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Humans are continuously exposed to environmental, occupational, consumer and household products, food, and pharmaceutical substances. Luteolin, a flavone from the flavonoids family of compounds, is found in different fruits and vegetables. LUT is a strong anti-inflammatory (via inhibition of NF-κB, ERK1/2, MAPK, JNK, IL-6, IL-8, and TNF-α) and antioxidant agent (reducing ROS and enhancement of endogenous antioxidants). LUT can chelate transition metal ions responsible for ROS generation and consequently repress lipoxygenase. It has been proven that NF-κB, as a commom cellular pathway plays a considerable role in the progression of inflammatory process and stimulates the expression of genes encoding inducible pro-inflammatory enzymes (iNOS and COX-2) and cytokines including IL-1β, IL-6, and TNF-α. This review summarizes the available literature discussing LUT and its potential protective role against pharmaceuticals-, metals-, and environmental compounds-induced toxicities. Furthermore, the review explains the involved protective mechanisms, especially inhibition of the NF-κB pathway.

Loads of new therapeutic regimes have been turned up to manage Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), particularly in elderly patients who are unfit for intensive chemotherapy. Despite accumulating research, the best MDS and AML management approach is indeterminate. Myelodysplastic syndrome implies a group of various hematopoietic stem cell disorders that may progress to acute myeloid leukemia. These disorders are more frequent in older adults. To the high rate of morbidity and abundant toxicities related to the therapeutic approaches, also, the treatment would be challenging. The clinical effectiveness of valproic acid, a histone deacetylase inhibitor, in MDS and AML patients is unknown, even though it has demonstrated positive activities to promote differentiation and apoptosis in cancer cells. We investigated the clinical research on the effects of valproic acid in conjunction with various drugs, including low-dose cytarabine, all-trans retinoic acid, DNA-hypomethylating agents, hydrazine, and theophylline. We conclude that VPA is a safe and effective treatment option for MDS and AML patients, particularly when used in conjunction with all-trans retinoic acid, DNA-hypomethylating drugs, and hydralazine. However, more randomized clinical studies are required to identify an ideal regimen.

The PI3K/Akt/GSK3β pathway is crucial in regulating cardiomyocyte growth and survival. It has been shown that activation of this pathway alleviates the negative impact of ischemia-reperfusion. Glycogen synthase kinase-3 (GSK3β) induces apoptosis through stimulation of transcription factors, and its phosphorylation has been suggested as a new therapeutic target for myocardial ischemia-reperfusion injury (MIRI). GSK3β regulatory role is mediated by the reperfusion injury salvage kinase (RISK) pathway, and its inhibition by Akt activation blocks mitochondrial permeability transition pore (mPTP) opening and enhances myocardial survival. The present article discusses the involvement of the PI3K/Akt/GSK3β pathway in cardioprotective effects of natural products against MIRI.

Background Pulmonary hypertension (PH) is a pathophysiological disorder, which involves multiple clinical conditions such as the upregulation of the Rho/ROCK signaling pathway. On the other hand, fasudil as a Rho kinase inhibitor has been investigated in the treatment of PH in some clinical studies. Objectives The present systematic review and meta-analysis aimed to evaluate the human clinical trials regarding the efficacy of fasudil in the management of PH. Methods Databases were searched with pre-defined search terms, up to December 2021. Efficacy measures were such as mean pulmonary arterial pressure (mPAP), systolic PAP (sPAP), pulmonary vascular resistance (PVR), systolic vascular resistance (SVR) and cardiac index (CI). Results A total of 12 studies involving 575 PH patients were included in our research. Eight short-term trials and four mid-term trials were found (no clinical trials on the long-term effects). Short-term trials had a before-after study design and measuring pulmonary hemodynamic parameters’ intervention revealed a statistically significant improvement of mPAP, sPAP, PVR, SVR, and CI in the meta-analysis of five eligible studies. Three mid-term trials also revealed improvement in some pulmonary hemodynamic parameters with fasudil and in another mid-term trial, fasudil significantly decreased rehospitalization and mortality in PH patients. No serious adverse effects with fasudil were reported in these trials. Conclusion Fasudil therapy is efficacious and probably safe in the improvement of some hemodynamics in PH patients along short and mid-term periods. However, long-term randomized controlled trials comparing fasudil with placebo and other treatments are warranted for confirmation of these benefits.

Insufficiency in coronary blood supply results in myocardial ischemia and consequently, various clinical syndromes and irreversible injuries. Myocardial damage occurs as a result of two processes during acute myocardial infarction (MI): ischemia and subsequent reperfusion. According to the available evidence, oxidative stress, excessive inflammation reaction, reactive oxygen species (ROS) generation, and apoptosis are crucial players in the pathogenesis of myocardial ischemia/reperfusion (IR) injury. There is emerging evidence that Janus tyrosine kinase 2 (JAK2) signal transducer and activator of the transcription 3 (STAT3) pathway offers cardioprotection against myocardial IR injury. This article reviews therapeutics that exert cardioprotective effects against myocardial IR injury through induction of JAK2/STAT3 pathway.

Background and Aim. Disseminated intravascular coagulation (DIC) is a critical clinical condition that is expressed by systemic activation of the homeostatic system, leading to elevation of thrombin deposition and result in microvascular thrombi. Heparin makes a good effect on hypercoagulability states through inhibition of thrombin. The present study aimed to summarize and discuss the results of randomized clinical trials and cohort studies regarding the effect of heparin and its preparations on DIC mortality and duration of hospitalization. Methods. The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to November 2021. The quality of RCTs was assessed by Cochrane Collaboration’s tool and the risk of bias was assessed for cohort studies through NOS score. Results. Out of 3288 articles, eight studies were eligible to be included in this study. Our review retrieved six RCTs and two retrospective cohort studies consisting of 950 participants diagnosed by DIC. A significant effect of heparin on DIC mortality was identified in four studies. Furthermore, heparin was used as a control group in three studies. Conclusions. We concluded that administration of heparin and its preparations in DIC patients could reduce the mortality rate and duration of hospitalization, especially in the earlier stages of DIC.

There is an increasing number of therapeutic agents being developed for the treatment of pulmonary artery hypertension (PAH) which is a condition characterized by raised pulmonary artery pressure and right heart failure. Despite our better understanding of the pathophysiology of PAH, the treatment outcomes are still suboptimal. There is growing evidence suggesting the role of increases in the levels of aldosterone, which is a mineralocorticoid hormone, in the pathophysiology of PAH; however, the extent to which hyperaldosteronism is associated with PAH in patients is unclear. There are also a few studies assessing the effects of mineralocorticoid receptor antagonists (MRA) in PAH. MRAs are a recognized treatment for heart failure and hypertension. In this review, we focus on the relationship between aldosterone level in patients with PAH and right ventricular failure and the effect of MRAs on the PAH severity.