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1.
J Control Release ; 368: 548-565, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462044

RESUMO

Cancer treatment is challenged due to immunosuppressive inflammatory tumour microenvironment (TME) caused by infiltration of tumour-promoting and inhibition of tumour-inhibiting immune cells. Here, we report the engineering of chimeric nanomicelles (NMs) targeting the cell proliferation using docetaxel (DTX) and inflammation using dexamethasone (DEX) that alters the immunosuppressive TME. We show that a combination of phospholipid-DTX conjugate and PEGylated-lipid-DEX conjugate can self-assemble to form sub-100 nm chimeric NMs (DTX-DEX NMs). Anti-cancer activities against syngeneic and xenograft mouse models showed that the DTX-DEX NMs are more effective in tumour regression, enhance the survival of mice over other treatment modes, and alter the tumour stroma. DTX-DEX NMs cause a significant reduction in myeloid-derived suppressor cells, alter the polarization of macrophages, and enhance the accumulation of cytotoxic CD4+ and CD8+ T cells in tumour tissues, along with alterations in cytokine expression. We further demonstrated that these DTX-DEX NMs inhibit the synthesis of prostaglandins, especially PGE2, by targeting the cyclooxygenase 2 that is partly responsible for immunosuppressive TME. Therefore, this study presents, for the first time, the engineering of lithocholic acid-derived chimeric NMs that affect the prostaglandin pathway, alter the TME, and mitigate tumour progression with enhanced mice survival.


Assuntos
Antineoplásicos , Prostaglandinas , Humanos , Camundongos , Animais , Prostaglandinas/farmacologia , Linfócitos T CD8-Positivos , Docetaxel/uso terapêutico , Docetaxel/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Terapia de Imunossupressão , Microambiente Tumoral , Linhagem Celular Tumoral
2.
J Colloid Interface Sci ; 665: 274-285, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38531273

RESUMO

HYPOTHESIS: This study tested the hypothesis of how the nanopore size of membranes and how the surface charge of nanobubbles responds to its pinch-off from the nanopore. This study also tested the hypothesis that nanobubbles that remain in solution after production may increase the dissolved oxygen content in water. EXPERIMENTS: The effect of membrane pore size, hydrodynamic conditions (gas and liquid flow rates), and physicochemical parameters (pH and temperature) on volumetric mass transfer coefficient (kLa) for oxygen nanobubbles formed by the nanopore diffusion technique was investigated. This study experimentally determined the kLa by carefully removing the dissolved oxygen by nitrogen purging from nanobubble suspension to examine the sole contribution of nanobubble dissolution in water to the reaeration. RESULTS: Scaling estimates indicate that the nanobubble pinch-off radius and nanopore radius have a power-law correlation and that nanobubble size declines with the nanopore size. This is in line with our experimental results. The surface charge of nanobubbles delays its pinch-off at the gas-liquid interface. Nanobubbles offered 3-4 times higher kLa than microbubbles. Standard oxygen transfer efficiency in water was found to be 78%, significantly higher than that in microbubbles. However, dissolving stable nanobubbles in water does not considerably increase dissolved oxygen levels.

3.
J Infect Dis ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38437622

RESUMO

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. SARS-CoV-2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic mRNA vaccine response in retrospective and prospective cohorts with lymphoma and CLL, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active therapies, but non-response was also common within observation and post-treatment groups. Total IgA and IgM correlated with successful vaccine response. In individuals treated with CART-19, non-response was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to allow individualized vaccine timing.

4.
Inorg Chem ; 63(6): 3005-3018, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38300805

RESUMO

Homogeneous electrocatalytic systems based on readily available, earth-abundant, inexpensive base metals Ni, Co, and Cr have been formulated for the electro-oxidation of alcohols (methanol and ethanol) that constitute a key half-cell component of direct alcohol fuel cells (DAFCs). Notably, excellent results were obtained for both methanol as well as ethanol electro-oxidation while operating with a half-cell assembly based on all-non-noble working and counter electrode systems consisting of glassy carbon and graphite rod, respectively. Using NaOH as the supporting electrolyte, Ni/Co/Cr metal salts and their bis(iminopyridine) complexes have been used as anodic electrocatalysts for the alcohol half-cell reactions, and among them, catalytic systems based on Co outperformed the corresponding systems based on Ni and Cr. The system comprising CoCl2.·6H2O [10 mM] + NaOH [6 M] at room temperature emerged as the best electrocatalyst for both methanol [5 M] electro-oxidation (ca. 522.5 ± 13.5 mA cm-2 at 1.4 V) and ethanol [5 M] electro-oxidation (ca. 209 ± 25 mA cm-2 at 1.34 V). It was observed that regardless of the starting alcohol, the end product is carbon dioxide, all of which gets trapped as sodium carbonate (up to 97% yield), thereby mitigating any possible hazards of greenhouse gas emission. Inferences obtained from FETEM, FESEM, and EDS analysis of both the electrolyte solution and residues deposited on the electrode surface provide evidence for the mostly homogeneous nature of the reaction mixture with the molecular catalyst being the major contributor toward the electrocatalytic activity apart from the minor role played by trace heterogeneous particles. The current cell assembly operating with non-noble working and counter electrodes utilizing a catalytic system based on an earth-abundant, base metal salt/complex that not only results in good half-cell current densities for high-energy power-source DAFCs but also generates high-value sodium carbonate offers an exciting avenue.

5.
Langmuir ; 40(2): 1534-1543, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38176064

RESUMO

The existence of nanobubbles in pure water has been extensively debated in recent years, and it is speculated that nanobubbles may be ion-stabilized. However, nanobubbles in the alcohol-water mixture and pure alcohols are still controversial due to the lack of ions present in the alcohol system. This work tested the hypothesis that stable nanobubbles exist in pure alcohol. The ultrasound and oscillatory pressure fields are used to generate nanobubbles in pure alcohol. The size distribution, concentration, diameter, and scattering intensity of the nanobubbles were measured by nanoparticle tracking analysis. The light scattering method measures the zeta potential. The Mie scattering theory and electromagnetic wave simulation are utilized to estimate the refractive index (RI) of nanobubbles from the experimentally measured scattering light intensity. The average RI of the nanobubbles in pure alcohols produced by ultrasound and oscillating pressure fields was estimated to be 1.17 ± 0.03. Degassing the nanobubble sample reduces its concentration and increases its size. The average zeta potential of the nanobubbles in pure alcohol was measured to be -5 ± 0.9 mV. The mechanical stability model, which depends on force balance around a single nanobubble, also predicts the presence of nanobubbles in pure alcohol. The nanobubbles in higher-order alcohols were found to be marginally colloidally stable. In summary, both experimental and theoretical results suggest the existence of nanobubbles in pure alcohol.

6.
Heliyon ; 9(6): e17350, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37441386

RESUMO

The recent trends of vitrimer studies enhance the thermoset material with superior properties, therefore, it is particularly important to address the critical scientific inquiries in this area using their research metrics. The reported vitrimer systems have been highly required for future real-time applications; however, the inquisitiveness of material exchange mechanisms extends the research studies further. Significantly, more scientific information's are required to achieve the evident prospective outcomes via these materials. This article highlights the trends and developments of the most relevant publications, authors, articles, countries, and keywords in the vitrimer research field over the past 10 years. The represented bibliometric survey would elevate the basic understanding of the current vitrimer research stats and also help follow the particular research community to learn and develop insight. To generate bibliometric networks, bibliometric data has obtained from Scopus and visualised in VOS-viewer; as an overview of that, the highest number of publications were from China, United States, France, United Kingdom, and Spain.

7.
Crit Rev Food Sci Nutr ; : 1-29, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37267154

RESUMO

Green tomatoes contain significant levels of steroidal glycoalkoids (SGA) such as α-tomatine and green pigment chlorophyll. Tomatine is an admixture of two glycoalkoids; alpha tomatine and dehydrotomatine reported various health beneficial biological activities. Moreover, a hydrolyzed product of tomatine also contributes to age-related atrophy, and muscle weakness and helps the elderly recover from illness and injuries related to age. However, there is a lack of evidence regarding the absorption of tomatine in the human body concerning proposed biological activity, which should be an area of interest in the future. Once, the absorption study is established compounds concentrated in green tomatoes are potentially involved as protective compounds for several diseases and also used for functional food. To facilitate the use of green tomatoes in food processing, this comprehensive review provides data on the nutritional value of green tomatoes, with emphasis on the evolution of the physiological chemistry, analytical, medicinal, and pharmacological effects of the α-tomatine and chlorophyll in an experimental model. The broad aim of this review is to evaluate the health benefits of green tomatoes in addition to their nutritional value and to study the several features of the role of α-tomatine and chlorophyll in human health.

8.
Sci Adv ; 9(26): eadf2746, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37390205

RESUMO

Treatment of triple-negative breast cancer (TNBC) is challenging because of its "COLD" tumor immunosuppressive microenvironment (TIME). Here, we present a hydrogel-mediated localized delivery of a combination of docetaxel (DTX) and carboplatin (CPT) (called DTX-CPT-Gel therapy) that ensured enhanced anticancer effect and tumor regression on multiple murine syngeneic and xenograft tumor models. DTX-CPT-Gel therapy modulated the TIME by an increase of antitumorigenic M1 macrophages, attenuation of myeloid-derived suppressor cells, and increase of granzyme B+CD8+ T cells. DTX-CPT-Gel therapy elevated ceramide levels in tumor tissues that activated the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-mediated unfolded protein response (UPR). This UPR-mediated activation of apoptotic cell death led to release of damage-associated molecular patterns, thereby activating the immunogenic cell death that could even clear the metastatic tumors. This study provides a promising hydrogel-mediated platform for DTX-CPT therapy that induces tumor regression and effective immune modulation and, therefore, can be explored further for treatment of TNBC.


Assuntos
Hidrogéis , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Morte Celular Imunogênica , Linfócitos T CD8-Positivos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Ceramidas , Modelos Animais de Doenças , Imunossupressores , Resposta a Proteínas não Dobradas , Microambiente Tumoral
9.
J Cancer Res Clin Oncol ; 149(11): 8673-8680, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37115270

RESUMO

BACKGROUND: PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are widely used in the treatment of metastatic malignancies. Judiciously balancing disease control (DC) against development of immune-related adverse events (irAE) remains a crucial aspect of treatment. The effect of treatment discontinuation after sustained disease control (SDC) is unknown. The purpose of this analysis was to evaluate outcomes of responders to ICI who discontinue treatment after a minimum of 12 months (SDC). METHODS: We retrospectively reviewed the database of the University of New Mexico Comprehensive Cancer Center (UNMCCC) between 2014 and 2021 and identified patients who had received ICI. Patients with metastatic solid tumors who had stopped ICI therapy after achieving SDC [stable disease, partial response, complete response (SD, PR, CR)] were selected and outcomes reviewed from their electronic health records. RESULTS: We identified 204 patients who were treated with ICI for various solid cancers. Forty-four patients (21.6%) met the criteria, of whom 35 with follow-up data were included in the final analysis; including 11 melanoma, 5 non-small cell lung, 4 head & neck, 8 renal, 4 urothelial, 1 anal, 1 Merkel cell carcinoma, and 1 liposarcoma. Patients were divided into two groups: those who stopped ICI due to an irAE [irAE group, n = 14, median treatment time (MTT), 16.6 mo] and those who stopped due to other reasons (eg completion of 2 years of therapy, n = 20, non-cancer related surgery, n = 1) (non-irAE group, n = 21, MTT, 23.7 mo). Among the irAE group, the most common irAE included pneumonitis, rash, transaminitis, and fatigue. As of data cutoff date, 9 of 14 (64%) patients continued to show SDC. Only 5 of 14 (36%) patients in this group experienced progression of disease (PD), with 1 of 2 patients achieving DC (median follow-up of 19.2 mo after last dose of treatment, range 3-50.2 mo). Among the non-irAE group, 13 of 21 (62%) continued to have SDC. Eight of 21 (38%) experienced PD after stopping treatment, 7 of whom received ICI rechallenge, with 2 of 7 achieving DC (median follow-up of 22.2 mo, range 3.6-54.8 mo). At a median follow-up of 21.3 mo from stopping ICI therapy (range, 3-54.8 mo), 10 patients (71%) from the irAE group and 13 (61.9%) from the non-irAE group are in DC and have not experienced PD. CONCLUSIONS: We demonstrate that 22 (66%) patients experienced SDC, regardless of cancer type or development of irAE. After including patients who were re-challenged with ICI due to PD, 25 (71%) remain in DC. Future prospective malignancy-specific trials are warranted to evaluate optimal treatment duration.


Assuntos
Antineoplásicos Imunológicos , Neoplasias Renais , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Renais/patologia
10.
Brief Bioinform ; 24(2)2023 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-36682028

RESUMO

Alternative splicing (AS) is a key post-transcriptional modification that helps in increasing protein diversity. Almost 90% of the protein-coding genes in humans are known to undergo AS and code for different transcripts. Some transcripts are associated with diseases such as breast cancer, lung cancer and glioblastoma. Hence, these transcripts can serve as novel therapeutic and prognostic targets for drug discovery. Herein, we have developed a pipeline, Finding Alternative Splicing Events (FASE), as the R package that includes modules to determine the structure and concentration of transcripts using differential AS. To predict the correct structure of expressed transcripts in given conditions, FASE combines the AS events with the information of exons, introns and junctions using graph theory. The estimated concentration of predicted transcripts is reported as the relative expression in terms of log2CPM. Using FASE, we were able to identify several unique transcripts of EMILIN1 and SLK genes in the TCGA-BRCA data, which were validated using RT-PCR. The experimental study demonstrated consistent results, which signify the high accuracy and precision of the developed methods. In conclusion, the developed pipeline, FASE, can efficiently predict novel transcripts that are missed in general transcript-level differential expression analysis. It can be applied selectively from a single gene to simple or complex genome even in multiple experimental conditions for the identification of differential AS-based biomarkers, prognostic targets and novel therapeutics.


Assuntos
Processamento Alternativo , Perfilação da Expressão Gênica , Humanos , RNA-Seq , Perfilação da Expressão Gênica/métodos , Genoma , Éxons , Análise de Sequência de RNA
11.
Int J Mol Sci ; 25(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38203586

RESUMO

Immune checkpoint inhibitors (ICI) revolutionized cancer therapy by augmenting anti-tumor immunity via cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death-1/programmed death-ligand 1 (PD-1/PD-L1). However, this breakthrough is accompanied by immune-related adverse effects (irAEs), including renal complications. ICI-related nephritis involves complex mechanisms like auto-reactive T cells, auto-antibodies, reactivation of drug-specific T cells, and cytokine-driven inflammation culminating in AKI. ICI-AKI typically manifests weeks to months into treatment, often with other irAEs. Timely detection relies on monitoring creatinine levels and urine characteristics. Biomarkers, like soluble interleukin-2 receptor (sIL-2R) and urine cytokine levels, provide non-invasive insights, while renal biopsy remains the gold standard for confirmation. Management of ICI-AKI requires a balance between discontinuing ICI therapy and prompt immunosuppressive intervention, typically with corticosteroids. Some cases permit ICI therapy resumption, but varying renal recovery rates highlight the importance of vigilant monitoring and effective therapy. Beyond its clinical implications, the potential of irAEs to predict positive treatment responses in certain cancers raises intriguing questions. Data on nephritis-treatment response links are limited, and ongoing research explores this complex interaction. In summary, ICI therapy's transformative impact on cancer treatment is counterbalanced by irAEs, including nephritis. Early recognition and management are vital, with ongoing research refining diagnostic and treatment strategies.


Assuntos
Injúria Renal Aguda , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Nefrite , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Citocinas
12.
Langmuir ; 38(51): 15925-15936, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36508708

RESUMO

Droplets may rebound/levitate when deposited over a hot substrate (beyond a critical temperature) due to the formation of a stable vapor microcushion between the droplet and the substrate. This is known as the Leidenfrost phenomenon. In this article, we experimentally allow droplets to impact the hot surface with a certain velocity, and the temperature at which droplets show the onset of rebound with minimal spraying is known as the dynamic Leidenfrost temperature (TDL). Here we propose and validate a novel paradigm of augmenting the TDL by employing droplets with stable nanobubbles dispersed in the fluid. In this first-of-its-kind report, we show that the TDL can be delayed significantly by the aid of nanobubble-dispersed droplets. We explore the influence of the impact Weber number (We), the Ohnesorge number (Oh), and the role of nanobubble concentration on the TDL. At a fixed impact velocity, the TDL was noted to increase with the increase in nanobubble concentration and decrease with an increase in impact velocity for a particular nanobubble concentration. Finally, we elucidated the overall boiling behaviors of nanobubble-dispersed fluid droplets with the substrate temperature in the range of 150-400 °C against varied impact We through a detailed phase map. These findings may be useful for further exploration of the use of nanobubble-dispersed fluids in high heat flux and high-temperature-related problems and devices.

13.
Vaccines (Basel) ; 10(12)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36560569

RESUMO

This study aims to provide comparative data on clinical features and in-hospital outcomes among U.S. adults admitted to the hospital with COVID-19 and influenza infection using a nationwide inpatient sample (N.I.S.) data 2020. Data were collected on patient characteristics and in-hospital outcomes, including patient's age, race, sex, insurance status, median income, length of stay, mortality, hospitalization cost, comorbidities, mechanical ventilation, and vasopressor support. Additional analysis was performed using propensity matching. In propensity-matched cohort analysis, influenza-positive (and COVID-positive) patients had higher mean hospitalization cost (USD 129,742 vs. USD 68,878, p = 0.04) and total length of stay (9.9 days vs. 8.2 days, p = 0.01), higher odds of needing mechanical ventilation (OR 2.01, 95% CI 1.19-3.39), and higher in-hospital mortality (OR 2.09, 95% CI 1.03-4.24) relative to the COVID-positive and influenza-negative cohort. In conclusion, COVID-positive and influenza-negative patients had lower hospital charges, shorter hospital stays, and overall lower mortality, thereby supporting the use of the influenza vaccine in COVID-positive patients.

14.
RSC Adv ; 12(50): 32569-32582, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36425695

RESUMO

To achieve sustainable development goals, approaches towards the preparation of recyclable and healable polymeric materials is highly attractive. Self-healing polymers and thermosets based on bond-exchangeable dynamic covalent bonds, so called "vitrimers" could be a great effort in this direction. In order to match the industrial importance, enhancement of mechanical strength without sacrificing the bond exchange capability is a challenging issue, however, such concerns can be overcome through the developments of fiber-reinforced vitrimer composites. This article covers the outstanding features of fiber-reinforced vitrimer composites, including their reprocessing, recycling and self-healing properties, together with practical applications and future perspectives of this unique class of materials.

15.
Sensors (Basel) ; 22(19)2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36236573

RESUMO

Academics and the health community are paying much attention to developing smart remote patient monitoring, sensors, and healthcare technology. For the analysis of medical scans, various studies integrate sophisticated deep learning strategies. A smart monitoring system is needed as a proactive diagnostic solution that may be employed in an epidemiological scenario such as COVID-19. Consequently, this work offers an intelligent medicare system that is an IoT-empowered, deep learning-based decision support system (DSS) for the automated detection and categorization of infectious diseases (COVID-19 and pneumothorax). The proposed DSS system was evaluated using three independent standard-based chest X-ray scans. The suggested DSS predictor has been used to identify and classify areas on whole X-ray scans with abnormalities thought to be attributable to COVID-19, reaching an identification and classification accuracy rate of 89.58% for normal images and 89.13% for COVID-19 and pneumothorax. With the suggested DSS system, a judgment depending on individual chest X-ray scans may be made in approximately 0.01 s. As a result, the DSS system described in this study can forecast at a pace of 95 frames per second (FPS) for both models, which is near to real-time.


Assuntos
COVID-19 , Pneumotórax , Idoso , COVID-19/diagnóstico por imagem , Teste para COVID-19 , Humanos , Pulmão , Medicare , Estados Unidos , Raios X
16.
Int J Mol Sci ; 23(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36293264

RESUMO

Single nucleotide polymorphisms (SNPs) impacting the alternative splicing (AS) process (sQTLs) or isoform expression (iso-eQTL) are implicated as important cancer regulatory elements. To find the sQTL and iso-eQTL, we retrieved prostate cancer (PrCa) tissue RNA-seq and genotype data originating from 385 PrCa European patients from The Cancer Genome Atlas. We conducted RNA-seq analysis with isoform-based and splice event-based approaches. The MatrixEQTL was used to identify PrCa-associated sQTLs and iso-eQTLs. The overlap between sQTL and iso-eQTL with GWAS loci and those that are differentially expressed between cancer and normal tissue were identified. The cis-acting associations (FDR < 0.05) for PrCa-risk SNPs identified 42, 123, and 90 PrCa-associated cassette exons, intron retention, and mRNA isoforms belonging to 25, 95, and 83 genes, respectively; while assessment of trans-acting association (FDR < 0.05) yielded 59, 65, and 196 PrCa-associated cassette exons, intron retention and mRNA isoforms belonging to 35, 55, and 181 genes, respectively. The results suggest that functional PrCa-associated SNPs can play a role in PrCa genesis by making an important contribution to the dysregulation of AS and, consequently, impacting the expression of the mRNA isoforms.


Assuntos
Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata , Masculino , Humanos , Isoformas de RNA , Estudo de Associação Genômica Ampla/métodos , Locos de Características Quantitativas , Predisposição Genética para Doença , Neoplasias da Próstata/genética , Isoformas de Proteínas/genética
17.
Healthcare (Basel) ; 10(8)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-36011078

RESUMO

Purpose: To examine potential factors associated with maintaining or improving self-reported physical function (PF) among older cancer survivors participating in a gardening intervention impacted by the Coronavirus 2019 (COVID-19) pandemic. Methods: Thirty cancer survivors completed a home-based gardening intervention to encourage a healthier diet and a more active lifestyle. Device-based measures of physical activity (PA) and surveys to evaluate quality of life (QOL; PROMIS-57 questionnaire) were administered at baseline, mid-intervention (6 months), and post-intervention (9 months). Results: Depression, fatigue, and sleeplessness at baseline were significantly associated with worse average PF scores across follow-up (2.3 to 4.9 points lower for every decrease of 5 points in the QOL score; p-values < 0.02). Worsening of these QOL domains during the intervention was also associated with an additional decrease of 2.1 to 2.9 points in PF over follow-up (p values < 0.01). Better social participation and PA at baseline were significantly associated with better average PF scores during the intervention (2.8 to 5.2 points higher for every 5-point increase in social participation or 30 min more of PA; p values < 0.05). Every 5-point increase in pain at baseline, or increases in pain during the intervention, was associated with decreases of 4.9 and 3.0 points, respectively, in PF. Conclusions: Worse QOL scores before and during the intervention were significantly associated with worse PF over follow-up. Encouraging social participation and PA through interventions such as home-based gardening may improve long-term health among older cancer survivors.

18.
iScience ; 25(7): 104527, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35754725

RESUMO

The post-menopausal state in women is associated with increased cancer incidence, the reasons for which remain obscure. Curiously, increased circulating levels of beta-hCG (human chorionic gonadotropin) (a hormonal subunit linked with tumors of several lineages) are also often observed post-menopause. This study describes a previously unidentified interplay between beta-hCG and progesterone in tumorigenesis. Progesterone mediated apoptosis in beta-hCG responsive tumor cells via non-nuclear receptors. The transgenic expression of beta-hCG, particularly in the absence of the ovaries (a mimic of the post-menopausal state) constituted a potent pro-tumorigenic signal. Significantly, the administration of progesterone had significant anti-tumor effects. RNA-seq profiling identified molecular signatures associated with these processes. TCGA analysis revealed correlates between the expression of several newly identified genes and poor prognosis in post-menopausal patients of lung adenocarcinoma, colon adenocarcinoma, and glioblastoma. Specifically in these women, the detection of intra-tumoral/extra-tumoral beta-hCG may serve as a useful prognostic indicator, and treatment with progesterone on its detection may prove beneficial.

19.
Cell ; 185(11): 1875-1887.e8, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35523182

RESUMO

We examined antibody and memory B cell responses longitudinally for ∼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40%-50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells were efficiently reactivated by a 3rd dose of wild-type vaccine and correlated with the corresponding increase in neutralizing antibody titers. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit the added protection afforded by repeat short interval boosting. These data provide insight into the quantity and quality of mRNA-vaccine-induced immunity over time through 3 or more antigen exposures.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Humanos , RNA Mensageiro , SARS-CoV-2 , Vacinas Sintéticas , Vacinas de mRNA
20.
Artigo em Inglês | MEDLINE | ID: mdl-35457633

RESUMO

In this secondary analysis of a light-intensity physical activity intervention, we hypothesized that older cancer survivors would self-select a faster walking cadence to meet their daily step goals. Average steps/day and free-living walking cadence were measured in 41 participants (age 69 ± 3.1 years) with an ActivPAL monitor worn 7 days pre- and post-intervention. Besides peak and average walking cadence, stepping patterns associated with ambulatory intensity were sorted in cadence bands of 20 steps/min from 40−59 (incidental movement) to ≥120 steps/min (fast locomotor movement). Compared to the waitlist Control group (n = 17), the Intervention group (n = 24) increased their peak 30-min cadence (4.3 vs. 1.9 steps/minute; p = 0.03), average 10-min cadence (4.1 vs. −6.6 steps/minute; p = 0.04), and average 30-min cadence (5.7 vs. −0.8 steps/minute, p = 0.03). Steps taken in cadence bands denoting moderate-intensity physical activity (100−119 steps/min) increased by 478 (interquartile range (IQR): −121 to 1844) compared to decreasing by 92 (IQR: −510 to 181) steps/day for the intervention and Control groups, respectively (p < 0.01). Evaluation of free-living walking cadence and patterns of ambulatory behavior can inform future interventions targeting behavior change, especially in those populations most at risk for reduced physical activity and vulnerable to mobility deficits and loss of independence.


Assuntos
Sobreviventes de Câncer , Neoplasias , Idoso , Exercício Físico , Humanos , Caminhada
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