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1.
Cell Host Microbe ; 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39423813

RESUMO

The optimal vaginal microbiome is a Lactobacillus-dominant community. Apart from Lactobacillus iners, the presence of Lactobacillus species is associated with reduced vaginal inflammation and reduced levels of pro-inflammatory cytokines. Loss of Lactobacillus-dominance is associated with inflammatory conditions, such as bacterial vaginosis (BV). We have identified that Lactobacillus crispatus, a key vaginal bacterial species, produces a family of ß-carboline compounds with anti-inflammatory activity. These compounds suppress nuclear factor κB (NF-κB) and interferon (IFN) signaling downstream of multiple pattern recognition receptors in primary human cells and significantly dampen type I IFN receptor (IFNAR) activation in monocytes. Topical application of an anti-inflammatory ß-carboline compound, perlolyrine, was sufficient to significantly reduce vaginal inflammation in a mouse model of genital herpes infection. These compounds are enriched in cervicovaginal lavage (CVL) of healthy people compared with people with BV. This study identifies a family of compounds by which vaginal lactobacilli mediate host immune homeostasis and highlights a potential therapeutic avenue for vaginal inflammation.

2.
Cancer Immunol Immunother ; 73(12): 237, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39358651

RESUMO

Human lung cancer carries high genetic alterations, expressing high tumor-specific neoantigens. Although orthotopic murine lung cancer models recapitulate many characteristics of human lung cancers, genetically engineered mouse models have fewer somatic mutations than human lung cancer, resulting in scarce immune cell infiltration and deficient immune responses. The endogenous mouse lung cancer model driven by Kras mutation and Trp53 deletion (KP model) has minimal immune infiltration because of a scarcity of neoantigens. Fine-tuning tumor antigenicity to trigger the appropriate level of antitumor immunity would be key to investigating immune responses against human lung cancer. We engineered the KP model to express antigens of OVA peptides (minOVA) as neoantigens along with ZsGreen, a traceable fluorescent conjugate. The KP model expressing minOVA exhibited stronger immunogenicity with higher immune cell infiltration comprised of CD8+ T cells and CD11c+ dendritic cells (DCs). Consequently, the KP model expressing minOVA exhibits suppressed tumor growth compared to its origin. We further analyzed tumor-infiltrated DCs. The majority of ZsGreen conjugated with minOVA was observed in the conventional type 2 DCs (cDC2), whereas cDC1 has minimal. These data indicate that tumor immunogenicity regulates host immune responses, and tumor neoantigen is mostly recognized by cDC2 cells, which may play a critical role in initiating antitumor immune responses in an orthotopic murine lung cancer model.


Assuntos
Antígenos de Neoplasias , Células Dendríticas , Neoplasias Pulmonares , Animais , Feminino , Humanos , Camundongos , Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Modelos Animais de Doenças , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/genética , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
3.
Environ Res ; 263(Pt 2): 120137, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39393452

RESUMO

The activity of supported noble metal (e.g., palladium (Pd)) catalysts is often governed by the combined effects of multiple factors (e.g., electronic and geometric properties of the support, surface chemistry of metal nanoparticles (NPs), and metal-support interactions). Pd/titanium dioxide (TiO2) catalyst has been developed as a highly efficient photocatalytic degradation (PCD) system against gaseous toluene based on high-temperature pretreatment (300 and 450 °C) in a mixed stream of hydrogen (H2) and (N2). The interaction of Pd NPs with TiO2 synergistically improves the PCD efficiency of toluene through the efficient adsorption and activation of toluene as well as molecular oxygen (O2) and water (H2O) for the facile generation of reactive oxygen species (ROS (e.g., superoxide anion (•O2-) and hydroxyl (•OH) radicals)). The PCD efficiency of the prepared sample against 5 ppm toluene (at 20% relative humidity (RH)) is 79.6% with the values of maximum reaction rate, quantum yield, space-time yield, and clean air delivery rate as 9.9 µmol g-1 h-1, 1.68E-03 molecules photon-1, 1.68E-02 molecules photon-1 g-1, and 4.8 L h-1, respectively. Based on this research, the PCD mechanism of gaseous toluene has been explored along with the dynamic behavior of O2 and H2O for ROS generation and their relative contribution to the PCD of toluene. As such, this research offers a perspective for designing advanced photocatalysts through surface defect engineering.

4.
Biomedicines ; 12(10)2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39457511

RESUMO

Background/Objectives: Recently, antimicrobial-resistant pathogens and cancers have emerged as serious global health problems, highlighting the immediate need for novel therapeutics. Consequently, we aimed to isolate and characterize endophytic Streptomyces strains from the rhizospheres of the Himalayan region of Nepal and identify specialized metabolites with antibacterial, antifungal, and cytotoxic potential. Methods: To isolate Streptomyces sp., we collected two soil samples and cultured them on an ISP4 medium after pretreatment. We isolated and identified the strains PY108 and PY109 using a combination of morphological observations and 16S rRNA gene sequencing. Results: The BLAST results showed that PY108 and PY109 resembled Streptomyces hundungensis PSB170 and Streptomyces sp. Ed-065 with 99.28% and 99.36% nucleotide similarity, respectively. Antibacterial assays of ethyl acetate (EA) extracts from both isolates PY108 and PY109 in a tryptic soy broth (TSB) medium were conducted against four pathogenic bacteria. They showed significant antibacterial potential against Staphylococcus aureus and Klebsiella pneumoniae. Similarly, these extracts exhibited moderate antifungal activities against Saccharomyces cerevisiae and Aspergillus niger. Cytotoxicity assays on cervical cancer cells (HeLa) and breast cancer cells (MCF-7) revealed significant potential for both extracts. LC-MS/MS profiling of the EA extracts identified 27 specialized metabolites, including diketopiperazine derivatives, aureolic acid derivatives such as chromomycin A, and lipopeptide derivatives. In comparison, GC-MS analysis detected 34 metabolites, including actinomycin D and γ-sitosterol. Furthermore, a global natural product social molecular networking (GNPS)-based molecular networking analysis dereplicated 24 metabolites in both extracts. Conclusions: These findings underscore the potential of endophytic Streptomyces sp. PY108 and PY109 to develop new therapeutics in the future.

5.
Int J Syst Evol Microbiol ; 74(10)2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39453699

RESUMO

A novel Gram-stain-positive, facultatively anaerobic, non-motile, catalase-positive, oxidase-negative and ovoid cocci, designated as A1S7T, was isolated from the gut of a marine sandworm (Alitta virens). Strain A1S7T exhibited optimal growth at temperatures of 20-30 ℃, pH 6-8 and in the presence of 2-4% (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain A1S7T belonged to the genus Janibacter, exhibiting a similarity of 99.0% to Janibacter cremeus KCTC 49873T, followed by Janibacter anophelis KCTC 19282T (98.8%), Janibacter hoylei KCTC 49872T (98.4%), Janibacter limosus KACC 20518T (98.2%) and Janibacter corallicola KACC 21120T (97.2%). The complete genome sequence of strain A1S7T revealed a genome size of 3360920 bp with a genomic G+C content of 70.1 mol%. The orthologous average nucleotide identity and the digital DNA-DNA hybridization values between strain A1S7T and Janibacter cremeus KCTC 49873T were determined to be 89.5 and 37.2%, respectively. The major respiratory quinone was MK-8(H4). The predominant fatty acids (>10%) included iso-C16:0, C17:1 ω8c, C18:1 ω9c and C17:0. Polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, one unknown phosphoglycolipid and three unknown polar lipids. The cell-wall peptidoglycan type was A1γ. The major whole-cell sugars were ribose, mannose and glucose. Based on phenotypic, phylogenetic, genotypic and chemotaxonomic properties, strain A1S7T represents a novel species in the genus Janibacter, for which the name Janibacter alittae sp. nov. is proposed. The type strain is A1S7T (=KCTC 49714T = JCM 36706T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Vitamina K 2 , RNA Ribossômico 16S/genética , Animais , DNA Bacteriano/genética , Vitamina K 2/análogos & derivados , Vitamina K 2/análise , Fosfolipídeos/análise , Peptidoglicano , Poliquetos/microbiologia , Genoma Bacteriano
6.
Korean J Gastroenterol ; 84(3): 111-122, 2024 Sep 25.
Artigo em Coreano | MEDLINE | ID: mdl-39319432

RESUMO

Endoscopic retrograde cholangiopancreatography (ERCP) is a procedure that requires abundant clinical experience and endoscopic skills, and can lead to various complications, some of which may progress to life-threatening conditions. With expanding indications and technological advancements, ERCP is widely utilized, enhancing procedural accessibility. However, without proper quality management, the procedure can pose significant risks. Quality management in ERCP is essential to ensure safe and successful procedures and meet societal demands for improved healthcare competitiveness. To address these concerns, the Korean Society of Pancreatobiliary Endoscopy has developed a Korean-specific ERCP quality indicator reflecting domestic medical environments and realities. Initially, based on a review of foreign ERCP quality indicators and related literatures, key questions were formulated for five pre-procedural items, three intra-procedural items, and four post-procedural items. Descriptions and recommendations for each item were selected through peer evaluation. The developed Korean-specific ERCP quality indicator was reviewed by external experts based on the latest evidence and consensus in this fields. This Korean-specific indicator is expected to significantly contribute to improving ERCP quality in Korea, as it is tailored to local needs.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Indicadores de Qualidade em Assistência à Saúde , Colangiopancreatografia Retrógrada Endoscópica/normas , Humanos , República da Coreia
7.
J Microbiol Biotechnol ; 34(11): 1-9, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39300961

RESUMO

Alopecia, while not life-threatening, significantly impacts mental health, identity, and self-esteem of those afflicted. Current pharmacological and surgical treatments often have side effects and are limited in their ability to regenerate hair follicles (HF). Therefore, effective solutions for alopecia remain elusive. We developed an innovative hair tonic capable of stimulating HF regeneration by harnessing abandoned electric energy generated during human activities, such as the frictional electric field from walking and the electric fields from electronic devices. We devised a convenient, non-volatile, and conductive hair tonic to capture these naturally occurring electric fields. We identified 6-pentyl-α-pyrone (6PP) from Trichoderma gamsii as an antifungal agent effective against the dandruff-associated fungus Malassezia that can influence alopecia and adopted it into our conductive bio-harvesting tonic (CBT). Testing on hair follicle dermal papilla cells (HFDPC) and SKH1 mice showed that CBT significantly enhanced HF proliferation and increased growth factors in vitro and in vivo. In SKH1 mice, application of CBT under electric stimulation visibly increased hair shaft length and follicle counts. Additionally, tests on actual human hair follicles demonstrated delayed hair follicle regression when electric stimulation and 6PP were applied. In conclusion, our innovative CBT offers a promising and convenient approach for improving hair growth and combating alopecia.

8.
Foods ; 13(17)2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39272568

RESUMO

Rice is one of the plants proven to possess antioxidant, anti-inflammatory, anti-proliferative, and whitening properties, making it one of the most beneficial plants in this regard. This study aimed to introduce a novel natural cosmetic and pharmaceutical product based on rice callus as a source of active ingredients that can inhibit skin melanoma cell (B16F10) proliferation and brighten the skin. The 2,4-D hormone at concentrations of 1 µg/mL and 1.5 µg/mL was used to induce rice callus formation. Rice callus extracts were then prepared using aqueous and ethanolic solvents, with a concentration of 1 mg/mL used for characterization tests. To determine the optimal hormone concentration, the phenols/flavonoids, antioxidant activity, proteins, and carbohydrates in the extracts were measured. The optimal concentration of the hormone was found to be 1 µg/mL. Finally, the anti-melanocyte and skin-whitening activity of the extracts was assessed through measurements of their cytotoxicity and inhibition of melanin synthesis-related enzymes. Cellular cytotoxicity measurements revealed that the ethanolic extract induced more cytotoxicity than the aqueous extract, with IC50 values of 566.3 µg/mL for the ethanolic extract and 1327 µg/mL for the aqueous extract. Skin-whitening-related tests demonstrated that the extracts were 1.7 times more effective than arbutin in inhibiting factors that cause hyperpigmentation. The aqueous extract achieved 85% inhibition of melanin biosynthesis at a concentration of 3200 µg/mL, compared to 68% for the ethanolic extract and 50% for arbutin. Based on these findings, rice callus extract can be introduced as a new, effective substance for skin-lightening and anti-melanocyte products in cosmeceutical and pharmaceutical formulations.

9.
Chem Soc Rev ; 53(20): 9976-10011, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39282873

RESUMO

Anthropogenic emissions of greenhouse gases (GHG; e.g., CO2) are regarded as the most critical cause of the current global climate crisis. To combat this issue, a plethora of CO2 capture, utilization, and storage (CCUS) technologies have been proposed and developed based on a number of technical principles (e.g., post-combustion capture, chemical looping, and catalytic conversion). In this light, the potential utility of dendritic fibrous nanosilica (DFNS) materials is recognized for specific CCUS applications (such as adsorptive capture of CO2 and its catalytic conversion into a list of value-added products (e.g., methane, carbon monoxide, and cyclic carbonates)) with the highly tunable properties (e.g., high surface area, pore volume, multifunctional surface, and open pore structure). This review has been organized to offer a comprehensive evaluation of the approaches required for tuning the textural/morphological/surface properties of DFNS (based on multiple synthesis and modification scenarios) toward CCUS applications. It further discusses the effects of such approaches on the properties of DFNS materials in relation to their CCUS performance. This review is thus expected to help develop and implement advanced strategies for DFNS-based CCUS technologies.

10.
Front Pharmacol ; 15: 1406623, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39263565

RESUMO

Populus × tomentiglandulosa (PT), a tree endemic to Korea, shows promising potential as a natural therapeutic agent owing to its potent anti-inflammatory properties. However, the isolation and analysis of phytochemical compounds in PT and related species remains underexplored. Therefore, this study aims to investigate the biochemical profile of PT and evaluate its extracts and fractions for anti-inflammatory activities. Nine compounds were isolated, including two novel flavonoids (luteolin 7-O-ß-d-glucuronide butyl ester and chrysoeriol 7-O-ß-d-glucuronide butyl ester) from the Salicaceae family for the first time. The ethyl acetate fraction exhibited significant radical scavenging activity against various radicals, including DPPH, ABTS+, •OH, and O2 - radicals. PT extracts and the ethyl acetate fraction showed minimal cytotoxicity in Raw 264.7 macrophages at concentrations below 500 and 100 µg/mL, respectively. Furthermore, PT extracts and fractions significantly suppressed the protein expression of proinflammatory mediators (iNOS and IL-6) in LPS-stimulated Raw 264.7 macrophages, highlighting their potent anti-inflammatory effects. These findings suggest that PT holds promise as a valuable natural therapeutic intervention for various oxidative stress and inflammation-related disorders, underscoring the need for further exploration of its clinical applications.

11.
J Hazard Mater ; 478: 135412, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39126855

RESUMO

A prototype air purifier (AP) module has been constructed using bismuth-doped titanium dioxide (Bix-P25: x(%) as Bi/Ti molar ratios of 1.1, 2.1, 3.3, 5.3, and 8.7). The reactive adsorption property of Bix-P25 materials is evaluated against H2S gas at a recirculation rate of 160 L min-1 in a 17 L closed chamber. The AP (Bi5.3-P25) exhibits superior performance against 10 ppm H2S in dry air under dark conditions (i.e., without light irradiation), with a removal efficiency (XH2S)= 99% in 5 mins, reaction kinetic rate (r (at X = 10%))= 7.3 mmol h-1g-1, and partition coefficient= 0.18 mol kg-1 Pa-1. As such, its superiority is evident over the reference AP (P25) filter with XH2S < 10%. The clean air delivery rate (CADR) of AP (Bi5.3-P25) increases noticeably from 9.9 to 17.8 L min-1 with increasing relative humidity (RH) from 0 to 80%, respectively. In contrast, the CADR decreases from 9.9 to 5.8 L min-1 as the H2S increases from 10 to 20 ppm. According to density functional theory (DFT), the presence of H2O vapor enhances the hydroxylation of Bix-P25 surface to promote H2S mineralization through the formation of TiS3 (i.e., thermodynamic reaction of S atom with the catalytic surface). Complete removal of H2S on the Bi5.3-P25 surface is also confirmed consistently through gas chromatography-mass spectrometry (GC-MS), in-situ diffuse reflection infrared spectroscopy (in-situ DRIFTS), and elemental analysis (EA). This work represents the first utilization of Bix-P25 materials fabricated on an AP platform toward the desulfurization of H2S at room temperature (RT). The practical utility of Bix-P25 is overall validated by its eminent role in reactive adsorption and catalytic oxidation (RACO) of H2S from the air.

12.
Chem Biol Interact ; 402: 111192, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39127184

RESUMO

The genus Salix spp. has long been recognized as a healing herb for its use in treating fever, inflammation, and pain relief, as well as a food source for its nutritional value. In this study, we aimed to explore the potential bioactive natural products in the leaves of Salix chaenomeloides, commonly known as Korean pussy willow, for their protective effects against skin damage, including aging. Utilizing LC/MS-guided chemical analysis of the ethanol extract of S. chaenomeloides leaves, with a focus on major compounds, we successfully isolated two main phenolic compounds, tremulacin (1) and tremuloidin (2). Subsequently, we investigated the protective effects of tremulacin (1) and tremuloidin (2) in TNF-α-stimulated human dermal fibroblasts (HDFs). The results revealed that both tremulacin (1) and tremuloidin (2) inhibited TNF-α-stimulation-induced ROS, suppressed matrix metalloproteinase-1 (MMP-1) expression, and enhanced collagen secretion. This implies that both tremulacin (1) and tremuloidin (2) hold promise as preventive agents against photoaging-induced skin aging. Furthermore, we assessed the activity of mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and heme oxygenase 1 (HO-1) to elucidate the mechanism of photoaging inhibition by tremuloidin (2), which exhibited superior efficacy. We found that tremuloidin (2) inhibited ERK and p38 phosphorylation and notably suppressed COX-2 expression while significantly upregulating HO-1 expression. These findings suggest potent anti-inflammatory and antioxidant properties of tremuloidin (2), positioning it as a potential candidate for combating photoaging-induced skin aging.


Assuntos
Fibroblastos , Fenóis , Folhas de Planta , Salix , Envelhecimento da Pele , Fator de Necrose Tumoral alfa , Humanos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Folhas de Planta/química , Salix/química , Fenóis/farmacologia , Fenóis/química , Fenóis/isolamento & purificação , Envelhecimento da Pele/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/citologia , Metaloproteinase 1 da Matriz/metabolismo , Colágeno/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ciclo-Oxigenase 2/metabolismo , Heme Oxigenase-1/metabolismo
13.
Adv Colloid Interface Sci ; 332: 103264, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39116585

RESUMO

MXenes belong to one of the recently developed advanced materials with tremendous potential for diverse sensing applications. To date, various types of MXene-based materials have been developed to generate direct/indirect ultrasensitive sensing signals against various forms of analytes via fluorescence quenching or enhancement. In this work, the fluorescence sensing/biosensing capabilities of the MXene-based materials have been explored and evaluated against a list of ionic/emerging pollutants in environment and food matrices. The suitability of an MXene-based sensing approach is also validated through the assessment of the performance based on the basic quality assurance parameters, e.g., limit of detection (LOD), sensing range, and response time. Accordingly, the best performing MXene-based materials are selected and recommended for the given target(s) to help facilitate their scalable applications under real-world conditions.


Assuntos
Técnicas Biossensoriais , Técnicas Biossensoriais/métodos , Contaminação de Alimentos/análise , Fluorescência , Poluentes Ambientais/análise , Espectrometria de Fluorescência , Corantes Fluorescentes/química , Íons/análise , Íons/química , Análise de Alimentos/métodos
14.
Medicine (Baltimore) ; 103(32): e39139, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39121273

RESUMO

Calcinosis cutis is classified into 5 main types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. However, it is occasionally misdiagnosed as a malignancy and its management remains challenging. Therefore, in this study, we report our diagnostic and treatment experiences with patients with calcinosis cutis and suggest strategies for improving patient care. This retrospective study included 7 patients (4 men, 3 women; 44.4 ±â€…32.0 years old) who visited our hospital between March 2013 and December 2022 and were diagnosed with calcinosis cutis through histopathological procedures. The patients underwent complete excision of the mass without a safety margin. Frozen biopsy was not performed during surgery. No significant intraoperative or postoperative complications were noted after the application of various imaging techniques for diagnosis and follow-up. All patients showed complete recovery. Follow-up showed no recurrence or complications in the 6 patients who completed 1 year of follow-up. Radiological tests such as plain radiography, ultrasonography, computed tomography, and magnetic resonance imaging are important for accurate diagnosis and treatment of calcinosis cutis. This approach can ensure precise assessment of preoperative lesions, leading to safe and less invasive patient treatment, recurrence prevention, and complications of calcinosis cutis.


Assuntos
Calcinose , Dermatopatias , Humanos , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Dermatopatias/diagnóstico , Dermatopatias/patologia , Dermatopatias/cirurgia , Calcinose Cutânea
15.
iScience ; 27(8): 110495, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39148712

RESUMO

The isolation of a natural product conventionally precedes its chemical synthesis. Often, the isolation and structure determination of a natural product present in minute quantities in its natural source pose formidable challenges, akin to finding "a needle in a haystack." On the other hand, leveraging plausible biosynthetic insights and biomimetic synthetic expertise would allow for the prior synthesis of presumed natural products, followed by their verification in natural sources. In this study, we unveil two novel securinega alkaloids, securingines H and I, employing the natural product anticipation through synthesis approach. Structural analysis of securingines H and I suggests that they are biosynthetic derivatives of secu'amamine E and securinol A, respectively. We posit that this "synthesis first" strategy represents a valuable approach to the discovery of new natural products.

16.
Int J Pharm ; 663: 124577, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39137820

RESUMO

This study investigates the impact of intravenous (IV) infusion protocols on the stability of Intravenous Immunoglobulin G (IVIG) and Rituximab, with a particular focus on subvisible particle generation. Infusion set based on peristaltic movement (Medifusion DI-2000 pump) was compared to a gravity-based infusion system (Accu-Drip) at different flow rates. The impacts of different diluents (0.9 % saline and 5.0 % dextrose) and plastic syringes with or without silicone oil (SO) were also investigated. The results from the aforementioned particular case demonstrated that peristaltic pumps generated high levels of subvisible particles (prominently < 25 µm), exacerbated by increasing flow rates, specifically in formulations lacking surfactants. Other factors, such as diluent type and syringe composition, also increased the number of subvisible particles. Strategies that can help overcome these complications include surfactant addition as well as the use of SO-free syringes and a gravity infusion system, which aid in reducing particle formation and preserving antibody monomer during administration. Altogether, these findings highlight the importance of the careful selection of formulations and infusion protocols to minimize particle generation during IV infusion both for patients' safety and treatment efficacy.


Assuntos
Estabilidade de Medicamentos , Imunoglobulinas Intravenosas , Rituximab , Seringas , Rituximab/administração & dosagem , Rituximab/química , Infusões Intravenosas , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/química , Bombas de Infusão , Tensoativos/química , Óleos de Silicone/química , Embalagem de Medicamentos , Plásticos/química , Glucose/química , Humanos
17.
Sci Immunol ; 9(97): eadn6509, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39028827

RESUMO

Most patients treated with US Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR T cells have not been curative against solid cancers and several hematological malignancies such as T cell lymphomas, which have very poor prognoses. One of the main barriers to the clinical success of adoptive T cell immunotherapies is CAR T cell dysfunction and lack of expansion and/or persistence after infusion. In this study, we found that CD5 inhibits CAR T cell activation and that knockout (KO) of CD5 using CRISPR-Cas9 enhances the antitumor effect of CAR T cells in multiple hematological and solid cancer models. Mechanistically, CD5 KO drives increased T cell effector function with enhanced cytotoxicity, in vivo expansion, and persistence, without apparent toxicity in preclinical models. These findings indicate that CD5 is a critical inhibitor of T cell function and a potential clinical target for enhancing T cell therapies.


Assuntos
Antígenos CD5 , Imunoterapia Adotiva , Linfócitos T , Animais , Imunoterapia Adotiva/métodos , Antígenos CD5/imunologia , Camundongos , Humanos , Linfócitos T/imunologia , Linfócitos T/transplante , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Linhagem Celular Tumoral , Sistemas CRISPR-Cas , Feminino
18.
Environ Res ; 260: 119664, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39048069

RESUMO

The preparation of nitrogen-doped TiO2 (i.e., N-TiO2) catalysts is a highly effective option to improve the photocatalytic activity of TiO2. Nonetheless, relatively little is known about the effects of dopant precursors selected for their preparation with regard to the photocatalytic efficacy. In this study, three types of dopants are selected and used as N sources (urea (U), melamine (M), and aqueous ammonia (A)) for N-TiO2 samples with the name codes of NTU, NTM, and NTA, respectively. The photocatalytic efficacy of these N-TiO2 samples is examined against toluene in a packed bed flow reactor. Under optimal conditions (e.g., relative humidity (RH) = 20% and gas hourly space velocity (GHSV) = 1698 h-1), the superiority of NTA is evident over others with a quantum efficiency (QE) of 7.03 × 10-4 molecules photon-1, a space time yield (STY) of 1.38 × 10-4 molecules photon-1 mg-1, and a specific clean air delivery rate (SCADR) of 1148.8 L g-1 h-1. The analysis based on in-situ diffuse reflectance infrared Fourier transform spectroscopy and gas chromatography-mass spectrometry confirms the formation of several intermediates such as benzyl alcohol, benzaldehyde, benzoic acid, and alkane species through ring opening reactions. In addition, the prepared NTA photocatalyst exhibits the highest toluene photocatalytic degradation efficiency among all TiO2-based catalysts surveyed to date. Overall, this study offers as a valuable guideline for the development of advanced TiO2 catalytic systems (such as N-TiO2) for the treatment of aromatic hydrocarbons in indoor air.


Assuntos
Nitrogênio , Titânio , Tolueno , Titânio/química , Tolueno/química , Catálise , Nitrogênio/química , Poluentes Atmosféricos/química , Poluentes Atmosféricos/análise , Triazinas/química , Processos Fotoquímicos , Fotólise
19.
J Hazard Mater ; 476: 135016, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38986407

RESUMO

Formaldehyde (FA) is a hazardous indoor air pollutant with carcinogenic propensity. Oxidation of FA in the dark at low temperature (DLT) is a promising strategy for its elimination from indoor air. In this light, binary manganese-cobalt oxide (0.1 to 5 mol L-1-MnCo2O4) is synthesized and modified in an alkaline medium (0.1-5 mol L-1 potassium hydroxide) for FA oxidation under room temperature (RT) conditions. Accordingly, 1-MnCo2O4 achieves 100 % FA conversion at RT (50 ppm and 7022 h-1 gas hourly space velocity (GHSV)). The catalytic activity of 1-MnCo2O4 is assessed further as a function of diverse variables (e.g., catalyst mass, relative humidity, FA concentration, molecular oxygen (O2) content, flow rate, and time on-stream). In situ diffuse reflectance infrared Fourier-transform spectroscopy confirms that FA molecules are adsorbed onto the active surface sites of 1-MnCo2O4 and oxidized into water (H2O) and carbon dioxide (CO2) through dioxymethylene (DOM) and formate (HCOO-) as the reaction intermediates. According to the density functional theory simulations, the higher catalytic activity of 1-MnCo2O4 can be attributed to the combined effects of its meritful surface properties (e.g., the firmer attachment of FA molecules, lower energy cost of FA adsorption, and lower desorption energy for CO2 and H2O). This work is the first report on the synthesis of alkali (KOH)-modified MnCo2O4 and its application toward the FA oxidative removal at RT in the dark. The results of this study are expected to provide valuable insights into the development of efficient and cost-effective non-noble metal catalysts against indoor FA at DLT.

20.
J Nat Prod ; 87(7): 1881-1887, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-38950087

RESUMO

A family of pyrazinone metabolites (1-11) were characterized from Staphylococcus xylosus ATCC 29971. Six of them were hydroxylated or methoxylated, which were proposed to be produced by the rare noncatalytic oxa-Michael addition reaction with a water or methanol molecule. It was confirmed that isopropyl alcohol can also be the Michael donor of the reaction. 1-7 and the synthetic precursor 2a showed significant inhibition of breast cancer cell migration.


Assuntos
Pirazinas , Staphylococcus , Humanos , Movimento Celular/efeitos dos fármacos , Estrutura Molecular , Pirazinas/química , Pirazinas/farmacologia , Staphylococcus/efeitos dos fármacos
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