-
European Journal of Nuclear Medicine... Jun 2024Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal...
Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.
PURPOSE
Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT.
METHODS
A propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test.
RESULTS
Median follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis.
CONCLUSIONS
Overall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.
PubMed: 38940843
DOI: 10.1007/s00259-024-06802-x -
The Science of the Total Environment Jun 2024Crystalline silica (CS) particles are ubiquitously present in the environment, particularly in occupational settings, and exposure to respirable CS causes silicosis,...
Crystalline silica (CS) particles are ubiquitously present in the environment, particularly in occupational settings, and exposure to respirable CS causes silicosis, imposing a significant disease burden. However, the pathogenesis of silicosis remains unclear. Exposure to external stimuli, such as CS, leads to the accumulation of unfolded proteins and triggers endoplasmic reticulum (ER) stress, disrupting tissue immune homeostasis and accelerating pathological progression. While pulmonary macrophages phagocytose CS particles to initiate the immune response, the role of ER stress in this process is unknown. Herein, we used a murine model of silicosis to simulate the pathological progression from acute inflammation to fibrosis in silicosis and conducted in vivo pharmacological inhibition of ER stress to explore the underlying mechanism. Using flow cytometry, we further classified pulmonary macrophages into monocyte-like macrophages (monocytes), interstitial macrophages (IMs), and alveolar macrophages (AMs). Our results showed that CS-induced ER stress primarily contributed to the augmentation of IMs and thereby exerted a significant impact on pulmonary macrophages. Despite coexpressing M1- and M2-like markers, IMs predominantly exhibited an M1-like polarization state and played a proinflammatory role by expressing the cytokines pro-IL-1β and TNF-α during the pathological progression of silicosis. Additionally, IMs recruited by CS-induced ER stress also exhibited high expression of MHCII and exerted active immunomodulatory effects. Overall, our study demonstrates that ER stress induced by CS particles triggers a proinflammatory immune microenvironment dominated by IMs and reveals novel insights into the pulmonary toxicological effects of CS particles.
PubMed: 38936737
DOI: 10.1016/j.scitotenv.2024.174299 -
Hepatology Communications Jul 2024Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the... (Observational Study)
Observational Study
BACKGROUND
Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs.
METHODS
We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT.
RESULTS
One hundred twenty-seven patients were included (male = 90%, 64 ± 11 y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61 mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline α-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014).
CONCLUSIONS
These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.
Topics: Humans; Liver Neoplasms; Male; Carcinoma, Hepatocellular; Female; Middle Aged; Retrospective Studies; Aged; Neoplasm Staging; Brachytherapy; Yttrium Radioisotopes; Treatment Outcome
PubMed: 38934702
DOI: 10.1097/HC9.0000000000000475 -
Pharmaceutics May 2024Astatine-211 (At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in... (Review)
Review
Astatine-211 (At) has emerged as a promising radionuclide for targeted alpha therapy of cancer by virtue of its favorable nuclear properties. However, the limited in vivo stability of At-labeled radiopharmaceuticals remains a major challenge. This review provides a comprehensive overview of the current strategies for At radiolabeling, including nucleophilic and electrophilic substitution reactions, as well as the recent advances in the development of novel bifunctional coupling agents and labeling approaches to enhance the stability of At-labeled compounds. The preclinical and clinical applications of At-labeled radiopharmaceuticals, including small molecules, peptides, and antibodies, are also discussed. Looking forward, the identification of new molecular targets, the optimization of At production and quality control methods, and the continued evaluation of At-labeled radiopharmaceuticals in preclinical and clinical settings will be the key to realizing the full potential of At-based targeted alpha therapy. With the growing interest and investment in this field, At-labeled radiopharmaceuticals are poised to play an increasingly important role in future cancer treatment.
PubMed: 38931860
DOI: 10.3390/pharmaceutics16060738 -
Sensors (Basel, Switzerland) Jun 2024Heavy nuclides like uranium and their decay products are commonly found in nuclear industries and can pose a significant health risk to humans due to their...
Heavy nuclides like uranium and their decay products are commonly found in nuclear industries and can pose a significant health risk to humans due to their alpha-emitting properties. Traditional alpha detectors require close contact with the contaminated surface, which can be time-consuming, labour-intensive, and put personnel at risk. Remote detection is urgently needed but very challenging. To this end, a candidate detection mechanism is alpha-induced radio-luminescence. This approach uses the emission of photons from radio-ionised excited nitrogen molecules to imply the presence of alpha emitters from a distance. Herein, the use of this phenomenon to remotely image various alpha emitters with unparalleled levels of sensitivity and spatial accuracy is demonstrated. Notably, the system detected a 29 kBq Am-241 source at a distance of 3 m within 10 min. Furthermore, it demonstrated the capability to discern a 29 kBq source positioned 7 cm away from a 3 MBq source at a 2 m distance. Additionally, a 'sandwich' filter structure is described that incorporates an absorptive filter between two interference filters to enhance the ambient light rejection. The testing of the system is described in different lighting environments, including room light and inside a glovebox. This method promises safer and more efficient alpha monitoring, with applications in nuclear forensics, waste management and decommissioning.
PubMed: 38931565
DOI: 10.3390/s24123781 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic...
Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated from a Chinese medicinal herb with various pharmacological activities, such as anti-inflammatory and analgesic properties. However, the underlying mechanisms of these effects are not fully understood. In the present study, we aimed to investigate DAP's anti-inflammatory and analgesic effects and explore the underlying mechanisms of action. The NP model was established as chronic constrictive injury (CCI) of the sciatic nerve, and pain sensitivity was evaluated by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). The activation of microglia in the spinal dorsal horn was measured via immunofluorescence staining. Protein levels were measured using a western blot assay. Using a mass-spectrometry proteomics platform and an LC-MS/MS-based metabolomics platform, proteins and metabolites in spinal cord tissues were extracted and analyzed. DAP treatment ameliorated the MWT and TWT in CCI rats. The expression of IL-1β, IL-6, and TNF-α was inhibited by DAP treatment in the spinal cords of CCI rats. Moreover, the activation of microglia was suppressed after DAP treatment. The elevation in the levels of P2X, IRF8, IRF5, BDNF, and p-P38/P38 in the spinal cord caused by CCI was inhibited by DAP. Proteomics and metabolomics results indicated that DAP ameliorated the imbalance of glycerophospholipid metabolism in the spinal cords of CCI rats. DAP can potentially ameliorate NP by regulating microglial responses and glycerophospholipid metabolism in the CCI model. This study provides a pharmacological justification for using DAP in the management of NP.
PubMed: 38931456
DOI: 10.3390/ph17060789 -
Plants (Basel, Switzerland) Jun 2024Lamiaceae is a botanical family rich in aromatic species that are in high demand such as basil, lavender, mint, oregano, sage, and thyme. It has great economical,... (Review)
Review
Lamiaceae is a botanical family rich in aromatic species that are in high demand such as basil, lavender, mint, oregano, sage, and thyme. It has great economical, ecological, ethnobotanical, and floristic importance. The aim of this work is to provide an updated view on the aerobiology of species from the family Lamiaceae, with an emphasis on novelties and emerging applications. From the aerobiology point of view, the greatest interest in this botanical family is related to the volatile organic compounds emitted by the plants and, to a much lesser extent, their pollen. Research has shown that the major volatile organic compounds emitted by the plants from this botanical family are monoterpenes and sesquiterpenes. The most important monoterpenes reported across studies include α-pinene, β-pinene, 1,8-cineole, menthol, limonene, and γ-terpinene. Most reports tend to cover species from the subfamily Nepetoideae. Volatile oils are produced by glandular trichomes found on aerial organs. Based on general morphology, two main types are found in the family Lamiaceae, namely peltate and capitate trichomes. As a result of pollinator-mediated transfer of pollen, Lamiaceae species present a reduced number of stamens and quantity of pollen. This might explain the low probability of pollen presence in the air from these species. A preliminary synopsis of the experimental evidence presented in this work suggests that the interplay of the organic particles and molecules released by these plants and their environment could be leveraged for beneficial outcomes in agriculture and landscaping. Emerging reports propose their use for intercropping to ensure the success of fructification, increased yield of entomophilous crops, as well as in sensory gardens due to the therapeutic effect of volatiles.
PubMed: 38931119
DOI: 10.3390/plants13121687 -
Micromachines May 2024Magnetic abrasive finishing (MAF) is an efficient finishing process method using magnetic abrasive particles (MAPs) as finishing tools. In this study, two iron-based...
Magnetic abrasive finishing (MAF) is an efficient finishing process method using magnetic abrasive particles (MAPs) as finishing tools. In this study, two iron-based alumina magnetic abrasives with different particle size ranges were synthesized by the plasma molten metal powder and powder jetting method. Characterization of the magnetic abrasives in terms of microscopic morphology, phase composition, magnetic permeability, particle size distribution, and abrasive ability shows that the magnetic abrasives are spherical in shape, that the hard abrasives are combined in the surface layer of the iron matrix and remain sharp, and that the hard abrasives combined in the surface layer of the magnetic abrasives with smaller particle sizes are sparser than those of the magnetic abrasives with larger particle sizes. The magnetic abrasives are composed of α-Fe and AlO; the magnetic permeability of the magnetic abrasives having smaller particle sizes is slightly higher than that of the magnetic abrasives having larger particle sizes; the two magnetic abrasives are distributed in a range of different particle sizes; the magnetic abrasives have different magnetic permeabilities, which are higher than those of the larger ones; both magnetic abrasives are distributed in the range of smaller particle sizes; and AZ31B alloy can obtain smaller surface roughness of the workpiece after the grinding process of the magnetic abrasives with a small particle size.
PubMed: 38930679
DOI: 10.3390/mi15060709 -
Materials (Basel, Switzerland) Jun 2024This study reveals the relationship between the Cu precipitates and mechanical properties of a Cu-baring ultra-low carbon steel after two-phase zone quenching and...
This study reveals the relationship between the Cu precipitates and mechanical properties of a Cu-baring ultra-low carbon steel after two-phase zone quenching and tempering at 923 K for 0.5-2.5 h. The tensile and microstructural properties were investigated as a function of heat treatment time. The contribution of the precipitation-strengthening mechanism to yield strength was calculated. The size, morphology, and distribution of the precipitated particles were observed using TEM. As the heat treatment time increased, the strength gradually decreased and then remained stable, and the elongation gradually increased and then remained stable. Additionally, the contributions of each strengthening mechanism to the yield strength under different heat treatments were 117, 107, 102, and 89 MPa, respectively. The size and quantity of the precipitates increased with the increase in heat treatment time. After tempering for more than 2 h, the precipitates continued to coarsen, but their quantity decreased. The precipitated Cu had a 3R structure with a length of approximately 17.1 nm and a width of approximately 9.7 nm, with no twinning inside. The stacking order was ABC/ABC. The stable Cu precipitation structure was FCC, maintaining a K-S orientation relationship 11¯1 //(0 1 1) , 1¯10//[11¯1] .
PubMed: 38930400
DOI: 10.3390/ma17123031 -
Antioxidants (Basel, Switzerland) Jun 2024Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders....
Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders. This study investigated the ethanolic extract of fruits for its phenolic and flavonoid contents, antioxidant activity, and impact on melanogenesis pathways using qRT-PCR and Western blot analysis. Utilizing network pharmacology, molecular docking, and dynamics simulations, researchers explored fruit extract's active compounds, targets, and pharmacological effects on hyperpigmentation. fruit extract exhibited antioxidant properties, scavenging DPPH and ABTS radicals radicals and chelating copper. It inhibited cellular tyrosinase activity and melanin content in stimulated B16F10 cells, downregulating TYR, TRP-1, phosphorylated CREB, CREB, and MITF proteins along with transcription levels of MITF, TYR, and TRP-2. LC-MS analysis identified thirty-three metabolites, with seventeen compounds selected for further investigation. Network pharmacology revealed 41 hyperpigmentation-associated genes and identified significant GO terms and KEGG pathways, including cancer-related pathways. Kaempferol-3-O-α-L-rhamnoside exhibited high binding affinity against MAPK3/ERK1, potentially regulating melanogenesis by inhibiting tyrosinase activity. Stable ligand-protein interactions in molecular dynamics simulations supported these findings. Overall, this study suggests that the ethanolic extract of fruits possesses significant antioxidant, tyrosinase inhibitory, and anti-melanogenic properties mediated through key molecular targets and pathways.
PubMed: 38929152
DOI: 10.3390/antiox13060713