Background: It appears that ivermectin can potentially act against COVID-19 infection. Today, it is an urgent need to evaluate the efficacy and safety of ivermectin. The effect of ivermectin therapy on mild to severe COVID-19 patients was investigated.Methods: A 45-days randomized, double-blind, placebo-controlled, multicenter, phase 2 clinical trial was designed at five hospitals. A total number of 180 mild to severe hospitalized patients with confirmed PCR and chest image tests were enrolled. The radiographic findings, hospitalization and low O2 saturation duration, and clinical outcomes such as mortality and variables of blood samples were analyzed using standard statistical analyses in SPSS (V20).Results: Average age of the participants was 56 years (45-67) and 50% were women. The primary and secondary results showed significant changes between day zero and day five of admission (∆ 0/5) in terms of ΔALC5/0, ΔPLT5/0, ΔESR5/0, ΔCRP5/0, duration of low O2 saturation, and duration of hospitalization (CI = 95% ). Risk of mortality was also decreased significantly in the study groups.Conclusion: Ivermectin as an adjunct reduced the rate of mortality, low O2 duration, and duration of hospitalization in adult COVID 19 patients. The improvement of other clinical parameters showed that the ivermectin, with a wide margin of safety, had a high therapeutic effect on COVID-19.Trial Registration: This trial was registered with the Iranian Registry of Clinical Trials website (registration ID IRCT20200408046987N1).

Targeted radionuclide therapy, known as molecular radiotherapy is a novel therapeutic module in cancer medicine. β-radiating radionuclides have definite impact on target cells via interference in cell cycle and particular signalings that can lead to tumor regression with minimal off-target effects on the surrounding tissues. Radionuclides play a remarkable role not only in apoptosis induction and cell cycle arrest, but also in the amelioration of other characteristics of cancer cells. Recently, application of novel β-radiating radionuclides in cancer therapy has been emerged as a promising therapeutic modality. Several investigations are ongoing to understand the underlying molecular mechanisms of β-radiating elements in cancer medicine. Based on the radiation dose, exposure time and type of the β-radiating element, different results could be achieved in cancer cells. It has been shown that β-radiating radioisotopes block cancer cell proliferation by inducing apoptosis and cell cycle arrest. However, physical characteristics of the β-radiating element (half-life, tissue penetration range, and maximum energy) and treatment protocol determine whether tumor cells undergo cell cycle arrest, apoptosis or both and to which extent. In this review, we highlighted novel therapeutic effects of β-radiating radionuclides on cancer cells, particularly apoptosis induction and cell cycle arrest.

Influenza type A is considered as a severe public health concern. The mechanism of drugs applied for the control of this virus depends on two surface glycoproteins with antigenic properties, namely hemagglutinin (HA) and neuraminidase (NA). HA aids the virus to penetrate cells in the early stage of infection and NA is an enzyme with the ability to break glycoside bonds, which enables virion spread through the host cell membrane. Since NA contains a relatively preserved active site, it has been an important target in drug design. Oseltamivir is a common drug used for the treatment of influenza infections, for which cases of resistance have recently been reported, giving rise to health concerns. Flavonoids are natural polyphenolic compounds with potential blocking effects in the neuraminidase active site. Based on their antiviral effect, the flavonoids quercetin, catechin, naringenin, luteolin, hispidulin, vitexin, chrysin and kaempferol were selected in the present study and compared alongside oseltamivir on molecular docking, binding energy and active site structure, in order to provide insight on the potential of these compounds as targeted drugs for the control and treatment of influenza type A. The molecular characterization of flavonoids with binding affinity was performed using AutoDock Vina software. The results indicated that these compounds may effectively block the NA active site. Therefore, these natural compounds derived from fruits have the potential for development into drugs for controlling influenza, which may aid overcome the clinical challenge of the H1N1 strain epidemic.

Tyrosinase is a tetrameric enzyme that plays an important role in pigment production. Overproduction of melanin, which may lead to several skin disorders, is a result of tyrosinase activity. Hence, tyrosinase inhibitors are of key importance in the treatment of these disorders. In the present study, four flavonoid inhibitors, namely chrysin, naringin, quercetin, and kaempferol, were evaluated physiochemically, and the inhibitory effects of these compounds on tyrosinase activity were evaluated using the molecular dynamics (MD) simulation method. To create the best conformation of the enzyme-substrate/inhibitor, the docking process for enzyme-substrate, i.e., enzymechrysin, enzyme-quercetin, enzyme-naringin, and enzyme-kaempferol, was performed. The complexes with the best binding energies were selected as the models for the MD simulation process. Furthermore, the structural (RMSD, Rg, RMSF, and Distance) and the thermodynamics properties of the complexes were evaluated. Additionally, the PMF was conducted to calculate the binding free energies. The results showed that chrysin, quercetin and the substrate were at similar distances to the amino acids of the active site, but naringin and kaempferol were closer to the active site of the enzyme than the substrate. Moreover, the analysis of the binding energy revealed that the substrates, chrysin, kaempferol, quercetin, and naringin bound to the enzyme with binding energies of !7.8, !3.1, !7.1, !3.9, and !8.4 kcal/mol, respectively, which confirms that naringin has the highest inhibitory effect on tyrosinase among other inhibitors, which makes it an appropriate candidate as a whitening agent in skin disorders.

Hepatocellular carcinoma (HCC) is the most prevalent type of malignant liver disease worldwide. Molecular changes in HCC collectively contribute to Wnt/β-catenin, as a tumor proliferative signaling pathway, toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB), as well as the c-Jun NH2-terminal kinase (JNK), predominant signaling pathways linked to the release of tumor-promoting cytokines. It should also be noted that the Hippo signaling pathway plays an important role in organ size control, particularly in promoting tumorigenesis and HCC development. Nowadays, mesenchymal stromal cells (MSCs)-based therapies have been the subject of in vitro, in vivo, and clinical studies for liver such as cirrhosis, liver failure, and HCC. At present, despite the importance of basic molecular pathways of malignancies, limited information has been obtained on this background. Therefore, it can be difficult to determine the true concept of interactions between MSCs and tumor cells. What is known, these cells could migrate toward tumor sites so apply effects via paracrine interaction on HCC cells. For example, one of the inhibitory effects of MSCs is the overexpression of dickkopf-related protein 1 (DKK-1) as an important antagonist of the Wnt signaling pathway. A growing body of research challenging the therapeutic roles of MSCs through the secretion of various trophic factors in HCC. This review illustrates the complex behavior of MSCs and precisely how their inhibitory signals interface with HCC tumor cells.