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2.
Nano Lett ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38781101

ABSTRACT

Biocompatible fluorescent agents are key contributors to the theranostic paradigm by enabling real-time in vivo imaging. This study explores the optical properties of phenylenediamine carbon dots (CDs) and demonstrates their potential for fluorescence imaging in cells and brain blood vessels. The nonlinear absorption cross-section of the CDs was measured and achieved values near 50 Goeppert-Mayer (GM) units with efficient excitation in the 775-895 nm spectral range. Mesoporous vaterite nanoparticles were loaded with CDs to examine the possibility of a biocompatible imaging platform. Efficient one- and two-photon imaging of the CD-vaterite composites uptaken by diverse cells was demonstrated. For an in vivo scenario, CD-vaterite composites were injected into the bloodstream of a mouse, and their flow was monitored within the blood vessels of the brain through a cranial window. These results show the potential of the platform for high-brightness biocompatible imaging with the potential for both sensing and simultaneous drug delivery.

3.
Front Bioeng Biotechnol ; 12: 1355133, 2024.
Article in English | MEDLINE | ID: mdl-38558793

ABSTRACT

Harnessing solar energy is one of the most important practical insights highlighted to mitigate the severe climate change (CC) phenomenon. Therefore, this study aims to focus on the use of hybrid solar dryers (HSDs) within an environmentally friendly framework, which is one of the promising applications of solar thermal technology to replace traditional thermal technology that contributes to increasing the severity of the CC phenomenon. The HSD, based on a traditional electrical energy source (HSTEE) and electrical energy from photovoltaic panels (HSPVSE), was evaluated compared to a traditional electrical (TE) dryer for drying some medicinal and aromatic plants (MAPs). This is done by evaluating some of the drying outputs, energy consumed, carbon footprint, and financial return at 30, 40, and 50°C. The best quality of dried MAP samples in terms of essential oil (EO, %) and microbial load was achieved at 40°C. The HSTEE dryer has reduced energy consumption compared to the TE dryer by a percentage ranging from 37% to 54%. The highest CO2 mitigated ratio using the HSTEE dryer was recorded in thyme, marjoram, and lemongrass samples, with values ranging from 45% to 54% at 30, 40, and 50°C. The highest financial return obtained from energy consumption reduction and carbon credit footprint was achieved at 50°C, with values ranging from 5,313.69 to 6,763.03 EGP/year (EGP ≈ 0.0352 USD) when coal was used as a fuel source for the generation of electricity. Moreover, the HSPVSE dryer achieved a 100% reduction in traditional energy consumption and then reduced CO2 emissions by 100%, which led to a 100% financial return from both energy reduction and carbon credit. The highest financial returns were observed at 50°C, with values ranging from 13,872.56 to 15,007.02, 12,927.28 to 13,984.43, and 11,981.99 to 12,961.85 EGP/year (EGP ≈ 0.0352 USD) for coal, oil, and natural gas, respectively. The HS dryers show potential for environmental conservation contribution; furthermore, earning money from energy savings and carbon credit could help improve the living standards and maximize benefits for stakeholders.

4.
Blood ; 143(4): 336-341, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-37647641

ABSTRACT

ABSTRACT: Assessment of measurable residual disease (MRD) by quantitative reverse transcription polymerase chain reaction is strongly prognostic in patients with NPM1-mutated acute myeloid leukemia (AML) treated with intensive chemotherapy; however, there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype. We analyzed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved complete remission (CR)/CR with incomplete hematological recovery following treatment with venetoclax and hypomethylating agents (HMAs) or low-dose cytarabine (LDAC). A total of 44 patients (58%) achieved bone marrow (BM) MRD negativity, and a further 14 (18%) achieved a reduction of ≥4 log10 from baseline as their best response, with no difference between HMAs and LDAC. The cumulative rates of BM MRD negativity by the end of cycles 2, 4, and 6 were 25%, 47%, and 50%, respectively. Patients achieving BM MRD negativity by the end of cycle 4 had 2-year overall of 84% compared with 46% if MRD was positive. On multivariable analyses, MRD negativity was the strongest prognostic factor. A total of 22 patients electively stopped therapy in BM MRD-negative remission after a median of 8 cycles, with 2-year treatment-free remission of 88%. In patients with NPM1-mutated AML attaining remission with venetoclax combination therapies, NPM1 MRD provides valuable prognostic information.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Leukemia, Myeloid, Acute , Nucleophosmin , Sulfonamides , Humans , Prognosis , Mutation , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Cytarabine , Neoplasm, Residual/genetics
5.
Leukemia ; 37(10): 2066-2072, 2023 10.
Article in English | MEDLINE | ID: mdl-37558736

ABSTRACT

Patients with FLT3-mutated AML have a high relapse rate and suboptimal outcomes. Many have co-mutations suitable for measurable residual disease (MRD) monitoring by RT-qPCR and those destined to relapse can be identified by high or rising levels of MRD, called molecular failure.  This provides a window for pre-emptive intervention, but there is little evidence to guide treatment. The use of FLT3 inhibitors (FLT3i) appears attractive but their use has not yet been evaluated.  We identified 56 patients treated with FLT3i at molecular failure.  The FLT3 mutation was an ITD in 52, TKD in 7 and both in 3. Over half of patients had previously received midostaurin. Molecular failure occurred at a median 9.2 months from diagnosis and was treated with gilteritinib (n = 38), quizartinib (n = 7) or sorafenib (n = 11). 60% achieved a molecular response, with 45% reaching MRD negativity. Haematological toxicity was low, and 22 patients were bridged directly to allogeneic transplant with another 6 to donor lymphocyte infusion. 2-year overall survival was 80% (95%CI 69-93) and molecular event-free survival 56% (95%CI 44-72). High-sensitivity next-generation sequencing for FLT3-ITD at molecular failure identified patients more likely to benefit. FLT3i monotherapy for molecular failure is a promising strategy which merits evaluation in prospective studies.


Subject(s)
Leukemia, Myeloid, Acute , Salvage Therapy , Humans , fms-Like Tyrosine Kinase 3/antagonists & inhibitors , fms-Like Tyrosine Kinase 3/genetics , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Mutation , Neoplasm Recurrence, Local , Prospective Studies , Protein Kinase Inhibitors/therapeutic use
7.
Cell ; 184(24): 5902-5915.e17, 2021 11 24.
Article in English | MEDLINE | ID: mdl-34752731

ABSTRACT

Increasing evidence indicates that the brain regulates peripheral immunity, yet whether and how the brain represents the state of the immune system remains unclear. Here, we show that the brain's insular cortex (InsCtx) stores immune-related information. Using activity-dependent cell labeling in mice (FosTRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (dextran sulfate sodium [DSS]-induced colitis and zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Thus, we show that the brain can store and retrieve specific immune responses, extending the classical concept of immunological memory to neuronal representations of inflammatory information.


Subject(s)
Immunity , Insular Cortex/physiology , Neurons/physiology , Animals , Colitis/chemically induced , Colitis/complications , Colitis/immunology , Colon/pathology , Dextran Sulfate , Female , Inflammation/pathology , Male , Mice , Mice, Inbred C57BL , Peritoneum/pathology , Peritonitis/complications , Peritonitis/immunology , Peritonitis/pathology , Synapses/metabolism , Zymosan
8.
Clin Lab ; 63(5): 1027-1034, 2017 May 01.
Article in English | MEDLINE | ID: mdl-28627830

ABSTRACT

BACKGROUND: FLT3-ITD mutations are common in AML subgroups, particularly in Acute Promyelocytic Leukemia (APL). It infers poor prognosis in AML patients; however, its prognostic value in APL is still controversial. We aimed to assess the distribution and prognostic value of FLT3-ITD mutation within AML subgroups, focusing on APL. METHODS: In NCI, Cairo University, 346 newly diagnosed AML patients were included. Morphological, immunophenotypic and cytogenetic analysis were done at presentation and fixed follow-up points with monitoring in follow up visits of patients. FLT3-ITD mutations were detected using RT-PCR. RESULTS: FLT3-ITD mutations were detected in 18.5% of AML patients with significant higher incidence in M3 patients (35.5%, p = 0.027) in comparison to other types. There was significant negative association between FLT3ITD mutations and CD34 expression (p = 0.026). FLT3 wild patients had a significantly better response on Day 35 than the mutant group (p = 0.046). Overall Survival (OS) of the wild group was significantly better than that of the mutant group (p = 0.003). In APL patients, OS of wild-FLT3 patients was significantly better than of those with mutant FLT3 (p = 0.018). In non-APL patients, favorable cytogenetic changes - t(8;21) and inv(16) - are more common in FLT3 wild group (12.8%) than in FLT3 mutant group (6.3%). In non-APL patients, FLT3-ITD mutation retained its adverse prognostic effect (p = 0.016). CD34 expression affected survival in both FLT3 mutant and wild groups. CONCLUSIONS: We conclude that FLT3-ITD mutations infer poor prognostic effects both in AML patients generally and in the APL group specifically. CD34 may have a prognostic impact in FLT3-ITD mutant patients, which is to be further investigated.


Subject(s)
Leukemia, Myeloid, Acute/genetics , fms-Like Tyrosine Kinase 3/genetics , Egypt , Humans , Leukemia, Myeloid, Acute/diagnosis , Mutation , Prognosis
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