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Oncotarget Jun 2024Prostate cancer (PCa) poses significant challenges in treatment, particularly when it progresses to a metastatic, castrate-resistant state. Conventional therapies,... (Review)
Review
Prostate cancer (PCa) poses significant challenges in treatment, particularly when it progresses to a metastatic, castrate-resistant state. Conventional therapies, including chemotherapy, radiotherapy, and hormonal treatments, often fail due to toxicities, off-target effects, and acquired resistance. This research perspective defines an alternative therapeutic strategy focusing on the metabolic vulnerabilities of PCa cells, specifically their reliance on non-essential amino acids such as cysteine. Using an engineered enzyme cyst(e)inase to deplete the cysteine/cystine can induce oxidative stress and DNA damage in cancer cells. This depletion elevates reactive oxygen species (ROS) levels, disrupts glutathione synthesis, and enhances DNA damage, leading to cancer cell death. The combinatorial use of cyst(e)inase with agents targeting antioxidant defenses, such as thioredoxins, further amplifies ROS accumulation and cytotoxicity in PCa cells. Overall, in this perspective provides a compressive overview of the previous work on manipulating amino acid metabolism and redox balance modulate the efficacy of DNA repair-targeted and immune checkpoint blockade therapies in prostate cancer.
Topics: Humans; DNA Damage; Immunotherapy; Prostatic Neoplasms; Reactive Oxygen Species; Male; Oxidative Stress; DNA Repair; Animals; Cysteine
PubMed: 38900609
DOI: 10.18632/oncotarget.28595 -
RSC Pharmaceutics Jun 2024Mitonafide-loaded liposomes are a promising strategy to overcome the neurotoxicity observed in clinical trials for this drug. This study investigates the influence of...
Mitonafide-loaded liposomes are a promising strategy to overcome the neurotoxicity observed in clinical trials for this drug. This study investigates the influence of loaded mitonafide or a dimer analogue on different liposomal formulations and their therapeutic efficacy . Physicochemical properties of the liposomes were manipulated using different loading methods (namely bilayer or core loading) and varying the rigidity of the bilayer using distinct phospholipid compositions. Our results demonstrated that the mitonafide dimer analogue had a comparable encapsulation efficiency (EE%) into the liposomes when loaded into rigid or flexible bilayers in contrast to the low mitonafide monomer EE%. A pH gradient core loading method resulted in a more efficient mechanism to load the monomer into the liposomes. DOSY NMR and spectrofluorometric studies revealed key differences in the structure of the vesicles and the arrangement of the monomer or the dimer in the bilayer or the core of the liposomes. The assessment of the formulations using MDA-MB-231 and RT-112 cells revealed that a flexible lipid bilayer allows a faster drug release, which correlated well with the spectroscopy studies. This study investigated for the first time that the characteristics of the lipid bilayer and the loading method influence the encapsulation efficacy, colloidal properties, photoactivity and stability of mono and bis-naphthalimides loaded in a liposomal carrier, essential factors that will impact the performance of the formulation in a biological scenario.
PubMed: 38899150
DOI: 10.1039/d3pm00060e -
Frontiers in Psychology 2024This study explores the stability of scores on psychometrically validated trait questionnaires over time. We illustrate potential pitfalls through a larger study that...
INTRODUCTION
This study explores the stability of scores on psychometrically validated trait questionnaires over time. We illustrate potential pitfalls through a larger study that used the Ruminative Response Scale (RRS) to categorize participants prior to study inclusion into two groups based on their habitual tendency to ruminate. Surprisingly, when we re-administered the RRS at the start of an experimental session, significant score changes occurred, resulting in participants shifting between the two groups.
METHODS
To address this, we modified our recruitment process, aiming to reduce careless responses, including an online RRS assessment a week before the lab appointment. We analyzed the different samples prior to and after changing the recruitment procedure, as well as the total sample regarding the psychometric properties of the RRS. We also explored various indices to identify and predict score changes due to careless responding; however, only a subgroup of participants was successfully identified.
RESULTS
Our findings suggest that Mahalanobis distances are effective for identifying substantial score changes, with baseline state rumination emerging as a marginally significant predictor.
DISCUSSION
We discuss the importance of conducting manipulation checks and offer practical implications for research involving psychometrically validated trait questionnaires.
PubMed: 38899126
DOI: 10.3389/fpsyg.2024.1368390 -
Applied Microbiology and Biotechnology Jun 2024Camptothecin (CPT), an indole alkaloid popular for its anticancer property, is considered the third most promising drug after taxol and famous alkaloids from Vinca for... (Review)
Review
Camptothecin (CPT), an indole alkaloid popular for its anticancer property, is considered the third most promising drug after taxol and famous alkaloids from Vinca for the treatment of cancer in humans. Camptothecin was first identified in Camptotheca acuminata followed by several other plant species and endophytic fungi. Increased harvesting driven by rising global demand is depleting the availability of elite plant genotypes, such as Camptotheca acuminata and Nothapodytes nimmoniana, crucial for producing alkaloids used in treating diseases like cancer. Conservation of these genotypes for the future is imperative. Therefore, research on different plant tissue culture techniques such as cell suspension culture, hairy roots, adventitious root culture, elicitation strategies, and endophytic fungi has been adopted for the production of CPT to meet the increasing demand without affecting the source plant's existence. Currently, another strategy to increase camptothecin yield by genetic manipulation is underway. The present review discusses the plants and endophytes that are employed for camptothecin production and throws light on the plant tissue culture techniques for the regeneration of plants, callus culture, and selection of cell lines for the highest camptothecin production. The review further explains the simple, accurate, and cost-effective extraction and quantification methods. There is enormous potential for the sustainable production of CPT which could be met by culturing of suitable endophytes or plant cell or organ culture in a bioreactor scale production. Also, different gene editing tools provide opportunities for engineering the biosynthetic pathway of CPT, and the overall CPT production can be improved . KEY POINTS: • Camptothecin is a naturally occurring alkaloid with potent anticancer properties, primarily known for its ability to inhibit DNA topoisomerase I. • Plants and endophytes offer a potential approach for camptothecin production. • Biotechnology approaches like plant tissue culture techniques enhanced camptothecin production.
Topics: Camptothecin; Biotechnology; Endophytes; Camptotheca; Antineoplastic Agents, Phytogenic; Humans
PubMed: 38896329
DOI: 10.1007/s00253-024-13187-2 -
BioRxiv : the Preprint Server For... Jun 2024Tools for acute manipulation of protein localization enable elucidation of spatiotemporally defined functions, but their reliance on exogenous triggers can interfere...
Tools for acute manipulation of protein localization enable elucidation of spatiotemporally defined functions, but their reliance on exogenous triggers can interfere with cell physiology. This limitation is particularly apparent for studying mitosis, whose highly choreographed events are sensitive to perturbations. Here we exploit the serendipitous discovery of a phosphorylation-controlled, cell cycle-dependent localization change of the adaptor protein PLEKHA5 to develop a system for mitosis-specific protein recruitment to the plasma membrane that requires no exogenous stimulus. Mitosis-enabled Anchor-away/Recruiter System (MARS) comprises an engineered, 15-kDa module derived from PLEKHA5 capable of recruiting functional protein cargoes to the plasma membrane during mitosis, either through direct fusion or via GFP-GFP nanobody interaction. Applications of MARS include both knock sideways to rapidly extract proteins from their native localizations during mitosis and conditional recruitment of lipid-metabolizing enzymes for mitosis-selective editing of plasma membrane lipid content, without the need for exogenous triggers or perturbative synchronization methods.
PubMed: 38895347
DOI: 10.1101/2024.06.05.597552 -
Materials (Basel, Switzerland) May 2024A novel method is introduced in this study for producing ceramisite coarse aggregates that are both lightweight and possess high strength. The process involves utilizing...
A novel method is introduced in this study for producing ceramisite coarse aggregates that are both lightweight and possess high strength. The process involves utilizing fly ash as the primary material, along with coal ash floating beads (CAFBs) that have high softening temperature and a spherical hollow structure serving as the template for forming pores. This study examined the impact of varying particle size and quantity of floating beads on the composition and characteristics of ceramisite aggregates. Results showed that the high softening temperature of floating beads provided stability to the spherical cavity structure throughout the sintering process. Furthermore, the pore structure could be effectively tailored by manipulating the size and quantity of the floating beads in the manufacturing procedure. The obtained ceramisite aggregates feature a compact outer shell and a cellular inner core with uniformly distributed pores that are isolated from each other and mostly spherical in form. They achieve a low density ranging from 723 to 855 kg/m, a high cylinder compressive strength between 8.7 and 13.5 MPa, and minimal water absorption rates of 3.00 to 4.09%. The performance metrics of these coarse aggregates significantly exceeded the parameters specified in GB/T 17431.1-2010 standards.
PubMed: 38893878
DOI: 10.3390/ma17112613 -
Materials (Basel, Switzerland) May 2024Two-dimensional (2D) violet phosphorus (VP) plays a significant role in the applications of photonic and optoelectronic devices due to its unique optical and electrical...
Two-dimensional (2D) violet phosphorus (VP) plays a significant role in the applications of photonic and optoelectronic devices due to its unique optical and electrical properties. The ultrafast carrier dynamics and nonlinear optical absorption properties were systematically investigated here. The intra- and inter-band ultrafast relaxation times of 2D VP nanosheets were measured to be ~6.83 ps and ~62.91 ps using the pump-probe method with a probe laser operating at 1.03 μm. The nonlinear absorption coefficient βeff, the saturation intensity Is, the modulation depth ΔR, and the nonsaturable loss were determined to be -2.18 × 10 cm/MW, 329 kW/cm, 6.3%, and 9.8%, respectively, by using the Z-scan and I-scan methods, indicating the tremendous saturable absorption property of 2D VP nanosheets. Furthermore, the passively Q-switched Nd:YVO laser was realized with the 2D VP nanosheet-based SA, in which the average output power of 700 mW and the pulse duration of 478 ns were obtained. These results effectively reveal the nonlinear optical absorption characteristics of VP nanosheets, demonstrating their outstanding light-manipulating capabilities and providing a basis for the applications of ultrafast optical devices. Our results verify the excellent saturable absorption properties of 2D VP, paving the way for its applications in pulsed laser generation.
PubMed: 38893849
DOI: 10.3390/ma17112585 -
Journal of Clinical Medicine May 2024Ophthalmic three-dimensional (3D) digital surgery can reproduce high-definition surgical images; however, 3D digital surgery is limited by recording capacities. We...
Ophthalmic three-dimensional (3D) digital surgery can reproduce high-definition surgical images; however, 3D digital surgery is limited by recording capacities. We examined the relationship between the minimum image quality required to reproduce surgical images and recording capacity. Patients who underwent simultaneous vitrectomy and cataract surgery by the same surgeon using a 3D digital surgery system at Juntendo University Urayasu Hospital between February and October 2021 were evaluated. Various quality (Q) and frame rate (FR) settings were used for each case. Four vitreous surgeons evaluated the reproducibility of recorded images of macular manipulation for epiretinal membrane (ERM) and macular hole (MH) cases and those of peripheral retinal manipulation for rhegmatogenous retinal detachment (RRD) cases. The video bitrate and minimum settings required to reproduce surgical images and factors affecting surgical image reproducibility were examined. A total of 129 eyes of 129 patients were observed. The minimum image quality required to reproduce surgical images was 11.67 Mbps. The Q and FR for periretinal processing and Q for macular manipulation affected surgical image reproducibility ( = 0.025, = 0.019, and = 0.07, respectively). The minimum recording settings required to obtain highly reproducible images were Q = 3 and FR = 40. The total file size for vitrectomy video recordings with these settings was as compact as 3.17 GB for 28 min. During 3D digital surgery, highly reproducible surgical images can be obtained with a small storage capacity using settings of at least Q = 3 and FR = 40.
PubMed: 38892762
DOI: 10.3390/jcm13113051 -
Nutrients May 2024Irritable bowel syndrome (IBS) symptoms can be effectively managed with the low FODMAP diet. However, its efficacy in reducing inflammation is not yet proven. On the...
INTRODUCTION
Irritable bowel syndrome (IBS) symptoms can be effectively managed with the low FODMAP diet. However, its efficacy in reducing inflammation is not yet proven. On the contrary, the Mediterranean diet has anti-inflammatory properties with proven efficacy in treating chronic low-grade inflammation-related diseases.
AIM
To publicly share our protocol evaluating the efficacy of the Mediterranean low-FODMAP (MED-LFD) versus NICE recommendations (British National Institute for Health and Care Excellence) diet in managing IBS symptoms and quality of life.
MATERIALS AND METHODS
Participants meeting the Rome IV criteria will be randomly assigned to MED-LFD or NICE recommendations and they will be followed for six months. Efficacy, symptom relief, quality of life and mental health will be assessed using validated questionnaires. In addition, fecal samples will be analyzed to assess gut microbiota, and to measure branched and short-chain fatty acids, and volatile organic compounds (metabolic byproducts from bacteria). Expected results and discussion: By publicly sharing this clinical study protocol, we aim to improve research quality in the field of IBS management by allowing for peer review feedback, preventing data manipulation, reducing redundant research efforts, mitigating publication bias, and empowering patient decision-making. We expect that this protocol will show that MED-LFD can effectively alleviate IBS symptoms and it will provide pathophysiology insights on its efficacy. The new dietary pattern that combines the LFD and the MED approaches allows for the observation of the synergistic action of both diets, with the MED's anti-inflammatory and prebiotic properties enhancing the effects of the LFD while minimizing its limitations. Identifier in Clinical Trials: NCT03997708.
Topics: Irritable Bowel Syndrome; Humans; Gastrointestinal Microbiome; Diet, Mediterranean; Quality of Life; Diet, Carbohydrate-Restricted; Feces; Treatment Outcome; Adult; Female; Randomized Controlled Trials as Topic; FODMAP Diet
PubMed: 38892525
DOI: 10.3390/nu16111592 -
International Journal of Molecular... Jun 2024This report describes major pathomechanisms of disease in which the dysregulation of host inflammatory processes is a major factor, with cardiovascular disease (CVD) as... (Review)
Review
This report describes major pathomechanisms of disease in which the dysregulation of host inflammatory processes is a major factor, with cardiovascular disease (CVD) as a primary model, and reviews strategies for countermeasures based on synergistic interaction between various agents, including drugs and generally regarded as safe (GRAS) natural medical material (NMM), such as , spice phytochemicals, and fruit seed flavonoids. The 15 well-defined CVD classes are explored with particular emphasis on the extent to which oxidative stressors and associated ischemia-reperfusion tissue injury contribute to major symptoms. The four major categories of pharmaceutical agents used for the prevention of and therapy for CVD: statins, beta blockers (β-blockers), blood thinners (anticoagulants), and aspirin, are presented along with their adverse effects. Analyses of major cellular and molecular features of drug- and NMM-mediated cardioprotective processes are provided in the context of their development for human clinical application. Future directions of the evolving research described here will be particularly focused on the characterization and manipulation of calcium- and calcineurin-mediated cascades of signaling from cell surface receptors on cardiovascular and immune cells to the nucleus, with the emergence of both protective and pathological epigenetic features that may be modulated by synergistically-acting combinations of drugs and phytochemicals in which phytochemicals interact with cells to promote signaling that reduces the effective dosage and thus (often) toxicity of drugs.
Topics: Humans; Phytochemicals; Cardiovascular Diseases; Animals
PubMed: 38892364
DOI: 10.3390/ijms25116176