This research aimed to evaluate the therapeutic effect of corilagin (Cor) against angiotensin II (Ang II)-induced cardiac fibrosis and its underlying mechanisms. C57BL/6 mice (male, 8-10 weeks) received saline or Ang II (2.0 mg/kg/day) via subcutaneous infusion and intraperitoneal injection of Cor (30 mg/kg) for 28 days. Ang II induction increased the fibrotic area, whereas Cor treatment inhibited the fibrotic area significantly. Cor markedly reduced the Ang II-induced cardiac fibroblasts. Cor significantly inhibited Ang II-induced increase in expressions of smooth muscle alpha-actin (α-SMA), collagen I, collagen III, transforming growth factor beta 1 (TGF-β1), fibronectin, and connective tissue growth factor (CTGF). Cor suppressed the intracellular reactive oxygen species (ROS) production. Cor therapy reduced Ang II-induced malondialdehyde (MDA) content, whereas superoxide dismutase (SOD) and catalase (CAT) activities were increased (all, P < .001). Moreover, Ang II induction elevated the expression of phosphorylated phosphatase and tensin homolog (p-PTEN), phosphorylated protein kinase B (p-AKT) (Ser473) and phosphorylated mammalian target of rapamycin (p-mTOR) (Ser 2448), whereas Cor reduced their expressions. Cor treatment inhibited the migration ability of the cardiac fibroblast, whereas a PTEN inhibitor, VO-ohpic, increased the migration capability. Cor could have a protective effect against Ang II-induced cardiac fibrosis via inhibition of the PTEN/AKT/mTOR pathway.

Introduction: Parkinson’s disease (PD) is characterized by dopamine deficiency in the corpus striatum due to the degeneration of dopaminergic neurons in the substantia nigra. Symptoms include bradykinesia, resting tremors, unstable posture, muscular rigidity, and a shuffled gait. Thalictrum foetidum is traditionally used for neurodegenerative disorders. Objectives: This study aimed to explore the therapeutic potential of aqueous ethanolic extract of Thalictrum foetidum (AETF) against Parkinson-like symptoms and to investigate its underlying mechanism. Methodology: Thirty-six albino mice were randomly divided into 6 groups (n = 6): normal control, disease control, standard treatment (levodopa/carbidopa, 100/25 mg/kg), and 3 treatment groups (AETF at 200, 400, and 600 mg/kg). One hour before treatment, haloperidol (1 mg/kg, i. p.) was administered to induce Parkinson’s disease in all groups except the normal control group. Results: Behavioral analysis showed significant improvement ( P < .001) in motor function, muscular coordination, and reduced muscular rigidity and tremors. AETF also reduced oxidative stress. Histological examination of the brain showed reduced Lewy bodies, neurofibrillary tangles, and plaque formation. Conclusion: AETF alleviated PD symptoms by reducing neurodegeneration, modulating oxidative stress, and inhibiting the expression of nuclear factor-κB (NF-κB) and associated inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).

Caffeine citrate (CC)-induced excessive energy expenditure, diuresis, natriuresis, and other CC-associated potential side effects (CC-APSEs) result in lower daily weight gain (WG) in premature neonates. This study aimed to assess higher CC-doses' effect on the mean daily-WG (MD-WG) and CC-APSE development, considering 5mg/kg/day as the standard regimen. This retrospective cohort study included neonates of ≤36weeks gestational age and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15-28 and 29-42days of life (DOL). Based on daily CC-dose, formed group-I=(5mg/kg/day), group-II=(>5-7mg/kg/day), and group-III=(>7mg/kg/day). Data was analyzed separately for group-II and group-III using group-I as the standard. The study included 284 neonates. During phase-I, the MD-WG was significantly higher in group-I than group-II (19.9 ± .88g/kg/d vs 17.5 ± .49, P = .031) and group-III (19.9 ± .88g/kg/d vs 16.7 ± .71, P < .001). During 29-42 DOL, the MD-WG of group-I was only significantly higher than group-III (21.5 ± .42g/kg/d vs 18.1 ± .39g/kg/d, P = .003) and comparable with group-II. During 15-28 DOL, CC-APSEs were significantly higher in group-II and group-III but during 29-42 DOL was significant only in group-III. Exposure to higher caffeine doses in this study cohort is associated with lower postnatal WG in preterm neonates than standard daily doses may be due to its catabolic effects and CC-APSEs.

Arsenic (As) is a highly toxic and carcinogenic pollutant commonly found in soil and water, posing significant risks to human health and plant growth. The objectives of this study to evaluate morphological, biochemical, and physiological markers, as well as ion homeostasis, to alleviate the toxic effects of As in sunflowers through the exogenous application of salicylic acid (SA), γ-aminobutyric acid (GABA), and their combination. A pot experiment was conducted using two sunflower genotypes, FH-779 and FH-773, subjected to As stress (60mg kg-1) to evaluate the effects of SA at 100mg L-1, GABA at 200mg L-1, and their combination on growth and related physiological and biochemical attributes under As stress. The study revealed that As toxicity had a detrimental effect on various growth parameters, chlorophyll pigments, relative water content, total proteins, and nutrient uptake in sunflower plants. It also led to increased oxidative stress, as indicated by higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), along with As accumulation in the roots and leaves. However, the application of SA and GABA protected against As-induced damage by enhancing the enzymatic antioxidant defense system. This was achieved through the activation of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as an increase in osmolytes. They also improved nutrient acquisition and plant growth under As toxicity. We investigated the regulatory roles of SA and GABA in mitigating arsenic-induced phytotoxic effects on sunflower. Our results revealed a significant interaction between SA and GABA in regulating growth, photosynthesis, metabolites, antioxidant defense systems, and nutrient uptake in sunflower under As stress. These findings provide valuable insights into plant defense mechanisms and strategies to enhance stress tolerance in contaminated environments. In the future, SA and GABA could be valuable tools for managing stress in other important crops facing abiotic stress conditions.

Radiation therapy has been a critical and effective treatment for cancer. However, not all cells are destroyed by radiation due to the presence of tumor cell radioresistance. In the current study, we investigated the effect of low-dose radiation (LDR) on the tumor suppressive effect of high-dose radiation (HDR) and its mechanism from the perspective of tumor cell death mode and DNA damage repair, aiming to provide a foundation for improving the efficacy of clinical tumor radiotherapy. We found that LDR pre-irradiation strengthened the HDR-inhibited A549 cell proliferation, HDR-induced apoptosis, and G2 phase cell cycle arrest under co-culture conditions. RNA-sequencing showed that differentially expressed genes after irradiation contained pyroptosis-related genes and DNA damage repair related genes. By detecting pyroptosis-related proteins, we found that LDR could enhance HDR-induced pyroptosis. Furthermore, under co-culture conditions, LDR pre-irradiation enhances the HDR-induced DNA damage and further suppresses the DNA damage-repairing process, which eventually leads to cell death. Lastly, we established a tumor-bearing mouse model and further demonstrated that LDR local pre-irradiation could enhance the cancer suppressive effect of HDR. To summarize, our study proved that LDR pre-irradiation enhances the tumor-killing function of HDR when cancer cells and immune cells were coexisting.

Ciprofol is a new sedative anesthetic drug that can be used for gastrointestinal endoscopy and induction of general anesthesia, but the appropriate dosage for use in elderly patients has not been determined. Sufentanil is a commonly used opioid in clinical practice, and this study was designed to induce anesthesia in elderly patients using sufentanil in combination with ciprofol. However, the optimal dosage of ciprofol when it is co-administered with sufentanil has not yet been established. This study was designed to find the median effective dose (ED50) and 95% confidence interval (95% CI) of ciprofol for intravenous anesthesia when combined with sufentanil. We studied 57 patients who were scheduled to undergo a diagnostic upper gastrointestinal endoscopy. According to age, it was divided into two groups: 65∼74 years old (group A) and over 75 years old (group B). Using the modified Dixon sequence test method, intravenous bolus of 0.1μg/kg sufentanil was given 3 min before ciprofol is administered, the initial dose of ciprofol was 0.4mg/kg, the upper gastrointestinal endoscopy was placed after reaching the depth of sedation, and vital signs and adverse events were recorded at each perioperative time point (T0-T7). In the group A, when combined with 0.1 μg/kg sufentanil, the ED50 of ciprofol to inhibiting responses to insertion of upper gastrointestinal endoscopy was 0.23mg/kg, and the 95% CI was 0.09∼0.30mg/kg; in the group B, the ED50 was 0.18mg/kg, and the 95% CI was 0.13∼0.22mg/kg. The ED50 of ciprofol in combination with sufentanil (0.1μg/kg) for upper gastrointestinal endoscopy in elderly patients: 0.23mg/kg in group A and 0.18mg/kg in group B.

We have been conducting a collaborative study on the thresholds of mutagens. In our previous examinations of cell activity and cell proliferation as endpoints, both displayed hormesis. This time, we conducted experiments to determine thresholds using the micronucleus test as an endpoint. The micronucleus test was conducted using Chinese hamster CHL/IU cells and mouse lymphoid L5178Y cells. Additionally, we conducted preliminary investigations into the gene expression using human TK6 cells. When adhesive CHL/IU cells were treated with mitomycin C (MMC), and the hormetic response was examined, hormesis was not observed clearly. When L5178Y cells were treated with methyl methanesulfonate (EMS), AF-2, MMC, and colchicine, all of them exhibited an adaptive response. Additionally, cross-adaptive responses using AF-2 and MMC or EMS and MMC were conducted, both combinations showed a cross-adaptive response. When the gene expression patterns of six genes were investigated by RT-PCR after treatment with MMC, EMS, and H2O2 using TK6 cells, two genes, GADD45A and P21, were induced in a dose- and time-dependent manner. Adaptive responses arise from preconditioning. As hormesis is inherently linked to preconditioning, adaptive responses observed in this study strongly suggest that hormesis was induced, hence existence of thresholds.

This is an editorial from the new editor-in-chief, EIC, who starts his role in March 2024. Due to the remarkable advance of various research fields in terms of its concepts and technology, the emerging concepts of "Exposome" and associated "Exposomics" have been introduced into the toxicology research. Therefore, the mission of "Dose-Response" will remain adhered to the original goals but will incorporate with these new concepts as the next chapter's principle and strategies. Accordingly, although it remains with special interest in the biological response to low-dose (level) ranges of stresses. The types and contents of interested manuscripts will be extended with more diverse, newer concepts from a wide range of disciplines. We wish this journal can open a door for various discipline scientists and researchers to share their state-of-the-art discoveries to shed new insight to understand the impact of environmental and toxicological medicine and develop more specific and effective intervention strategies.

Isoproterenol (ISO), a chemically synthesized catecholamine, belongs to β-adrenoceptor agonist used to treat bradycardia. The β-adrenergic agonist is an essential regulator of myocardial metabolism and contractility; however, excessive exposure to ISO can initiate oxidative stress and inflammation. This study aims to investigate the molecular mechanisms underlying ISO-induced cardiac remodeling, the protective efficacy of resveratrol (RSVR), and its liposomal formulation (L-RSVR) against such cardiac change. Wistar albino rats were evenly divided into 4 groups. Control group, ISO group received ISO (50mg/kg, s.c.) twice a week for 2weeks, and RSVR- and L-RSVR-treated groups in which rats received either RSVR or L-RSVR (20mg/kg/day, p.o.) along with ISO for 2weeks. ISO caused a significant elevation of the expression levels of BAX and MEF2 mRNA, S100A1 and cytochrome C proteins, as well as DNA fragmentation in cardiac tissue compared to the control group. Treatment with either RSVR or L-RSVR for 14days significantly ameliorated the damage induced by ISO, as evidenced by the improvement of all measured parameters. The present study shows that L-RSVR provides better cardio-protection against ISO-induced cardiac injury in rats, most likely through modulation of cardiac S100A1 protein expression and inhibition of inflammation and apoptosis.