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1.
Nature ; 595(7867): 394-398, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34262211

RESUMO

The evolution of the global carbon and silicon cycles is thought to have contributed to the long-term stability of Earth's climate1-3. Many questions remain, however, regarding the feedback mechanisms at play, and there are limited quantitative constraints on the sources and sinks of these elements in Earth's surface environments4-12. Here we argue that the lithium-isotope record can be used to track the processes controlling the long-term carbon and silicon cycles. By analysing more than 600 shallow-water marine carbonate samples from more than 100 stratigraphic units, we construct a new carbonate-based lithium-isotope record spanning the past 3 billion years. The data suggest an increase in the carbonate lithium-isotope values over time, which we propose was driven by long-term changes in the lithium-isotopic conditions of sea water, rather than by changes in the sedimentary alterations of older samples. Using a mass-balance modelling approach, we propose that the observed trend in lithium-isotope values reflects a transition from Precambrian carbon and silicon cycles to those characteristic of the modern. We speculate that this transition was linked to a gradual shift to a biologically controlled marine silicon cycle and the evolutionary radiation of land plants13,14.


Assuntos
Ciclo do Carbono , Carbono , Isótopos , Lítio , Silício , Organismos Aquáticos , Carbono/análise , Carbono/metabolismo , Sedimentos Geológicos/química , Isótopos/análise , Lítio/análise , Plantas , Água do Mar/química , Silício/análise , Silício/metabolismo
2.
Invest New Drugs ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141261

RESUMO

Pembrolizumab has been associated with episodes of uveitis, and the clinical characteristics between them are unknown. The aim of this study was to investigate the clinical characteristics of pembrolizumab-induced uveitis and to provide reference for prevention, diagnosis and treatment. We collected studies related to pembrolizumab-induced uveitis by searching databases for retrospective analysis until April 30, 2024. The median age of the 31 patients was 63 years (range 7, 82), and the median duration of uveitis onset was 12 weeks (range 0.4, 108). Decreased vision (41.9%) and blurred vision (25.8%) were the most common complaints. Uveitis can be manifested as Vogt-Koyanagi-Harada disease-like uveitis (22.6%) and Birdshot uveitis (6.5%). Uveitis mainly affects both eyes and is related to anterior uveitis (35.5%), panuveitis (25.8%) and posterior uveitis (19.4%). Patients receiving topical steroid drops, systemic steroids, and withdrawal of pembrolizumab significantly improved symptoms at a median time of 4 weeks (range 2, 16). The possibility of uveitis should be considered when patients are treated with pembrolizumab and experience eye symptoms such as blurred vision and decreased vision. Depending on the severity of uveitis, treatment with topical and systemic steroids may be selected.

3.
Invest New Drugs ; 42(1): 53-59, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063991

RESUMO

Gastritis has recently been reported to be associated with nivolumab, and the clinical characteristics of nivolumab induced gastritis remain unclear. To explore the clinical characteristics of nivolumab induced gastritis, and to provide reference for the classification and treatment guidelines of immune checkpoint inhibitors -related gastritis. Case reports, case series, and clinical studies of nivolumab induced gastritis were retrospectively analyzed by searching the database from the establishment of the database until September 30, 2023. Forty-seven were included, with a median age of 57 years (range 16, 93). The median time of symptom onset was 6 months (range 0.5,36) and 6.5 cycles (range 2, 62). Nausea (29 cases, 61.7%), vomiting (29 cases, 61.7%), and epigastric pain (28 cases, 59.6%) were the most common complaints. Esophagogastroduodenoscopy mainly showed erythema (28 cases, 59.6%). Gastric mucosa biopsy showed epithelial inflammatory cell infiltration (22 cases, 46.8%) and apoptosis (15 cases, 31.9%). Most patients' symptoms and gastric mucosa improved or recovered after receiving systemic steroid and proton pump inhibitor therapy regardless of whether nivolumab was discontinued. Two patients died from gastritis related events. Gastritis should be considered as the cause of unexplained epigastric symptoms in the administration of nivolumab. Understanding the clinical features of nivolumab induced gastritis is very important for accurate diagnosis and timely management of these patients.


Assuntos
Gastrite , Nivolumabe , Humanos , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Prognóstico , Gastrite/induzido quimicamente , Gastrite/diagnóstico , Inibidores de Checkpoint Imunológico
4.
Invest New Drugs ; 42(4): 369-375, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38829427

RESUMO

Acute pancreatitis (AP) is a rare adverse event of pembrolizumab with unclear clinical features. This study investigated the clinical features of pembrolizumab-induced AP to provide a reference for prevention and treatment. Case reports, case series and clinical studies of pembrolizumab-induced AP were collected by searching Chinese and English databases up to January 31, 2024. Thirty-one patients were included, with a median age of 59 years (range 39, 82). The median time from administration to onset of AP was 5.05 months (range 0.5, 16) and the median cycle was 7 cycles (range 1, 35). Twenty-two (71.0%) patients had elevated pancreatic amylase with a median value of 860 IU/L (range 105-12562), and 16 (51.6%) patients had elevated lipase with a median value of 282 IU/L (range 153-1034). Pancreatic biopsy showed neutrophil infiltration (9.7%) and lymphocyte infiltration (6.5%). Immunohistochemical staining showed CD8 dominated inflammatory infiltration (6.5%). The computed tomography showed diffuse enlargement (51.6%) and focal enlargement (51.6%) of the pancreas. Endoscopic ultrasound showed enlarged hypoechoic pancreas(16.1%). PET/CT showed increased FDG uptake (16.1%). The magnetic resonance cholangial pancreatography showed narrowing of main pancreatic duct (12.9%). AP symptoms and pancreatic enzymes improved after discontinuation of pembrolizumab and administration of steroids and infliximab. Clinicians should be aware that AP is a rare adverse reaction to pembrolizumab. Pembrolizumab induced AP can be initiated with steroids for control, and infliximab can be initiated with steroid-refractory AP.


Assuntos
Anticorpos Monoclonais Humanizados , Pancreatite , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Pancreatite/induzido quimicamente , Pancreatite/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Adulto , Antineoplásicos Imunológicos/efeitos adversos , Doença Aguda , Resultado do Tratamento
5.
Vet Res ; 55(1): 27, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443986

RESUMO

Bovine viral diarrhea virus (BVDV) belongs to the genus Pestivirus within the family Flaviviridae. Mitophagy plays important roles in virus-host interactions. Here, we provide evidence that non-cytopathic (NCP) BVDV shifts the balance of mitochondrial dynamics toward fission and induces mitophagy to inhibit innate immune responses. Mechanistically, NCP BVDV triggers the translocation of dynamin-related protein (Drp1) to mitochondria and stimulates its phosphorylation at Ser616, leading to mitochondrial fission. In parallel, NCP BVDV-induced complete mitophagy via Parkin-dependent pathway contributes to eliminating damaged mitochondria to inhibit MAVS- and mtDNA-cGAS-mediated innate immunity responses, mtROS-mediated inflammatory responses and apoptosis initiation. Importantly, we demonstrate that the LIR motif of ERNS is essential for mitophagy induction. In conclusion, this study is the first to show that NCP BVDV-induced mitophagy plays a central role in promoting cell survival and inhibiting innate immune responses in vitro.


Assuntos
Vírus da Diarreia Viral Bovina , Mitofagia , Animais , Apoptose , Imunidade Inata , Diarreia/veterinária
6.
Sensors (Basel) ; 24(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38400243

RESUMO

Computing resource measurement and computing routing are essential technologies in the computing first network (CFN), serving as its foundational elements. This paper introduces a Software Defined Computing First Network (SD-CFN) architecture. Building upon this framework, a Dynamic-Static Integrated Computing Resource Measurement Mechanism (DCRMM) is proposed, incorporating methods such as the entropy weight method and K-Means clustering. The DCRMM algorithm outperforms the Maximum-closest Static Algorithm (MSA) and Maximum Closest Dynamic Algorithm (MDA) in terms of node stability, node utilization, and node matching accuracy. Additionally, a Reinforcement Learning and Software Defined Computing First Networking Routing (RSCR) algorithm is presented as a software-defined computing routing solution within the SD-CFN. RSCR introduces a knowledge plane responsible for computing routing calculations. It comprehensively considers factors such as link latency, available bandwidth, and packet loss rate. Simulation experiments conducted on the GÉANT topology demonstrate that RSCR outperforms the OSPF algorithm in terms of link latency, packet loss rate, and throughput. DCRMM and RSCR offer innovative solutions for computing resource measurement and computing routing in computing first networks.

7.
Angew Chem Int Ed Engl ; 63(7): e202315325, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38155608

RESUMO

An atom- and step-economical and redox-neutral cascade reaction enabled by asymmetric bimetallic relay catalysis by merging a ruthenium-catalyzed asymmetric borrowing-hydrogen reaction with copper-catalyzed asymmetric Michael addition has been realized. A variety of highly functionalized 2-amino-5-hydroxyvaleric acid esters or peptides bearing 1,4-non-adjacent stereogenic centers have been prepared in high yields with excellent enantio- and diastereoselectivity. Judicious selection and rational modification of the Ru catalysts with careful tuning of the reaction conditions played a pivotal role in stereoselectivity control as well as attenuating undesired α-epimerization, thus enabling a full complement of all four stereoisomers that were otherwise inaccessible in previous work. Concise asymmetric stereodivergent synthesis of the key intermediates for biologically important chiral molecules further showcases the synthetic utility of this methodology.


Assuntos
Cobre , Rutênio , Aminoácidos/química , Catálise , Cobre/química , Peptídeos , Estereoisomerismo
8.
J Am Chem Soc ; 145(5): 2779-2786, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36706215

RESUMO

Herein, a novel strategy for the catalytic asymmetric synthesis of enantioenriched 3-cis- and 3-trans-substituted prolines has been successfully established via an unprecedented cascade radical addition/cyclization enabled by synergistic photoredox/Brønsted acid catalysis and subsequent base-assisted epimerization. The current protocol provides a unique de novo access to all four stereoisomers of 3-substituted prolines which are not readily achieved via currently established methods. This methodology could be further extended to the asymmetric synthesis of the full complement of stereoisomers of 3-substituted pipecolinic acids.

9.
Clin Exp Immunol ; 211(2): 85-92, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36426591

RESUMO

Myasthenia gravis (MG) is a rare but life-threatening adverse event with pembrolizumab. What is known about pembrolizumab-induced MG is largely based on case reports. This analysis collected pembrolizumab-induced MG cases from Chinese and English databases published from September 1, 2014, to June 30, 2022. Demographic and clinical information of the patients, management, and outcome data were collected and analyzed. Sixty-five patients with a median age of 73 years (range 30-86), including 43 male patients (66.2%), were included. Eight patients (12.3%) with prior MG experienced worsening symptoms after receiving pembrolizumab. The median time to the onset of MG was four weeks (range 0.7-27). The most common symptoms were ptosis (81.5%, 53 patients), diplopia (50.8%, 33 patients), dyspnea (44.6%, 29 patients), trunk or peripheral weakness (43.1%, 28 patients), and dysphagia (30.8%, 20 patients). Concurrent myositis and myocarditis occurred in 13 (20.0%) and 17 patients (26.2%). Pembrolizumab was discontinued in 63 patients (96.9%). Forty-four patients (67.7%) received combination therapies based on steroids (intravenous immune globulin, plasmapheresis, or immunosuppressants). Twenty-seven patients (41.5%) had symptoms completely recovered. Fourteen patients (21.5%) died from immunotoxicity or primary cancers. Clinicians should consider the possibility of pembrolizumab-induced MG, especially during the first eight weeks of therapy. Patients should be treated as early as possible, regardless of the severity of the initial symptoms.


Assuntos
Miastenia Gravis , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Miastenia Gravis/induzido quimicamente , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Terapia Combinada
10.
Invest New Drugs ; 41(2): 333-339, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36988830

RESUMO

BACKGROUND: To investigate the clinical features of nivolumab-induced myasthenia gravis (MG) and provide evidence for the rational use of nivolumab in the clinic. METHODS: We collected case reports and case series of nivolumab-induced MG for retrospective analysis by searching Chinese and English databases from 2014 to October 31, 2022. RESULTS: Of the 67 patients included, the median age was 72.5 years (range 34-86), including 44 males (65.7%). MG occurred in the median 2nd treatment cycle (range, 1st-6th) after nivolumab treatment, being mild in 12 patients (17.9%) and moderate to severe in 44 patients (65.7%). Ptosis (n = 48,71.6%), diplopia (n = 34,50.7%), dyspnea (n = 30, 44.8%), limb muscle weakness (n = 30, 44.8%) and dysphagia (n = 27, 40.3%) were the most common symptoms. Fifty-six patients (83.6%) were classified as having generalized myasthenia gravis (GMG), the remaining 11 patients (16.4%) isolated ocular myasthenia gravis (OMG). Twenty-one patients (31.3%) had MG combined with myositis, 10 patients (14.9%) had myocarditis, and 9 patients (13.4%) had both myositis and myocarditis. Forty patients (59.7%) were positive for anti-acetylcholine receptor antibodies. The serum creatine kinase level was significantly increased in 37 patients (55.2%), with a median value of 4000 IU/L (219,14229). After discontinuation of nivolumab and immunosuppressive therapy, 46 patients (68.7%) finally recovered or improved their MG symptoms, while 15 patients (22.4%) did not recover. Eleven patients (16.4%) died of MG complications. CONCLUSION: MG is a serious and rare adverse reaction to nivolumab. Nivolumab-induced MG should be timely and correctly identified, and immunotherapy should be given.


Assuntos
Miastenia Gravis , Miocardite , Miosite , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Miocardite/induzido quimicamente , Miocardite/complicações , Miocardite/tratamento farmacológico , Miastenia Gravis/induzido quimicamente , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/complicações , Miosite/induzido quimicamente , Miosite/diagnóstico , Miosite/tratamento farmacológico , Resultado do Tratamento
11.
Invest New Drugs ; 41(6): 834-841, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897650

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal adverse reaction to pembrolizumab. The clinical characteristics of pembrolizumab induced HLH are unknown. Exploring the clinical features of pembrolizumab induced HLH is crucial for the treatment and prevention of immune checkpoint inhibitor-induced HLH. METHODS: The literature related to pembrolizumab induced HLH was collected for retrospective analysis by searching the Chinese and English databases from inception until August 31, 2023. RESULTS: A total of 24 patients were included, including 17 men (70.8%) with a median age of 61 years (41,80). The time between the last infusion and the start of HLH ranged from 2 to 46 days, with a median time of 14 days. Fever (100%) was the most common symptom, accompanied by splenomegaly (14 cases, 58.3%) and hepatomegaly (6 cases, 25.0%). Laboratory examination revealed revealed anemia (18 cases, 75.0%), leukopenia (12 cases, 50.0%), thrombocytopenia (20 cases, 83.3%), hypertriglyceridemia (11 cases, 45.8%), hypofibrinogenemia (11 cases, 45.8%). decreased natural killer cell function (7 cases, 29.2%), and elevated soluble CD25(15 cases, 62.5%). All patients developed hyperferriinemia, with a median of 30,808 ng/mL (range 1303 ~ 100,000). Bone marrow biopsy showed hemophagocytosis (15 cases, 62.5%). After discontinuation of pembrolizumab and treatment with steroids, etoposide, intravenous immunoglobulin, cytokine blocking, and immunosuppression, 17 patients recovered or improved, and 5 patients eventually died. CONCLUSION: HLH should be suspected when unexplained fever, cytopenia, splenomegaly, and elevated aminotransferase occur in patients using pembrolizumab. Screening for risk factors before treatment with pembrolizumab may be necessary to prevent HLH.


Assuntos
Anemia , Linfo-Histiocitose Hemofagocítica , Masculino , Humanos , Pessoa de Meia-Idade , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/complicações , Estudos Retrospectivos , Esplenomegalia/complicações , Anticorpos Monoclonais Humanizados/efeitos adversos
12.
Invest New Drugs ; 41(6): 802-807, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37773473

RESUMO

BACKGROUND: Bullous pemphigoid (BP) is a serious and rare complication of nivolumab. This study aimed to explore the clinical characteristics of nivolumab-induced BP and provide a reference for prevention and treatment of BP. METHODS: Literature on nivolumab-induced BP was collected for retrospective analysis by searching both Chinese and English databases as of July 31, 2023. RESULTS: Sixty patients were included, with a median age of 71 years (range 30 to 85 years), and they were predominantly male (78.3%). The median time to onset of BP was 31 weeks (range 2.4, 216) after nivolumab administration. Tense bullae (93.3%), pruritus (55.0%), and urticarial plaques (31.7%) were the most common manifestations. Lesions were found on the limbs (50.0%), trunk (38.3%), palms and soles (15.0%). Skin biopsies mainly showed subepidermal bullous/blister (50.0%) and eosinophilic infiltration (46.7%). Direct immunofluorescence showed mainly linear deposition of C3 and IgG (46.7%) at the dermal-epidermal junction. The patients stopped taking nivolumab and received systemic steroids (73.3%), topical steroids (63.3%), monoclonal antibodies (21.7%), doxycycline/minocycline (30.0%) and other treatments. Symptoms improved or were relieved in 88.4% of patients but did not improve in 8.3% of patients. CONCLUSION: Clinicians should closely monitor symptoms of BP in those receiving and discontinuing nivolumab, especially in older men. Early diagnosis and timely initiation of treatment may improve patient outcomes.


Assuntos
Penfigoide Bolhoso , Humanos , Masculino , Idoso , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Feminino , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/diagnóstico , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Pele/patologia , Esteroides/uso terapêutico
13.
Cardiovasc Diabetol ; 22(1): 25, 2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732747

RESUMO

BACKGROUND: Increased acid sphingomyelinase (ASMase) activity is associated with insulin resistance and cardiac dysfunction. However, the effects of ASMase on diabetic cardiomyopathy (DCM) and the molecular mechanism(s) underlying remain to be elucidated. We here investigated whether ASMase caused DCM through NADPH oxidase 4-mediated apoptosis. METHODS AND RESULTS: We used pharmacological and genetic approaches coupled with study of murine and cell line samples to reveal the mechanisms initiated by ASMase in diabetic hearts. The protein expression and activity of ASMase were upregulated, meanwhile ceramide accumulation was increased in the myocardium of HFD mice. Inhibition of ASMase with imipramine (20 mg Kg-1 d-1) or siRNA reduced cardiomyocyte apoptosis, fibrosis, and mitigated cardiac hypertrophy and cardiac dysfunction in HFD mice. The similar effects were observed in cardiomyocytes treated with high glucose (HG, 30 mmol L-1) + palmitic acid (PA, 100 µmol L-1) or C16 ceramide (CER, 20 µmol L-1). Interestingly, the cardioprotective effect of ASMase inhibition was not accompanied by reduced ceramide accumulation, indicating a ceramide-independent manner. The mechanism may involve activated NADPH oxidase 4 (NOX4), increased ROS generation and triggered apoptosis. Suppression of NOX4 with apocynin prevented HG + PA and CER incubation induced Nppb and Myh7 pro-hypertrophic gene expression, ROS production and apoptosis in H9c2 cells. Furthermore, cardiomyocyte-specific ASMase knockout (ASMaseMyh6KO) restored HFD-induced cardiac dysfunction, remodeling, and apoptosis, whereas NOX4 protein expression was downregulated. CONCLUSIONS: These results demonstrated that HFD-mediated activation of cardiomyocyte ASMase could increase NOX4 expression, which may stimulate oxidative stress, apoptosis, and then cause metabolic cardiomyopathy.


Assuntos
Diabetes Mellitus , Cardiomiopatias Diabéticas , Camundongos , Animais , NADPH Oxidase 4/genética , Esfingomielina Fosfodiesterase/genética , Esfingomielina Fosfodiesterase/metabolismo , Esfingomielina Fosfodiesterase/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/prevenção & controle , Ceramidas/farmacologia , Ceramidas/metabolismo , Miócitos Cardíacos/metabolismo , Apoptose , NADPH Oxidases
14.
Nature ; 541(7637): 386-389, 2017 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-28002400

RESUMO

The macronutrient phosphorus is thought to limit primary productivity in the oceans on geological timescales. Although there has been a sustained effort to reconstruct the dynamics of the phosphorus cycle over the past 3.5 billion years, it remains uncertain whether phosphorus limitation persisted throughout Earth's history and therefore whether the phosphorus cycle has consistently modulated biospheric productivity and ocean-atmosphere oxygen levels over time. Here we present a compilation of phosphorus abundances in marine sedimentary rocks spanning the past 3.5 billion years. We find evidence for relatively low authigenic phosphorus burial in shallow marine environments until about 800 to 700 million years ago. Our interpretation of the database leads us to propose that limited marginal phosphorus burial before that time was linked to phosphorus biolimitation, resulting in elemental stoichiometries in primary producers that diverged strongly from the Redfield ratio (the atomic ratio of carbon, nitrogen and phosphorus found in phytoplankton). We place our phosphorus record in a quantitative biogeochemical model framework and find that a combination of enhanced phosphorus scavenging in anoxic, iron-rich oceans and a nutrient-based bistability in atmospheric oxygen levels could have resulted in a stable low-oxygen world. The combination of these factors may explain the protracted oxygenation of Earth's surface over the last 3.5 billion years of Earth history. However, our analysis also suggests that a fundamental shift in the phosphorus cycle may have occurred during the late Proterozoic eon (between 800 and 635 million years ago), coincident with a previously inferred shift in marine redox states, severe perturbations to Earth's climate system, and the emergence of animals.


Assuntos
Evolução Biológica , Fósforo/metabolismo , Animais , Atmosfera/química , Carbono/metabolismo , Planeta Terra , Sedimentos Geológicos/química , História Antiga , Ferro/análise , Nitrogênio/metabolismo , Oxirredução , Oxigênio/metabolismo , Fósforo/história , Água do Mar/química
15.
J Am Chem Soc ; 144(43): 20025-20034, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36264302

RESUMO

An enantiomerically enriched 3-hydroxymethyl pentenal unit is one of the key structural cores in plenty of natural products and drug candidates with significant biological activities. However, very few synthetic methodologies for the facile construction of the related skeletons have been reported to date. Herein, an elegant iridium-catalyzed asymmetric cascade allylation/retro-Claisen reaction of readily available ß-diketones with VEC was successfully developed, and a wide range of functionalized chiral 3-hydroxymethyl pentenal derivatives could be prepared in good yields with excellent enantioselectivities. Various 1,3-diketones and functionalized ketones containing different electron-withdrawing groups on the ß-position were well tolerated as outstanding partners with high reactivity and excellent regio-/chemo-/enantioselectivity. The synthetic utility of product chiral 3-hydroxymethyl pentenal derivatives was well shown through gram-scale transformation, hydrogenation, cyclopropanation, hydroboration, and olefin metathesis. Moreover, this elegant protocol demonstrated synthetic applications in the concise synthesis of synthetically useful chiral building block (S)-Taniguchi lactone and the formal synthesis of natural product cytisine. A rational reaction pathway was proposed based on the experimental results and control experiments.


Assuntos
Irídio , Cetonas , Irídio/química , Estereoisomerismo , Hidrogenação , Cetonas/química , Catálise
16.
Invest New Drugs ; 40(5): 1153-1159, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35867286

RESUMO

Knowledge of dasatinib-induced nephrotic syndrome is largely based on case reports. The clinical features of dasatinib-induced nephrotic syndrome are unknown. We collected case reports of 25 patients with nephrotic syndrome and analyzed their clinical characteristics. Overall, the onset of nephrotic syndrome ranged from 10 days to 5 years after dasatinib administration. Nine patients (36.0%) had clinical symptoms, mainly periorbital edema and lower-extremity edema. Serum albumin ranged from 1.2 g/dL to 3.7 g/dL in 10 patients (38.5%). The 24-h urine protein values ranged from 3.54 g/day to 118 g/day. Kidney biopsy of 13 patients (52.0%) mainly showed focal foot process effacement, mesangial hyperplasia, endothelial cell damage and focal segmental glomerulosclerosis. Proteinuria resolved or recovered after dasatinib discontinuation or dose reduction or switching to other tyrosine kinase inhibitors (TKIs).


Assuntos
Glomerulosclerose Segmentar e Focal , Síndrome Nefrótica , Dasatinibe/efeitos adversos , Glomerulosclerose Segmentar e Focal/induzido quimicamente , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Humanos , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Proteinúria/induzido quimicamente , Proteinúria/diagnóstico , Albumina Sérica
17.
Infection ; 50(5): 1217-1224, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35288847

RESUMO

PURPOSE: Previous knowledge about the relationship between voriconazole exposure and periostitis was mainly based on limited case reports and few retrospective studies. The purpose of this study was to assess the clinical characteristics, diagnosis and management of voriconazole-associated periostitis. METHODS: Case reports and case series from 1998 to November 30, 2021 on periostitis induced by voriconazole were collected for retrospective analysis. RESULTS: Forty four patients (18 male and 26 female) from 34 studies were included in total. The median age was 58 years (29-74). The majority of patients had undergone organ transplantation (50.0%) or suffered from hematologic malignancy (31.81%). The median onset time of symptoms was 6 months after the start of voriconazole. The most common initial symptom was diffuse skeletal pain (68.28%) which can be severe and even disabling (66.7%). Ribs (37.21%), femurs (32.56%), scapulae (25.58%), humerus (23.26%), and clavicle (23.26%) were the common involved locations. Most cases were accompanied by different degrees of elevated serum alkaline phosphatase and fluoride level, while some presented with elevated bone-specific alkaline phosphatase. The main radiological features included periosteal reaction and multifocal high radiotracer uptake on bone scintigraphy. The formation of new bone was characterized with bilateral, irregular, nodular, as well as high density. The resolution of symptoms was observed with discontinuation of voriconazole in all patients, of whom 18 patients (52.94%) were relieved within a week. Itraconazole, posaconazole or isavuconazole were safe alternatives to voriconazole in voriconazole-induced periostitis. CONCLUSION: Voriconazole-induced periostitis is an infrequent complication characterized by bone inflammation involving one or multiple skeletal areas. Bony pain, elevated serum alkaline phosphatase as well as fluoride level are suspicious signs during voriconazole treatment.


Assuntos
Doenças Ósseas , Periostite , Fosfatase Alcalina/efeitos adversos , Antifúngicos/efeitos adversos , Feminino , Fluoretos/efeitos adversos , Humanos , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Periostite/diagnóstico , Periostite/diagnóstico por imagem , Estudos Retrospectivos , Voriconazol/efeitos adversos
18.
Ann Pharmacother ; 56(2): 205-212, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34105395

RESUMO

OBJECTIVE: To analyze and discuss the clinical characteristics of dipeptidyl peptidase-4 inhibitor (DPP4i)-induced bullous pemphigoid (BP). DATA SOURCES: We collected case reports of DPP4i-induced BP by searching databases from 2006 to mid-May 2021, as a retrospective analysis. STUDY SELECTION AND DATA EXTRACTION: Relevant case reports and case analyses of DPP4i-induced BP were included. DATA SYNTHESIS: The median time of symptom onset was 9 months (range 0.5-59 months). BP most often occurred in patients receiving vildagliptin (52.63%) followed by linagliptin (27.19%) and sitagliptin (17.54%). Tense bullae and blisters (85.51%) and erythema (82.61%) on the extremities and trunk were the most common presenting symptoms. In total, 64.06% of BP patients were anti-BP180 autoantibody positive, 58.97% were BP180NC16a autoantibody positive, and 31.25% were anti-BP230 autoantibody positive. Skin biopsy revealed subepidermal bulla eosinophil infiltration in 93.85% of BP patients, lymphocyte infiltration in 56.93%, and neutrophil infiltration in 44.62%. Direct immunofluorescence was positive in 98.94% of BP patients with linear deposition of IgG (97.80%) and/or complement C3 (98.94%) along the basement membrane zone. Indirect immunofluorescence was positive in 87.88% of BP patients. Complete remission of BP was achieved in 83.64% of patients on DPP4i withdrawal and after 4 months (range 0.13-72 months) of follow-up. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review analyzes and discusses the clinical characteristics of DPP4i-induced BP and provides a reference for the safe and reasonable clinical application of DPP4i. CONCLUSIONS: DPP4i drugs are related to the occurrence of BP in diabetic patients, especially elderly men taking vildagliptin.


Assuntos
Inibidores da Dipeptidil Peptidase IV , Penfigoide Bolhoso , Idoso , Autoanticorpos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Dipeptidil Peptidases e Tripeptidil Peptidases , Humanos , Masculino , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/tratamento farmacológico , Estudos Retrospectivos , Vildagliptina
19.
Am J Emerg Med ; 52: 203-207, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34959022

RESUMO

BACKGROUND: Understanding the relationship between contrast agents and Kounis syndrome (KS) is mainly based on case reports. The purpose of this research is to explore the clinical characteristics of contrast media induced KS. METHODS: We searched for contrast-induced KS case reports through Chinese and English databases from 1991 to October 31, 2021. RESULTS: A total of 26 patients (19 men and 7 women,) were included, with a median age of 60 years (range 30-83). The contrast agents that cause KS mainly included gadolinium-based contrast agent (7 cases), iodine-containing contrast media (12 cases). KS mainly occurred within 30 min after administration and mainly manifests as chest pain and allergic reactions. Electrocardiogram (ECG) mainly showed ST elevation. Echocardiography mainly revealed normal. Coronary angiography showed normal, coronary vasospasm, stent thrombosis, occlusion and stenosis. After treatment with steroids, antihistamines and anti-ischemic therapy, 24 patients recovered completely and 2 patients died. CONCLUSIONS: KS is a rare adverse reaction of contrast media. Radiologists should recognize this rare but serious disease to ensure rapid diagnosis and proper management.


Assuntos
Meios de Contraste/efeitos adversos , Síndrome de Kounis/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Pharmacology ; 107(7-8): 351-358, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35381593

RESUMO

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP/SMX) causes hyperkalemia, and hyponatremia caused by TMP/SMX is a challenge for clinicians. We described the clinical features of hyponatremia induced by TMP/SMX after collecting cases. SUMMARY: The median age of the 24 patients (10 males and 14 females) was 67 years (range: 28-90 years). Hyponatremia induced by TMP/SMX manifested as nausea (41.7%) and vomiting (29.2%) or asymptomatic hyponatremia (20.8%). The median duration of hyponatremia was 5 days (range: 3-10 days). The median serum sodium concentration was 118 mmol/L (range: 101-128.1 mmol/L). The serum sodium levels gradually returned to the normal range at 4 days (median; range: 2-14 days) after withdrawing TMP/SMX. KEY MESSAGES: TMP/SMX-induced hyponatremia is a rare and serious adverse reaction. Clinicians should be aware of electrolyte disturbances caused by TMP/SMX and should always consider electrolyte monitoring.


Assuntos
Hiperpotassemia , Hiponatremia , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletrólitos/efeitos adversos , Feminino , Humanos , Hiperpotassemia/induzido quimicamente , Hiponatremia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Sódio , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
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