Poisoning Research Articles

Preliminary results of hypofractionated radiotherapy in breast cancer in Chandigarh, India: single-centre, non-inferiority, open-label, randomised, phase 3 trial

Globally, most of the randomised trials with hypofractionation in patients with breast cancer have used 3-dimensional conformal radiotherapy technique (3D-CRT). As facilities for 3D-CRT technique may not be available in low-resource settings, there is a need to see if hypofractionation is feasible and safe with 2-dimensional (2-D) technique. In this study, we compared a 3-week radiation schedule with a 2-week schedule of hypofractionated radiotherapy in patients with breast cancer with 2-D technique. The current study was an open-label, randomised, phase 3 trial. Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomised in the Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India; to 34Gy in 10 fractions over 2 weeks (2-week arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (3-week arm). Boost dose when indicated was 8-10Gy/2-4#/2-4 days in both the arms. Patients were planned on a 2-dimensional (2D) simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) grading scale. Assessments were carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scale. The toxicity rates between the two arms were compared using Fisher's exact tests. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number NCT04075058. This study included 1121 eligible patients from June 2015 to December 2020. Median follow-up was 35 months (6-84 months). Mean age was 48 years (24-75 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3-week arm and more node-positive patients in the 2-week arm. There were more oestrogen receptor-positive tumors in the 3-week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 100 (18%) and 82 (15%); and 16 (3%) and 12 (2%) in the 3-week and 2-week arm (p=0.21), respectively. Cosmetic outcome was assessed as Excellent or Good for 89% of patients in the 3-week arm as compared to 94% in the 2-week arm (p=0.004). The two radiation schedules were comparable in terms of acute skin toxicity. The cosmetic outcome was better with the 2-week schedule. The preliminary findings indicate 2-week radiotherapy schedule with 2-D technique was better than the 3-week schedule in patients with breast cancer. However, disease outcomes and late-term toxicities need to be further checked. This study was funded by Science and Engineering Research Board (SERB), India.

Cytotoxicity, anti-inflammatory effect, and acute oral toxicity of a novel Attalea phalerata kernel oil-loaded nanocapsules

The kernel oil of the Attalea phalerata Mart. Ex Spreng (Acurí) is traditionally used in several Latin American countries to treat respiratory problems, inflammation, and fever. However, it cannot be found on the literature any attend to use this oil in pharmaceutical formulation. In this paper, it was developed Acurí oil-loaded nanocapsules, and it was evaluated the cytotoxicity against cancer cells, the antinflammatory activity and the oral acute toxicity in rats. Acurí oil contains lauric acid as the predominant saturated fatty acid (433.26 mg/g) and oleic acid as the main unsaturated fatty acid (180.06 mg/g). The Acurí oil-loaded nanocapsules showed a size of 237 nm, a polydispersity index of 0.260, and a high ζ-potential of −78.75 mV. It was obtained an encapsulation efficiency of 88.77%, and the nanocapsules remain stable on the shelf for 180 days. The nanocapsules showed a rapid release profile (98.25% in 40 minutes). Nanocapsules at a dose of 10 mg/kg exhibit an anti-inflammatory effect similar to indomethacin at the same dose. The nanocapsules showed excellent antiproliferative effect and selectivity index against prostate tumor cells (IC50 2.09 µg/mL, SI=119.61) and kidney tumor cells (IC50 3.03 µg/mL, SI=82.50). Both Acurí oil and Acurí oil-loaded nanocapsules are nontoxic at a dose of 2000 mg/kg. Additionally, they reduce serum triglyceride and total cholesterol levels in rat and could find application in nutraceutical formulations. The Acurí oil-loaded nanocapsules emerge as a promising candidate for new antitumor therapies.

Antiplasmodial activity and toxicity of the leaves, stem and roots of Parinari robusta Oliv [CHRYSOBALANACEAE] in animal model

Malaria continues to wreak havoc on various populations as a result of the mortality and economic burden associated with the disease. Progress made in the therapeutics of the disease is threatened by the emerging parasite resistance to currently used first line treatment drugs. This has prompted the search for new, effective, and safe antimalarial agents. Parinari robusta is one plant in use with inadequate evidence about its efficacy. This study therefore aimed to assess the in vivo and in vitro antimalarial potential, and the safety of the leaves, stem and roots of the plant. Acute toxicity was carried out according to OECD guidelines. In vivo antimalarial activity of the hydroethanolic extracts were assessed using the Peter's 4-day suppressive and Rane's curative tests. In vitro antiplasmodial activity of the hydroethanolic crude extracts were evaluated using the SYBR Green I fluorescence assay on the chloroquine sensitive (3D7) and chloroquine resistant (Dd2) strains of P. falciparum. P. robusta was safe with the lethal dose above 3000 mg/kg. All the extracts significantly (p < 0.001) suppressed parasitaemia in the Peter's suppressive and Rane's curative test in a dose dependent manner. The extracts showed highly to weakly active in vitro antiplasmodial activity with an IC50 between 2.629 μg/ml to 30.320 μg/ml against 3D7 and Dd2 strain of P. falciparum. Leaf and stem extract gave the most superior activity against the Dd2 and 3D7 P. falciparum strains. The findings of this study provide scientific evidence supporting the traditional use of P. robusta in the treatment of malaria.

Acute toxicity of bee venom from Apis mellifera L. in mice: A histopathological study

Acute toxicity of bee venom from Apis mellifera L. in mice: A histopathological study

Cryo-Milled β-Glucan Nanoparticles for Oral Drug Delivery

Gemcitabine is a nucleoside analog effective against a number of cancers. However, it has an oral bioavailability of less than 10%, due to its high hydrophilicity and low permeability through the intestinal epithelium. Therefore, the aim of this project was to develop a novel nanoparticulate drug delivery system for the oral delivery of gemcitabine to improve its oral bioavailability. In this study, gemcitabine-loaded β-glucan NPs were fabricated using a film-casting method followed by a freezer-milling technique. As a result, the NPs showed a small particle size of 447.6 ± 14.2 nm, and a high drug entrapment efficiency of 64.3 ± 2.1%. By encapsulating gemcitabine into β-glucan NPs, a sustained drug release profile was obtained, and the anomalous diffusion release mechanism was analyzed, indicating that the drug release was governed by diffusion through the NP matrix as well as matrix erosion. The drug-loaded NPs had a greater ex vivo drug permeation through the porcine intestinal epithelial membrane compared to the plain drug solution. Cytotoxicity studies showed a safety profile of the β-glucan polymers, and the IC50s of drug solution and drug-loaded β-glucan NPs were calculated as 228.8 ± 31.2 ng·mL−1 and 306.1 ± 46.3 ng·mL−1, respectively. Additionally, the LD50 of BALB/c nude mice was determined as 204.17 mg/kg in the acute toxicity studies. Notably, pharmacokinetic studies showed that drug-loaded β-glucan NPs could achieve a 7.4-fold longer T1/2 and a 5.1-fold increase in oral bioavailability compared with plain drug solution. Finally, in vivo pharmacodynamic studies showed the promising capability of gemcitabine-loaded β-glucan NPs to inhibit the 4T1 breast tumor growth, with a 3.04- and 1.74-fold reduction compared to the untreated control and drug solution groups, respectively. In conclusion, the presented freezer-milled β-glucan NP system is a suitable drug delivery method for the oral delivery of gemcitabine and demonstrates a promising potential platform for oral chemotherapy.

From Zimbabwean Indigenous Knowledge: Scientific Substantiation of the Aphrodisiac Efficacy and Safety of Pittosporum viridiflorum in Male Rat Models

Introduction: Pittosporum viridiflorum, the multi habitat thriving plant species is widely believed to have been the source of sexual prowess for the polygamous kings and elites of the mighty medieval empire known as ‘Great Zimbabwe’. Despite the lack of systematic scientific validation, the macerated roots fractions continue to be the aphrodisiacs of choice among Zimbabweans.&#x0D; Aims: To scientifically validate the aphrodisiac claims using male rats’ sexual performance investigation protocols. To evaluate the toxicity profile and to identify the pharmacologically active metabolites present in the lyophilized hydro-ethanolic crude extracts.&#x0D; Methodology: Four concentrations of prepared Pittosporum viridiflorum root extract doses of 200, 400, 800 and 2000mg/kg as well as a commercial 5 mg/kg sildenafil citrate (standard) and distilled water (control) dosages were gavaged to male rats (n = 5 animals per group) for 21 days. The crude extract was subjected to screening protocols for various secondary metabolites of pharmacological relevance as well as acute oral toxicity profiling using OECD 425 TG. The sexual behaviour, mating parameters and hormonal changes in the male rats were evaluated accordingly.&#x0D; Observation and Results: Compared with the control, a significant increase in mating behaviour, mating performance and the serum hormonal levels were observed in test animals which showed a dose‑dependent bias. The phytoscreening evaluation confirmed the presence of saponins, phytosterols, flavonoids, di-terpenoids, tannins, and polyphenols. The Extract was toxicological safe with an LD50 above 2000mg/kg body weight.&#x0D; Conclusion: Pittosporum viridiflorum has excellent aphrodisiac activity on rats and is toxicologically safe for oral use. The abundant phytochemicals found are known to be pharmacologically active with regards to modulation of sexual hormones as well as sexual enhancement. It was further concluded that the traditional belief is valid, the plant can indeed be used as an alternative to modern medicines for various sexual dysfunctions and sexual performance enhancement.

Acute toxicity induced by treated sewage to zebrafish (Danio rerio)

Objetivo: Se evaluaron marcadores de toxicidad aguda en pez cebra causados por la exposición a aguas residuales tratadas de dos plantas de tratamiento de aguas residuales para obtener información precisa y relevante sobre los riesgos potenciales para la salud ambiental asociados con estas aguas.&#x0D; Diseño/metodología/aproximación: La evaluación de la toxicidad aguda se realizó de acuerdo a los lineamientos propuestos por la Organización para la Cooperación y el Desarrollo Económicos (OECD). Para determinar la Dilución Letal Media (LDil50) se analizaron cinco proporciones de cada tipo de agua tratada con agua del grifo declorada (20, 40, 60, 80 y 100%). La descripción de los efectos teratogénicos se realizó mediante el biomarcador de columna vertebral.&#x0D; Resultados: Los resultados revelaron que la mezcla de agua residual tratada (mCl) y el agua residual tratada desinfectada con hipoclorito de sodio (NaClO) causaron efectos tóxicos en los embriones del pez cebra, como letalidad, malformaciones y alteraciones cardiacas. Por otra parte, el agua residual tratada de la Macroplanta de Bahía de Banderas (BBdClO) no fue tóxica a 96 horas de exposición.&#x0D; Limitaciones del estudio/implicaciones: Sería recomendable caracterizar las aguas residuales tratadas de estas dos plantas de tratamiento.&#x0D; Hallazgos/conclusiones: Estos hallazgos subrayan la importancia de evaluar la toxicidad de las aguas residuales tratadas y sus efectos a corto y largo plazo en los organismos acuáticos, proporcionando información valiosa para la gestión de recursos hídricos y la protección del medio ambiente.

Rapid Characterization of Undeclared Pharmaceuticals in Herbal Preparations by Ambient Ionization Mass Spectrometry for Emergency Care.

In Asia, some herbal preparations have been found to be adulterated with undeclared synthetic medicines to increase their therapeutic efficiency. Many of these adulterants were found to be toxic when overdosed and have been documented to bring about severe, even life-threatening acute poisoning events. The objective of this study is to develop a rapid and sensitive ambient ionization mass spectrometric platform to characterize the undeclared toxic adulterated ingredients in herbal preparations. Several common adulterants were spiked into different herbal preparations and human sera to simulate the clinical conditions of acute poisoning. They were then sampled with a metallic probe and analyzed by the thermal desorption-electrospray ionization mass spectrometry. The experimental parameters including sensitivity, specificity, accuracy, and turnaround time were prudently optimized in this study. Since tedious and time-consuming pretreatment of the sample is unnecessary, the toxic adulterants could be characterized within 60 s. The results can help emergency physicians to make clinical judgments and prescribe appropriate antidotes or supportive treatment in a time-sensitive manner.

Prognosis prediction of procalcitonin within 24 h for acute diquat poisoning

BackgroundTo explore the predictive value of procalcitonin (PCT) within 24 h after poisoning for prognosis of acute diquat poisoning.MethodsThis retrospective study included acute diquat poisoning patients in the Nanyang City Hospital between May 2017 and July 2021.ResultsAmong the 45 patients included, 27 survived. The maximum PCT value within 24 h after poisoning was significantly higher in the non-survival patients [9.65 (2.63, 22.77) vs. 0.15 (0.10, 0.50) µg/mL, P < 0.001] compared to the survival patients. The area under the ROC curve (AUC) indicated that the maximum PCT value within 24 h had a good predictive value (AUC = 0.905, 95% CI: 0.808-1.000) compared to ingested quantity (AUC = 0.879, 95% CI: 0.776–0.981), serum creatinine (AUC = 0.776, 95% CI: 0.640–0.912), or APACHE II score (AUC = 0.778, 95% CI: 0.631–0.925). The predictive value of maximum PCT value within 24 h was comparable with blood lactate (AUC = 0.904, 95%CI: 0.807-1.000).ConclusionsThe maximum PCT value within 24 h after poisoning might be a good predictor for the prognosis of patients with acute diquat poisoning.

Chemical Composition, Antioxidant, Acute Toxicity and Antinociceptive Activity of Aqueous Extract of Marrubium vulgare L.

Marrubium vulgare L. has a long history of use in traditional herbal medicine for the treatment of respiratory tract infections, inflammatory conditions, and pain. This study aimed to investigate the chemical composition, acute toxicity, and antinociceptive effects of the aqueous extract from M. vulgare leaves (AEMV). Antioxidant activity was evaluated using DPPH and reducing power assays. The chemical composition of AEMV was determined through LC-MS/MS, and the levels of total phenolics, flavonoids, and condensed tannins were quantified. Acute oral toxicity was assessed in male Swiss mice with a single oral dose of AEMV (1, 2, 5 g/kg). The analgesic impact was examined through writhing, hot plate, and formalin tests. Our findings not only confirmed the safety of the extract in animal models but also revealed significant antioxidant activity in AEMV. High-performance liquid chromatography (HPLC) analysis identified important bioactive compounds, with marrubiin being a major component. Furthermore, AEMV demonstrated robust antinociceptive properties in all conducted tests, highlighting its potential as a valuable natural source of bioactive compounds suitable for a wide range of therapeutic applications.

Discovery of Novel Aryl Triazolone Dihydropyridines (ATDPs) Targeting Highly Conserved Residue W229 as Promising HIV-1 NNRTIs.

NNRTI is an important component of the highly active antiretroviral therapy (HAART), but the rapid emergence of drug resistance and poor pharmacokinetics limited their clinical application. Herein, a series of novel aryl triazolone dihydropyridines (ATDPs) were designed by structure-guided design with the aim of improving drug resistance profiles and pharmacokinetic profiles. Compound 10n (EC50 = 0.009-17.7 μM) exhibited the most active potency, being superior to or comparable to that of doravirine (DOR) against the whole tested viral panel. Molecular docking was performed to clarify the reason for its higher resistance profiles. Moreover, 10n demonstrated excellent pharmacokinetic profile (T1/2 = 5.09 h, F = 108.96%) compared that of DOR (T1/2 = 4.4 h, F = 57%). Additionally, 10n was also verified to have no in vivo acute or subacute toxicity (LD50 > 2000 mg/kg), suggesting that 10n is worth further investigation as a novel oral NNRTIs for HIV-1 therapy.

Trametes versicolor Laccase-Based Magnetic Inorganic-Protein Hybrid Nanobiocatalyst for Efficient Decolorization of Dyes in the Presence of Inhibitors

In the present investigation, an ecofriendly magnetic inorganic-protein hybrid system-based enzyme immobilization was developed using partially purified laccase from Trametes versicolor (TvLac), Fe3O4 nanoparticles, and manganese (Mn), and was successfully applied for synthetic dye decolorization in the presence of enzyme inhibitors. After the partial purification of crude TvLac, the specific enzyme activity reached 212 U∙mg total protein−1. The synthesized Fe3O4/Mn3(PO4)2-laccase (Fe3O4/Mn-TvLac) and Mn3(PO4)2-laccase (Mn-TvLac) nanoflowers (NFs) exhibited encapsulation yields of 85.5% and 90.3%, respectively, with relative activities of 245% and 260%, respectively, compared with those of free TvLac. One-pot synthesized Fe3O4/Mn-TvLac exhibited significant improvements in catalytic properties and stability compared to those of the free enzyme. Fe3O4/Mn-TvLac retained a significantly higher residual activity of 96.8% over that of Mn-TvLac (47.1%) after 10 reuse cycles. The NFs showed potential for the efficient decolorization of synthetic dyes in the presence of enzyme inhibitors. For up to five reuse cycles, Fe3O4/Mn-TvLac retained a decolorization potential of 81.1% and 86.3% for Coomassie Brilliant Blue R-250 and xylene cyanol, respectively. The synthesized Fe3O4/Mn-TvLac showed a lower acute toxicity towards Vibrio fischeri than pure Fe3O4 nanoparticles did. This is the first report of the one-pot synthesis of biofriendly magnetic protein-inorganic hybrids using partially purified TvLac and Mn.

The use of Phytochemical, GC-MS Analysis and Hepatoprotective Effect of the Methanol Leaf Extract of Camellia Sinensis (L.) Kuntze on Paracetamol-Induced Liver Injury in Wistar Rats

BACKGROUND AND OBJECTIVES: Camellia sinensis is a tree popularly called green tea used as a strong antioxidant and for treating diseases such as cancer. This present study was aimed at assessing the phytochemicals and evaluating the hepatoprotective activity of leaf extract in Wistar rats. METHODS: The phytochemical screening was performed by standard methods, acute toxicity study and hepatoprotective activity were evaluated in randomly groups of five rats or six rats in paracetamol-induced liver toxicity. RESULTS: The phytochemical screening of leaf extract revealed the presence of major metabolites. The GC-MS analysis showed 18 bioactive compounds which are mainly fatty acids with retention times between 7.436 and 18.462 min. A high total phenolic content (TPC) of 1425.22 mg GAE/g and a total flavonoid content (TFC) of 802.01 mg QE/g were obtained. The acute toxicity did not produce any sign of toxicity at a dose of 5,000 mg/kg of extract. The extract produced a dose-dependent activity on the liver. These protections were statistically significant (p&lt;0.05) when compared to the standard drug silymarin. There were no elevated values in liver function biomarkers in all the animal groups as well as histopathological damages to the liver after eight weeks of treatment at 200 and 400 mg/kg b.w. of extract doses. CONCLUSION: In conclusion, the study showed that C. sinensis methanol leaf extract contains important phytochemicals that are protective against paracetamol-induced liver injuries, thus, the plant was considered safe for use as ethnomedicinal remedies for liver disease in traditional medicine.

Behavioral toxicity and neurotoxic mechanisms of PLA-PBAT biodegradable microplastics in zebrafish

Escalation of ecological concern due to biodegradable plastics has attracted the attention of many contemporary researchers. This study searched to investigate the acute and sub-chronic toxicity of polylactic acid (PLA) and polybutyleneadipate-co-terephthalate (PLA-PBAT) bio-microplastics on 3-month-old zebrafish to elucidate their potential toxic mechanisms. Acute toxicity assessments revealed 96 h-LC50 value of 12.69 mg/L for PLA-PBAT. Sub-chronic exposure of over 21 days revealed deviations in critical behavioral patterns and physiological indicators. In treated groups, weight gain and specific growth rates were significantly lower than those obtained for the control group, such that high doses induced significant reductions in total organ coefficient (p < 0.05). A positive correlation was observed between zebrafish mortality and increased doses. Detailed behavioral evaluations revealed a dose-dependent decrease in the speed and range of swimming, along with modifications in shoaling behavior, anxiety-like responses, and avoidance behaviors. Brain tissues transcriptomic analyses revealed the molecular responses underlying sub-chronic exposure to PLA-PBAT. Totally 702 DEGs and 5 KEGG pathways were significantly identified in low-dose group, with the top 2 significant pathways being ribosome pathway and cytokine-cytokine receptor interaction pathway. Totally 650 DEGs and 5 KEGG pathways were significantly identified in medium-dose group, with the top 2 significant pathways being Herpes simplex virus 1 infection pathway and complement and coagulation cascades pathway. Totally 1778 DEGs and 16 KEGG pathways were significantly identified in high-dose group, with the top 2 significant pathways being metabolism of xenobiotics by cytochrome P450 and drug metabolism - cytochrome P450 pathway. Most significantly enriched pathways are associated with immune responses. The validation of key gene in cytokine-cytokine receptor interaction pathway also confirmed its high correlation with behavioral indicators. These results indicate that PLA-PBAT is likely to cause behavioral abnormalities in zebrafish by triggering immune dysregulation in the brain.

Development of phytosterol-loaded silver nanoparticles for ameliorating haemorrhoidal complications via the AMPK pathway—a mechanistic approach

The aim of the current study was to synthesize silver nanoparticles (PLSNPs) using green technology by means of phytosterol-enriched fractions from Blumea lacera extracts (EAF) and evaluate their toxicological and anti-haemorrhoidal potential. The average size of the synthesized particles was found to be 85.64 nm by scanning electron microscopy and transmission electron microscopy. Energy dispersive spectroscopy showed the elemental composition of PLSNPs to be 12.59% carbon and 87.41% silver, indicating the capping of phytochemicals on the PLSNPs. The PLSNPs were also standardized for total phytosterol content using chemical methods and high-perfromance liquid chromatography. The PLSNPs were found to be safe up to 1000 mg kg−1 as no toxicity was observed in the acute and sub-acute toxicity studies performed as per OECD guidelines. After the induction of haemorrhoids, experimental animals were treated with different doses of EAF, PLSNPs and a standard drug (Pilex) for 7 d, and on the eighth day the ameliorative potential was assessed by evaluating the haemorrhoidal (inflammatory severity index, recto-anal coefficient) and biochemical (tumour necrosis factor-alpha and interleukin-6) parameters and histology of the recto-anal tissue. The results showed that treatment with PLSNPs and Pilex significantly (p < 0.05) reduced haemorrhoidal and biochemical parameters. This was further supported by restoration of altered antioxidant status. Further, a marked reduction in the inflammatory zones along with minimal dilated blood vessels was observed in the histopathological study. The results of molecular docking studies also confirmed the amelioration of haemorrhoids via AMP-activated protein kinase (AMPK)-mediated reduction of inflammation and endothelin B receptor modification by PLSNPs. In conclusion, PLSNPs could be a good alternative for the management of haemorrhoids.

Enhanced treatment of acute organophosphorus pesticide poisoning using activated charcoal-embedded sodium alginate-polyvinyl alcohol hydrogel.

The adsorption of activated charcoal is currently a major clinical treatment for acute organophosphorus pesticide poisoning (AOPP). However, the adsorption duration and efficiency of this method is unstable. In this study, a hydrogel embedding activated charcoal was prepared and its alleviating effects on AOPP were investigated. A composite hydrogel using sodium alginate and polyvinyl alcohol (SA-PVA) hydrogel was prepared in this study. The structural properties of the SA-PVA hydrogel were characterized via multiple analysis including FTIR, TGA, XRD, SEM, tensile strength and expansion rate. Based on these, activated charcoal (AC) was embedded within the SA-PVA hydrogel (SA-PVA-AC) and it was used for the treatment of AOPP. Structural characterization indicated SA-PVA hydrogel possesses excellent mechanical properties and biocompatibility. The invivo study demonstrated that SA-PVA-AC significantly alleviated the inflammation and oxidative damage in the liver, as evidenced by reduced levels of IL-6, TNF-α, and, IL-1β, SOD, and MDA. Furthermore, SA-PVA-AC treatment effectively re-regulated the activities of serum AST and ALT, exhibiting an improved effect on liver function. The findings suggest that activated charcoal embedded within SA-PVA hydrogel has significant potential as a therapeutic agent in treating AOPP, and offering a novel approach to managing pesticide-induced toxicity.

Nanosized Particles of Synthetic Silicon Dioxide Delay the Regeneration of Gastric Ulcers Created by N-Methyl-N′-Nitro-N-Nitrosoguanidine and Induce Hyper-Trophic Gastritis-like Symptoms

Synthetically produced silicon dioxide used as a food additive exhibits nanoparticle size and shape during the early stages of manufacturing. Even when processed into food products, these nanoparticles are detected. Although processing food ingredients into nanoparticles can improve absorption rates or enhance texture, there are concerns about the specific biological effects of nanoparticles. In this study, three types of silica particles, including nanosized particles, were repetitively administered to the stomach using a gastric tube or exposed to a single injection into the submucosal layer of the stomach. Macroscopic and microscopic examinations did not reveal acute toxicity. However, when silica particles were administered to the stomach during the healing and regeneration process of gastric ulcers (induced by injecting the alkylating agent of N-Methyl-N′-Nitro-N-Nitrosoguanidine into the submucosal layer), silica particles with a diameter of 70 nm (SiNPs-70) delayed regeneration more strongly than microsized silica particles with diameters of 300 nm or 1000 nm (SiMPs-300, -1000). Furthermore, fibrosis for tissue regeneration spread throughout the entire mucosa of the stomach, resulting in hypertrophic gastritis-like symptoms. The frequency of this symptom was over 50% with SiNPs-70, 20% with SiMPs-300, and 0% with SiMPs-1000. Although the silica particles used in this study differ from actual samples found in food, the impact of particle size, particularly the effects unique to nanosize, was identified as toxicity in the stomach healing process.

Phyllodulcin from the hexane fraction of Hydrangea macrophylla inhibits glucose-induced lipid accumulation and reactive oxygen species (ROS) generation in Caenorhabditis elegans.

We confirmed that the hexane layer of Hydrangea macrophylla leaf extract (HLH) is rich in phyllodulcin (PD), an alternative sweetener through HPLC analysis. To investigate in vivo activity of HLH and its PD, acute toxicity and growth rate of Caenorhabditis elegans were tested and there are no clinical abnormalities at 125-500μg/mL of HLH. HLH decreased the total lipid and TG contents dose-dependently glucose (GLU) induced obese worms. Also, HLH increased survival rates under oxidative and thermal stress and decreased body ROS contents significantly. Such antioxidant properties of HLH were attributed to the enhanced activity of the antioxidant enzyme catalase. To determine whether the effect of HLH was by PD, worms were treated with PD (concentration contained in HLH), and inhibitory effects on total lipids and ROS were observed. Our results suggest that HLH and its PD as a natural alternative sweetener can be material to improve metabolic diseases.

Proton beam reirradiation for locally recurrent rectal cancer patients with prior pelvic irradiation.

The aim of the present study was to report the feasibility of proton beam reirradiation for patients with locally recurrent rectal cancer (LRRC) with prior pelvic irradiation. The study population included patients who were treated with proton beam therapy (PBT) for LRRC between 2008 and December 2019 in our institution. Those who had a history of distant metastases of LRRC, with or without treatment, before reirradiation, were excluded. Overall survival (OS), progression-free survival (PFS) and local control (LC) were estimated using the Kaplan-Meier method. Ten patients were included in the present study. The median follow-up period was 28.7months, and the median total dose of prior radiotherapy (RT) was 50Gy (range, 30Gy-74.8Gy). The median time from prior RT to reirradiation was 31.5months (range, 8.1-96.6months), and the median reirradiation dose was 72Gy (relative biological effectiveness) (range, 56-77Gy). The 1-year/2-year OS, PFS and LC rates were 100%/60.0%, 20.0%/10.0% and 70.0%/58.3%, respectively, with a median survival time of 26.0months. Seven patients developed a Grade 1 acute radiation dermatitis, and no Grade≥2 acute toxicity was recorded. Grade≥3 late toxicity was recorded in only one patient, who had developed a colostomy due to radiation-related intestinal bleeding. Reirradiation using PBT for LRRC patients who had previously undergone pelvic irradiation was feasible. However, the indications for PBT reirradiation for LRRC patients need to be considered carefully due to the risk of severe late GI toxicity.

Imaging gastrointestinal damage due to acute mercury poisoning using a mitochondria-targeted dual near-infrared fluorescent probe

Mercury (Hg) is one of the most widespread pollutants that pose serious threats to public health and the environment. People are inevitably exposed to Hg via different routes, such as respiration, dermal contact, drinking or diet. Hg poisoning could cause gingivitis, inflammation, vomiting and diarrhea, respiratory distress or even death. Especially during the developmental stage, there is considerable harm to the brain development of young children, causing serious symptoms such as intellectual disability and motor impairments, and delayed neural development. Therefore, it’s of great significance to develop a specific, quick, practical and labor-saving assay for monitoring Hg2+. Herein, a mitochondria-targeted dual (excitation 700 nm and emission 728 nm) near-infrared (NIR) fluorescent probe JZ-1 was synthesized to detect Hg2+, which is a turn-on fluorescent probe designed based on the rhodamine fluorophore thiolactone, with advantages of swift response, great selectivity, and robust anti-interference capability. Cell fluorescence imaging results showed that JZ-1 could selectively target mitochondria in HeLa cells and monitor exogenous Hg2+. More importantly, JZ-1 has been successfully used to monitor gastrointestinal damage of acute mercury poisoning in a drug-induced mouse model, which provided a great method for sensing Hg species in living subjects, as well as for prenatal diagnosis.