Biological Effects Research Articles

Biochemistry and Clinical Significance of Il-3: A Review Article

Interleukin-3 (IL-3) is a cytokine of many activities, centrally important for hematopoiesis and regulation of immune responses. It is produced by activated T cells and mast cells with a large influence on blood cell lineage proliferation and differentiation. Given the biochemistry of IL-3, elucidating its role in health and disease—especially immune responses and pathological conditions—is a high priority. Interleukin-3 is a cytokine profoundly important in the regulation of hematopoiesis and immune responses. The ability of this factor to modulate a wide variety of cellular responses serves to underscore its central involvement in almost all physiological as well as pathological processes. In the present article, the authors summarize recent knowledge on the mechanisms by which IL-3 exerts biological effects, with special emphasis placed on receptor signaling, downstream pathways, and functional responses.

Chemical compositions and enzyme inhibitory activities of the essential oils of Amomum putrescens D. Fang from Vietnam

Amomum putrescens D. Fang is a member of the genus Amomum Roxb. (Zingiberaceae), which is found in Vietnam and China. To date, the chemical components and bioactivities of A. putrescens essential oils (EOs) have not been investigated. In this work, the rhizome and pseudo-stem EOs of A. putrescens from Northern Vietnam were extracted by hydrodistillation and analyzed using gas chromatography-mass spectrometry (GC-MS). These EOs were evaluated for their biological effects by inhibiting α-amylase and tyrosinase enzymes. Regarding the chemical composition profile, thirty-two and thirty-six volatile components accounted for 97.88% and 98.37% of the rhizome and pseudo-stem EOs, respectively. The main constituents in these EOs were β-pinene, myrtenyl acetate, α-pinene, and trans-pinocarvyl acetate. Notably, β-phellandrene (5.87%) was found only in the pseudo-stem EO but absent in the rhizome EO. In the enzyme inhibitory test, both EOs revealed inhibitory activity against α-amylase (IC50 = 122.37 ± 26.55 μg/mL for rhizomes and IC50 = 108.48 ± 0.44 μg/mL for pseudostems) and tyrosinase (IC50 = 910.85 ± 70.40 μg/mL for pseudo-stems), while rhizome EO had no inhibitory effect on the tyrosinase enzyme. The evidence explored in the present work will lay a scientific foundation for further research on the bioactivities and the extracted components of different parts of A. putrescens, especially the volatile oil components.

Biological Effects of Calceolarioside A as a Natural Compound: Anti-Ovarian Cancer, Anti-Tyrosinase, and Anti-HMG-CoA Reductase Potentials with Molecular Docking and Dynamics Simulation Studies.

One kind of hydroxycinnamic acid is calceolarioside A. Plantago coronopus, Cassinopsis madagascariensis, and other organisms for whom data are available are known to have this naturally occurring compound. IC50 values of Calceolarioside A for ovarian cell lines (NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, UWB1.289) were 24.42, 13.50, 9.31, 14.90, 20.07, and 16.18µM, respectively. IC50 values were 19.83 and 73.48µM for tyrosinase and HMG-CoA reductase enzymes. The chemical activities of Calceolarioside A against HMG-CoA reductase and tyrosinase were assessed by conducting the molecular docking study, MM/GBSA calculation, and molecular dynamics (MD) simulation. The anticancer activities of this compound were evaluated against some ovarian cancer cells, such as NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, and UWB1.289 cell lines. The chemical activities of Calceolarioside A against some of the expressed surface receptor proteins (folate receptor, CD44, EGFR, Formyl Peptide Receptor-Like 1, M2 muscarinic receptor, and estrogen receptors) were investigated using computational methods. The results exhibited the interplay among atoms. The compound formed robust associations with both the enzymes and receptors. Calceolarioside A can hinder the functioning of these enzymes and the proliferation of malignant cells.

Biodegradable Vanadium-Based Nanomaterials for Photothermal-Enhanced Tumor Ferroptosis and Pyroptosis.

The designability and high reactivity of nanotechnology provide strategies for antitumor therapy by regulating the redox state in tumor cells. Here, we synthesize a kind of vanadium dioxide nanoparticle encapsulated in bovine serum albumin and containing disulfide bonds (VSB NPs) for photothermal-enhanced ferroptosis and pyroptosis effects. Mechanism studies show that disulfide bonds can effectively consume overexpressed glutathione (GSH) in the tumor microenvironment, leading to a decrease in glutathione peroxidase 4 (GPX4) activity. Simultaneously, tetravalent vanadium can induce a catalytic reaction of overexpressed H2O2, producing plenty of toxic hydroxyl radicals (·OH) and singlet oxygen (1O2), leading to tumor cell ferroptosis. In addition, the consumption of disulfide bonds can also lead to the degradation of nanoparticles into high-valent vanadates, activating thermal protein domain-associated protein 3 (NLRP3) inflammasomes and causing tumor cell pyroptosis. It is worth mentioning that VSB NPs can not only ablate tumor cells under near-infrared light irradiation but also further disrupt the redox homeostasis of the tumor microenvironment, thereby enhancing the ferroptosis and pyroptosis of tumor cells induced by biodegradable vanadium-based nanomaterials. This strategy, based on the biological effects of vanadium to regulate the redox state in tumor cells, provides possibilities for cancer treatment.

Boric acid impedes glioblastoma growth in a rat model: insights from multi-approach analysis

Limited advancements in managing malignant brain tumors have resulted in poor prognoses for glioblastoma (GBM) patients. Standard treatment involves surgery, radiotherapy, and chemotherapy, which lack specificity and damage healthy brain tissue. Boron-containing compounds, such as boric acid (BA), exhibit diverse biological effects, including anticancer properties. This study aimed to examine whether boron supplementation, as BA, can inhibit glioblastoma growth in a xenograft animal model. Using MRI-based tumor size measurement, survival rates, hematological, clinical biochemistry analyses, and genotoxicity parameters, we assessed the impact of BA. Histopathological, immunohistochemical, and immunofluorescence examinations were also conducted. All BA doses (3.25, 6.5, and 13 mg kg−1 b.w.) extended survival compared to GBM controls after 14 days, with a dose-dependent anti-GBM effect observed in MRI analyses. BA treatment improved hematological (WBC and PLT counts) and biochemical parameters (LDL-C, CREA, and ALP). Histopathological examination revealed a significant reduction in tumor diameter with 6.5 and 13 mg kg−1 BA. Immunohistochemical and immunofluorescence staining showed modulation of intracytoplasmic Ki67, cytoplasmic CMPK2, and GFAP expressions in tumor cells post-BA treatment. Additionally, BA did not increase micronuclei formations, indicating its non-genotoxic nature. In conclusion, targeting tumor suppressor networks with boron demonstrates significant therapeutic potential for GBM treatment.

Non-thermal plasma as promising anti-cancer therapy against bladder cancer by inducing DNA damage and cell cycle arrest

Bladder cancer often recurs, necessitating innovative treatments to reduce recurrence. We investigated non-thermal plasma’s potential as a novel anti-cancer therapy, focusing on plasma-activated solution (PAS), created by exposing saline to non-thermal plasma. Our study aims to elucidate the biological effects of PAS on bladder cancer cell lines in vitro, as well as the combination with mitomycin C (MMC), using clinically relevant settings. PAS treatment exerts a potent cytotoxic effect through the production of intracellular reactive oxygen species, resulting in DNA damage and subsequent induction of G1 cell cycle arrest/senescence. This is induced via upregulation of cell cycle checkpoint signalling and DNA damage repair pathways using LC-M/MS-based phospho-proteomics. Importantly, combining PAS with MMC reveals a synergistic effect (Combination Index of 0.59–0.67), suggesting the potential of utilizing PAS in combination therapies. Our findings demonstrate PAS’s mode of action and suggest its potential as a promising treatment for bladder cancer, warranting further clinical studies.

Defective homologous recombination and genomic instability predict increased responsiveness to carbon ion radiotherapy in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is notably resistant to conventional chemotherapy and radiation treatment. However, clinical trials indicate that carbon ion radiotherapy (CIRT) with concurrent gemcitabine is effective for unresectable locally advanced PDAC. This study aimed to identify patient characteristics predictive of CIRT response. We utilized a panel of human PDAC cell lines with diverse genetic profiles to determine their sensitivity to CIRT compared to γ-rays, assessing relative biological effectiveness (RBE) at 10% survival, which ranged from 1.96 to 3.04. Increased radiosensitivity was linked to impaired DNA double-strand break (DSB) repair, particularly in cell lines with deficiencies in the homologous recombination (HR) repair pathway and/or elevated genomic instability from replication stress. Furthermore, pretreatment with the HR inhibitor B02 significantly enhanced CIRT sensitivity in a radioresistant PDAC cell line when irradiated in the spread-out Bragg peak but not at the entry position of the beam. These findings suggest that PDAC tumors with HR pathway mutations or high replication stress are more likely to benefit from CIRT while minimizing normal tissue toxicity.

Effects of intra-tumoral cellular heterogeneity of oxygen partial pressure on biological effectiveness of hydrogen-, helium-, carbon-, oxygen-, and neon-ion beams

Objective.The tumor microenvironment characterized by heterogeneously organized vasculatures causes intra-tumoral heterogeneity of oxygen partial pressurepat the cellular level, which cannot be measured by current imaging techniques. The intra-tumoral cellularpheterogeneity may lead to a reduction of therapeutic effects of radiation. The purpose of this study was to investigate the effects of the heterogeneity on biological effectiveness of H-, He-, C-, O-, and Ne-ion beams for different oxygenation levels, prescribed dose levels, and cell types.Approach.The intra-tumoral cellularpdistributions were simulated with a numerical tumor model for average oxygen pressuresp¯tranging from 2.5 to 15 mmHg. The relative biological effectiveness (RBE)-weighted dose distributions of 3-15 Gy prescribed doses were planned for a cuboid target with the five ion species for constantp¯tvalues. Radiosensitivities of human salivary gland tumor (HSG) and Chinese hamster ovary (CHO) cells were investigated. The planned dose distributions were then recalculated by taking thepheterogeneity into account.Main results.Asp¯tdecreased and prescribed dose increased, the biological effectiveness of the ion beams decreased due to thepheterogeneity. The reduction in biological effectiveness was pronounced for lighter H- and He-ion beams compared to heavier C-, O-, and Ne-ion beams. The RBE-weighted dose in the target for HSG (CHO) cells decreased by 41.2% (44.3%) for the H-ion beam, while it decreased by 16.7% (14.7%) for the Ne-ion beam at a prescribed dose of 15 Gy under ap¯tof 2.5 mmHg.Significance.The intra-tumoral cellularpheterogeneity causes a significant reduction in biological effectiveness of ion beams. These effects should be considered in estimation of therapeutic outcomes.

Mapping neutron biological effectiveness for DNA damage induction as a function of incident energy and depth in a human sized phantom

We present new developments for an ab-initio model of the neutron relative biological effectiveness (RBE) in inducing specific classes of DNA damage. RBE is evaluated as a function of the incident neutron energy and of the depth inside a human-sized reference spherical phantom. The adopted mechanistic approach traces neutron RBE back to its origin, i.e. neutron physical interactions with biological tissues. To this aim, we combined the simulation of radiation transport through biological matter, performed with the Monte Carlo code PHITS, and the prediction of DNA damage using analytical formulas, which ground on a large database of biophysical radiation track structure simulations performed with the code PARTRAC. In particular, two classes of DNA damage were considered: sites and clusters of double-strand breaks (DSBs), which are known to be correlated with cell fate following radiation exposure. Within a coherent modelling framework, this approach tackles the variation of neutron RBE in a wide energy range, from thermal neutrons to neutrons of hundreds of GeV, and reproduces effects related to depth in the human-sized receptor, as well as to the receptor size itself. Besides providing a better mechanistic understanding of neutron biological effectiveness, the new model can support better-informed decisions for radiation protection: indeed, current neutron weighting (ICRP)/quality (U.S. NRC) factors might be insufficient for use in some radiation protection applications, because they do not account for depth. RBE predictions obtained with the reported model were successfully compared to the currently adopted radiation protection standards when the depth information is not relevant (at the shallowest depth in the phantom or for very high energy neutrons). However, our results demonstrate that great care is needed when applying weighting factors as a function of incident neutron energy only, not explicitly considering RBE variation in the target. Finally, to facilitate the use of our results, we propose look-up RBE tables, explicitly considering the depth variable, and an analytical representation of the maximal RBE vs. neutron energy.

Unraveling Cholesterol-Dependent Interactions of Alkylphospholipids with Supported Lipid Bilayers.

Alkylphospholipids are single-chain lipid amphiphiles that possess clinically relevant biological activities driven by membrane-destabilizing interactions. Subtle variations in alkylphospholipid structure can lead to significant differences in their biological effects, yet corresponding membrane interactions remain underexplored. Herein, we employed the quartz crystal microbalance-dissipation (QCM-D) technique to characterize the real-time membrane interactions of three alkylphospholipids-edelfosine, miltefosine, and perifosine-on supported lipid bilayers with varying cholesterol fractions. Our findings reveal that the tested alkylphospholipids had distinct membrane-interaction profiles: (1) edelfosine exhibited irreversible binding and caused weak membrane disruption; (2) miltefosine caused major disruption by affecting membrane packing; and (3) perifosine exhibited reversible binding while triggering structural rearrangements and modest disruption. Overall, alkylphospholipid micelles showed greater activity than monomers, and higher membrane cholesterol fractions resulted in more extensive disruption, highlighting the interplay between membrane stiffness and responsiveness. These results provide biophysical evidence that different alkylphospholipids have distinct membrane-interaction behaviors that align well with reported biological activities. Our supported lipid bilayer approach offers a valuable platform for designing and assessing alkylphospholipids with tailored membrane-interaction profiles.

Feasibility and safety of Taipei Veterans General Hospital Heavy Ion Therapy Center: The first carbon-ion irradiation facility in Taiwan.

Unlike conventional photon radiotherapy, particle therapy has the advantage of dose distribution. Carbon-ion radiotherapy is also advantageous in terms of biological effectiveness and other radiobiological aspects. These benefits lead to a higher response probability for previously known radioresistant tumor types. Therefore, Taipei Veterans General Hospital, which is located in the northern district of Taipei, built the first carbon-ion irradiation facility in Taiwan. Taipei Veterans General Hospital completed a phase 1 trial to evaluate the safety of carbon-ion radiotherapy. Six patients (4 males and 2 females with prostate adenocarcinoma, sacral chordoma, hepatocellular carcinoma, lung adenocarcinoma, or parotid high-grade carcinoma) were enrolled in this study. The mean age of the patients was 62.7 years. The mean dose was 57.3 Gy(RBE) (fraction range, 4-16 Gy(RBE)). During this phase 1 trial, all patients were monitored for 3 months to evaluate acute toxicity and short-term outcomes after treatment with carbon irradiation. Only 2 patients experienced grade 2 toxicity, which resolved without medication 1 month after completing treatment. The tumor response demonstrated 1 complete response, 1 partial response, and 4 cases of stable disease. Carbon-ion radiotherapy was determined to be an effective and safe treatment.

SNORA37/CMTR1/ELAVL1 feedback loop drives gastric cancer progression via facilitating CD44 alternative splicing

BackgroundEmerging evidence shows that small nucleolar RNA (snoRNA), a type of highly conserved non-coding RNA, is involved in tumorigenesis and aggressiveness. However, the roles of snoRNAs in regulating alternative splicing crucial for cancer progression remain elusive.MethodsHigh-throughput RNA sequencing and comprehensive analysis were performed to identify crucial snoRNAs and downstream alternative splicing events. Biotin-labeled RNA pull-down, mass spectrometry, cross-linking RNA immunoprecipitation, and in vitro binding assays were applied to explore interaction of snoRNAs with protein partners. Alternative splicing and gene expression was observed by real-time quantitative RT-PCR and western blot assays. In vitro and in vivo studies were performed to investigate biological effects of snoRNAs and their protein partners in gastric cancer. Survival analysis was undertaken by using Kaplan-Meier method and log-rank test.ResultsSNORA37 was identified as an up-regulated snoRNA essential for tumorigenesis and aggressiveness of gastric cancer. Gain- and loss-of-function studies indicated that SNORA37 promoted the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo. Mechanistically, as an ELAV like RNA binding protein 1 (ELAVL1)-generated snoRNA, SNORA37 directly bound to cap methyltransferase 1 (CMTR1) to facilitate its interaction with ELAVL1, resulting in nuclear retention and activity of ELAVL1 in regulating alternative splicing of CD44. Rescue studies revealed that SNORA37 exerted oncogenic roles in gastric cancer progression via facilitating CMTR1-ELAVL1 interaction. In clinical gastric cancer cases, high levels of SNORA37, CMTR1, ELAVL1, or CD44 were associated with shorter survival and poor outcomes of patients.ConclusionsThese results indicated that SNORA37/CMTR1/ELAVL1 feedback loop drives gastric cancer progression via facilitating CD44 alternative splicing.

Uncovering the whole genome silencers of human cells via Ss-STARR-seq

Silencers, the yin to enhancers’ yang, play a pivotal role in fine-tuning gene expression throughout the genome. However, despite their recognized importance, comprehensive identification of these regulatory elements in the genome is still in its early stages. We developed a method called Ss-STARR-seq to directly determine the activity of silencers in the whole genome. In this study, we applied Ss-STARR-seq to human cell lines K562, LNCaP, and 293 T, and identified 134,171, 137,753, and 125,307 silencers on a genome-wide scale, respectively, these silencers function in various cells in a cell-specific manner. Silencers exhibited a substantial enrichment of transcriptional-inhibitory motifs, including REST, and demonstrated overlap with the binding sites of repressor transcription factors within the endogenous environment. Interestingly, H3K27me3 did not reflect silencer activity but facilitated the silencer’s inhibitory role on gene expression. Additionally, the silencer did not have any significant histone markers at the genome-wide level. Our findings unveil that aspect-silencers not only transition into enhancers throughout diverse cell lines but also achieve functional conversion with insulators. Regarding to biological effects, knockout experiments underscored the functional redundancy and specificity of silencers in regulating gene expression and cell proliferation. In summary, this study pioneers the elucidation of the genome-wide silencer landscape in human cells, delineates their global regulatory features, and identifies specific silencers influencing cancer cell proliferation.

Merged Red and NIR Light Sources for Photobiomodulation Therapy in Diabetic Wound Healing.

Photobiomodulation (PBM) is considered an effective and safe therapeutic modality in supporting the treatment of complications from a global pandemic-diabetes. In this study, PBM therapy is investigated to accelerate wound healing in diabetic mice (DM), under the combined biological effects of red light from a red organic light-emitting diode (ROLED) and near-infrared (NIR) light from an NIR conversion film (NCF) with dispersed CuInS2/ZnS quantum dots (QDs). The QD concentration and the NCF structure were optimized to maximize the optical properties and mechanical stability. A merged red/NIR device (MRND) was produced by integrating the optimized NCF and ROLED for PBM therapy. As a result of irradiating DM with MRND at a dose of 2 J/cm2, after 10 days, the wounds recovered three times faster than DM without MRND. Additionally, MRND light not only restored the epidermal thickness to normal but also significantly reduced the levels of pro-inflammatory cytokines. The experimental results show that the proposed PBM therapy has the potential to improve the quality of life of diabetic patients by helping them with rapid wound healing.

GLP-1 Therapy in Cancer and Its Mechanism

L-advocating cells generate the hormone glucagon-like peptide-1 (GLP-1), which is important for weight loss and the management of type 2 diabetes mellitus (T2DM).Recent studies have shown that it also reduces the risk of cardiovascular disease, reduces high blood pressure and other effects. In addition, it also has the effect of improving fatty liver, polycystic ovary syndrome. But when it comes to cancer, there are still gaps in its biological effects and mechanisms of action. In order to determine the indirect inhibitory effect of GLP-1RA on cancer as well as the metabolic regulation mechanisms of the cancer microenvironment by directly acting on the PI3K/AKT and ERK/MARK pathways, this paper analyzed studies on GLP-1 and its receptor agonist (GLP-1RA) in lowering cancer prevalence and inhibiting cancer. In turn, it effectively inhibits prostate cancer (PCa), ovarian cancer (OC) and other cancers. This study provides a reference for the indirect and direct mechanisms of GLP-1 and GLP-1RA in reducing cancer prevalence and inhibiting cancer. However, there are still gaps in other synergistic mechanisms that cannot be solved. It is hoped that future studies can focus on the anticancer mechanisms of other GLP-1 drugs.

Environmental art design from a biomechanical perspective: Exploration of the psychological and physiological effects of the integration of transparent materials and traditional cultural elements on residential spaces

With the advancement of urbanization, environmental art design is becoming increasingly important in contemporary Chinese interior design, especially in the design of modern rural villas. The integration of traditional culture and art has become an important way to enhance the artistic value and cultural significance of residential spaces. This article explores the psychological and physiological effects of interior design that combines transparent materials with traditional art elements from a biological perspective on residents. Transparent materials are like delicate optical structures in the biological world. They not only give the space a sense of lightness and openness, but their interaction with light also has a profound impact on the human body. From a biomechanical perspective, just like the sensitive capture of light signals by the biological visual system, transparent materials of different colors and materials can adjust light and shadow, and then act on the human nervous system and psychological state. Bright light passing through transparent materials is like a strong stimulus perceived by organisms, which can stimulate vitality; soft light is like a soothing signal, which can bring a relaxing effect. In addition, the integration of traditional cultural elements enhances the spiritual satisfaction of residents by evoking cultural identity and emotional resonance. This paper also combines case studies, such as Hiroshima Optical Glass House and Türkiye Draman Villa, to analyze how transparent materials can achieve the balance of visual, emotional and biological effects in the modern living environment, providing a new perspective for improving the quality of life of residents. The research results indicate that the organic combination of transparent materials and traditional cultural elements can not only improve the biological experience of residential spaces, but also promote physical and mental health, enhance the emotional value and cultural depth of the space. By applying insights from biomechanics, designers can create environments that support human physiology, ultimately improving residents' quality of life. This interdisciplinary approach offers a novel perspective on how interior design can significantly influence well-being and cultural depth in modern living environments.

Low-intensity pulsed ultrasound enhances the osteogenic potential of PDLSCs-derived extracellular vesicles through COMP/PI3K/AKT.

The therapeutic potential of extracellular vesicles (EVs) in bone regeneration is noteworthy; however, their clinical application is impeded by low yield and limited efficacy. This study investigated the effect of low-intensity pulsed ultrasound (LIPUS) on the therapeutic efficacy of EVs derived from periodontal ligament stem cells (PDLSCs) and preliminarily explored its mechanism. PDLSCs were cultured with osteogenic media and stimulated with or without LIPUS, and then EVs and LIPUS-stimulated EVs (L-EVs) were isolated separately. We investigated the biological characteristics and effects of these two EVs on cell proliferation, migration, osteogenic differentiation, and bone regeneration invivo and invitro, and explored the potential mechanism by analyzing protein profiles. LIPUS significantly stimulated the secretion of PDLSCs-EVs, and L-EVs exhibited stronger efficacy in promoting cell proliferation, migration, and osteogenic differentiation, thereby enhancing new bone formation. LIPUS stimulation affected the protein profile of PDLSCs-EVs, and 42 proteins were upregulated and 4 proteins downregulated in L-EVs when compared with EVs. LIPUS significantly upregulated the level of cartilage oligomeric matrix protein (COMP) in EVs, which enhanced EVs' osteogenic ability via the PI3K/AKT pathway. This study proposes that LIPUS has potential as an optimization method for enhancing the therapeutic effects of EVs in tissue regeneration.

The role of vitamin K2 in cognitive impairment: linking vascular health to brain health

Cognitive impairment, marked by a decline in essential mental aspects such as attention, memory, and problem-solving, is significantly correlated with advancing age. This condition presents a major challenge for the elderly, adversely affecting quality of life, diminishing independence, and imposing substantial burdens on healthcare systems. Recent research indicates that vitamin K2 may be vital for preserving brain health and cognitive function. Traditionally recognized primarily for its role in blood coagulation, vitamin K has emerged in recent years as a nutrient with diverse biological effects essential for healthy aging. A growing body of evidence from both observational and interventional studies underscores the pivotal role of vitamin K2 in mitigating arterial calcification. This mechanism may link vascular health to cognitive function, suggesting that vitamin K2 could play a critical role in the prevention of cognitive impairment in aging populations.

Large variability in the alkaloid content of Corydalis yanhusuo dietary supplements

IntroductionExtracts from the rhizome of the traditional Chinese medicinal plant Corydalis yanhusuo (CY) mediate a number of biologic effects that are associated with its content of isoquinoline alkaloids. CY alkaloids have shown analgesic, cardioprotective, and anti-addictive effects in animal models of disease. Since CY alkaloids are available to consumers as dietary supplements we analyzed the content of alkaloids in 14 products including open powders, capsules, and liquid formulations, capturing a majority of the products available online in the US.MethodsNineteen alkaloids were quantified using HPLC analyses with diode array detection after extraction using a weak cation exchange column.ResultsTotal alkaloid content was highly variable among the products, ranging from below quantifiable in some to ≈11 mg/g in others. Five of the products had comparable content of alkaloids (9.5 ± 1.6 mg/g), equaling about the amount of alkaloids of an extract prepared from CY rhizome (12.7 mg/g). The other samples had much lower content (1.8 ± 0.9 mg/g), or alkaloids were below quantifiable. One of the products was highly enriched in tetrahydropalmatine (≈5 mg/g), suggesting adulteration from the natural product, and raising concerns about possible toxicologic liability.DiscussionConsidering alkaloid content as a key quality criterium for CY supplements, the large variability among the products seems unacceptable and makes it difficult for consumers to select products with an appropriate content of alkaloids.

Real-world comparative outcomes and toxicities after definitive radiotherapy using proton beam therapy versus intensity-modulated radiation therapy for prostate cancer: a retrospective, single-institutional analysis.

This retrospective study aimed to compare the clinical outcomes of intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT). A total of 606 patients diagnosed with prostate cancer between January 2008 and December 2018 were included. Of these patients, 510 received PBT up to a dose of 70-78Gy (relative biological effectiveness) and 96 patients received IMRT up to a dose of 70-78Gy. The median follow-up period was 82months (range: 32-140months). Patients in the PBT group had significantly higher 7-year rates of biochemical relapse-free survival (bRFS) and disease-free survival (DFS) rates: 95.1% for PBT vs 89.9% for IMRT (P = 0.0271) and 93.1% for PBT vs 85.0% for IMRT (P = 0.0019). After matching analysis, 94 patients were assigned to both groups, and the PBT group showed significantly higher 7-year bRFS and DFS rates: 98.9% for PBT vs 89.7% for IMRT (P = 0.023) and 93.4% for PBT vs 84.6% for IMRT (P = 0.022), respectively. In the subgroup analysis of intermediate-risk patients, the PBT group showed a significantly higher 7-year bRFS rate (98.3% for PBT vs 90.5% for IMRT; P = 0.007). The V60 of the bladder in the PBT group (18.1% ± 10.1%) was higher than that in the IMRT group (14.4% ± 7.6%) (P = 0.024). This study found that the treatment outcomes of PBT potentially surpassed those of IMRT specifically concerning bRFS and DFS in real-world settings. However, it should be noted that attention is warranted for late bladder complication of PBT.