Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 834
Filtrar
1.
Acta Pharmacol Sin ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095509

RESUMO

The study of traditional medicine has garnered significant interest, resulting in various research areas including chemical composition analysis, pharmacological research, clinical application, and quality control. The abundance of available data has made databases increasingly essential for researchers to manage the vast amount of information and explore new drugs. In this article we provide a comprehensive overview and summary of 182 databases that are relevant to traditional medicine research, including 73 databases for chemical component analysis, 70 for pharmacology research, and 39 for clinical application and quality control from published literature (2000-2023). The review categorizes the databases by functionality, offering detailed information on websites and capacities to facilitate easier access. Moreover, this article outlines the primary function of each database, supplemented by case studies to aid in database selection. A practical test was conducted on 68 frequently used databases using keywords and functionalities, resulting in the identification of highlighted databases. This review serves as a reference for traditional medicine researchers to choose appropriate databases and also provides insights and considerations for the function and content design of future databases.

2.
Arch Med Sci ; 20(3): 1038-1042, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050154

RESUMO

Introduction: Tuberculous meningitis (TBM) is a severe extra-pulmonary tuberculosis with high fatality. This meta-analysis aimed to assess the impact of linezolid on TBM treatment outcomes. Methods: We searched multiple databases for studies published up to May 18, 2024 comparing the effects of linezolid on TBM. Meta-analysis was conducted using Review Manager 5.4. Results: Our findings indicated that linezolid may reduce treatment failure risk (RR = 0.42 (0.20, 0.89), p = 0.02) and improve temperature recovery (RR = 1.56 (1.21, 2.02), p < 0.001) in TBM patients. Conclusions: The analysis suggests a positive association between linezolid treatment and therapeutic improvements, with no significant adverse reactions reported.

3.
Diagnostics (Basel) ; 14(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39001321

RESUMO

Single photon emission tomography/computed tomography (SPECT/CT) is a mature imaging technology with a dynamic role in the diagnosis and monitoring of a wide array of diseases. This paper reviews the technological advances, clinical impact, and future directions of SPECT and SPECT/CT imaging. The focus of this review is on signal amplifier devices, detector materials, camera head and collimator designs, image reconstruction techniques, and quantitative methods. Bulky photomultiplier tubes (PMTs) are being replaced by position-sensitive PMTs (PSPMTs), avalanche photodiodes (APDs), and silicon PMs to achieve higher detection efficiency and improved energy resolution and spatial resolution. Most recently, new SPECT cameras have been designed for cardiac imaging. The new design involves using specialised collimators in conjunction with conventional sodium iodide detectors (NaI(Tl)) or an L-shaped camera head, which utilises semiconductor detector materials such as CdZnTe (CZT: cadmium-zinc-telluride). The clinical benefits of the new design include shorter scanning times, improved image quality, enhanced patient comfort, reduced claustrophobic effects, and decreased overall size, particularly in specialised clinical centres. These noticeable improvements are also attributed to the implementation of resolution-recovery iterative reconstructions. Immense efforts have been made to establish SPECT and SPECT/CT imaging as quantitative tools by incorporating camera-specific modelling. Moreover, this review includes clinical examples in oncology, neurology, cardiology, musculoskeletal, and infection, demonstrating the impact of these advancements on clinical practice in radiology and molecular imaging departments.

4.
Yi Chuan ; 46(7): 581-586, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39016091

RESUMO

Biodiversity losses along with the exponential growth of global human population and human-provoked over-exploitation of natural resources. Genetic factors played an important role in the conservation of endangered species. Conservation genetics is a cross-field disciplinary of genetics and conservation biology. The course of conservation genetics is not available in colleges and universities, and the course of genetics does not directly reflect the content of biological conservation. We have taught genetics with integrative thoughts of conservation biology. In the form of case studies, we have integrated recent advances of research and technology in the relevant fields into the genetics classroom. As a result, we improved the undergraduates' motivation and interest in active learning, provoked the mutual promotion of "basic knowledge of genetics, awareness of ecological protection, and cultivate interdisciplinary thinking", and set up the groundwork for cultivating interdisciplinary talents who not only master solid basic knowledge, but also have the concept of ecological civilization.


Assuntos
Conservação dos Recursos Naturais , Genética , Conservação dos Recursos Naturais/métodos , Humanos , Genética/educação , Ensino , Biologia/educação
6.
J Control Release ; 371: 484-497, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38851537

RESUMO

The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury.


Assuntos
Benzofuranos , Sistemas de Liberação de Medicamentos , Lipossomos , Células-Tronco Mesenquimais , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/terapia , Masculino , Benzofuranos/administração & dosagem , Isquemia Encefálica/terapia , Materiais Biomiméticos/química , Materiais Biomiméticos/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Células-Tronco Mesenquimais/métodos
7.
Sci Rep ; 14(1): 13549, 2024 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866854

RESUMO

Whilst. pharmacological therapies remain the cornerstone of pain management in chronic pain, factors including the current opioid epidemic have led to non-pharmacological techniques becoming a more attractive proposition. We explored the prevalence of medical device use and their treatment efficacy in non-cancer pain management. A systematic methodology was developed, peer reviewed and published in PROSPERO (CRD42021235384). Key words of medical device, pain management devices, chronic pain, lower back pain, back pain, leg pain and chronic pelvic pain using Science direct, PubMed, Web of Science, PROSPERO, MEDLINE, EMBASE, PorQuest and ClinicalTrials.gov. All clinical trials, epidemiology and mixed methods studies that reported the use of medical devices for non-cancer chronic pain management published between the 1st of January 1990 and the 30th of April 2022 were included. 13 studies were included in systematic review, of these 6 were used in the meta-analysis. Our meta-analysis for pain reduction showed that transcutaneous electrical nerve stimulation combined with instrument-assisted soft tissue mobilization treatment and pulsed electromagnetic therapy produced significant treatment on chronic lower back pain patients. Pooled evidence revealed the use of medical device related interventions resulted in 0.7 degree of pain reduction under a 0-10 scale. Significant improvement in disability scores, with a 7.44 degree reduction in disability level compared to a placebo using a 50 score range was also seen. Our analysis has shown that the optimal use of medical devices in a sustainable manner requires further research, needing larger cohort studies, greater gender parity, in a more diverse range of geographical locations.


Assuntos
Teorema de Bayes , Dor Crônica , Manejo da Dor , Humanos , Dor Crônica/terapia , Manejo da Dor/métodos , Dor Lombar/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Equipamentos e Provisões , Resultado do Tratamento
8.
Cancer Lett ; 593: 216963, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38768682

RESUMO

Neoadjuvant tyrosine kinase inhibitor (TKI) therapy is an important treatment option for advanced renal cell carcinoma (RCC). Many RCC patients may fail to respond or be resistant to TKI therapy. We aimed to explore the key mechanisms of neoadjuvant therapy résistance. We obtained tumor samples from matched pre-treatment biopsy and post-treatment surgical samples and performed single-cell RNA sequencing. Sunitinib-resistant ccRCC cell lines were established. Ferroptosis was detected by ferrous ion and lipid peroxidation levels. Tumor growth and resistance to Sunitinib was validated in vitro and vivo. Immunohistochemistry was used to validate the levels key genes and lipid peroxidation. Multi-center cohorts were included, including TCGA, ICGC, Checkmate-025 and IMmotion151 clinical trial. Survival analysis was performed to identify the associated clinical and genomic variables. Intratumoral heterogeneity was first described in the whole neoadjuvant management. The signature of endothelial cells was correlated with drug sensitivity and progression-free survival. Ferroptosis was shown to be the key biological program in malignant cell resistance. We observed tissue lipid peroxidation was negatively correlated with IL6 and tumor response. TKI-resistant cell line was established. SLC7A11 knockdown promoted cell growth and lipid peroxidation, increased the ferroptosis level, and suppressed the growth of tumor xenografts significantly (P < 0.01). IL6 could reverse the ferroptosis and malignant behavior caused by SLC7A11 (-) via JAK2/STAT3 pathway, which was rescued by the ferroptosis inducer Erastin. Our data indicate that ferroptosis is a novel strategy for advanced RCC treatment, which activated by IL6, providing a new idea for resistance to TKIs.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Carcinoma de Células Renais , Resistencia a Medicamentos Antineoplásicos , Ferroptose , Neoplasias Renais , Terapia Neoadjuvante , Sunitinibe , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Terapia Neoadjuvante/métodos , Sunitinibe/farmacologia , Animais , Linhagem Celular Tumoral , Camundongos , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Inibidores de Proteínas Quinases/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Feminino , Masculino , Terapia de Alvo Molecular , Interleucina-6/metabolismo , Interleucina-6/genética , Progressão da Doença
9.
Cancers (Basel) ; 16(10)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38791939

RESUMO

Background: Total hysterectomy with bilateral salpingo-oophorectomy via minimally invasive surgery (MIS) has emerged as the standard of care for early-stage endometrial cancer (EC). Prior systematic reviews and meta-analyses have focused on outcomes reported solely from randomised controlled trials (RCTs), overlooking valuable data from non-randomised studies. This inaugural systematic review and network meta-analysis comprehensively compares clinical and oncological outcomes between MIS and open surgery for early-stage EC, incorporating evidence from randomised and non-randomised studies. Methods: This study was prospectively registered on PROSPERO (CRD42020186959). All original research of any experimental design reporting clinical and oncological outcomes of surgical treatment for endometrial cancer was included. Study selection was restricted to English-language peer-reviewed journal articles published 1 January 1995-31 December 2021. A Bayesian network meta-analysis was conducted. Results: A total of 99 studies were included in the network meta-analysis, comprising 181,716 women and 14 outcomes. Compared with open surgery, laparoscopic and robotic-assisted surgery demonstrated reduced blood loss and length of hospital stay but increased operating time. Compared with laparoscopic surgery, robotic-assisted surgery was associated with a significant reduction in ileus (OR = 0.40, 95% CrI: 0.17-0.87) and total intra-operative complications (OR = 0.38, 95% CrI: 0.17-0.75) as well as a higher disease-free survival (OR = 2.45, 95% CrI: 1.04-6.34). Conclusions: For treating early endometrial cancer, minimal-access surgery via robotic-assisted or laparoscopic techniques appears safer and more efficacious than open surgery. Robotic-assisted surgery is associated with fewer complications and favourable oncological outcomes.

10.
PLoS One ; 19(5): e0302155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38701096

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).


Assuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Glucosídeos , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/complicações , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Pessoa de Meia-Idade , Masculino , Método Duplo-Cego , Feminino , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Adulto , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Quimioterapia Combinada , Glicemia/metabolismo , Idoso , Resultado do Tratamento
11.
J Immunother Cancer ; 12(5)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802271

RESUMO

BACKGROUND: Relapsed/refractory (R/R) central nervous system lymphomas (CNSLs) are associated with a poor prognosis. Relmacabtagene autoleucel (relma-cel), expressing the same chimeric antigen receptor (CAR) as lisocabtagene maraleucel, with an optimized commercial-ready process developed in China, demonstrated remarkable efficacy and manageable safety in the pivotal RELIANCE study. However, no published data are available on the "real-world" use of relma-cel, especially for patients with CNS involvement. PATIENTS AND METHODS: Retrospective analyses were conducted for commercial relma-cel used in patients with R/R CNSL at 12 clinics. The primary endpoint was to evaluate the proportion of patients who achieved complete response (CR) at 3 months. Secondary endpoints included best complete response (BCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and the incidence of adverse events. RESULTS: Among the 22 CNSL patients (12 primary CNSLs; 10 secondary CNSLs), the best overall response rate was 90.9% and the BCR rate was 68.2%. With median follow-up of 316 days (range, 55-618 days), the estimated 1-year PFS rate, DOR, and OS rate were 64.4%, 71.5%, and 79.2%, respectively. Significant clinical benefits were observed in patients who were in durable CR or partial response to the most recent prior therapy preleukapheresis and received relma-cel as consolidation therapy (n=8), with 1-year PFS rate of 100.0% versus 41.7% (p=0.02). In addition, in terms of primary endpoint, non-CR at 3 months postinfusion seemed to be predictive of a worse prognosis, with an estimated 1-year PFS of 83.3% versus 37.0% (p=0.03), respectively. CRS occurred in 72.9% of patients (grade 3: 4.5%) and immune effector cell-associated neurotoxicity syndrome in 36.4% of patients (grade 3: 4.5%). With the add-on agent PD-1 inhibitor (tislelizumab) to the ongoing BTKi, significant re-expansions of CAR T-cell were detected by quantitative PCR or flow cytometry after a median of 2 weeks (range, 12-32 days). CONCLUSIONS: This study was the first and largest real-world study of commercial relma-cel for R/R CNSL, demonstrating promising efficacy and acceptable safety. We reaffirmed the benefit of immuno-agents such as BTKi or PD-1 inhibitor on CAR T-cell re-expansion and hypothesized a dual-agent CAR-T related combinatorial therapies, which warrants further validation. Most importantly, we highlighted the earlier use of CAR T-cell therapy as a consolidative therapy for patients sensitive to salvage therapy, which provided an impetus and inspired-future strategy.


Assuntos
Neoplasias do Sistema Nervoso Central , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/terapia , China , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Linfoma/terapia , Linfoma/tratamento farmacológico , Receptores de Antígenos Quiméricos/uso terapêutico , Estudos Retrospectivos
12.
J Cancer Res Clin Oncol ; 150(4): 189, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605258

RESUMO

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).


Assuntos
Antineoplásicos , Arsênio , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Antineoplásicos/efeitos adversos , Arsênio/uso terapêutico , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pandemias , Resultado do Tratamento
13.
Toxicol Ind Health ; 40(6): 312-322, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38590048

RESUMO

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.


Assuntos
Biomarcadores , Chaperona BiP do Retículo Endoplasmático , Exposição Materna , Estresse Oxidativo , Ácidos Ftálicos , Placenta , Humanos , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/urina , Feminino , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Masculino , Placenta/efeitos dos fármacos , Placenta/metabolismo , Biomarcadores/urina , Estudos Prospectivos , Adulto , Exposição Materna/efeitos adversos , Fatores Sexuais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Estudos de Coortes
14.
AMB Express ; 14(1): 48, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678482

RESUMO

Escherichia coli Nissle 1917 (EcN) is an important chassis strain widely used for the development of live biotherapeutic products (LBPs). EcN strain naturally harbors two cryptic plasmids with unknown function. During the development of LBPs using EcN strain, the cryptic plasmids were cured usually to avoid plasmid incompatibility or alleviate metabolic burdens associated with these cryptic plasmids. While the cryptic plasmids curing in EcN may appear to be a routine procedure, the comprehensive impact of cryptic plasmids curing on the EcN strain remains incompletely understood. In the present study, the effects of cryptic plasmids curing on EcN were investigated using transcriptome sequencing. The results revealed that only a small number of genes showed significant changes in mRNA levels after cryptic plasmid curing (4 upregulated and 6 downregulated genes), primarily involved in amino acid metabolism. Furthermore, the flu gene showed the most significant different expression, encoding Antigen 43 (Ag43) protein, a Cah family adhesin. Mass spectrometry analysis further confirmed the significant increase in Ag43 expression. Ag43 is commonly present in Escherichia coli and mediates the bacterial autoaggregation. However, despite the upregulation of Ag43 expression, no Ag43-mediated cell self-sedimentation was observed in the cured EcN strain. These findings contribute to making informed decisions regarding the curing of the cryptic plasmids when Escherichia coli Nissle 1917 is used as the chassis strain.

15.
J Hematol Oncol ; 17(1): 23, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38659046

RESUMO

BACKGROUND: The autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up. METHODS: Participants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated. RESULTS: Seventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes. CONCLUSIONS: These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma. TRIAL REGISTRATION: LEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.


Assuntos
Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Mieloma Múltiplo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno de Maturação de Linfócitos B/imunologia , Seguimentos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Receptores de Antígenos Quiméricos/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Indução de Remissão , Taxa de Sobrevida
17.
J Immunother Cancer ; 12(4)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589248

RESUMO

BACKGROUND: Despite the encouraging outcome of chimeric antigen receptor T cell (CAR-T) targeting B cell maturation antigen (BCMA) in managing relapsed or refractory multiple myeloma (RRMM) patients, the therapeutic side effects and dysfunctions of CAR-T cells have limited the efficacy and clinical application of this promising approach. METHODS: In this study, we incorporated a short hairpin RNA cassette targeting PD-1 into a BCMA-CAR with an OX-40 costimulatory domain. The transduced PD-1KD BCMA CAR-T cells were evaluated for surface CAR expression, T-cell proliferation, cytotoxicity, cytokine production, and subsets when they were exposed to a single or repetitive antigen stimulation. Safety and efficacy were initially observed in a phase I clinical trial for RRMM patients. RESULTS: Compared with parental BCMA CAR-T cells, PD-1KD BCMA CAR-T cell therapy showed reduced T-cell exhaustion and increased percentage of memory T cells in vitro. Better antitumor activity in vivo was also observed in PD-1KD BCMA CAR-T group. In the phase I clinical trial of the CAR-T cell therapy for seven RRMM patients, safety and efficacy were initially observed in all seven patients, including four patients (4/7, 57.1%) with at least one extramedullary site and four patients (4/7, 57.1%) with high-risk cytogenetics. The overall response rate was 85.7% (6/7). Four patients had a stringent complete response (sCR), one patient had a CR, one patient had a partial response, and one patient had stable disease. Safety profile was also observed in these patients, with an incidence of manageable mild to moderate cytokine release syndrome and without the occurrence of neurological toxicity. CONCLUSIONS: Our study demonstrates a design concept of CAR-T cells independent of antigen specificity and provides an alternative approach for improving the efficacy of CAR-T cell therapy.


Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Antígeno de Maturação de Linfócitos B/genética , Antígeno de Maturação de Linfócitos B/metabolismo , Regulação para Baixo , Mieloma Múltiplo/terapia , Fenótipo , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T , Ensaios Clínicos Fase I como Assunto
18.
J Agric Food Chem ; 72(13): 7438-7456, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38513720

RESUMO

Aristolochic acid analogues (AAAs) are well-known toxins. We performed the first comprehensive screening on AAAs in Asari Radix et Rhizoma (underground part of Asarum heterotropoides Schmidt), the only Aristolochiaceae plant widely used in clinical practice. LC-HRMS revealed 70 trace AAAs using polygonal mass defect filtering and precursor ion list strategies, 38 of which were newly discovered in A. heterotropoides. UHPLC-QTrap-MS/MS was then utilized for quantitative/semiquantitative analysis of 26 abundant compounds. Seventeen AAAs were detected from 91 batches of A. heterotropoides and 20 AAAs from 166 consumable products. For 141 Asari-containing proprietary products, aristolactam I and aristolactam II-glucoside exhibited the widest distribution, present in 98% products. AA IVa was the most abundant, detected in 91%. Notably, 60% of the products contained AA I (0.03-0.79 ppm). The safety was assessed using linear extrapolation, permitted daily exposure, cumulative amount, and the margin of exposure. It is recommended that AA I content be limited to 3 ppm.


Assuntos
Ácidos Aristolóquicos , Medicamentos de Ervas Chinesas , Rizoma , Espectrometria de Massas em Tandem , Medição de Risco
19.
Ying Yong Sheng Tai Xue Bao ; 35(2): 339-346, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38523090

RESUMO

Forest type and stand age are important biological factors affecting soil enzyme activities. However, the changes in soil enzyme activities across stand ages and underlying mechanisms under the two forest restoration strate-gies of plantations and natural secondary forests remain elusive. In this study, we investigated the variations of four soil enzyme activities including cello-biohydrolase (CBH), ß-1,4-glucosidase (ßG), acid phosphatase (AP) and ß-1,4-N-acetylglucosaminidase (NAG), which were closely associated with soil carbon, nitrogen, and phosphorus cycling, across Cunninghamia lanceolata plantations and natural secondary forests (5, 8, 21, 27 and 40 years old). The results showed that soil enzyme activities showed different patterns across different forest types. The acti-vities of AP, ßG and CBH in the C. lanceolata plantations were significantly higher than those in the natural secon-dary forests, and there was no significant difference in the NAG activity. In the plantations, AP activity showed a decreasing tendency with the increasing stand ages, with the AP activity in the 5-year-old plantations significantly higher than other stand ages by more than 62.3%. The activities of NAG and CBH decreased first and then increased, and ßG enzyme activity fluctuated with the increasing stand age. In the natural secondary forests, NAG enzyme activity fluctuated with the increasing stand age, with that in the 8-year-old and 27-year-old stand ages being significantly higher than the other stand ages by more than 14.9%. ßG and CBH enzyme activities increased first and then decreased, and no significant difference was observed in the AP activity. Results of the stepwise regression analyses showed that soil predictors explained more than 34% of the variation in the best-fitting models predicting soil enzyme activities in the C. lanceolata plantations and natural secondary forests. In conclusion, there would be a risk of soil fertility degradation C. lanceolata plantations with the increasing stand age, while natural secondary forests were more conducive to maintaining soil fertility.


Assuntos
Cunninghamia , Humanos , Adulto , Pré-Escolar , Criança , Solo , Florestas , Nitrogênio/análise , Fósforo/análise , Carbono/análise , Microbiologia do Solo , China
20.
J Am Chem Soc ; 146(11): 7140-7145, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38466365

RESUMO

Molecular photocatalysis has shown tremendous success in sustainable energy and chemical synthesis. However, visualizing the transient open-shell intermediates in photocatalysis is a significant and long-standing challenge. By employing our recently developed innovative time-resolved electron paramagnetic resonance technique, we directly observed all radicals and radical ions involved in the photocatalytic addition of pempidine to tert-butyl acrylate. The full picture of the photocatalytic cycle is vividly illustrated by the fine structures, chemical kinetics, and dynamic spin polarization of all open-shell intermediates directly observed in this prototypical system. Given the universality of this methodology, we believe it greatly empowers the research paradigm of direct observation in both photocatalysis and radical chemistry.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA