Protocol for extraction, characterization, and computational analysis of uranium from seawater.

Here, we present a protocol for uranium extraction from seawater (UES) and its characterization and computational-based structure analysis. We describe formulating batch adsorption experiments for adsorptive separation of uranium using thin film (TFCH) of Hydrogen-bonded Organic Framework (CSMCRIHOF-1). We then detail the recovery of uranium using eluent mixtures and the steps to regenerate TFCH for recyclability studies. Finally, we describe the spectroscopic characterizations of TFCH and uranium adsorbed TFCH, followed by computational analysis of the structures and binding sites. For complete details on the use and execution of this protocol, please refer to Kaushik et al. (2022).1.

Integration of Universal Germline Genetic Testing for All New Breast Cancer Patients.

BACKGROUND: The American Society of Breast Surgeons recommends genetic testing (GT) for all women with breast cancer (BC), but implementation and uptake of GT has not been well-described. METHODS: A retrospective chart review was performed for newly diagnosed BC patients or patients with a newly identified recurrence of BC seen in a multidisciplinary clinic (MDBC) who were offered genetic counseling (GC) and GT. RESULTS: The 138 women attending the MDBC had a median age of 54 years and comprised non-Hispanic whites (46%), Asians (28%), Hispanics (17%), blacks (4%), and other (5%). Of the 105 (76%) patients without prior GT, 100 (95%) accepted GC, with 93 (93%) of these 100 patients undergoing GT. The patients meeting the National Comprehensive Cancer Network (NCCN) guidelines for GT were more likely to undergo GT. Testing was performed with a 67- to 84-gene panel, together with an 8- to 9-gene STAT panel if needed. Among 120 patients with reports available, including 33 patients previously tested, 15 (12%) were positive (1 BLM, 1 BRCA1, 3 BRCA2, 1 BRIP1, 1 CFTR, 1 CHEK2, 1 MUTYH, 1 PALB2, 1 PRSS1, 1 RAD50, 1 RET, and 2 TP53), 44 (37%) were negative, and 61 (51%) had an uncertain variant. The median time to STAT results (n = 50) was 8 days. The STAT results were available before surgery for 47 (98%) of the 48 STAT patients undergoing surgery. CONCLUSIONS: New BC patients attending the MDBC demonstrated high rates of acceptance of GC and GT. The combination of GC and GT can offer timely information critical to patient risk assessment and treatment planning.

Development of a safe pediatric liquisolid self-nanoemulsifying system of triclabendazole for the treatment of fascioliasis.

Fascioliasis, a common parasitic infection observed in the pediatric patient population, is a leading cause of concern in countries with poor/unhealthy water resources. To treat this condition first line agent such as triclabendazole (TBZ) has been the choice therapy. However, there is a major hurdle in exploiting TBZ. Characterized with poor aqueous solubility (0.1 mg/L), its solubility has been the rate limiting factor, rendering requirement of large doses of TBZ. To address the same, the focus of the current study was to develop a self-nano emulsifying drug delivery system (TBZ-SNEDDS) for TBZ and developing dose customizable pediatric dispersible color-coded tablets. TBZ-SNEDDS were successfully formulated by using Kolliphor®EL, as a surfactant, a lipid phase of medium chain triglyceride and α-tocopherol in the ratio of (1:1), with dimethylacetamide (DMA) as a solvent. It was observed during in vitro release studies that there was a significant effect of fed conditions on the rate of TBZ release from the formulation. greater than 85 % TBZ was observed to release in fed conditions in comparison to fasted conditions. As currently TBZ is prescribed on a weight-based dosage regimen, it is imperative to develop a dose-customizable fast dissolving pediatric formulation. Hence, TBZ-SNEDDS could prove to be pivotal in helping countless children around the world in desperate conditions to get cheap yet effective therapy.

Impacts of Commonly Used Edible Plants on the Modulation of Platelet Function.

Cardiovascular diseases (CVDs) are a primary cause of deaths worldwide. Thrombotic diseases, specifically stroke and coronary heart diseases, account for around 85% of CVDs-induced deaths. Platelets (small circulating blood cells) are responsible for the prevention of excessive bleeding upon vascular injury, through blood clotting (haemostasis). However, unnecessary activation of platelets under pathological conditions, such as upon the rupture of atherosclerotic plaques, results in thrombus formation (thrombosis), which can cause life threatening conditions such as stroke or heart attack. Therefore, antiplatelet medications are usually prescribed for people who are at a high risk of thrombotic diseases. The currently used antiplatelet drugs are associated with major side effects such as excessive bleeding, and some patients are resistant to these drugs. Therefore, numerous studies have been conducted to develop new antiplatelet agents and notably, to establish the relationship between edible plants, specifically fruits, vegetables and spices, and cardiovascular health. Indeed, healthy and balanced diets have proven to be effective for the prevention of CVDs in diverse settings. A high intake of fruits and vegetables in regular diet is associated with lower risks for stroke and coronary heart diseases because of their plethora of phytochemical constituents. In this review, we discuss the impacts of commonly used selected edible plants (specifically vegetables, fruits and spices) and/or their isolated compounds on the modulation of platelet function, haemostasis and thrombosis.

Healthcare Utilization and Costs Associated with New-Onset Pain in a Medicare Population.

BACKGROUND: Chronic pain is a common and growing problem in the United States with variable strategies for its treatment. Surgical interventions are necessary in some cases but not required for all patients with new-onset pain. For some patients, interventional pain management (IPM) techniques can treat chronic pain without the cost or risk associated with surgical intervention. OBJECTIVE: The objective of this study was to compare healthcare utilization and costs for new-onset chronic pain treated by IPM specialists to those treated by providers with surgical specialties (i.e., orthopedists and neurosurgeons). STUDY DESIGN: This was a retrospective observational study of qualifying patients over 36-months (2016-2019). SETTING: This study was conducted using 100% Medicare FFS Parts A, B, and Prescription Drug Event (PDE) Part D data, including enrollment and claims. METHODS: Patients with a diagnosis of pain were identified in the claims data. Twelve months of pre-period claims were examined to ensure the incident diagnosis of pain, and 2 additional pain diagnoses were required after initial diagnosis. Patients were assigned either to the IPM cohort or a Surgical cohort based on the specialty of the provider involved in their first pain-related visit after initial diagnosis. Key outcomes, such as the utilization of healthcare services and cost of care, were evaluated for both cohorts over the 24-months following the index diagnosis of pain. RESULTS: 106,658 beneficiaries were included in the study with roughly 36% in the IPM cohort. Patients in the IPM cohort were less healthy and had lower incomes in the baseline period compared to the Surgical cohort. Fewer members of the IPM cohort had an inpatient stay in the 24-months post index pain diagnosis (40% compared to 43% in the surgery cohort) and the IPM cohort had fewer patients with a post-acute care stay (29% compared to 31% in the inpatient stay cohort). The IPM cohort had lower risk-adjusted total costs of care than the Surgical cohort, driven by lower inpatient, outpatient, and post-acute care costs. LIMITATIONS: Retrospective claims data may not include some factors important to patients with a pain diagnosis (such as over-the-counter medications, holistic treatments, or pain scores). CONCLUSION(S): By shifting patients from higher-cost and more invasive surgical procedures, IPM's multidisciplinary approach to pain treatment can reduce surgical utilization and costs for certain chronic pain patients. This shift away from more expensive surgical treatments fits well with Medicare's move toward value-based care, driven by a focus on patient outcomes including health care utilization and costs.

A universal pocket in fatty acyl-AMP ligases ensures redirection of fatty acid pool away from coenzyme A-based activation.

Fatty acyl-AMP ligases (FAALs) channelize fatty acids towards biosynthesis of virulent lipids in mycobacteria and other pharmaceutically or ecologically important polyketides and lipopeptides in other microbes. They do so by bypassing the ubiquitous coenzyme A-dependent activation and rely on the acyl carrier protein-tethered 4'-phosphopantetheine (holo-ACP). The molecular basis of how FAALs strictly reject chemically identical and abundant acceptors like coenzyme A (CoA) and accept holo-ACP unlike other members of the ANL superfamily remains elusive. We show that FAALs have plugged the promiscuous canonical CoA-binding pockets and utilize highly selective alternative binding sites. These alternative pockets can distinguish adenosine 3',5'-bisphosphate-containing CoA from holo-ACP and thus FAALs can distinguish between CoA and holo-ACP. These exclusive features helped identify the omnipresence of FAAL-like proteins and their emergence in plants, fungi, and animals with unconventional domain organizations. The universal distribution of FAALs suggests that they are parallelly evolved with FACLs for ensuring a CoA-independent activation and redirection of fatty acids towards lipidic metabolites.

Self-injectable extended release formulation of Remdesivir (SelfExRem): A potential formulation alternative for COVID-19 treatment.

There has been a growing and evolving research to find a treatment or a prevention against coronavirus 2019 (COVID-19). Though mass vaccination will certainly help in reducing number of COVID-19 patients, an effective therapeutic measure must be available too. Intravenous remdesivir (RDV) was the first drug receiving Food and Drug Administration (FDA) approval for the treatment of COVID-19. However, in a pandemic like COVID-19, it is essential that drug formulations are readily available, affordable and convenient to administer to every patient around the globe. In this study, we have developed a Self-injectable extended release subcutaneous injection of Remdesivir (SelfExRem) for the treatment of COVID-19. As opposed to intravenous injection, extended release subcutaneous injection has the benefits of reducing face-to-face contact, minimizing hospitalization, reducing dosing frequency and reducing overall health care cost. SelfExRem was developed using a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), dissolved in a biocompatible vehicle. Six different batches were formulated using 2 different grades of low molecular weight PLGA and 3 different PLGA concentration. The force of injection of various polymeric solutions through 23-30-gauge needles were analyzed using a TA.XTplus texture analyzer. The time required for injection was evaluated both manually and by using an autoinjector. In vitro release of all the batches were carried out in 1% v/v tween 80 in phosphate buffer saline. The study indicated that SelfExRem developed with15% w/v PLGA(75:25) provided a steady release of drug for 48 h and may be a breakthrough approach for the treatment of COVID-19.

Isorhapontigenin, a resveratrol analogue selectively inhibits ADP-stimulated platelet activation.

Isorhapontigenin is a polyphenolic compound found in Chinese herbs and grapes. It is a methoxylated analogue of a stilbenoid, resveratrol, which is well-known for its various beneficial effects including anti-platelet activity. Isorhapontigenin possesses greater oral bioavailability than resveratrol and has also been identified to possess anti-cancer and anti-inflammatory properties. However, its effects on platelet function have not been reported previously. In this study, we report the effects of isorhapontigenin on the modulation of platelet function. Isorhapontigenin was found to selectively inhibit ADP-induced platelet aggregation with an IC50 of 1.85 µM although it displayed marginal inhibition on platelet aggregation induced by other platelet agonists at 100 µM. However, resveratrol exhibited weaker inhibition on ADP-induced platelet aggregation (IC50 > 100 µM) but inhibited collagen induced platelet aggregation at 50 µM and 100 µM. Isorhapontigenin also inhibited integrin αIIbß3 mediated inside-out and outside-in signalling and dense granule secretion in ADP-induced platelet activation but interestingly, no effect was observed on α-granule secretion. Isorhapontigenin did not exert any cytotoxicity on platelets at the concentrations of up to 100 µM. Furthermore, it did not affect haemostasis in mice at the IC50 concentration (1.85 µM). In addition, the mechanistic studies demonstrated that isorhapontigenin increased cAMP levels and VASP phosphorylation at Ser157 and decreased Akt phosphorylation. This suggests that isorhapontigenin may interfere with cAMP and PI3K signalling pathways that are associated with the P2Y12 receptor. Molecular docking studies emphasised that isorhapontigenin has greater binding affinity to P2Y12 receptor than resveratrol. Our results demonstrate that isorhapontigenin has selective inhibitory effects on ADP-stimulated platelet activation possibly via P2Y12 receptor.

Chemotherapy-induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol.

BACKGROUND: Muscle wasting, anorexia, and metabolic dysregulation are common side-effects of cytotoxic chemotherapy, having a dose-limiting effect on treatment efficacy, and compromising quality of life and mortality. Extracts of Cannabis sativa, and analogues of the major phytocannabinoid Δ9-tetrahydrocannabinol, have been used to ameliorate chemotherapy-induced appetite loss and nausea for decades. However, psychoactive side-effects limit their clinical utility, and they have little efficacy against weight loss. We recently established that the non-psychoactive phytocannabinoid cannabigerol (CBG) stimulates appetite in healthy rats, without neuromotor side-effects. The present study assessed whether CBG attenuates anorexia and/or other cachectic effects induced by the broad-spectrum chemotherapy agent cisplatin. METHODS: An acute cachectic phenotype was induced in adult male Lister-hooded rats by 6 mg/kg (i.p.) cisplatin. In total 66 rats were randomly allocated to groups receiving vehicle only, cisplatin only, or cisplatin and 60 or 120 mg/kg CBG (po, b.i.d.). Feeding behavior, bodyweight and locomotor activity were recorded for 72 hours, at which point rats were sacrificed for post-mortem analyses. Myofibre atrophy, protein synthesis and autophagy dysregulation were assessed in skeletal muscle, plasma metabolic profiles were obtained by untargeted 1H-NMR metabonomics, and levels of endocannabinoid-like lipoamines quantified in plasma and hypothalami by targeted HPLC-MS/MS lipidomics. RESULTS: CBG (120 mg/kg) modestly increased food intake, predominantly at 36-60hrs (p<0.05), and robustly attenuated cisplatin-induced weight loss from 6.3% to 2.6% at 72hrs (p<0.01). Cisplatin-induced skeletal muscle atrophy was associated with elevated plasma corticosterone (3.7 vs 13.1ng/ml, p<0.01), observed selectively in MHC type IIx (p<0.05) and IIb (p<0.0005) fibres, and was reversed by pharmacological rescue of dysregulated Akt/S6-mediated protein synthesis and autophagy processes. Plasma metabonomic analysis revealed cisplatin administration produced a wide-ranging aberrant metabolic phenotype (Q2Y=0.5380, p=0.001), involving alterations to glucose, amino acid, choline and lipid metabolism, citrate cycle, gut microbiome function, and nephrotoxicity, which were partially normalized by CBG treatment (Q2Y=0.2345, p=0.01). Lipidomic analysis of hypothalami and plasma revealed extensive cisplatin-induced dysregulation of central and peripheral lipoamines (29/79 and 11/26 screened, respectively), including reversible elevations in systemic N-acyl glycine concentrations which were negatively associated with the anti-cachectic effects of CBG treatment. CONCLUSIONS: Endocannabinoid-like lipoamines may have hitherto unrecognized roles in the metabolic side-effects associated with chemotherapy, with the N-acyl glycine subfamily in particular identified as a potential therapeutic target and/or biomarker of anabolic interventions. CBG-based treatments may represent a novel therapeutic option for chemotherapy-induced cachexia, warranting investigation in tumour-bearing cachexia models.

Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism.

The folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis of nucleotides and amino acids and epigenetic modifications. This cycle might also release formaldehyde, a potent protein and DNA crosslinking agent that organisms produce in substantial quantities. Here we show that supplementation with tetrahydrofolate, the essential cofactor of this cycle, and other oxidation-prone folate derivatives kills human, mouse and chicken cells that cannot detoxify formaldehyde or that lack DNA crosslink repair. Notably, formaldehyde is generated from oxidative decomposition of the folate backbone. Furthermore, we find that formaldehyde detoxification in human cells generates formate, and thereby promotes nucleotide synthesis. This supply of 1C units is sufficient to sustain the growth of cells that are unable to use serine, which is the predominant source of 1C units. These findings identify an unexpected source of formaldehyde and, more generally, indicate that the detoxification of this ubiquitous endogenous genotoxin creates a benign 1C unit that can sustain essential metabolism.

Quantity of lymph nodes correlates with improvement in lymphatic drainage in treatment of hind limb lymphedema with lymph node flap transfer in rats.

PURPOSE: This study was conducted to investigate the correlation between the number of vascularized lymph nodes (LN) transferred and resolution of hind limb lymphedema in a rat model. METHODS: Unilateral hind limb lymphedema was created in 18 male Sprague-Dawley rats following inguinal and popliteal LN resection and radiation. A para-aortic LN flap based on the celiac artery was subsequently transferred to the affected groin. The three study groups consisted of Group A (no LN transfer), Group B (transfer of a single vascularized LN), and Group C (transfer of three vascularized LNs). Volumetric analysis of bilateral hind limbs was performed using micro-CT imaging at 1, 2, and 3 months postoperatively. Lymphatic drainage was assessed with Tc(99) lymphoscintigraphy preoperatively and at 3 months postoperatively. RESULTS: A statistically significant volume reduction was seen in Groups B and C compared to Group A at all time points. Volume reduction of Group A vs.Group B at 1 month (8.6% ± 2.0% vs. 2.7% ± 2.6%, P < 0.05), 2 months (9.3% ± 2.2% vs. -4.3% ± 2.7%, P < 0.05), and 3 months (7.6% ± 3.3% vs. -8.9% ± 5.2%, P < 0.05). Volume reduction of Group A vs. Group C at 1 month (8.6% ± 2.0% vs. -6.6% ± 3.1%, P < 0.05), 2 months (9.3% ± 2.2% vs. -10.2% ± 4.6%, P < 0.05), and 3 months (7.6% ± 3.3% vs. -9.1% ± 3.1%, P < 0.05). Of note, comparison of Groups B and C demonstrated greater volume reduction in Group C at 1 (P < 0.02) and 2 (P = 0.07) months postoperatively. CONCLUSIONS: LN flap transfer is an effective procedure for the treatment of lymphedema. The number of vascularized LNs transferred correlates positively with the degree of volume reduction.

RNA-seq of Arabidopsis pollen uncovers novel transcription and alternative splicing.

Pollen grains of Arabidopsis (Arabidopsis thaliana) contain two haploid sperm cells enclosed in a haploid vegetative cell. Upon germination, the vegetative cell extrudes a pollen tube that carries the sperm to an ovule for fertilization. Knowing the identity, relative abundance, and splicing patterns of pollen transcripts will improve our understanding of pollen and allow investigation of tissue-specific splicing in plants. Most Arabidopsis pollen transcriptome studies have used the ATH1 microarray, which does not assay splice variants and lacks specific probe sets for many genes. To investigate the pollen transcriptome, we performed high-throughput sequencing (RNA-Seq) of Arabidopsis pollen and seedlings for comparison. Gene expression was more diverse in seedling, and genes involved in cell wall biogenesis were highly expressed in pollen. RNA-Seq detected at least 4,172 protein-coding genes expressed in pollen, including 289 assayed only by nonspecific probe sets. Additional exons and previously unannotated 5' and 3' untranslated regions for pollen-expressed genes were revealed. We detected regions in the genome not previously annotated as expressed; 14 were tested and 12 were confirmed by polymerase chain reaction. Gapped read alignments revealed 1,908 high-confidence new splicing events supported by 10 or more spliced read alignments. Alternative splicing patterns in pollen and seedling were highly correlated. For most alternatively spliced genes, the ratio of variants in pollen and seedling was similar, except for some encoding proteins involved in RNA splicing. This study highlights the robustness of splicing patterns in plants and the importance of ongoing annotation and visualization of RNA-Seq data using interactive tools such as Integrated Genome Browser.

Ciprofloxacin-resistant Aeromonas hydrophila infection following leech therapy: a case report and review of the literature.

Compromised flap perfusion can lead to the use of leech therapy to aid in flap salvage. Aeromonas hydrophila, a symbiont of the leech, is a well-known bacterial pathogen that has the potential to cause infection in patients receiving leech therapy. Ciprofloxacin is commonly regarded as the antibiotic of choice for prophylaxis against this pathogen. We present patient who underwent leech therapy during salvage attempts for a venous congested flap. A resultant infection developed despite being on appropriate antibiotics. Culture sensitivities indicated that A. hydrophila was resistant to ciprofloxacin.

The secreted purple acid phosphatase isozymes AtPAP12 and AtPAP26 play a pivotal role in extracellular phosphate-scavenging by Arabidopsis thaliana.

Orthophosphate (P(i)) is an essential but limiting macronutrient for plant growth. Extensive soil P reserves exist in the form of organic P (P(o)), which is unavailable for root uptake until hydrolysed by secretory acid phosphatases (APases). The predominant purple APase (PAP) isozymes secreted by roots of P(i)-deficient (-P(i)) Arabidopsis thaliana were recently identified as AtPAP12 (At2g27190) and AtPAP26 (At5g34850). The present study demonstrated that exogenous P(o) compounds such as glycerol-3-phosphate or herring sperm DNA: (i) effectively substituted for P(i) in supporting the P nutrition of Arabidopsis seedlings, and (ii) caused upregulation and secretion of AtPAP12 and AtPAP26 into the growth medium. When cultivated under -P(i) conditions or supplied with P(o) as its sole source of P nutrition, an atpap26/atpap12 T-DNA double insertion mutant exhibited impaired growth coupled with >60 and >30% decreases in root secretory APase activity and rosette total P(i) concentration, respectively. Development of the atpap12/atpap26 mutant was unaffected during growth on P(i)-replete medium but was completely arrested when 7-day-old P(i)-sufficient seedlings were transplanted into a -P(i), P(o)-containing soil mix. Both PAPs were also strongly upregulated on root surfaces and in shoot cell-wall extracts of -P(i) seedlings. It is hypothesized that secreted AtPAP12 and AtPAP26 facilitate the acclimation of Arabidopsis to nutritional Pi deficiency by: (i) functioning in the rhizosphere to scavenge P(i) from the soil's accessible P(o) pool, while (ii) recycling P(i) from endogenous phosphomonoesters that have been leaked into cell walls from the cytoplasm. Thus, AtPAP12 and AtPAP26 are promising targets for improving crop P-use efficiency.

Complications of acellular dermal matrices in abdominal wall reconstruction.

BACKGROUND: Acellular dermal matrices have been increasingly used in abdominal wall reconstruction. Unique characteristics of these grafts have allowed surgeons to reconstruct increasingly complex abdominal wall defects. This has resulted in a myriad of complications related to the acellular dermal matrix with unique management strategies as compared with synthetic mesh. METHODS: A review of the literature was performed to identify studies evaluating the use and efficacy of acellular dermal matrices in abdominal wall reconstruction. Complication profiles were identified and are compared. Differences between porcine and human derivatives were identified. RESULTS: Hernia recurrence, infection, skin necrosis, and fluid collections were among the most common complications following abdominal wall reconstruction identified in the literature. Differences among various acellular dermal matrix products make certain types more suitable for abdominal wall reconstruction. CONCLUSIONS: Complications are frequent in abdominal wall reconstruction. Many acellular dermal matrices have properties that allow for conservative management and maintenance of reconstruction when complications occur. With traditional synthetic mesh reconstruction, complications likely result in mesh explantation and prolonged morbidity. With acellular dermal matrix reconstruction, however, more conservative treatment strategies will allow for mesh salvage.

Sir Victor Horsley's contributions to the study and treatment of gunshot wounds of the head.

Sir Victor Horsley'S many contributions to neurological surgery include experimental and clinical studies of gunshot wounds (GSW) of the head. Horsley's publications from 1894 to 1897 and 1914 to 1915 on GSWs were reviewed. Horsley described GSWs in animal and clay models, illustrating characteristics of the primary missile tract and secondary cavitation. A transcranial GSW model in 67 dogs related intracranial damage to the projectile's velocity and sectional area, producing a marked sudden increase in intracranial pressure that presumably "tunneled" to the medullary respiratory and cardiac centers. If the resultant sudden apnea was treated with artificial respiration and prompt surgical decompression, the animal often survived. In these animal experiments, Horsley clearly described increased intracranial pressure, hypertension, and bradycardia-later recognized as the Cushing response or triad. With the onset of World War I, Horsley again reviewed the ballistics of military weaponry, emphasizing projectile spin and velocity as the main wounding mechanisms. He was outspoken against the "wicked tradition" of neglecting cranial GSWs and personally treated cases with aggressive respiratory support and prompt decompression of devitalized tissue. Horsley's contributions to the experimental and clinical aspects of GSWs to the head are consistent with his other important contributions to neurosurgery and have largely stood the test of time.

Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse models of prostate and intestinal carcinogenesis: relationship with silibinin levels.

Silibinin, a flavonolignan from milk thistle seeds, possesses cancer chemopreventive properties in rodent models of carcinogenesis. We tested the hypotheses that silibinin or silipide, silibinin formulated with phospholipids, delays tumour development in TRAMP or Apc(Min) mice, genetic models of prostate or intestinal malignancies, respectively. Mice received silibinin or silipide with their diet (0.2% silibinin equivalents) from weaning. Intervention with silipide reduced the size of well differentiated TRAMP adenocarcinomas by 31%. Silipide and silibinin decreased the incidence of poorly differentiated carcinomas by 61% compared to mice on control diet. Silipide decreased plasma levels of insulin-like growth factor (IGF)-1 by 36%. Levels of circulating IGF binding protein (IGFBP)-3 in mice on silipide or silibinin were 3.9- or 5.9-fold, respectively, elevated over those in control TRAMP mice. In Apc(Min) mice silibinin, but not silipide, had only a marginal adenoma number-reducing effect. The results cautiously support the advancement of silipide to the stage of clinical investigation in prostate cancer.