Background: Aluminum phosphide (AlP), also known as “rice tablet,” is widely used as an effective pesticide. However, AlP poisoning is a common cause of mortality in many countries, such as Iran. Unfortunately, there is no specific antidote for AlP toxicity to date. AlP releases phosphine gas when it is exposed to moisture and acid. Phosphine is a robust mitochondrial toxin that could significantly inhibit cellular energy metabolism. AlP poisoning is an emergency condition that needs instant and effective intervention. Dihydroxyacetone (DHA) is a simple saccharide used for several pharmacological as well as cosmetic purposes. Previously, we found that DHA could significantly prevent mitochondrial impairment induced by toxic agents such as cyanide and phosphine in various in vitro and in vivo experimental models.Methods: Hospitalized patients (n = 111) were evaluated for eligibility criteria. Among these patients, n = 35 cases were excluded due to incomplete data (n = 11) and suspicion of poisoning rather than AlP (n = 24). Meanwhile, n = 76 cases with confirmed AlP poisoning were included in the study. AlP-poisoned patients who did not receive DHA (n =18) were used as the control group.Patients (n = 58) received at least one dose of DHA (500 ml of 5% DHA solution w/v, i.v.) in addition to routine treatment of AlP poisoning. Arterial blood gas (ABG), blood pH, bicarbonate levels, and other vital signs and biochemical measurements were monitored. Moreover, the mortality rate and time of hospitalization were evaluated in both DHA-treated (n = 58) and AlP-poisoned patients without DHA administration (n = 18). Several biomarkers were assessed before (upon hospitalization) and after DHA treatment. The routine tests for AlP-poisoned patients in this study were the measurement of electrolytes (K+ and Na+), WBC, RBC, hemoglobin, INR, carbonate (HCO3), blood pH, PaCO2, and PaO2 and SGPT, SGOT, BUN, Cr. Results: Upon patients' admission, significant decreases in blood pH (acidosis), blood PaO₂, and HCO₃ levels were the hallmarks of AlP poisoning. It was found that DHA significantly alleviated biomarkers of AlP poisoning and tremendously enhanced patients’ survival rate compared to patients treated based on hospital routine AlP poisoning protocols (no DHA). No significant adverse effects were evident in DHA-treated patients in the current study.Interpretation: These data suggest that parenteral DHA is a novel and effective antidote against AlP poisoning.Trial registration: IR.SUMS.REC.1394.102

Extracellular vesicles (EVs) are enclosed by a lipid-bilayer membrane and secreted by all types of the cells under various physiological conditions. EVs play important roles in intercellular communication and crosstalk between tissues in the body. They are classified into three groups, such as apoptotic bodies, microvesicles, and exosomes. Exosomes were isolated from biofluids including blood, urine, milk, and cell culture media. Exosomes have significant potential for drug delivery and diagnosis. However, the method of isolation affects the physical and biological properties of exosomes. Several methods based on different principles have been developed for exosome isolation. These include ultrafiltration, precipitation, ultracentrifugation, size-exclusion chromatography, and microfluidics. In this study, we applied three common methods, such as ultrafiltration, precipitation, and ultracentrifugation, to isolate exosomes from the cell culture medium and investigated the effects of these different isolation methods on the size distribution and quality of the isolated exosomes. Field emission scanning electron microscopy (FESEM) images, size distribution, total protein content, and the effect of exosomes on the viability of hypoxic cells were analyzed in this study. The analysis revealed that compared to other methods, the ultracentrifugation method can isolate exosomes with smaller diameter (ranging from 20 to 80 nm), lower total protein content (50 µg/ml), and causing the increased viability of the hypoxic cells. The precipitation method does not require special equipment and is inexpensive, if the quality and purity of this method are solved, and it can be used as the best method for exosome isolation. This study can serve as a guide for choosing the best exosome isolation method for applications in medicine according to the needs, time, cost, and equipment.

The Myc gene, widely studied in numerous cancer types, serves as a pivotal regulator of crucial cellular processes implicated in tumorigenesis, such as cell growth, proliferation, invasion, metastasis, and therapy resistance. LncRNAs have been identified as relevant partners of Myc. LncRNAs modulate chromatin structure and function, transcription, splicing, stability, and translation of mRNAs, thereby emerging as pivotal regulators in cell differentiation, metabolism, signaling. An intricate crosstalk exists between Myc and lncRNAs in a wide range of cancers, wherein they can physically and functionally interact through direct and indirect mechanisms. Some lncRNAs can regulate Myc activity at post-transcriptional level, affecting its stability, translation, or interactions with other proteins, thus acting as oncogenes, while others act as tumor suppressors. On the other hand, Myc can target numerous lncRNA genes and modulate their expression, affecting the expression of downstream targets involved in tumorigenesis. Given the significant role of the Myc-lncRNA network in various cancer types, exploring therapeutic strategies targeting these crucial cellular regulators is of utmost importance. This review article focuses on breast cancer, analyzing those lncRNAs influencing Myc as well as the Myc-regulated lncRNAs.

Curcumin (CUR) is a phytochemical with potent anticancer activities as demonstrated by both preclinical and clinical studies. CUR bioformulations, including loading in biodegradable polymers, have been explored to increase CUR’s solubility and chemical stability, control its release, and improve its delivery to cancer cells. In this study, copolymers comprising poly (L-lactide)-poly (ethylene glycol)-poly (L-lactide) (PLA-PEG-PLA) and poly (ethylene glycol)-poly (L-lactide)-poly (ethylene glycol) (PEG-PLA-PEG) were designed and synthesized to assess and compare their curcumin delivery capacity and inhibitory potency on MCF-7 breast cancer cells. Molecular dynamics simulations indicated that PLA-PEG-PLA has a higher propensity to interact with the cell membrane and more negative free energy, suggesting it is the better carrier for cell membrane penetration. Our characterization indicated that the microsphere copolymers were synthesized successfully. Of the two formulations, PLA-PEG-PLA experimentally exhibited better results, with an initial burst release of 17.5%, followed by a slow, constant release of the encapsulated drug up to 80%. PLA-PEG-PLA-curcumin showed a significant increase in cell death in MCF-7 cancer cells (IC50 = 23.01 ± 0.85 µM) based on the MTT assay. These data were consistent with gene expression studies of Bax, Bcl2, and hTERT which showed that PLA-PEG-PLA-CUR induced apoptosis more efficiently in these cells. Our study integrates in vitro and in silico approaches to identify an optimal co-polymer for the delivery of CUR to cancer cells.