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1.
Heliyon ; 10(11): e32331, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38947484

ABSTRACT

The correlation between sports participation and psychological well-being is well-documented, revealing a complex interplay influenced by competition level and cultural context. This is particularly relevant in Korea, where the university sports culture significantly impacts student life. This study evaluates how competitive versus non-competitive sports affect Korean university students' psychological well-being using a quantitative approach with SmartPLS 4 for multi-group analysis. Findings reveal that competitive sports significantly enhance mental toughness and stress management through structured coping mechanisms and robust social support, improving coping strategy effectiveness by 34 % compared to non-competitive sports. Conversely, participants in non-competitive sports experience greater general well-being with a 40 % higher use of informal support. These insights suggest that university sports programs could benefit from targeted interventions incorporating specific coping strategies and social support frameworks tailored to the competitive context. This research underscores the need for precise stress management techniques and resilience-building exercises in sports curricula to optimize psychological well-being across different sports environments in Korean universities.

2.
Clin Cancer Res ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949888

ABSTRACT

PURPOSE: Patients with microsatellite instability high/mismatch repair deficient (MSI-H/dMMR) and high tumor mutational burden (TMB-H) prostate cancers are candidates for pembrolizumab. We define the genomic features, clinical course, and response to immune checkpoint blockade (ICB) in patients with MSI-H/dMMR and TMB-H prostate cancers without MSI (TMB-H/MSS). METHODS: We sequenced 3,244 tumors from 2,257 prostate cancer patients. MSI-H/dMMR prostate cancer was defined as MSIsensor score ≥10 or MSIsensor score ≥3 and <10 with a deleterious MMR alteration. TMB-H was defined as ≥10 mutations/megabase. PSA50 and RECIST responses were assigned. Overall survival (OS) and radiographic progression-free survival (rPFS) were compared using log rank test. RESULTS: 63 (2.8%) men had MSI-H/dMMR and 33 (1.5%) had TMB-H/MSS prostate cancers. Patients with MSI-H/dMMR and TMB-H/MSS tumors more commonly presented with grade group 5 and metastatic disease at diagnosis. MSI-H/dMMR tumors had higher TMB, indel and neoantigen burden compared with TMB-H/MSS. 27 patients with MSI-H/dMMR and 8 patients with TMB-H/MSS tumors received ICB, none of whom harbored POLE mutations. 45% of MSI-H/dMMR patients had a RECIST response and 65% had a PSA50 response. No TMB-H/MSS patient had a RECIST response and 50% had a PSA50 response. rPFS tended to be longer in MSI-H/dMMR patients than in TMB-H/MSS patients who received immunotherapy. Pronounced differences in genomics, TMB or MSIsensor score were not detected between MSI-H/dMMR responders and non-responders. CONCLUSIONS: MSI-H/dMMR prostate cancers have greater TMB, indel and neoantigen burden compared with TMB-H/MSS prostate cancers, and these differences may contribute to more profound and durable responses to ICB.

3.
JCO Precis Oncol ; 8: e2300274, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38691813

ABSTRACT

PURPOSE: Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials. METHODS: Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients. RESULTS: Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15% v 29%; P = .021). Alterations in CDKN2A/B were associated with shorter RFS. PIK3CA alterations were associated with LVI. Potentially actionable alterations were identified in more than 75% of tumors. CONCLUSION: Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease.


Subject(s)
Drug Resistance, Neoplasm , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Male , Female , Aged , Drug Resistance, Neoplasm/genetics , Middle Aged , Neoplasm Invasiveness , Gemcitabine , Neoadjuvant Therapy , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Cisplatin/therapeutic use , Genomics , Cystectomy
4.
Cureus ; 16(3): e57022, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38681462

ABSTRACT

Introduction Serum urea and creatinine levels are the most commonly recognized parameters for evaluating renal impairment in patients with diabetes mellitus (DM). Therefore, this study evaluated the correlation between urea and creatinine levels and thiamin levels in patients with type 1 DM (T1DM) and type 2 DM (T2DM). Methods This multi-center, cross-sectional study was conducted at diabetic outpatient clinics in Karachi. The duration of the study was six months, from 1st January 2023 to 30th June 2023. A total of 60 patients were enrolled and divided into two groups, i.e., T1DM and T2DM, each containing 30 patients of both genders between the ages of 24 and 42 years. Demographic data and biochemical variables, such as urea, creatinine, random blood sugar, fasting blood sugar, hemoglobin A1c, and serum thiamin levels, were assessed. The Mann-Whitney U test and independent t-test were used to associate the means between the two study groups. The chi-square test and Spearman's correlation coefficient were used to determine the associations between the variables and T1DM and T2DM. Results The study results revealed that patients with T2DM had a significantly higher frequency of hypertension (p = 0.039), neuropathy (p = 0.038), and coronary artery disease (p = 0.010) than those with T1DM, in both genders. The level of serum thiamin was found to be significantly higher (p < 0.001) in T2DM (14.8 ± 4.82) than in T1DM patients (7.34 ± 1.90). Similarly, serum creatinine was higher in T2DM than in T1DM patients (0.83 ± 0.12 vs. 0.76 ± 0.17, p = 0.025). Moreover, the correlation of urea and creatinine with thiamin levels in T1DM and T2DM patients revealed that in T1DM and T2DM patients, urea and creatinine showed an insignificant positive correlation with thiamin levels. Conclusion We found a significantly higher level of serum creatinine and thiamin levels in T2DM patients than in T1DM; however, there was no significant correlation between urea and creatinine levels and thiamin status in T1DM and T2DM patients. Therefore, we conclude that although serum urea, creatinine, and serum thiamin are important disease biomarkers in diabetic patients, there is no correlation between them.

5.
J Pak Med Assoc ; 74(2): 341-365, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38419237

ABSTRACT

Objective: To identify and critically appraise literature on true brachial artery aneurysm, exploring its demographic characteristics, aetiologies, clinical manifestations and different methods of repair along with complication rates to determine future treatment strategies. METHODS: The systematic review was conducted at Liaquat National Hospital, Karachi, from September 30, 2021, to November 30, 2022, in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Literature was searched on MEDLINE, EMBASE and Cochrane databases for relevant studies in English language or with English translation published till May 31, 2022. The key words used for the search were "brachial artery aneurysm". Data was noted on a proforma and was subjected to descriptive analysis. RESULTS: Of 113 articles, 6 (5.3%) were retrospective studies, 7 (6.1%) were case series and 100 (88.4%) were case reports. The total number of patients involved was 157 with mean age 43.1±23.4 years (range: 2 months to 84 years). The gender was mentioned for 152(96.8%) patients; 111(73%) males and 41(27%) females. The mean diameter of true brachial artery aneurysm was 36.2 ±17.5mm and 106(67.5%) patients presented with localised swelling, 65(41.4%) with pain, 41(26.1%) with distal ischaemic symptoms, and 28(17.8%) with median nerve compression. True brachial artery aneurysms were more common in renal failure patients having a history of arteriovenous fistula creation in the affected limb and were on immunosuppressant drugs due to renal transplant 81(51.5%). Less common causes included primary/idiopathic 27(17.1%), trauma 13(8.2%), connective tissue disorders 8(5%) and vasculitis 7(4.5%). The treatment of choice was aneurysmectomy in 142(90.4%) cases, with revascularisation of limb primarily with reversed great saphenous vein graft 79(50.3 %), followed by end-to-end anastomosis of brachial artery 17(10.8%) and synthetic grafting 17(10.8%). Endovascular intervention was performed in 6(3.8%) cases to exclude true brachial artery aneurysm, and to re-establish adequate blood flow to the associated limb. Conclusion: True brachial artery aneurysm, although a rarity, may lead to significant neurological and vascular problems if ignored. Arteriovenous fistula and immunosuppression are identified as two significant risk factors in the development of true brachial artery aneurysm. Therefore, an effective long-term follow up in renal failure patients is recommended to prevent its complications. Open surgical repair has been the most preferred mode of treatment, but further significant studies are needed to explore and compare different modes of surgical intervention, like open versus endovascular, to plan future treatment strategies.


Subject(s)
Aneurysm , Arteriovenous Fistula , Renal Insufficiency , Male , Female , Humans , Young Adult , Adult , Middle Aged , Aged , Brachial Artery/surgery , Retrospective Studies , Treatment Outcome , Aneurysm/surgery , Renal Insufficiency/complications
6.
Tob Control ; 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38176900

ABSTRACT

BACKGROUND: Taxation is the most cost-effective instrument to regulate the consumption of tobacco products. However, weak tax administration can compromise the effectiveness of taxation. This paper aimed to understand the process of the current tobacco tax administration system in Bangladesh, identify gaps and outline the policy priorities to strengthen the tobacco tax administration process in Bangladesh. METHODS: A sequential qualitative study was conducted in two linked phases: (a) document review and evidence synthesis; and (b) 20 key informant interviews and one workshop with relevant stakeholders to validate the findings generated from both phases. RESULTS: The complex tax system combined with weak tax administration leads to tax evasion in Bangladesh. The processes of procuring and collecting banderoles and tax stamps vary between cigarette and biri companies, and across large and small tax-paying companies. The use of banderoles at the factory level is maintained manually, and there is no system to routinely verify the authenticity of banderoles. Many unregistered small-scale tobacco manufacturing units often reuse the banderoles on new packs. Shortage of staff with inadequate training at the National Board of Revenue restricts adequate tobacco market monitoring. Electronic tax stamps and banderoles combined with a secure digital tracking and tracing system should be introduced to better monitor the supply, distribution and sale of tobacco products. Training needs to be provided to develop capacity of relevant officials. CONCLUSION: The tobacco tax administration needs to be strengthened to increase the government's tobacco tax revenue and protect public health.

7.
Sci Rep ; 14(1): 2101, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38267461

ABSTRACT

This paper focuses on the feasibility of deep neural operator network (DeepONet) as a robust surrogate modeling method within the context of digital twin (DT) enabling technology for nuclear energy systems. Machine learning (ML)-based prediction algorithms that need extensive retraining for new reactor operational conditions may prohibit real-time inference for DT across varying scenarios. In this study, DeepONet is trained with possible operational conditions and that relaxes the requirement of continuous retraining - making it suitable for online and real-time prediction components for DT. Through benchmarking and evaluation, DeepONet exhibits remarkable prediction accuracy and speed, outperforming traditional ML methods, making it a suitable algorithm for real-time DT inference in solving a challenging particle transport problem. DeepONet also exhibits generalizability and computational efficiency as an efficient surrogate tool for DT component. However, the application of DeepONet reveals challenges related to optimal sensor placement and model evaluation, critical aspects of real-world DT implementation. Addressing these challenges will further enhance the method's practicality and reliability. Overall, this study marks an important step towards harnessing the power of DeepONet surrogate modeling for real-time inference capability within the context of DT enabling technology for nuclear systems.

8.
J Cell Biochem ; 125(2): e30515, 2024 02.
Article in English | MEDLINE | ID: mdl-38213080

ABSTRACT

Vascular endothelial growth factor (VEGF) mediated angiogenesis is crucial for tumor progression. Isoforms of VEGF bind to different VEGF receptors (VEGFRs) to initiate angiogenesis specific cellular signaling. Inhibitors that target both the receptors and ligands are in clinical use to impede angiogenesis. Bevacizumab, a monoclonal antibody (mAb) approved by the Food and Drug Administration (FDA), binds in the VEGF receptor binding domain (RBD) of all soluble isoforms of VEGF and inhibits the VEGF-VEGFR interaction. Bevacizumab is also used in combination with other chemotherapeutic agents for a better therapeutic outcome. Understanding the intricate polymorphic character of VEGFA gene and the influence of missense or nonsynonymous mutations in the form of nonsynonymous polymorphisms (nsSNPs) on RBD of VEGF may aid in increasing the efficacy of this drug. This study has identified 18 potential nsSNPs in VEGFA gene that affect the VEGF RBD structure and alter its binding pattern to bevacizumab. The mutated RBDs, modeled using trRosetta, in addition to the changed pattern of secondary structure, post translational modification and stability compared to the wild type, have shown contrasting binding affinity and molecular interaction pattern with bevacizumab. Molecular docking analysis by ClusPro and visualization using PyMol and PDBsum tools have detected 17 nsSNPs with decreased binding affinity to bevacizumab and therefore may impact the treatment efficacy. Whereas VEGF RBD expressed due to rs1267535717 (R229H) nsSNP of VEGFA has increased affinity to the mAb. This study suggests that genetic characterization of VEGFA before bevacizumab mediated cancer treatment is essential in predicting the appropriate efficacy of the drug, as the treatment efficiency may vary at individual level.


Subject(s)
Antibodies, Monoclonal, Humanized , Vascular Endothelial Growth Factor A , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Vascular Endothelial Growth Factor A/metabolism , Molecular Docking Simulation , Antibodies, Monoclonal/pharmacology , Receptors, Vascular Endothelial Growth Factor/genetics , Protein Isoforms , Mutation , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic use
9.
Sci Rep ; 14(1): 339, 2024 01 03.
Article in English | MEDLINE | ID: mdl-38172184

ABSTRACT

Addressing the growing popularity of mobile health (m-Health) technology in the health industry, the current study examined consumers' intention and behaviour related to the usage of digital applications based on the unified theory of acceptance and use of technology (UTAUT). In particular, this study quantitatively assessed the moderating role of perceived product value and mediating role of intention to use m-Health application among Indonesians. This study adopted a cross-sectional design and collected quantitative data from conveniently selected respondents through an online survey, which involved 2068 Telegram users in Indonesia. All data were subjected to the analysis of partial least square- structural equation modeling (PLS-SEM). The obtained results demonstrated the moderating effect of perceived product value on the relationship between intention to use m-Health application (m-health app) and actual usage of m-Health app and the mediating effects of intention to use m-Health app on the relationships of perceived critical mass, perceived usefulness, perceived convenience, perceived technology accuracy, and perceived privacy protection on actual usage of m-Health app. However, the intention to use m-Health app did not mediate the influence of health consciousness and health motivation on the actual usage of m-Health app. Overall, this study's findings on the significance of intention to use m-Health app and perceived product value based on the UTAUT framework serve as insightful guideline to expand the usage of m-Health app among consumers.


Subject(s)
Mobile Applications , Telemedicine , Humans , Cross-Sectional Studies , Intention , Motivation
10.
Neuroradiol J ; 37(2): 137-151, 2024 Apr.
Article in English | MEDLINE | ID: mdl-36961518

ABSTRACT

The ulnar nerve is the second most commonly entrapped nerve after the median nerve. Although clinical evaluation and electrodiagnostic studies remain widely used for the evaluation of ulnar neuropathy, advancements in imaging have led to increased utilization of these newer / better imaging techniques in the overall management of ulnar neuropathy. Specifically, high-resolution ultrasonography of peripheral nerves as well as MRI has become quite useful in evaluating the ulnar nerve in order to better guide treatment. The caliber and fascicular pattern identified in the normal ulnar nerves are important distinguishing features from ulnar nerve pathology. The cubital tunnel within the elbow and Guyon's canal within the wrist are important sites to evaluate with respect to ulnar nerve compression. Both acute and chronic conditions resulting in deformity, trauma as well as inflammatory conditions may predispose certain patients to ulnar neuropathy. Granulomatous diseases as well as both neurogenic and non-neurogenic tumors can also potentially result in ulnar neuropathy. Tumors around the ulnar nerve can also lead to mass effect on the nerve, particularly in tight spaces like the aforementioned canals. Although high-resolution ultrasonography is a useful modality initially, particularly as it can be helpful for dynamic evaluation, MRI remains most reliable due to its higher resolution. Newer imaging techniques like sonoelastography and microneurography, as well as nerve-specific contrast agents, are currently being investigated for their usefulness and are not routinely being used currently.


Subject(s)
Neoplasms , Ulnar Nerve Compression Syndromes , Ulnar Neuropathies , Humans , Ulnar Nerve/diagnostic imaging , Ulnar Nerve/pathology , Wrist/pathology , Ulnar Nerve Compression Syndromes/diagnostic imaging , Ulnar Nerve Compression Syndromes/pathology , Ulnar Neuropathies/diagnostic imaging
11.
Curr Pharm Des ; 29(36): 2891-2901, 2023.
Article in English | MEDLINE | ID: mdl-38018194

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which first appeared in December 2019. Angiotensin I converting enzyme 2 (ACE2) receptor, present on the host cells, interacts with the receptor binding domain (RBD) of spike (S) protein of SARS-CoV-2 and facilitates the viral entry into host cells. METHODS: Non-synonymous single nucleotide polymorphisms (nsSNPs) in the ACE2 gene may have an impact on the protein's stability and its function. The deleterious or harmful nsSNPs of the ACE2 gene that can change the strength as well as the pattern of interaction with the RBD of S protein were selected for this study. RESULTS: The ACE2:RBD interactions were analyzed by protein-protein docking study. The missense mutations A242V, R708W, G405E, D292N, Y633C, F308L, and G405E in ACE2 receptor were found to interact with RBD of Omicron subvariants with stronger binding affinity. Among the other selected nsSNPs of human ACE2 (hACE2), R768W, Y654S, F588S, R710C, R710C, A191P, and R710C were found to have lower binding affinity for RBD of Omicron subvariants. CONCLUSION: The findings of this study suggest that the nsSNPs present in the human ACE2 gene alter the structure and function of the protein and, consequently, the susceptibility to Omicron subvariants.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/genetics , Angiotensin-Converting Enzyme 2/genetics , Polymorphism, Single Nucleotide/genetics , Protein Binding/genetics , Mutation
12.
Ecancermedicalscience ; 17: 1606, 2023.
Article in English | MEDLINE | ID: mdl-37799940

ABSTRACT

Background: Infections significantly predominate during induction chemotherapy for acute lymphoblastic leukaemia (ALL) in children. Antibacterial prophylaxis is one strategy that lowers the risk of these infections. This study evaluates the role of levofloxacin prophylaxis on the frequency of infections, febrile neutropenia (FN) and outcomes associated with it along with the development of drug-resistance. Subject and methods: This was a single-centre cohort study in which the data were collected from electronic health records between two cohorts of high-risk ALL patients in the induction phase: the first one before the initiation of levofloxacin prophylaxis and the second was after the implementation of levofloxacin prophylaxis. The variables were compared between both the groups and odds ratios were calculated for clinical outcomes. Results: Out of 227 patients, 115 were given levofloxacin prophylaxis and 112 were in the no prophylaxis group. Both cohorts were similar in demographic factors, treatment regimen and supportive care services. There was a significant difference in total in-patient admissions along with FN admissions (p = 0.026). Microbiologically documented infections and infection-related critical interventions were significantly higher in the no prophylaxis group (p < 0.05). Odds ratios with a 95% confidence interval were applied to both groups for clinical outcomes in patients with and without FN which also illustrated similar results. Overall mortality and drug resistance patterns were similar among both groups. Conclusion: This study emphasised that levofloxacin is effective in reducing inpatient admissions with FN and its complications but did not affect the drug-resistance pattern. Long-term monitoring for antibiotic resistance is mandatory.

14.
J Sep Sci ; 46(21): e2300582, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37675810

ABSTRACT

The extraction of berberine was carried out from Berberis vulgaris, Berberis aquifolium, and Hydrastis canadensis plants using ethanol and water (70:30, v/v). The extracted berberine was characterized by ultraviolet-visible and Fourier-transform infrared spectroscopy. The purity of berberine was ascertained by thin-layer chromatography using n-propanol-formic acid-water (95:1:4) and (90:1:9) solvents. hRf values were in the range of 44-49 with compact spots (diameter 0.2-0.4 cm). HPLC was carried out using ammonium acetate buffer and acetonitrile in gradient mode with Zodiac (4.6 × 150 mm, 3 µm) column. The flow rate was 1.0 mL/min and detection was at 220 nm. The values of separation and resolution factors of the standard and the extracted berberine were in the range of 1.13-1.16 and 1.40-1.71, respectively. A comparison has shown that both thin-layer chromatography and high-performance liquid chromatography (HPLC) methods found applications in different situations and requirements. The extracted berberine samples were used to treat Leishmaniosis and the results showed better activity of berberine in comparison to the standard drug Amphotericin B. Briefly, the reported research is a novel and may be used to extract berberine from plants, separation and identification of berberine by thin layer chromatography and HPLC and to treat Leishmaniosis.


Subject(s)
Berberine , Berberine/chemistry , Chromatography, High Pressure Liquid/methods , Chromatography, Thin Layer/methods , Solvents/analysis , Water
15.
Virology ; 587: 109874, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37690385

ABSTRACT

D'Ann Rochon passed away on November 29th 2022. She is remembered for her outstanding contributions to the field of plant virology, her strong commitment to high quality science and her dedication to the training and mentorship of the next generation of scientists. She was a research scientist for Agriculture and Agri-Food Canada and an Adjunct Professor for the University of British Columbia. Her research program provided new insights on the infection cycle of tombusviruses and related viruses, including ground-breaking research on the structure of virus particles, the mechanisms of virus transmission by fungal zoospores, and the complexity of plant-virus interactions. She also developed diagnostic antibodies for plum pox virus and little cherry virus 2 that have had a significant impact on the management of these viruses.

16.
Ambio ; 52(11): 1687-1696, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37715896

ABSTRACT

The challenges posed by climate change, biodiversity loss, and land-use are deeply interconnected and integrated solutions are needed. This paper presents results from 11 contributions to a special issue covering topics of integrated modeling and spatial prioritization, mass-balance studies, Earth Observation techniques, research infrastructure developments, and evaluation of policy measures and economic compensation schemes. The spatial scale of the studies ranges from detailed site-specific to a European scale. This paper briefly summarizes the main findings of these studies, makes some general overall conclusions, and identifies topics for further research and methods developments.

17.
Ambio ; 52(11): 1819-1831, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37725249

ABSTRACT

Integrated long-term, in-situ observations are needed to document ongoing environmental change, to "ground-truth" remote sensing and model outputs and to predict future Earth system behaviour. The scientific and societal value of in-situ observations increases with site representativeness, temporal duration, number of parameters measured and comparability within and across sites. Research Infrastructures (RIs) can support harmonised, cross-site data collection, curation and publication. Integrating RI networks through site co-location and standardised observation methods can help answers three questions about the terrestrial carbon sink: (i) What are present and future carbon sequestration rates in northern European forests? (ii) How are these rates controlled? (iii) Why do the observed patterns exist? Here, we present a conceptual model for RI co-location and highlight potential insights into the terrestrial carbon sink achievable when long-term in-situ Earth observation sites participate in multiple RI networks (e.g., ICOS and eLTER). Finally, we offer recommendations to promote RI co-location.

18.
ACS Omega ; 8(37): 33774-33784, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37744867

ABSTRACT

In this study, a new drug carrier based on gelled-oil nanoparticles (GNPs) was designed and synthesized for the encapsulation and release of the model hydrophobic drug, berberine chloride (BCl). Two compositions with different oil phases were examined, sesame oil (SO) and cinnamaldehyde (Cin), which were emulsified with water, stabilized with Tween 80 (Tw80), and gelled using an N-alkylated primary oxalamide low-molecular-weight gelator (LMWG) to give stable dispersions of GNPs between 100 and 200 nm in size. The GNP formulation with Cin was significantly favored over SO due to (1) lower gel melting temperatures, (2) higher gel mechanical strength, and (3) significantly higher solubility, encapsulation efficiency, and loading of BCl. Also, the solubility and loading of BCl in Cin were significantly increased (at least 7-fold) with the addition of cinnamic acid. In vitro release studies showed that the release of BCl from the GNPs was independent of gelator concentration and lower than that for BCl solution and the corresponding nanoemulsion (no LWMG). Also, cell internalization studies suggested that the N-alkylated primary oxalamide LMWG did not interfere with the internalization efficiency of BCl into mouse mast cells. Altogether, this work demonstrates the potential use of these new GNP formulations for biomedical studies involving the encapsulation of drugs and nutraceuticals and their controlled release.

19.
Cell Immunol ; 391-392: 104751, 2023.
Article in English | MEDLINE | ID: mdl-37480823

ABSTRACT

Mast cells initiate allergic inflammatory immune responses and play a role in disease by releasing various inflammatory and immunomodulatory mediators. Several mast cell-lines and primary cultured cells have been used as mast cell models with inconsistent results among research groups. Bone marrow-derived mast cells (BMMC) cultured from mouse bone marrow progenitor cells are often used as a representative model of mucosal mast cell behaviour, however their reported phenotype is variable due to inconsistent culture protocols. RBL-2H3 is a rat basophilic histamine-releasing cell line that has some characteristics of both mast cells and basophils but is not a true representation of either cell type. The murine mast cell line MC/9 is an IL-3-dependent mucosal mast cell model but has limited mast cell characteristics. In this study, we have compared the response of BMMC (derived from C57BL/6 male or female mice), two sources of RBL-2H3 (purchased directly from ATCC and a lab curated culture), and MC/9 (ATCC) at several critical stages to some common stimuli (IgE/Ag, A23187) and analyzed mast cell morphology, expression level of common mast cell surface markers (CD117 and FcεRI), protease expression, and function (growth kinetics, viability, ROS production, degranulation, cytokine release and FcεRI signaling). The objective of this study was to provide insight into the effects of culture conditions, biological sex, and age of the cells on variability among reported phenotypes and, to determine optimal conditions for activation of these cells. Our data show that factors that are often overlooked such as source, age and biological sex of mast cells play an integral role in phenotypic outcomes and may account for the reported variability in their function.


Subject(s)
Basophils , Mast Cells , Rats , Mice , Male , Female , Animals , Rodentia , Mice, Inbred C57BL , Cell Line , Cell Degranulation
20.
Pharmacol Rep ; 75(4): 907-922, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37440106

ABSTRACT

Natural compounds originating from plants offer a wide range of pharmacological potential and have traditionally been used to treat a wide range of diseases including cancer. Tanshinone IIA (Tan IIA), a bioactive molecule found in the roots of the Traditional Chinese Medicine (TCM) herb Salvia miltiorrhiza, has been shown to have remarkable anticancer properties through several mechanisms, such as inhibition of tumor cell growth and proliferation, metastasis, invasion, and angiogenesis, as well as induction of apoptosis and autophagy. It has demonstrated excellent anticancer efficacy against cell lines from breast, cervical, colorectal, gastric, lung, and prostate cancer by modulating multiple signaling pathways including PI3K/Akt, JAK/STAT, IGF-1R, and Bcl-2-Caspase pathways. This review focuses on the role of Tan IIA in the treatment of various cancers, as well as the underlying molecular mechanisms.


Subject(s)
Neoplasms , Phosphatidylinositol 3-Kinases , Male , Humans , Phosphatidylinositol 3-Kinases/metabolism , Abietanes/pharmacology , Signal Transduction , Apoptosis , Cell Proliferation , Cell Line, Tumor , Neoplasms/drug therapy
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