The therapeutic effect of a novel parenteral formulation of dihydroxyacetone in aluminum phosphide-intoxicated patients.

Background and objectives: Aluminum phosphide (AlP), 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 or acid. Phosphine is a potent 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 with poisons other 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.) as an adjuvant therapy in addition to the 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 hospitalization time were evaluated in DHA-treated and AlP-poisoned patients without DHA administration. 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 (65.52 % in DHA-treated vs 33.34 % in the control group) 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 and conclusions: These data suggest that parenteral DHA is a novel and effective antidote against AlP poisoning to be used as an adjuvant in addition to routine supportive treatment. Trial registration: IR.SUMS.REC.1394.102.

Moving beyond nanotechnology to uncover a glimmer of hope in diabetes medicine: Effective nanoparticle-based therapeutic strategies for the management and treatment of diabetic foot ulcers.

Hyperglycemia, a distinguishing feature of diabetes mellitus that might cause a diabetic foot ulcer (DFU), is an endocrine disorder that affects an extremely high percentage of people. Having a comprehensive understanding of the molecular mechanisms underlying the pathophysiology of diabetic wound healing can help researchers and developers design effective therapeutic strategies to treat the wound healing process in diabetes patients. Using nanoscaffolds and nanotherapeutics with dimensions ranging from 1 to 100 nm represents a state-of-the-art and viable therapeutic strategy for accelerating the wound healing process in diabetic patients, particularly those with DFU. Nanoparticles can interact with biological constituents and infiltrate wound sites owing to their reduced diameter and enhanced surface area. Furthermore, it is noteworthy that they promote the processes of vascularization, cellular proliferation, cell signaling, cell-to-cell interactions, and the formation of biomolecules that are essential for effective wound healing. Nanomaterials possess the ability to effectively transport and deliver various pharmacological agents, such as nucleic acids, growth factors, antioxidants, and antibiotics, to specific tissues, where they can be continuously released and affect the wound healing process in DFU. The present article elucidates the ongoing endeavors in the field of nanoparticle-mediated therapies for the management of DFU.

Awareness raising and dealing with methanol poisoning based on effective strategies.

Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5-4 h after ingestion. After ingestion, methanol concentrations in the blood that are greater than 50 mg/dl should raise some concern. Ingested methanol is typically digested by alcohol dehydrogenase (ADH), and it is subsequently redistributed to the body's water to attain a volume distribution that is about equivalent to 0.77 L/kg. Moreover, it is removed from the body as its natural, unchanged parent molecules. Due to the fact that methanol poisoning is relatively uncommon but frequently involves a large number of victims at the same time, this type of incident occupies a special position in the field of clinical toxicology. The beginning of the COVID-19 pandemic has resulted in an increase in erroneous assumptions regarding the preventative capability of methanol in comparison to viral infection. More than 1000 Iranians fell ill, and more than 300 of them passed away in March of this year after they consumed methanol in the expectation that it would protect them from a new coronavirus. The Atlanta epidemic, which involved 323 individuals and resulted in the deaths of 41, is one example of mass poisoning. Another example is the Kristiansand outbreak, which involved 70 people and resulted in the deaths of three. In 2003, the AAPCC received reports of more than one thousand pediatric exposures. Since methanol poisoning is associated with high mortality rates, it is vital that the condition be addressed seriously and managed as quickly as feasible. The objective of this review was to raise awareness about the mechanism and metabolism of methanol toxicity, the introduction of therapeutic interventions such as gastrointestinal decontamination and methanol metabolism inhibition, the correction of metabolic disturbances, and the establishment of novel diagnostic/screening nanoparticle-based strategies for methanol poisoning such as the discovery of ADH inhibitors as well as the detection of the adulteration of alcoholic drinks by nanoparticles in order to prevent methanol poisoning. In conclusion, increasing warnings and knowledge about clinical manifestations, medical interventions, and novel strategies for methanol poisoning probably results in a decrease in the death load.

Effective treatment of intractable diseases using nanoparticles to interfere with vascular supply and angiogenic process.

Angiogenesis is a vital biological process involving blood vessels forming from pre-existing vascular systems. This process contributes to various physiological activities, including embryonic development, hair growth, ovulation, menstruation, and the repair and regeneration of damaged tissue. On the other hand, it is essential in treating a wide range of pathological diseases, such as cardiovascular and ischemic diseases, rheumatoid arthritis, malignancies, ophthalmic and retinal diseases, and other chronic conditions. These diseases and disorders are frequently treated by regulating angiogenesis by utilizing a variety of pro-angiogenic or anti-angiogenic agents or molecules by stimulating or suppressing this complicated process, respectively. Nevertheless, many traditional angiogenic therapy techniques suffer from a lack of ability to achieve the intended therapeutic impact because of various constraints. These disadvantages include limited bioavailability, drug resistance, fast elimination, increased price, nonspecificity, and adverse effects. As a result, it is an excellent time for developing various pro- and anti-angiogenic substances that might circumvent the abovementioned restrictions, followed by their efficient use in treating disorders associated with angiogenesis. In recent years, significant progress has been made in different fields of medicine and biology, including therapeutic angiogenesis. Around the world, a multitude of research groups investigated several inorganic or organic nanoparticles (NPs) that had the potential to effectively modify the angiogenesis processes by either enhancing or suppressing the process. Many studies into the processes behind NP-mediated angiogenesis are well described. In this article, we also cover the application of NPs to encourage tissue vascularization as well as their angiogenic and anti-angiogenic effects in the treatment of several disorders, including bone regeneration, peripheral vascular disease, diabetic retinopathy, ischemic stroke, rheumatoid arthritis, post-ischemic cardiovascular injury, age-related macular degeneration, diabetic retinopathy, gene delivery-based angiogenic therapy, protein delivery-based angiogenic therapy, stem cell angiogenic therapy, and diabetic retinopathy, cancer that may benefit from the behavior of the nanostructures in the vascular system throughout the body. In addition, the accompanying difficulties and potential future applications of NPs in treating angiogenesis-related diseases and antiangiogenic therapies are discussed.

The effect of shear stress on cardiac differentiation of mesenchymal stem cells.

BACKGROUND: Stem cell therapy is developing as a valuable therapeutic trend for heart diseases. Most recent studies are aimed to find the most appropriate types of stem cells for the treatment of myocardial infarction (MI). The animal models have shown that bone marrow-derived mesenchymal stem cells (BMSCs) are a possible, safe, and efficient type of stem cell used in MI. The previous study demonstrated that 5-Azacytidine (5-Aza) could promote cardiac differentiation in stem cells. METHODS: This study used 5-Aza to induce cardiomyocyte differentiation in BMSCs both in static and microfluidic cell culture systems. For this purpose, we investigated the differentiation by using real-time PCR and Immunocytochemistry (ICC) Analysis. RESULTS: Our results showed that 5-Aza could cause to express cardiac markers in BMSCs as indicated by real-time PCR and immunocytochemistry (ICC). However, BMSCs are exposed to both 5-Aza and shear stress, and their synergistic effects could significantly induce cardiac gene expressions in BMSCs. This level of gene expression was observed neither in 5-Aza nor in shear stress groups only. CONCLUSIONS: These results demonstrate that when BMSCs expose to 5-Aza as well as mechanical cues such as shear stress, the cardiac gene expression can be increased dramatically.

The promising shadow of microbubble over medical sciences: from fighting wide scope of prevalence disease to cancer eradication.

Microbubbles are typically 0.5-10 µm in size. Their size tends to make it easier for medication delivery mechanisms to navigate the body by allowing them to be swallowed more easily. The gas included in the microbubble is surrounded by a membrane that may consist of biocompatible biopolymers, polymers, surfactants, proteins, lipids, or a combination thereof. One of the most effective implementation techniques for tiny bubbles is to apply them as a drug carrier that has the potential to activate ultrasound (US); this allows the drug to be released by US. Microbubbles are often designed to preserve and secure medicines or substances before they have reached a certain area of concern and, finally, US is used to disintegrate microbubbles, triggering site-specific leakage/release of biologically active drugs. They have excellent therapeutic potential in a wide range of common diseases. In this article, we discussed microbubbles and their advantageous medicinal uses in the treatment of certain prevalent disorders, including Parkinson's disease, Alzheimer's disease, cardiovascular disease, diabetic condition, renal defects, and finally, their use in the treatment of various forms of cancer as well as their incorporation with nanoparticles. Using microbubble technology as a novel carrier, the ability to prevent and eradicate prevalent diseases has strengthened the promise of effective care to improve patient well-being and life expectancy.

Janus nanoparticles: an efficient intelligent modern nanostructure for eradicating cancer.

In the modern age, the struggle to generate appropriate bio-based materials and nano-scaled colloidal particulates for developed application domains, has already resulted in remarkable attempts in the advancement of regulated size and shape, anisotropy, and characteristics of nanostructures. The bottom-up development strategies of components are among the most important science areas throughout nanotechnology, in which the designed building blocks are often utilized to generate novel structures by random self-assembly. In biomedical applications, Janus nanoparticles (JNPs) are necessary. This is due to their effective stimulus-responsive properties, tunable structure, biocompatibility, containing two surfaces with various hydrophobic characteristics and distinct functional groups. Featuring two parts with differing hydrophobicity has been the most critical aspect of the Janus amphiphilic particles. Development of JNPs has been afforded, using imaging agents (e.g. gold (AU) for photoacoustic imaging processing (PAI), silver for surface-enhanced Raman scattering (SERS), and Fe3O4 and MnO2 to magnetic resonance imaging (MRI)). It is also to be mentioned that a number of other properties become salient - properties such as integration imaging factors into JNPs (like quantum dots, fluorescent dyes), multiple imaging methods for screening and diagnosis application can indeed be accomplished. Janus nanostructures have been promising platforms for bioengineering as therapeutic carriers, drug delivery vehicles, and biosensor equipment; they may also be employed for the transport of bioactive hydrophilic and hydrophobic materials. The main production approaches and major advancement of JNPs in the biomedical sector and cancer therapy will be described in this paper.

Association of Serum Renalase Levels and Renalase rs10887800 Polymorphism with Unstable Angina Pectoris Patients Having Metabolic Syndrome.

PURPOSE: An increased risk of cardiovascular mortality and morbidity has been linked with metabolic syndrome (MetS), described as the secondary risk reduction target. These patients are predisposed to high complication levels such as unstable angina-pectoris (USAP) by MetS. As with the role of renalase in the regulation of blood pressure (BP), the study was carried out to determine the levels of renalase circulation in patients with USAP and MetS (USAP+MetS), as well as the association of renalase gene (RNLS) rs10887800 polymorphism and USAP and MetS susceptibility. PATIENTS AND METHODS: A total of 134 patients with USAP+MetS and 134 control subjects were recruited in this case-control study. RESULTS: Renalase was found to have a significantly higher level in USAP+MetS patients (23.28 ± 4.09 µg/dL) than in healthy ones (20.81 ± 2.73 µg/dL) (P < 0.001). Also, it was shown that renalase sensitivity and specificity values for the early diagnosis of USAP and MetS seemed to be 53.7% and 76.9, respectively. Moreover, the value for renalase area under curve (AUC) was 0.654 (95% CI: 0.58-0.72). The frequency of rs10887800 AG and GG genotypes of RNLS gene was significantly higher in USAP+MetS patients than in control subjects, suggesting that this genotype might be a risk factor against USAP+MetS (OR = 2.114 [95% CI 1.113-4.016]; P = 0.022) and (OR = 2.057 [95% CI 1.011-4.186]; P = 0.047), respectively. CONCLUSION: The present results showed that renalase serum levels increased in USAP and MetS patients. Moreover, the RNLS rs10887800 was reported to be associated with a higher risk of USAP+MetS.

Evaluation of Efficacy, Safety, and Satisfaction Taking Deferasirox Twice Daily Versus Once Daily in Patients With Transfusion-Dependent Thalassemia.

OBJECTIVE: Deferasirox is a once-daily oral iron-chelation agent approved by the US Food and Drug Administration in November 2005. The authors aimed to evaluate efficacy, safety, and satisfaction of patients regarding twice-daily dose of deferasirox in patients with thalassemia who are resistant to once-daily regimen. METHODS: In this historical cohort multicenter study, 34 patients with beta-thalassemia major resistant or intolerant to once-daily dose of deferasirox (35 mg/kg/d) were investigated in 2016. Patients were registered at 3 thalassemia referral centers in Shiraz, southern Iran and Tehran, the capital of Iran. All patients were followed for 1 year and monitored by regular physical examination, laboratory data, serum ferritin levels, and heart and liver T2 magnetic resonance imaging. RESULTS: Mean age of thalassemia patients was 25.6±8.1 (8 to 40) years, including 22 female individuals and 12 male individuals. Serum ferritin levels significantly decreased during the study period (2021±955 at baseline vs. 1228±894 at the end of the study, P<0.001). Liver T2 magnetic resonance imaging of the patients demonstrated a significant improvement during the study. 73.3% of patients showed normal values at the end of study compared with 28.1% at the baseline (P<0.001). Drug side effects were reported only in 2 patients (5.8%) including 1 patient with abdominal pain and 1 with leukopenia and thrombocytopenia. CONCLUSIONS: It seems that deferasirox can be used with increased dose and twice daily with acceptable efficacy in unresponsive or intolerant thalassemia patients to once-daily dose. Close monitoring of the patients is necessary to detect and manage any possible adverse events.