Understanding fenpropathrin-induced pulmonary toxicity: What apoptosis, inflammation, and pyreptosis reveal analyzing cross-links at the molecular, immunohistochemical, and immunofluorescent levels.

Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.

Impact of Coriandrum sativum seeds extract on albino rats' testicular toxicity caused by carbendazim.

Background: A broad spectrum carbamate fungicide called carbendazim (Carb) is used to combat a number of different fungal diseases. One of the extensively utilized medicinal plants in oriental countries is Coriandrum sativum. Aim: In the current study, the impact of C. sativum seeds extract (CSE) on albino rats' testicular toxicity caused by carbendazim was investigated. Materials and methods: A total of 50 male albino rats were classified into 5 groups [Gp1, Control Gp; Gp2, Coriandrum Gp (CSE); Gp 3, carbendazim Gp (Carb); Gp 4, Co treated CSE with Carb (CSE + Carb); Gp 5, Post treated Carb with CSE (Carb + CSE)]. Results: Carb induced elevation in serum LH. FSH, testicular malondialdehyde (MDA), testicular nitric oxide (NO) markers and testicular injury and it reduced serum testosterone, testicular glutathione (GSH), testicular catalase and PCNA. Treatments of Carb with CSE (CSE + Carb and/or Carb + CSE) improved these parameters and reduced testicular toxicity with best results for Carb + CSE than CSE + Carb. Conclusions: The above findings revealed that; Carb induced testicular toxicity and it supported the hypothesis that the antioxidant characteristics of one or more of CSE constituents can reduce the testicular toxicity of Carb.

Sugiol Masters Apoptotic Precision to Halt Gastric Cancer Cell Proliferation.

Sugiol, a natural compound with anticancer properties, has shown promise in various cancer types, but its potential in preventing gastric cancer remains uncertain. In this study, we aimed to examine the inhibitory effect of sugiol on human gastric cancer cell proliferation. Our findings demonstrate that sugiol effectively suppresses the proliferation of SNU-5 human gastric cancer cells, leading to apoptotic cell death. We assessed the chemo-preventive potential of sugiol via an MTT assay and confirmed the induction of oxidative stress using the H2DCFDA fluorescent dye. Treatment with sugiol at concentrations higher than 25 µM for 24 h resulted in an increase in intracellular levels of reactive oxygen species (ROS). This elevation of ROS levels inhibited cell-cycle progression and induced cell-cycle arrest at the G1 phase. Furthermore, our study revealed that sugiol reduces the viability and proliferation of SNU-5 cells in a dose-dependent manner. Importantly, ADME and toxicity analyses revealed that sugiol was effective and nontoxic at low doses. In parallel, we utilized the Swiss target prediction tool to identify potential targets for sugiol. Enzymes and nuclear receptors were identified as major targets. To gain insights into the molecular interactions, we performed structure-based molecular docking studies, focusing on the interaction between sugiol and STAT3. The docking results revealed strong binding interactions within the active site pocket of STAT3, with a binding affinity of -12.169 kcal/mole. Sugiol's -OH group, carbonyl group, and phenyl ring demonstrated hydrogen-bonding interactions with specific residues of the target protein, along with Vander Waals and hydrophobic interactions. These data suggest that sugiol has the potential to inhibit the phosphorylation of STAT3, which is known to play a crucial role in promoting the growth and survival of cancer cells. Targeting the dysregulated STAT3 signaling pathway holds promise as a therapeutic strategy for various human tumors. In combination with interventions that regulate cell cycle progression and mitigate the DNA damage response, the efficacy of these therapeutic approaches can be further enhanced. The findings from our study highlight the antiproliferative and apoptotic potential of sugiol against human gastric cancer cells (SNU-5). Moreover, the result underpins that sugiol's interactions with STAT3 may contribute to its inhibitory effects on cancer cell growth and proliferation. Further research is warranted to explore the full potential of sugiol as a therapeutic agent and its potential application in treating gastric cancer and other malignancies characterized by dysregulated STAT3 activity.

Unraveling Therapeutic Opportunities and the Diagnostic Potential of microRNAs for Human Lung Cancer.

Lung cancer is a major public health problem and a leading cause of cancer-related deaths worldwide. Despite advances in treatment options, the five-year survival rate for lung cancer patients remains low, emphasizing the urgent need for innovative diagnostic and therapeutic strategies. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets for lung cancer due to their crucial roles in regulating cell proliferation, differentiation, and apoptosis. For example, miR-34a and miR-150, once delivered to lung cancer via liposomes or nanoparticles, can inhibit tumor growth by downregulating critical cancer promoting genes. Conversely, miR-21 and miR-155, frequently overexpressed in lung cancer, are associated with increased cell proliferation, invasion, and chemotherapy resistance. In this review, we summarize the current knowledge of the roles of miRNAs in lung carcinogenesis, especially those induced by exposure to environmental pollutants, namely, arsenic and benzopyrene, which account for up to 1/10 of lung cancer cases. We then discuss the recent advances in miRNA-based cancer therapeutics and diagnostics. Such information will provide new insights into lung cancer pathogenesis and innovative diagnostic and therapeutic modalities based on miRNAs.

The effect of folic acid as an antioxidant on the hypothalamic monoamines in experimentally induced hypothyroid rat.

Thyroid hormones are recognized as key metabolic hormones that play a critical role in the central nervous system development throughout life. In the present study, we studied the biochemical changes of hypothalamus of hypothyroid rats at post-pubertal stage, and the possible ameliorating effect of folic acid. A total of 50 male albino rats were equally divided into five groups; the first and second groups were the control and folic acid groups, respectively, while the third group was the hypothyroid group in which rats received daily 6-n-propyl-2-thiouracil (PTU) in drinking water for 6 weeks to induce hypothyroidism. The fourth and fifth groups were hypothyroid rats treated with folic acid for 4 weeks during and after receiving PTU, respectively, and were dissected after 6 and 10 weeks, respectively. There was a significant increase in plasma total homocysteine, malondialdehyde (MDA), oxidized glutathione\reduced glutathione and total nitric oxide and hypothalamic MDA, serotonin and norepinephrine in the hypothyroid rats group as compared to the control group. This reflects hyperhomocysteinaemia and oxidative stress associated with hypothyroid state. On the other hand, hypothalamic total nitric oxide and dopamine in the hypothyroid rats group were significantly decreased when compared to the control group. Treatment of hypothyroid rats with folic acid improves the oxidative stress and hypothalamic monoamines. Our results revealed that, folic acid treatment was better if it is administered as an adjuvant after returning to the euthyroid state.