of the surgical piece revealed a granulomatous reaction with multinucleated foreign body-like giant cells, without evidence of malignancy (recurrence of lymphoma) nor inflammatory infiltrate suggesting CD. The patient currently remains asymptomatic with no new episodes of abdominal pain.

19.
RNA ; 29(10): 1535-1556, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37468167

RESUMO

Scaffold attachment factor B (SAFB) is a conserved RNA-binding protein that is essential for early mammalian development. However, the functions of SAFB in mouse embryonic stem cells (ESCs) have not been characterized. Using RNA immunoprecipitation followed by RNA-seq (RIP-seq), we examined the RNAs associated with SAFB in wild-type and SAFB/SAFB2 double-knockout ESCs. SAFB predominantly associated with introns of protein-coding genes through purine-rich motifs. The transcript most enriched in SAFB association was the lncRNA Malat1, which also contains a purine-rich region in its 5' end. Knockout of SAFB/SAFB2 led to differential expression of approximately 1000 genes associated with multiple biological processes, including apoptosis, cell division, and cell migration. Knockout of SAFB/SAFB2 also led to splicing changes in a set of genes that were largely distinct from those that exhibited changes in expression level. The spliced and nascent transcripts of many genes whose expression levels were positively regulated by SAFB also associated with high levels of SAFB, implying that SAFB binding promotes their expression. Reintroduction of SAFB into double-knockout cells restored gene expression toward wild-type levels, an effect again observable at the level of spliced and nascent transcripts. Proteomics analysis revealed a significant enrichment of nuclear speckle-associated and RS domain-containing proteins among SAFB interactors. Neither Xist nor Polycomb functions were dramatically altered in SAFB/2 knockout ESCs. Our findings suggest that among other potential functions in ESCs, SAFB promotes the expression of certain genes through its ability to bind nascent RNA.


Assuntos
Células-Tronco Embrionárias Murinas , RNA , Animais , Camundongos , Expressão Gênica , Íntrons , Mamíferos , Camundongos Knockout
20.
Med. clín (Ed. impr.) ; 161(2): 49-53, jul. 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-223273

RESUMO

Objetivo Estudio transversal prospectivo realizado para conocer la prevalencia y el patrón de consumo de alcohol (CA) de los pacientes con carcinoma hepatocelular (CHC) y evaluar la utilidad del AUDIT en estos. Métodos Se incluyeron 102 pacientes consecutivos atendidos en consulta entre febrero y marzo de 2022; se excluyeron aquellos con encefalopatía hepática en el momento de la entrevista, pacientes en lista de espera para trasplante por esta indicación y aquellos en seguimiento postrasplante. Resultados La prevalencia del CA en pacientes con diagnóstico de CHC es del 35%, si bien menos del 10% consume más de 100g de etanol a la semana. El CA fue más frecuente en varones, ambiente urbano, con diagnóstico de CHC hace más de un año y en pacientes en estadio inicial/muy inicial del BCLC. La puntuación AUDIT mayor o igual a 3 (AUROC 0,849) predice cualquier CA con una sensibilidad del 75% (IC 95%: 59,47-90,53%) y con una especificidad del 84% (IC 95%: 74,70-94,05%). Conclusiones A pesar del diagnóstico de CHC, más de un tercio de los pacientes consume alcohol. La puntuación AUDIT igual o mayor de 3 discrimina cualquier CA con una sensibilidad del 75% y una especificidad del 84% en esta población (AU)


Aim Prospective cross-sectional study conducted to determine the prevalence and pattern of alcohol consumption (AC) in patients with hepatocellular carcinoma (HCC) and to assess the utility of the AUDIT in HCC patients. Methods One hundred and two consecutive patients form our HCC monographic outpatient clinic visited between February and March 2022 were included. Patients with hepatic encephalopathy at the time of the interview, on the waiting list for liver transplantation and those undergoing post-transplant follow-up were excluded. Results The prevalence of AC in patients diagnosed with HCC is 35%, although less than 10% consume more than 100g per week. AC was more frequent in males, in an urban environment, with a diagnosis of HCC more than a year ago, and in patients in early/very early stages of BCLC. AUDIT score greater than or equal to 3 (AUROC 0.849) predicts any AC with a sensitivity of 75% (95% CI: 59.47-90.53%) and a specificity of 84% (95% CI: 74.70-94.05%). Conclusions Despite the diagnosis of HCC, more than a third of the patients consume alcohol. An AUDIT score equal to or greater than 3 discriminates any AC with a sensitivity of 75% and a specificity of 84% in this population (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Carcinoma Hepatocelular , Neoplasias Hepáticas , Entrevistas como Assunto , Estudos Transversais , Estudos Prospectivos , Prevalência
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