Pyrrolizidine Alkaloids in Foods, Herbal Drugs, and Food Supplements: Chemistry, Metabolism, Toxicological Significance, Analytical Methods, Occurrence, and Challenges for Future.

Consumers are increasingly seeking natural alternatives to chemical compounds, including the use of dried aromatic plants as seasonings instead of salt. However, the presence of pyrrolizidine alkaloids (PAs) in food supplements and dried plants has become a concern because of their link to liver diseases and their classification as carcinogenic by the International Agency for Research on Cancer (IARC). Despite European Union (EU) Regulation (EU) 2023/915, non-compliance issues persist, as indicated by alerts on the Rapid Alert System for Food and Feed (RASFF) portal. Analyzing PAs poses a challenge because of their diverse chemical structures and low concentrations in these products, necessitating highly sensitive analytical methods. Despite these challenges, ongoing advancements in analytical techniques coupled with effective sampling and extraction strategies offer the potential to enhance safety measures. These developments aim to minimize consumer exposure to PAs and safeguard their health while addressing the growing demand for natural alternatives in the marketplace.

The residues and health risk assessment of polychlorinated biphenyls (PCBs) in Pheretima (an earthworm-derived traditional medicine) from southeastern China.

Minimal research exists on polychlorinated biphenyl (PCB) exposure from traditional Chinese medicines (TCMs), despite their significant contributions to domestic and international health protection. This study is the first to investigate the levels, profiles, and health risks of PCB residue in Pheretima, a typical TCM produced from earthworm. Seventy-seven Pheretima samples from different regions of China were analyzed for 45 PCB congeners. PCBs were found in all samples exhibiting species-dependent discrepancies. ∑45PCBs was ranging from 0.532 to 25.2 µg/kg (mean 4.46 µg/kg), with CB-11 being the most abundant congener contributing 71.8% ± 10.8% to ∑45PCBs, followed by CB-47, which were all non-Aroclor congeners called unintentionally produced PCBs (UP-PCBs). The average estimated daily intake of ∑45PCBs, ∑7ID-PCBs (indicative polychlorinated biphenyls), and CB-11 were 0.71, 0.04, and 0.51 ng/kg bw/d, respectively. The ∑HQ of PCBs in Pheretima samples was 2.97 × 10-4-2.46 × 10-2 (mean 2.77 × 10-3, 95th 4.21 × 10-3), while the ∑RQ ranged from 1.19 × 10-8 to 2.88 × 10-6 (mean 4.87 × 10-7, 95th 2.31 × 10-6). These findings indicate that Pheretima ingestion does not pose significant non-carcinogenic risks. However, certain individual samples exhibit an acceptable level of potential risks, particularly when considering that PCBs are recognized as endocrine disruptors and classified as probable carcinogens. These results contribute to the safety evaluation of traditional medicines and suggest the potential use of Pheretima as a bioindicator for PCB pollution. It is advisable to monitor UP-PCBs as indicator congeners and gather additional toxicological data.

Immunomagnetic capture and traceless release of native tumor-derived exosomes from human plasma for exploring interaction with recipient cells by aptamer-functionalized nanoflowers.

BACKGROUND: Tumor-derived exosomes (TEXs) play an important role in the development process of cancer, which can transport a large number of carcinogenic molecules to normal cells, and subsequently promote tumor metastasis. However, TEXs that were utilized in most of previous researches were obtained from the cell medium of tumor cell lines, which cannot reflect the physiological state of primary cells in vivo. Isolation of native TEXs from human plasma with intact function is contributed to exploring the interaction between TEXs and recipient cells for understanding their true biological functions. RESULTS: We developed a strategy that involves both capture and release processes to obtain native TEXs from plasma of cancer patients. An MoS2-based immunomagnetic probe (Fe3O4@MoS2-Au-Aptamer, named as FMAA) with the advantages of high surface area, magnetic response and abundant affinity sites was designed and synthesized to capture TEXs through recognizing high-expression tumor-associated antigens of EpCAM. With the assistance of complementary sequences of EpCAM, TEXs were released with non-destruction and no residual labels. According to NTA analysis, 107-108 TEXs were recovered from per mL plasma of breast cancer patients. The interaction between native TEXs and normal epithelial cells confirms TEXs could induce significant activation of autophagy of recipient cells with co-culture for 12 h. Proteomics analysis demonstrated a total of 637 proteins inside epithelial cells had dynamic expression with the stimulation of TEXs and 5 proteins in the pathway of autophagy had elevated expression level. SIGNIFICANCE: This work not only obtains native TEXs from human plasma with non-destruction and no residual labels, but also explores the interaction between TEXs and recipient cells for understanding their true biological functions, which will accelerate the application of TEXs in the field of biomarkers and therapeutic drugs.

A probabilistic health risk assessment of potentially toxic elements in edible vegetable oils consumed in Hamadan, Iran.

In this study, potential toxic element (PTEs) including lead (Pb), arsenic (As), cadmium(Cd), iron (Fe) and zinc (Zn) in traditional and industrial edible vegetable oils (peanut, sunflower, olive and sesame) collected from Hamadan, west of Iran were determined using Inductivity Coupled Plasma Optical Emission Spectrometry (ICP-OES). Besides, probabilistic health risk assessment (non-carcinogenic and carcinogenic risks) was identified via total target hazard quotient (TTHQ) and cancer risk (CR) by the Monte Carlo Simulation (MCS) model. The ranking of concentration PTEs in traditional and industrial edible vegetable oils was Fe > Zn > As > Pb > Cd. The in all samples, content of PTEs in industrial oils were upper than traditional oils (p < 0.001). The level of PTEs in most of vegetable oils was lower than permissible concentration regulated by Codex and national standard. In term of non-carcinogenic, consumers were at acceptable range (TTHQ < 1) due to ingestion both traditional and industrial vegetable oils content of PTEs. In term of carcinogenic, CR the both adults and children was higher than acceptable range (CR < 1E-6), Hence consumer are at unacceptable risk due to ingestion industrial vegetable oils content of inorganic As. Therefore, it is recommended to implement control plans for PTEs in vegetable oils consumed in Hamadan, Iran.

Tellimagrandin-I and camptothin a exhibit chemopreventive effects in Salmonella enterica serovar Typhimurium strains and human lymphocytes.

Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.

Pyto-Architechture of Ag, Au and Ag-Au bi-metallic nanoparticles using waste orange peel extract for enable carcinogenic Congo red dye degradation.

Ecologically inspired to develop silver, gold and silver/gold bimetallic nanoparticles from discarded orange peel extract. The plant-derived compounds included in discarded orange peel extract have been accountable for the development of Ag, Au and Ag-Au bimetallic nanoparticles, that might be used in the biosynthetic process. The qualitative assessment of developed silver, gold and silver/gold bimetallic nanoparticles has been performed by UV-visible, XRD pattern, FT IR analysis, TEM/HRTEM, EDX and BET isotherm analysis. In this investigation, the photocatalytic effect of developed silver, gold and silver/gold bimetallic nanoparticles on Congo red dye breakdown efficiency was achieved at 96%, 94%, and 99.2%, respectively. Due to prolonged electron-hole recombination process was investigated using UV irradiation and reused for up to 5 consecutive runs without significant loss of photocatalytic activity. Moreover, silver, gold, and silver/gold bimetallic nanoparticles manufactured in an environmentally benign manner could potentially contribute to the ecological cleanup.

Acrylamide in potato chips in Iran, health risk assessment and mitigation.

This study aimed to determine the acrylamide content in potato chips sold in Kermanshah, Iran and assess the potential health concerns associated with acrylamide exposure. HPLC-DAD was used to analyse 120 samples across 40 brands. The possible non-carcinogenic risk index for adults was below 1 for all 40 brands (100%), but for children it was only below 1 for 9 brands (22.5%) and above 1 for 31 brands (77.5%). Regarding the possible carcinogenic risk index, for adults only 1 out of 40 brands rated > 10-4, whereas for children all brands rated > 10-4. This shows that children's exposure to acrylamide through potato chips consumption in Kermanshah can be considered a risk on cancer and exposure of adults requires attention and monitoring. The best way to reduce acrylamide in potato chips and associated health risks is to improve the production process, especially temperature and time.

Body weight gain and control: beneficial effect of extra virgin olive oil versus corn oil in an experimental model of mammary cancer.

Obesity is a known risk factor for breast cancer, the most common malignancy among women worldwide. We have previously described different effects of high-fat diets on mammary experimental carcinogenesis. In this work, we analyzed the animal growth data obtained in six experimental assays, in healthy and carcinogen-induced rats undergoing different dietary interventions. The animals were fed with three experimental diets administered at different periods of development: a control low-fat diet, and two isocaloric high-fat diets (rich in corn oil or in extravirgin olive oil -EVOO-). Weekly weight throughout the development of 818 animals have been compiled and reanalyzed using adjusted mathematical models. Molecular mechanisms have been investigated: ethanolamides in small intestine, neuropeptides controlling satiety in hypothalamus, and proteins controlling lipid metabolism in adipose and mammary tissues. The results indicated that the effect of diets depended on type of lipid, timing of intervention and health status. The high corn oil diet, but not the high EVOO diet, increased body weight and mass, especially if administered from weaning, in healthy animals and in those that received a moderate dose of carcinogen. The potential protective effect of EVOO on weight maintenance may be related to anorexigenic neuropeptides such as oxytocin and lipolysis/deposition balance in adipose tissue (increasing phospho-PKA, HSL, MGL and decreasing FAS). In animals with cancer, body weight gain was related to the severity of the disease. Taken together, our results suggest that EVOO has a beneficial effect on body weight maintenance in both health and cancer.

Functional effects of yacon (Smallanthus sonchifolius) and kefir on systemic inflammation, antioxidant activity, and intestinal microbiome in rats with induced colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers with high morbidity and mortality. The modulation of intestinal health through the administration of pro- and prebiotics may be a viable alternative to reduce the risk of CRC. This study aimed to evaluate the functional effects of yacon and kefir, isolated or associated, in rats with colorectal cancer. Adult Wistar rats were divided into five groups (n = 8): HC (healthy control AIN-93M diet), CC (CCR + AIN-93M diet), Y (CCR + AIN-93 M + yacon diet), K (CCR + AIN-93-M + kefir diet) and YK (CCR + AIN-93 M + yacon + kefir diet). Colorectal carcinogenesis was induced in groups CC, Y, K, and YK with 1,2-dimethylhydrazine (55 mg kg-1, subcutaneously) for 5 weeks. From the 6th week onwards, the experimental groups were fed the respective diets. In the 15th week, urine was collected for analysis of intestinal permeability and then the animals were euthanized. Yacon increased acetate levels, reduced pH and carcinogenic neoplastic lesions, and increased the abundance of bacteria related to the fermentation of non-digestible carbohydrates, such as the genera Dorea, Collinsela, and Bifidobacteria. On the other hand, kefir increased macroscopic neoplastic lesions and increased the abundance of Firmicutes and Clostridium. The association of yacon + kefir increased the number of carcinogenic lesions, despite a reduction in pH and beneficial bacteria prevalence. Thus, it is concluded that yacon, unlikely kefir, is a promising alternative to mitigate the manifestations of induced carcinogenesis in rats.

Validation of a full-shift benzene exposure empirical model developed for work on offshore petroleum installations on the Norwegian continental shelf.

Workers on offshore petroleum installations might be exposed to benzene, a carcinogenic agent. Recently, a full-shift benzene exposure model was developed based on personal measurements. This study aimed to validate this exposure model by using datasets not included in the model. The exposure model was validated against an internal dataset of measurements from offshore installations owned by the same company that provided data for the model, and an external dataset from installations owned by another company. We used Tobit regression to estimate GM (geometric mean) benzene exposure overall and for individual job groups. Bias, relative bias, precision, and correlation were estimated to evaluate the agreement between measured exposures and the levels predicted by the model. Overall, the model overestimated exposure when compared to the predicted exposure level to the internal dataset with a factor of 1.7, a relative bias of 73%, a precision of 0.6, a correlation coefficient of 0.72 (p = 0.019), while the Lin's Concordance Correlation Coefficient (CCC) was 0.53. The model underestimated exposure when compared to the external dataset with a factor of about 2, with a relative bias of -45%, a precision of 1.2, a correlation coefficient of 0.31 (p = 0.544), and a Lin's CCC of 0.25. The exposure model overestimated benzene exposure in the internal validation dataset, while the precision and the correlation between the measured and predicted exposure levels were high. Differences in measurement strategies could be one of the reasons for the discrepancy. The exposure model agreed less with the external dataset.

Euglena gracilis Extract Protects From Tobacco Smoke Carcinogen-Induced Lung Cancer by Altering Gut Microbiota Metabolome.

Extracts from Euglena gracilis have been shown to prevent cancer growth in mouse models. However, the molecular mechanism of this anti-cancer activity has not been determined nor has the effect of Euglena extracts on tobacco smoke carcinogen-induced carcinogenesis. Here, we investigate the hypothesis that this anti-cancer activity is a result of changes in the intestinal microbiota induced by oral administration of the extract. We found that a Euglena gracilis water extract prevents lung tumorigenesis induced by a tobacco smoke-specific carcinogen (NNK) in mice treated either 2 weeks before or 10 weeks after NNK injection. Both of these treatment regimens are associated with significant increases in 27 microbiota metabolites found in the mouse feces, including large increases in triethanolamine, salicylate, desaminotyrosine, N-acetylserine, glycolate, and aspartate. Increases in the short-chain fatty acids (SCFAs) including acetate, propionate and butyrate are also observed. We also detected a significant attenuation of lung carcinoma cell growth through the induction of cell cycle arrest and apoptosis caused by low levels of SCFAs. This study provides strong evidence of anti-cancer activity in Euglena gracilis extracts against tobacco smoke carcinogen-induced tumorigenesis and demonstrates that this activity is linked to increased production of specific gut microbiota metabolites and the resultant induction of cell cycle arrest and apoptosis of lung carcinoma cells.

Biogeochemical behaviour and toxicology of chromium in the soil-water-human nexus: A review.

Chromium (Cr) affects human health if it accumulates in organs to elevated concentrations. The toxicity risk of Cr in the ecosphere depends upon the dominant Cr species and their bioavailability in the lithosphere, hydrosphere, and biosphere. However, the soil-water-human nexus that controls the biogeochemical behaviour of Cr and its potential toxicity is not fully understood. This paper synthesizes information on different dimensions of Cr ecotoxicological hazards in the soil and water and their subsequent effects on human health. The various routes of environmental exposure of Cr to humans and other organisms are also discussed. Human exposure to Cr(VI) causes both carcinogenic and non-carcinogenic health effects via complicated reactions that include oxidative stress, chromosomal and DNA damage, and mutagenesis. Chromium(VI) inhalation can cause lung cancer; however, incidences of other types of cancer following Cr(VI) exposure are low but probable. The non-carcinogenic health consequences of Cr(VI) exposure are primarily respiratory and cutaneous. Research on the biogeochemical behaviour of Cr and its toxicological hazards on human and other biological routes is therefore urgently needed to develop a holistic approach to understanding the soil-water-human nexus that controls the toxicological hazards of Cr and its detoxification.

Distribution, sources, and health risk of polycyclic aromatic hydrocarbons and their derivatives in the watershed: the case of Yitong River, China.

Polycyclic aromatic hydrocarbons (PAHs) and substituted PAHs (SPAHs) are persistent organic pollutants prevalent globally, and SPAHs have received widespread attention in recent years due to their stronger toxicity and carcinogenicity compared to PAHs. There is a lack of systematic examination of PAHs and their derivatives in watersheds. Thus, to clarify the current status, possible sources, and potential risks of PAHs and their derivatives in watersheds, a study was conducted on Yitong River in China. The results showed that the concentrations of ∑PAHs, ∑OPAHs, and ∑NPAHs ranged from 297.9-1158.3 ng/L, 281.1-587.2 ng/L, and 65.7-269.1 ng/L, respectively. Diagnostic ratio analysis showed that the PAHs were mainly derived from petroleum sources, agricultural waste, and coal combustion. Nitrated PAHs (NPAHs) were mainly derived from liquid combustion sources, and oxygenated PAHs (OPAHs) were derived mainly from petroleum source emissions and atmospheric deposition. The exposure risk model of PAHs revealed that 86% of the studied sites would pose carcinogenic risks after dermal contact. The contaminant causing a major carcinogenic risk was DahA, and none of the sites produced non-carcinogenic risks. The lifetime carcinogenic risk of NPAHs was 8.85 × 10-10-1.44 × 10-4, and some surface waters presented with potential carcinogenic risks.

The Potential Chemopreventive Effect of Andrographis paniculata on 1,2-Dimethylhydrazine and High-Fat-Diet-Induced Colorectal Cancer in Sprague Dawley Rats.

Colorectal cancer (CRC) is responsible for a notable rise in the overall mortality rate. Obesity is found to be one of the main factors behind CRC development. Andrographis paniculata is a herbaceous plant famous for its medicinal properties, particularly in Southeast Asia for its anti-cancer properties. This study examines the chemopreventive impact of A. paniculata ethanolic extract (APEE) against a high-fat diet and 1,2-dimethylhydrazine-induced colon cancer in Sprague Dawley rats. Sprague Dawley rats were administered 1,2-dimethylhydrazine (40 mg/kg, i.p. once a week for 10 weeks) and a high-fat diet (HFD) for 20 weeks to induce colorectal cancer. APEE was administered at 125 mg/kg, 250 mg/kg, and 500 mg/kg for 20 weeks. At the end of the experiment, blood serum and organs were collected. DMH/HFD-induced rats had abnormal crypts and more aberrant crypt foci (ACF). APEE at a dose of 500 mg/kg improved the dysplastic state of the colon tissue and caused a 32% reduction in the total ACF. HFD increased adipocyte cell size, while 500 mg/kg APEE reduced it. HFD and DMH/HFD rats had elevated serum insulin and leptin levels. Moreover, UHPLC-QTOF-MS analysis revealed that APEE was rich in anti-cancer phytochemicals. This finding suggests that APEE has anti-cancer potential against HFD/DMH-induced CRC and anti-adipogenic and anti-obesity properties.

The World Trade Center Health Program: Cancer screening and cancer care best practices.

The events of September 11, 2001 (9/11) exposed nearly a half million persons to many carcinogenic chemicals and dusts, as well as psychological and physical stressors. Subsequent epidemiologic studies of 9/11-exposed persons have suggested elevated risks for some cancers, e.g., prostate cancer, thyroid cancer, and melanoma. To detect cancer at an early stage, the US Preventive Services Task Force recommends screening certain asymptomatic persons for lung, colorectal, cervical and breast cancer, but not for other cancers. High quality cancer diagnosis and treatment guidelines are available from the National Comprehensive Cancer Network and the National Cancer Institute. For enrolled members, the WTC Health Program provides coverage for cancer screening and diagnosis, and covers medically necessary treatment costs for all types of cancer, assuming 9/11-exposure and minimum latency requirements are met, and a Program-affiliated physician attests that 9/11 exposures were substantially likely to have been a significant factor in aggravating, contributing to, or causing the enrolled WTC member's cancer.

Occupational asbestos exposure and survival among lung cancer patients.

OBJECTIVE: This study investigated the association between occupational asbestos exposure (OAE) and survival in patients with histologically confirmed lung cancer (LC). METHODS: This monocentric study was conducted in the Comprehensive Cancer Centre Léon Bérard, Lyon, France. A systematic screening has been in place since 2014 for occupational exposure to carcinogens using a self-assessment questionnaire sent to all patients newly diagnosed with histologically confirmed LC identified through the multidisciplinary LC board from 2014 to 2019. When the physician suspected a work-related exposure from the questionnaire including job history, an occupational cancer consultation was carried out to detail carcinogen exposures and assess if the LC was work-related. Demographics, clinical characteristics and survival data were extracted from medical records. The association between asbestos exposure and overall survival (hazard ratio and 95% confidence intervals) was estimated by Cox proportional hazards regression. RESULTS: Overall, 702 patients were eligible to the present study, including 180 patients with OAE. In the crude analysis, LCs assessed as moderately or highly attributable to OAE were associated with decreased overall survival (HR = 1.32, 95 %CI 1.04-1.67) compared to LC without OAE or with a low degree of imputability to OAE (median follow-up 28.8 months). After adjustment for confounding (age at diagnosis, smoking status, stage, brain metastasis at diagnosis, and histology), the association of OAE with overall survival was no longer statistically significant (HR = 1.21, 95 %CI 0.94-1.56). CONCLUSION: Overall survival in occupationally asbestos exposed LC patients may be decreased in comparison with non-exposed LC patients, warranting further investigations in larger studies.

Complete Remission of BCG-Refractory High-grade Bladder CIS with Pharmacologic Ascorbate and Mistletoe.

Context: Bladder cancer is the fourth-most-common cancer in males in the U.S., who develop about 90% of the high-grade, carcinoma in situ (CIS) of non-muscle involved disease (NMIBC). Smoking and occupational carcinogens are well-known causes. For females without known risk factors, bladder cancer can be regarded as a sentinel environmental cancer. It's also one of the costliest to treat due to its high rate of recurrence. No treatment innovations have occurred in nearly two decades; intravesical instillation of Bacillus Calmette-Guerin (BCG), an agent in short supply globally, or Mitomycin-C (MIT-C) is effective in about 60% of cases. Cases refractory to BCG and MIT-C often undergo cystectomy, a procedure with numerous impacts on life styles and potential complications. The recent completion of a small Phase I trial of mistletoe in cancer patients that have exhausted known treatments at Johns Hopkins provides corroboration of its safety, with 25 % showing no disease progression. Objective: The study examined the benefits of pharmacologic ascorbate (PA) and mistletoe for a nonsmoking female patient with an environmental history of NMIBC refractory to BCG, in a non-smoking female with exposures in childhood and early adult life to several known carcinogens, including ultrafine particulate air pollution, benzene, toluene, and other organic solvents, aromatic amines and engine exhausts, and possibly arsenic in water. Design: The research team performed an integrative oncology case study on pharmacologic ascorbate (PA) and mistletoe, both agents shown to activate NK cells, enhance growth and maturation of T-cells, and induce dose-dependent pro-apoptotic cell death, suggesting shared and potentially synergistic mechanisms. Setting: The study began at the University of Ottawa Medical Center in Canada with treatment continuing over six years at St. Johns Hospital Center in Jackson, Wyoming, and George Washington University Medical Center for Integrative Medicine, with surgical, cytological, and pathological evaluations at University of California San Francisco Medical Center. Participant: The patient in the case study was a 76-year-old, well-nourished, athletic, nonsmoking female with high-grade CIS of the bladder. Her cancer was considered to be a sentinel environmental cancer. Intervention: Intravenous pharmacologic ascorbate (PA) and subcutaneous mistletoe (three times weekly) and intravenous and intravesical mistletoe (once weekly) were employed for an 8-week induction treatment, using a dose-escalation protocol as detailed below. Maintenance therapy was carried out with the same protocol for three weeks every three months for two years. Results: The patient has experienced a cancer-free outcome following 78 months of treatments that incorporated intravesical, intravenous, and subcutaneous mistletoe; intravenous PA; a program of selected nutraceuticals; exercise; and other supplementary treatments. Conclusions: This study is the first reported instance of combined treatments to achieve complete remission for high-grade NMIBC refractory to BCG and MIT-C, using intravesical, subcutaneous, and intravenous mistletoe and intravenous PA. It includes pharmacological information on possible mechanisms. In light of the global shortage of BCG, the high proportion of cases refractory to BCG and MIT-C, the unproven use of costly off-label pharmaceuticals, such as gemcitabine, and the relative cost-effectiveness of mistletoe and PA, clinicians should give serious consideration to employing these combined functional medicine treatments for BCG- and MIT-C-refractory NMIBC. Further research is needed with additional patients that can advance our understanding, including standardization of methods for systematically evaluating combined therapies-blinded and non-blinded, nomenclature regarding mistletoe preparation, doses, concentrations, regimes of administration, lengths of treatment, targeted cancer types, and other aspects.

Comprehensive GIS based risk surveillance of organochlorine pesticides (OCPs) in edible fish species of River Chenab, Pakistan.

The present study was conducted to evaluate Carcinogenic (TR) and non-carcinogenic (THQ) human health risk of organochlorine pesticides (OCPs) in three edible fish species (Labeo boga, Channa marulius and Wallago attu) of River Chenab, Pakistan using USEPA human health risk assessment model. Holistic GIS (Geographic information system) based Geo-Statistical approach has been employed for the first time in River Chenab, Pakistan to categorize contaminated risk zones of OCPs based on single pollution index. The ∑OCPs concentrations in fish species were ranged from 5.09 to 414 ng/g with the prevalence of dieldrin. Results of single pollution index of DDE, aldrin, dieldrin and ∑endosulfan revealed River Chenab as polluted and risk zone area. Distribution pattern assessed significantly higher (p < 0.05) concentrations of OCPs in downstream area suggesting substantial pollution of surrounded industrial region. The human health risk assessment depicted no harmful non-carcinogenic (THQ) risk except for ΣOCPs concentration of C. marulius. Significant carcinogenic (TR) health risk exhibited by all examined OCPs from maximum of the studied sites. Therefore, the high carcinogenic human health risk had highlighted an immediate removal of continuous disposal of OCPs in the River Chenab.

Dietary Phytochemicals as Potential Chemopreventive Agents against Tobacco-Induced Lung Carcinogenesis.

Lung cancer is the second most common cancer in the world. Cigarette smoking is strongly connected with lung cancer. Benzo[a]pyrene (BaP) and 4-(N-methyl-N-nitrosamine)-1-(3-pyridyl)-butanone (NNK) are the main carcinogens in cigarette smoking. Evidence has supported the correlation between these two carcinogens and lung cancer. Epidemiology analysis suggests that lung cancer can be effectively prevented through daily diet adjustments. This review aims to summarize the studies published in the past 20 years exploring dietary phytochemicals using Google Scholar, PubMed, and Web of Science databases. Dietary phytochemicals mainly include medicinal plants, beverages, fruits, vegetables, spices, etc. Moreover, the perspectives on the challenges and future directions of dietary phytochemicals for lung cancer chemoprevention will be provided. Taken together, treatment based on the consumption of dietary phytochemicals for lung cancer chemoprevention will produce more positive outcomes in the future and offer the possibility of reducing cancer risk in society.

Nitroso Impurities in Drug Products: An Overview of Risk Assessment, Regulatory Milieu, and Control Strategy.

Many nitrosamines have been recognized to be carcinogenic for many decades. Despite the fact that several nitrosamine precursors are frequently used in the manufacturing of pharmaceutical products, their potential presence in pharmaceutical products has previously been overlooked due to a lack of understanding on how they form during the manufacturing process. From the risk assessment, it is clear that nitrosamines or their precursors may be present in any component of the finished dosage form. As a risk mitigation strategy, components with a high potential to form nitrosamine should be avoided. In the absence of suitable alternatives, sufficient measures to maintain nitrosamines below acceptable intake levels must be applied. Excipient manufacturing pathways must be extensively studied in order to identify probable excipient components that may contribute to nitrosamine formation. The manufacturers must not solely rely on pharmacopeial specifications for APIs and excipients, rather, they should also develop and implement additional strategies to control nitrosamine impurities. The formulation can be supplemented with nitrosating inhibitors, such as vitamin C, to stop the generation of nitrosamine. The purpose of this review is to identify key risk factors with regard to nitrosamine formation in pharmaceutical dosage forms and provide an effective control strategy to contain them below acceptable daily intake limits.