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1.
Med J Malaysia ; 79(4): 470-476, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39086346

RESUMEN

INTRODUCTION: Tuberculosis (TB) is a global public health issue. The Southeast Asian region grapples with numerous challenges in TB management, with loss to follow-up (LTFU) emerging as a critical barrier to effective control of the disease. This review synthesised published articles to identify socioeconomic factors contributing to the burden of TB losses for follow-up in Southeast Asia. MATERIALS AND METHODS: This scoping review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework developed by the Joanna Briggs Institute (JBI). A total of 10 studies were identified as eligible from the title and abstract review. The mixed method quality appraisal tool (MMAT) version 2018 was used to assess the quality of the included quantitative studies. RESULTS: The results showed that poverty, unemployment, low education levels, migrant status, community support, male gender, substance abuse, and regional disparities significantly impact the occurrence of TB LTFU in Southeast Asia. CONCLUSION: The findings have significant implications for public health in Southeast Asia. Addressing these socioeconomic barriers through community-based strategies, educational initiatives, and policy reforms is vital for improving treatment outcomes and overall public health.


Asunto(s)
Factores Socioeconómicos , Tuberculosis , Humanos , Asia Sudoriental/epidemiología , Tuberculosis/epidemiología , Perdida de Seguimiento , Masculino
2.
Cancers (Basel) ; 16(13)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39001524

RESUMEN

Early cancer detection and accurate monitoring are crucial to ensure increased patient survival. Recent research has focused on developing non-invasive biomarkers to diagnose cancer early and monitor disease progression at low cost and risk. Extracellular vesicles (EVs), nanosized particles secreted into extracellular spaces by most cell types, are gaining immense popularity as novel biomarker candidates for liquid cancer biopsy, as they can transport bioactive cargo to distant sites and facilitate intercellular communications. A literature search was conducted to discuss the current approaches for EV isolation and the advances in using EV-associated proteins, miRNA, mRNA, DNA, and lipids as liquid biopsies. We discussed the advantages and challenges of using these vesicles in clinical applications. Moreover, recent advancements in machine learning as a novel tool for tumor marker discovery are also highlighted.

3.
Am J Cancer Res ; 14(5): 1957-1980, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38859839

RESUMEN

Cancer disease is the second leading cause of death worldwide. In 2023, about 2 million new cancer cases and 609,820 cancer deaths are projected to occur in the United States. The driving forces of cancer progression and metastasis are widely varied and comprise multifactorial events. Although there is significant success in treating cancer, patients still present with tumors at advanced stages. Therefore, the discovery of novel oncologic pathways has been widely developed. Tumor cells communicate with each other through small extracellular vesicles (sEVs), which contribute to tumor-stromal interaction and promote tumor growth and metastasis. sEV-specific inhibitors are being investigated as a next-generation cancer therapy. A literature search was conducted to discuss different options for targeting sEV pathways in cancer cells. However, there are some challenges that need to be addressed in targeting sEVs: i) specificity and toxicity of sEV inhibitor, ii) targeted delivery of sEV inhibitors, iii) combination of sEV inhibitors with current standard chemotherapy to improve patients' clinical outcomes, and iv) data reproducibility and applicability at distinct levels of the disease. Despite these challenges, sEV inhibitors have immense potential for effectively treating cancer patients.

4.
Front Public Health ; 12: 1271816, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628856

RESUMEN

Background: Benign prostatic hyperplasia (BPH) is a prevalent condition in older men, causing significant morbidity. Despite recent progress, essential concerns of the disease remain under-researched. This study aims to assess knowledge and estimate self-reported prevalence of BPH in Saudi Arabian men. Understanding BPH prevalence in Saudi Arabia is essential for healthcare planning, resource allocation, public awareness, early detection, intervention, research, and addressing regional variations. Method: A cross-sectional study was conducted from February to May 2022 using a validated questionnaire. Univariate and multivariate statistical methods assessed knowledge of BPH among 559 adult Saudi men (mean age: 47.2 years) and its association with demographic variables. Results: The self-reported prevalence rate of BPH for Saudi Arabian men was 12.0%. Most adults (74.2%) were aware that BPH is a risk factor for prostate cancer and 75% were aware of the increased risk of BPH in older people. Furthermore, 44.5% of participants associated nocturia with BPH, while 76.6% related urinary tract infection (UTI) with BPH. The study demonstrated a significant association between BPH awareness and marital status (p = 0.02), level of education (p = 0.02), and employment status (p = 0.04). Conclusion: While men in Saudi Arabia generally had sufficient knowledge about BPH, there was a knowledge gap regarding certain risk factors like obesity and cardiac diseases. To address this, an educational program should be developed for both the general population and those at high risk of BPH.


Asunto(s)
Hiperplasia Prostática , Masculino , Adulto , Humanos , Anciano , Persona de Mediana Edad , Arabia Saudita/epidemiología , Hiperplasia Prostática/epidemiología , Hiperplasia Prostática/complicaciones , Estudios Transversales , Autoinforme , Prevalencia
5.
Cureus ; 16(1): e51787, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38322089

RESUMEN

Cognitive dysfunction and behavioral change can be some of the manifestations of cancer, occurring as a part of paraneoplastic neurological syndrome, most commonly in small cell lung cancer. Paraneoplastic limbic encephalitis is the leading cause of cognitive disturbance and abnormal behavior in paraneoplastic syndromes, which is usually autoantibody-mediated. Autoantibodies are the main contributors to the development of cognitive dysfunction and behavioral change in cancer patients, with studies suggesting a higher liability for antibody-positive cancer patients to be affected. Anti-NMDAR and anti-AMPAR are antibodies targeted against surface antigens, manifesting predominantly as memory disturbance, abnormal behavior, psychiatric symptoms, and seizures. Other surface antigen-targeted antibodies include anti-GABA, anti-CASPR2, and anti-LGI1, which were shown to have cognitive function impairment and abnormal behavior as some of the main presentations, predominantly affecting memory. Cognitive deterioration and changes in behavior were also relatively common with some of the intracellular antigen-targeted antibodies, including anti-Hu, anti-SOX1, anti-PCA2, and anti-Zic2. Affected behavior and cognition, however, were reported less commonly in other paraneoplastic antibodies against intracellular antigens (anti-Yo, anti-GAD, anti-Ma2, anti-Ri, anti-CV2, and anti-KLHL11). Our article will provide a comprehensive review of the clinical manifestations of cognitive impairment and behavioral changes among cancer patients who develop paraneoplastic syndrome. Additionally, this review will discuss the role of specific paraneoplastic autoantibodies and the clinical spectrum linked to each separately.

6.
Cureus ; 15(11): e48398, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38073910

RESUMEN

BACKGROUND: Psoriasis is a worldwide disease. It is a chronic immune-mediated inflammatory disease with cutaneous and systemic symptoms that is characterized by erythematous squamous plaques. OBJECTIVES: To study the perception and assessment of psoriasis among the general population of Jazan, Saudi Arabia. MATERIALS AND METHODS: This was a cross-sectional study that used a self-administrated electronically distributed questionnaire that enrolled 410 people. RESULTS: Most participants (79%) were familiar with the term "psoriasis," with family, friends, or acquaintances being the primary source of knowledge. Personal experience with psoriasis was reported by 28.3% of participants, with women being more likely to know someone with the condition. If affected by psoriasis, the majority of respondents would consult a dermatologist (89.3%). Although 48% of participants considered psoriasis to be a significant burden for affected individuals, negative attitudes and discrimination towards those with the condition were prevalent, with a significant proportion stating that they would not want to eat at the same table, shake hands, or be in a personal relationship with someone with psoriasis. Additionally, most participants reported feeling sorry for psoriasis patients but also expressed disgust towards them. Awareness of public actions related to psoriasis was generally low, with only a small percentage of participants familiar with the WHO resolution on psoriasis or World Psoriasis Day. CONCLUSION: This study highlights the need for increased education and awareness about psoriasis to address misunderstandings and reduce the burden of the condition on patients. Additionally, efforts are needed to reduce stigma and discrimination towards those with psoriasis, which can significantly impact their quality of life.

7.
Nano Lett ; 23(22): 10132-10139, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37909501

RESUMEN

Nanomotors in solution have many potential applications. However, it has been a significant challenge to realize the directional motion of nanomotors. Here, we report cadmium chloride tetrahydrate (CdCl2·4H2O) nanomotors with remarkable directional movement under electron beam irradiation. Using in situ liquid phase transmission electron microscopy, we show that the CdCl2·4H2O nanoparticle with asymmetric surface facets moves through the liquid with the flat end in the direction of motion. As the nanomotor morphology changes, the speed of movement also changes. Finite element simulation of the electric field and fluid velocity distribution around the nanomotor assists the understanding of ionic self-diffusiophoresis as a driving force for the nanomotor movement; the nanomotor generates its own local ion concentration gradient due to different chemical reactivities on different facets.

8.
ACS Appl Mater Interfaces ; 15(40): 47649-47660, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37782678

RESUMEN

Intercalation is the process of inserting chemical species into the heterointerfaces of two-dimensional (2D) layered materials. While much research has focused on the intercalation of metals and small gas molecules into graphene, the intercalation of larger molecules through the basal plane of graphene remains challenging. In this work, we present a new mechanism for intercalating large molecules through monolayer graphene to form confined oxide materials at the graphene-substrate heterointerface. We investigate the intercalation of phosphorus pentoxide (P2O5) molecules directly from the vapor phase and confirm the formation of confined P2O5 at the graphene-substrate heterointerface using various techniques. Density functional theory (DFT) corroborates the experimental results and reveals the intercalation mechanism, whereby P2O5 dissociates into small fragments catalyzed by defects in the graphene that then permeates through lattice defects and reacts at the heterointerface to form P2O5. This process can also be used to form new confined metal phosphates (e.g., 2D InPO4). While the focus of this study is on P2O5 intercalation, the possibility of intercalation from predissociated molecules catalyzed by defects in graphene may exist for other types of molecules as well. This in-depth study advances our understanding of intercalation routes of large molecules via the basal plane of graphene as well as heterointerface chemical reactions leading to the formation of distinctive confined complex oxide compounds.

9.
Pharmaceutics ; 15(10)2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37896179

RESUMEN

Parkinson's disease (PD) is a gradual deterioration of dopaminergic neurons, leading to motor impairments. Social isolation (SI), a recognized stressor, has recently gained attention as a potential influencing factor in the progress of neurodegenerative illnesses. We aimed to investigate the intricate relationship between SI and PD progression, both independently and in the presence of manganese chloride (MnCl2), while evaluating the punicalagin (PUN) therapeutic effects, a natural compound established for its cytoprotective, anti-inflammatory, and anti-apoptotic activities. In this five-week experiment, seven groups of male albino rats were organized: G1 (normal control), G2 (SI), G3 (MnCl2), G4 (SI + MnCl2), G5 (SI + PUN), G6 (MnCl2 + PUN), and G7 (SI + PUN + MnCl2). The results revealed significant changes in behavior, biochemistry, and histopathology in rats exposed to SI and/or MnCl2, with the most pronounced effects detected in the SI rats concurrently exposed to MnCl2. These effects were associated with augmented oxidative stress biomarkers and reduced antioxidant activity of the Nrf2/HO-1 pathway. Additionally, inflammatory pathways (HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1 and JAK-2/STAT-3) were upregulated, while dysregulation of signaling pathways (PI3K/AKT/GSK-3ß/CREB), sustained endoplasmic reticulum stress by activation PERK/CHOP/Bcl-2, and impaired autophagy (AMPK/SIRT-1/Beclin-1 axis) were observed. Apoptosis induction and a decrease in monoamine levels were also noted. Remarkably, treatment with PUN effectively alleviated behaviour, histopathological changes, and biochemical alterations induced by SI and/or MnCl2. These findings emphasize the role of SI in PD progress and propose PUN as a potential therapeutic intervention to mitigate PD. PUN's mechanisms of action involve modulation of pathways such as HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1, JAK-2/STAT-3, PI3K/AKT/GSK-3ß/CREB, AMPK/SIRT-1, Nrf2/HO-1, and PERK/CHOP/Bcl-2.

10.
Ann Hematol ; 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37736806

RESUMEN

Gene therapy represents a significant potential to revolutionize the field of hematology with applications in correcting genetic mutations, generating cell lines and animal models, and improving the feasibility and efficacy of cancer immunotherapy. Compared to different genetic engineering tools, clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated protein 9 (Cas9) emerged as an effective and versatile genetic editor with the ability to precisely modify the genome. The applications of genetic engineering in various hematological disorders have shown encouraging results. Monogenic hematological disorders can conceivably be corrected with single gene modification. Through the use of CRISPR-CAS9, restoration of functional red blood cells and hemostasis factors were successfully attained in sickle cell anemia, beta-thalassemia, and hemophilia disorders. Our understanding of hemato-oncology has been advanced via CRIPSR-CAS9 technology. CRISPR-CAS9 aided to build a platform of mutated genes responsible for cell survival and proliferation in leukemia. Therapeutic application of CRISPR-CAS9 when combined with chimeric antigen receptor (CAR) T cell therapy in multiple myeloma and acute lymphoblastic leukemia was feasible with attenuation of CAR T cell therapy pitfalls. Our review outlines the latest literature on the utilization of CRISPR-Cas9 in the treatment of beta-hemoglobinopathies and hemophilia disorders. We present the strategies that were employed and the findings of preclinical and clinical trials. Also, the review will discuss gene engineering in the field of hemato-oncology as a proper tool to facilitate and overcome the drawbacks of chimeric antigen receptor T cell therapy (CAR-T).

11.
ACS Sens ; 8(9): 3370-3379, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37642461

RESUMEN

Herein, we develop colorimetric multigas sensor arrays assembling chemo-reactive fluorescent patch arrays and 10 × 10 indium gallium zinc oxide phototransistor arrays and apply them to an artificial olfactory platform to recognize five different volatile organic compounds (VOCs). Porous nanofibers, coupled with two organic emitters and emitting fluorescence, rapidly respond to gas-phased VOCs and offer unique fluorescent patterns associated with particular gas conditions, including gas kinds, concentrations, and exposure times by forming patch arrays with different fluorophore component ratios. These VOC-induced fluorescent patterns could be quantified and amplified by indium gallium zinc oxide (IGZO) phototransistor arrays functioning as a signal-generating component, resulting in gas-fingerprint patterns regarding electrical signals. Thus, the pattern library associated with VOCs and their concentration enables us to determine each airborne analyte as the artificial olfactory platform. Therefore, this system could achieve rapid, early quantitative recognition of hazardous gases and be applied as a preventative, portable, and wearable multigas identifier in various fields.


Asunto(s)
Galio , Compuestos Orgánicos Volátiles , Óxido de Zinc , Colorimetría , Indio , Colorantes Fluorescentes , Gases
12.
Cureus ; 15(6): e40742, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37485097

RESUMEN

A promising future for oncology treatment has been brought about by the emergence of a novel approach utilizing oncolytic viruses in cancer immunotherapy. Oncolytic viruses are viruses that have been exploited genetically to assault malignant cells and activate a robust immune response. Several techniques have been developed to endow viruses with an oncolytic activity through genetic engineering. For instance, redirection capsid modification, stimulation of anti-neoplastic immune response, and genetically arming viruses with cytokines such as IL-12. Oncolytic viral clinical outcomes are sought after, particularly in more advanced cancers. The effectiveness and safety profile of the oncolytic virus in clinical studies with or without the combination of standard treatment (chemotherapy, radiotherapy, or primary excision) has been assessed using response evaluation criteria in solid tumors (RECIST). This review will comprehensively outline the most recent clinical applications and provide the results from various phases of clinical trials in a variety of cancers in the latest published literature.

13.
Artif Cells Nanomed Biotechnol ; 51(1): 361-370, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37524306

RESUMEN

BACKGROUND: Curcumin has been used in the treatment of several diseases; however, its low pharmacologic profile reduces its therapeutic use. Towards improving its biological activity, nanoformulations have emerged. Thus, we aimed to determine whether curcumin nanoparticles (Cur-NPs) coated with PEG/chitosan improve the treatment of liver cancer (LC) cells and underpin the molecular mechanisms underlying their anti-cancer activity. METHODS: Cur-NPs were synthesised in the form of Cur-PLGA-PEG/chitosan NPs. The effect of Cur-NPs was assessed in HepG2 and Huh 7 LC cells and THLE-2 normal liver cells. RESULTS: The size of synthesised Cur-NPS was determined in the standard range of 141.2 ± 47.5 nm. Compared to THLE-2 cells, LC cells treated with Cur-NPs exerted cytotoxicity at 6.25 µg/mL after 48h. Treatment of HepG-2 cells with 2.5 µg/mL of Cur-NPs inhibited cell migration and this inhibition was augmented at 10 µg/mL (p < 0.001). Treatment of chicken embryo with 5 µg/mL Cur-NPs reduced angiogenesis (p < 0.001) of 4-day-old embryos. The nanoformulation upregulated Bax and p53 and downregulated Bcl-2 in a concentration-dependent manner and subsequently induce apoptosis in HepG-2 cells. CONCLUSION: Treatment of LC cells with Cur-NPs decreased cell proliferation, migration, and angiogenesis, and induced cell death by promoting the proapoptotic pathway.


Curcumin nanoparticles (Cur-NPs) increase the anticancer efficiency of Curcumin against liver cancer cells.Cur-NPs induce apoptotic cell death of Liver cancer cells.Cur-NPs have ant-angiogenesis and metastasis effect.


Asunto(s)
Quitosano , Curcumina , Neoplasias Hepáticas , Nanopartículas , Embrión de Pollo , Animales , Curcumina/farmacología , Curcumina/uso terapéutico , Línea Celular Tumoral , Quitosano/farmacología , Apoptosis , Neoplasias Hepáticas/tratamiento farmacológico
14.
Sci Rep ; 13(1): 9100, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37277370

RESUMEN

The perovskite solar cells (PSCs) are still facing the two main challenges of stability and scalability to meet the requirements for their potential commercialization. Therefore, developing a uniform, efficient, high quality and cost-effective electron transport layer (ETL) thin film to achieve a stable PSC is one of the key factors to address these main issues. Magnetron sputtering deposition has been widely used for its high quality thin film deposition as well as its ability to deposit films uniformly on large area at the industrial scale. In this work, we report on the composition, structural, chemical state, and electronic properties of moderate temperature radio frequency (RF) sputtered SnO2. Ar and O2 are employed as plasma-sputtering and reactive gases, respectively. We demonstrate the possibility to grow a high quality and stable SnO2 thin films with high transport properties by reactive RF magnetron sputtering. Our findings show that PSC devices based on the sputtered SnO2 ETL have reached a power conversion efficiency up to 17.10% and an average operational lifetime over 200 h. These uniform sputtered SnO2 thin films with improved characteristics are promising for large photovoltaic modules and advanced optoelectronic devices.

15.
Int J Mol Sci ; 24(9)2023 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-37176114

RESUMEN

The adaptive acquisition of resistance to BRAF and MEK inhibitor-based therapy is a common feature of melanoma cells and contributes to poor patient treatment outcomes. Leveraging insights from a proteomic study and publicly available transcriptomic data, we evaluated the predictive capacity of a gene panel corresponding to proteins differentially abundant between treatment-sensitive and treatment-resistant cell lines, deciphering predictors of treatment resistance and potential resistance mechanisms to BRAF/MEK inhibitor therapy in patient biopsy samples. From our analysis, a 13-gene signature panel, in both test and validation datasets, could identify treatment-resistant or progressed melanoma cases with an accuracy and sensitivity of over 70%. The dysregulation of HMOX1, ICAM, MMP2, and SPARC defined a BRAF/MEK treatment-resistant landscape, with resistant cases showing a >2-fold risk of expression of these genes. Furthermore, we utilized a combination of functional enrichment- and gene expression-derived scores to model and identify pathways, such as HMOX1-mediated mitochondrial stress response, as potential key drivers of the emergence of a BRAF/MEK inhibitor-resistant state in melanoma cells. Overall, our results highlight the utility of these genes in predicting treatment outcomes and the underlying mechanisms that can be targeted to reduce the development of resistance to BRAF/MEK targeted therapy.


Asunto(s)
Melanoma , Proteínas Proto-Oncogénicas B-raf , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Proteómica , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo
16.
Aging Dis ; 14(3): 992-1012, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37191407

RESUMEN

Aging modifies risk in all cancers, but age is used as a clinical staging criterion uniquely in thyroid cancer (TC). The molecular drivers of age-dependent TC onset and aggressiveness remain poorly understood. We applied an integrative, multi-omics data analysis approach to characterize these signatures. Our analysis reveals that aging, independent of BRAFV600E mutational status, drives a significant accumulation of aggressiveness-related markers and poorer survival outcomes, most noticeably at age 55 and over. We identified that chromosomal alterations in loci 1p/1q as aging-associated drivers of aggressiveness, and that depleted infiltration with tumor surveillant CD8+T and follicular helper T cells, dysregulation of proteostasis- and senescence-related processes, and ERK1/2 signaling cascade are key features of the aging thyroid and TC onset/progression and aggressiveness in aging patients but not in young individuals. A panel of 23 genes, including those related to cell division such as CENPF, ERCC6L, and the kinases MELK and NEK2, were identified and rigorously characterized as aging-dependent and aggressiveness-specific markers. These genes effectively stratified patients into aggressive clusters with distinct phenotypic enrichment and genomic/transcriptomic profiles. This panel also showed excellent performance in predicting metastasis stage, BRAFV600E, TERT promoter mutation, and survival outcomes and was superior to the American Thyroid Association (ATA) methodology in predicting aggressiveness risk. Our analysis established clinically relevant biomarkers for TC aggressiveness factoring in aging as an important component.

17.
ACS Nano ; 17(8): 7685-7694, 2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37043483

RESUMEN

Monolayer transition metal dichalcogenide (TMDC) semiconductors exhibit strong excitonic optical resonances, which serve as a microscopic, noninvasive probe into their fundamental properties. Like the hydrogen atom, such excitons can exhibit an entire Rydberg series of resonances. Excitons have been extensively studied in most TMDCs (MoS2, MoSe2, WS2, and WSe2), but detailed exploration of excitonic phenomena has been lacking in the important TMDC material molybdenum ditelluride (MoTe2). Here, we report an experimental investigation of excitonic luminescence properties of monolayer MoTe2 to understand the excitonic Rydberg series, up to 3s. We report a significant modification of emission energies with temperature (4 to 300 K), thereby quantifying the exciton-phonon coupling. Furthermore, we observe a strongly gate-tunable exciton-trion interplay for all the Rydberg states governed mainly by free-carrier screening, Pauli blocking, and band gap renormalization in agreement with the results of first-principles GW plus Bethe-Salpeter equation approach calculations. Our results help bring monolayer MoTe2 closer to its potential applications in near-infrared optoelectronics and photonic devices.

18.
Mar Drugs ; 21(4)2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-37103355

RESUMEN

Metastatic castration-resistant prostate cancer (mCRPC) cells can de novo biosynthesize their own cholesterol and overexpress proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 proved to contribute to mCRPC cell motility since PCSK9 knockdown (KD) in mCRPC CWR-R1ca cells led to notable reductions in cell migration and colony formation. Human tissue microarray results proved a higher immunohistoscore in patients ≥ 65 years old, and PCSK9 proved to be expressed higher at an early Gleason score of ≤7. The fermentation product pseurotin A (PS) suppressed PCSK9 expression, protein-protein interactions with LDLR, and breast and prostate cancer recurrences. PS suppressed migration and colony formation of the CWR-R1ca cells. The progression and metastasis of the CWR-R1ca-Luc cells subcutaneously (sc) xenografted into male nude mice fed a high-fat diet (HFD, 11% fat content) showed nearly 2-fold tumor volume, metastasis, serum cholesterol, low-density lipoprotein cholesterol (LDL-C), prostate-specific antigen (PSA), and PCSK9 levels versus mice fed a regular chow diet. Daily oral PS 10 mg/kg treatments prevented the locoregional and distant tumor recurrence of CWR-R1ca-Luc engrafted into nude mice after primary tumor surgical excision. PS-treated mice showed a significant reduction in serum cholesterol, LDL-C, PCSK9, and PSA levels. These results comprehensively validate PS as an mCRPC recurrence-suppressive lead by modulating the PCSK9-LDLR axis.


Asunto(s)
Proproteína Convertasa 9 , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Ratones , Animales , Anciano , Proproteína Convertasa 9/genética , Proproteína Convertasa 9/metabolismo , Ratones Desnudos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Serina Endopeptidasas/metabolismo , Proproteína Convertasas/metabolismo , Antígeno Prostático Específico , Receptores de LDL/genética , Receptores de LDL/metabolismo , Colesterol
19.
Artículo en Inglés | MEDLINE | ID: mdl-36728152

RESUMEN

Achieving control over the motion of dissolved particles in liquid metals is of importance for the meticulous realization of hierarchical particle assemblies in a variety of nanofabrication processes. Brownian forces can impede the motion of such particles, impacting the degree of perfection that can be realized in assembled structures. Here, we show that light-induced Marangoni flow in liquid metals (i.e., liquid-gallium) with Laguerre-Gaussian (LGpl) lasers as heating sources is an effective approach to overcome Brownian forces on particles, giving rise to predictable assemblies with a high degree of order. We show that by carefully engineering surface tension gradients in liquid-gallium using non-Gaussian LGpl lasers, the Marangoni and convective flow that develops in the fluid drives the trajectory of randomly dispersed particles to assemble into 100 µm wide ring-shaped particle assemblies. Careful control over the parameters of the LGpl laser (i.e., laser mode, spot size, and intensity of the electric field) can tune the temperature and fluid dynamics of the liquid-gallium as well as the balance of forces on the particle. This in turn can tune the structure of the ring-shaped particle assembly with a high degree of fidelity. The use of light to control the motion of particles in liquid metals represents a tunable and rapidly reconfigurable approach to spatially design surface tension gradients in fluids for more complex assembly of particles and small-scale solutes. This work can be extended to a variety of liquid metals, complementary to what has been realized in particle assembly out of ferrofluids using magnetic fields.

20.
Environ Toxicol ; 38(2): 266-277, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36447373

RESUMEN

Prodigiosin (PDG) is a bacterial metabolite with numerous biological and pharmaceutical properties. Exposure to aluminium is considered a root etiological factor in the pathological progress of Alzheimer's disease (AD). Here, in this investigation, we explored the neuroprotective potential of PDG against aluminium chloride (AlCl3 )-mediated AD-like neurological alterations in rats. For this purpose, rats were gavaged either AlCl3 (100 mg/kg), PDG (300 mg/kg), or both for 42 days. As a result of the analyzes performed on the hippocampal tissue, it was observed that AlCl3 induced biochemical, molecular, and histopathological changes like those related to AD. PDG pre-treatment significantly decreased acetylcholinesterase activity and restored the levels of brain-derived neurotrophic factor, monoamines (dopamine, norepinephrine, and serotonin), and transmembrane protein (Na+ /K+ -ATPase). Furthermore, PDG boosted the hippocampal antioxidant capacity, as shown by the increased superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents. These findings were accompanied by decreases in malondialdehyde and nitric oxide levels. The antioxidant effect may promote the upregulation of the expression of antioxidant genes (Nrf2 and HO-1). Moreover, PDG exerted notable anti-inflammatory effects via the lessening of interleukin-1 beta, tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor kappa B, and decreases in the gene expression of inducible nitric oxide synthase. In addition, noteworthy decreases in pro-apoptotic (Bax and caspase-3) levels and increases in anti-apoptotic (Bcl-2) biomarkers suggested an anti-apoptotic effect of PDG. In support, the hippocampal histological examination validated the aforementioned changes. To summarize, the promising neuromodulatory, antioxidative, anti-inflammatory, and anti-apoptotic activities of PDG establish it as a potent therapeutic option for AD.


Asunto(s)
Enfermedad de Alzheimer , Fármacos Neuroprotectores , Animales , Ratas , Acetilcolinesterasa/metabolismo , Cloruro de Aluminio/toxicidad , Cloruro de Aluminio/uso terapéutico , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Glutatión/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo , Prodigiosina/metabolismo , Prodigiosina/farmacología , Prodigiosina/uso terapéutico
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