Recent update on the protective potentials of resveratrol against cisplatin-induced ototoxicity: a systematic review.

INTRODUCTION: Although cancer treatment with cisplatin is effective, dose-dependent adverse effects such as ototoxicity occurs often, which limits its clinical use. The use of resveratrol may alleviate the cisplatin-induced ototoxic effects. This study is aimed to review the potential otoprotective effects of resveratrol against cisplatin-induced ototoxicity. METHOD: According to the PRISMA guideline, a systematic search was accomplished to identify all relevant scientific papers on "the role of resveratrol against cisplatin-induced ototoxicity" in different electronic databases up to May 2021. Fifty-five articles were screened based on a pre-defined set of inclusion and exclusion criteria. Eight eligible studies were finally included in the current systematic review. The in-vitro findings revealed that cisplatin administration significantly decreased the HEI-OC1 cell viability compared to the untreated cells; however, resveratrol co-treatment (in a dose-dependent manner) could protect HEI-OC1 cells against cisplatin-induced decrease in cell viability. RESULTS: Furthermore, the in-vivo finding showed a decreased value of DPOAE, and increased values of ABR threshold, ABR-I, ABR-IV, and ABR I-IV interval in cisplatin-treated animals; in contrast, resveratrol co-administration demonstrated an opposite pattern on these parameters. CONCLUSION: Thus, it can be mentioned that resveratrol co-treatment alleviates cisplatin-induced ototoxicity. Mechanically, resveratrol exerts its otoprotective effects through various mechanisms such as anti-oxidant, anti-apoptosis, and anti-inflammatory.

Evaluation of Cholesterol Thickness of Blood Vessels Using Photoacoustic Technology.

One of the primary indicators of plaque vulnerability is the lipid composition of atherosclerotic plaques. Therefore, the medical industry requires a method to evaluate necrotic nuclei in atherosclerosis imaging with sensitivity. In this regard, photoacoustic imaging is a plaque detection method that provides chemical information on lipids and cholesterol thickness in the arterial walls of the patient. This aspect aims to increase the low-frequency axial resolution by developing a new photoacoustic-based system. A photoacoustic system has been developed to detect the cholesterol thickness of the blood vessels to observe the progression of plaque in the heart's blood vessels. The application of the coherent photoacoustic discontinuous correlation tomography technique, which is based on a novel signal processing, significantly increased the cholesterol oleate's sensitivity to plaque necrosis. By enhancing the quality of thickness detection, the system for measuring the thickness of cholesterol in blood vessels has been reduced to approximately 23 microns. The results show that the phase spectrum peaked at 100 Hz at 58.66 degrees, and at 400 Hz, the phase spectrum was 46.37 degrees. The minimum amplitude is 1.95 at 100 Hz and 17.67 at 400 Hz. In conclusion, it can be stated that photoacoustic imaging as a method based on new technologies is of great importance in medical research, which is based on the use of nonionizing radiation to perform diagnostic processes and measure different types of body tissues.

Neuroprotective and Anti-Inflammatory Effects of Pioglitazone on Parkinson's Disease: A Comprehensive Narrative Review of Clinical and Experimental Findings.

Parkinson's disease (PD) is a chronic and progressive neurological disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). The pathogenesis of PD is strongly related to mitochondrial dysfunction, oxidative stress, and neuroinflammation. This indicates that PD can be treated with anti-oxidative substitutes and anti-inflammatory compounds. The neuroprotective and anti-inflammatory effects of peroxisome proliferator-activated receptor γ (PPAR-γ) agonists decrease cell death and halt the increase in neurodegeneration, which is why they have been given a lot of importance in research. Antidiabetic and anti-inflammatory effects have been observed to be generated by pioglitazone (PG), a selective peroxisome proliferator-activated receptor γ (PPAR-γ) agonist that regulates neural plasticity in various neurodegenerative disorders. The neuroprotective and anti-inflammatory effects of PG are assessed in this article. It was found that the patients with DM who received PG treatment were noticeably at a lower risk of PD. However, some clinical studies have not proven a strong link between the therapeutic effects of PG on PD. As per suggestions of preclinical studies, the therapeutic effects of PG treatment include; increased life expectancy of neurons, decreased oxidative stress, halted microglial activity, lower inflammation (reduced NF-κB, COX-2, and iNOS), reduced mitochondrial dysfunction, rise in motor function (motor agility) and non-motor function (lowered cognitive dysfunction). In conclusion, we determined that PG exerts neuroprotective and anti-inflammatory effects in PD models and it can be considered a potential therapeutic candidate for PD.

Concanavalin A as a promising lectin-based anti-cancer agent: the molecular mechanisms and therapeutic potential.

Concanavalin A (ConA), the most studied plant lectin, has been known as a potent anti-neoplastic agent for a long time. Since initial reports on its capacity to kill cancer cells, much attention has been devoted to unveiling the lectin's exact molecular mechanism. It has been revealed that ConA can bind to several receptors on cancerous and normal cells and modulate the related signaling cascades. The most studied host receptor for ConA is MT1-MMP, responsible for most of the lectin's modulations, ranging from activating immune cells to killing tumor cells. In this study, in addition to studying the effect of ConA on signaling and immune cell function, we will focus on the most up-to-date advancements that unraveled the molecular mechanisms by which ConA can induce autophagy and apoptosis in various cancer cell types, where it has been found that P73 and JAK/STAT3 are the leading players. Moreover, we further discuss the main signaling molecules causing liver injury as the most significant side effect of the lectin injection. Altogether, these findings may shed light on the complex signaling pathways controlling the diverse responses created via ConA treatment, thereby modulating these complex networks to create more potent lectin-based cancer therapy. Video Abstract.

RETRACTED: The pathogenicity of COVID-19 and the role of pentraxin-3: An updated review study.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. In investigating concerns regarding the contributions of the authors to this article, the editors reached out to the authors for an explanation. In addition to the concerns regarding the contribution of each author, the editors discovered suspicious changes in authorship between the original submission and the revised version of this paper. The names of the authors Ameer A Alameri and Zanko Hassan Jawhar were added to the revised version of the article without explanation and without the exceptional approval by the handling Editor, which is contrary to the journal policy on changes to authorship. The authors were unable to provide a reasonable explanation for either of the issues raised. The editor therefore feels that the findings of the manuscript cannot be relied upon and that the article needs to be retracted.

Synthesis of Bioactive Yttrium-Metal-Organic Framework as Efficient Nanocatalyst in Synthesis of Novel Pyrazolopyranopyrimidine Derivatives and Evaluation of Anticancer Activity.

Novel Yttrium-metal-organic framework (Y-MOF) was synthesized under optimal conditions of microwave with a power of 20 W, the temperature of 30 degrees of centigrade, and time duration of 10 min. The products were characterized by SEM (morphology and size distribution), TGA (thermal stability), BET technique (surface area), and FTIR (characterization of the related group). The Yttrium-metal-organic framework (Y-MOF) synthesized in this study, after identifying and confirming the structure, was used as an efficient and recyclable catalyst in the synthesis of new pyrazolopyranopyrimidine derivatives. Following the study of the properties and applications of Y-MOF, its anticancer properties on breast cancer cells based on the MTT method were evaluated, and significant results were observed. In addition, the anticancer properties of the pyrazolopyranopyrimidine derivatives were investigated.

Apigenin alleviates resistance to doxorubicin in breast cancer cells by acting on the JAK/STAT signaling pathway.

BACKGROUND: Breast cancer is the most frequent cancer among women. Despite the effectiveness of Doxorubicin (DOX) as a chemotherapeutic for the treatment of breast cancer, the therapy-resistance remains unsolvable. Apigenin is a natural dietary flavonoid with potential anticancer activities. Our study's intention was to evaluate the effect of Apigenin on DOX resistance in MCF-7 cells. METHODS: DOX-resistant MCF-7 cell line (MCF-7R) was developed by treating MCF-7 cells with increasing concentrations of DOX (0-100 µM). The viability of cell lines was assayed using MTT method. Quantitative polymerase chain reaction method was performed to measure multidrug-resistance 1 (MDR1) gene expression level. The expression of MDR1, Janus kinase 2 (JAK2) and Signal transducer and activator of transcription 3 (STAT3) proteins were determined by western blotting. RESULTS: MCF-7R cell line showed resistance to DOX in comparison to MCF-7 cells. Apigenin had a significant effect on the reduction of viability of both MCF-7 and MCF-7R cell lines. However, DOX-resistance in the MCF-7 cell line was considerably decreased due to the co-treatment of MCF-7R cells with Apigenin. This natural compound also downregulated the expression of MDR1 at mRNA and protein levels both in resistant and non-resistant cells. Apigenin significantly prohibited the phosphorylation and activation of JAK2 and STAT3 proteins both in MCF-7 and MCF-7R cell lines. CONCLUSIONS: The present results suggested, for the first time, Apigenin as an ideal therapeutic for ameliorating DOX resistance in breast cancer. These data also proposed a novel mechanism for the anti-resistance activity of Apigenin by regulating the JAK2/STAT3/MDR1 axis.

Type 2 alveolar epithelial cell-derived circulating extracellular vesicle-encapsulated surfactant protein C as a mediator of cardiac inflammation in COVID-19.

Among the countless endeavours made at elucidating the pathogenesis of COVID-19, those aimed at the histopathological alterations of type 2 alveolar epithelial cells (AT2) are of outstanding relevance to the field of lung physiology, as they are the building blocks of the pulmonary alveoli. A merit of high regenerative and proliferative capacity, exocytotic activity resulting in the release of extracellular vesicles (EVs) is particularly high in AT2 cells, especially in those infected with SARS-CoV-2. These AT2 cell-derived EVs, containing the genetic material of the virus, might enter the bloodstream and make their way into the cardiovascular system, where they may infect cardiomyocytes and bring about a series of events leading to heart failure. As surfactant protein C, a marker of AT2 cell activity and a constituent of the lung surfactant complex, occurs abundantly inside the AT2-derived EVs released during the inflammatory stage of COVID-19, it could potentially be used as a biomarker for predicting impending heart failure in those patients with a history of cardiovascular disease.

Neuroprotective and Anti-inflammatory Effects of Pioglitazone on Traumatic Brain Injury.

Traumatic brain injury (TBI) is still a major cause of concern for public health, and out of all the trauma-related injuries, it makes the highest contribution to death and disability worldwide. Patients of TBI continue to suffer from brain injury through an intricate flow of primary and secondary injury events. However, when treatment is provided in a timely manner, there is a significant window of opportunity to avoid a few of the serious effects. Pioglitazone (PG), which has a neuroprotective impact and can decrease inflammation after TBI, activates peroxisome proliferator-activated receptor-gamma (PPARγ). The objective of the study is to examine the existing literature to assess the neuroprotective and anti-inflammatory impact of PG in TBI. It also discusses the part played by microglia and cytokines in TBI. According to the findings of this study, PG has the ability to enhance neurobehavior, decrease brain edema and neuronal injury following TBI. To achieve the protective impact of PG the following was required: (1) stimulating PPARγ; (2) decreasing oxidative stress; (3) decreasing nuclear factor kappa B (NF-κB), interleukin 6 (IL-6), interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and C-C motif chemokine ligand 20 (CCL20) expression; (4) limiting the increase in the number of activated microglia; and (5) reducing mitochondrial dysfunction. The findings indicate that when PIG is used clinically, it may serve as a neuroprotective anti-inflammatory approach in TBI.

Prediction of COVID-19 manipulation by selective ACE inhibitory compounds of Potentilla reptant root: In silico study and ADMET profile.

In the novel SARS-CoV-2 (COVID-19) as a global emergency event, the main reason of the cardiac injury from COVID-19 is angiotensin-converting enzyme 2 (ACE2) targeting in SARS-CoV-2 infection. The inhibition of ACE2 induces an increase in the angiotensin II (Ang II) and the angiotensin II receptor type 1 (AT1R) leading to impaired cardiac function or cardiac inflammatory responses. The ethyl acetate fraction of Potentilla reptans L. root can rescue heart dysfunction, oxidative stress, cardiac arrhythmias and apoptosis. Therefore, isolated components of P. reptans evaluated to identify natural anti-SARS-CoV-2 agents via molecular docking. In silico molecular docking study were carried out using the Auto Dock software on the isolated compounds of Potentilla reptans root. The protein targets of selective ACE and others obtained from Protein Data Bank (PDB). The best binding pose between amino acid residues involved in active site of the targets and compounds was discovered via molecular docking. Furthermore, ADMET properties of the compounds were evaluated. The triterpenoids of P. reptans showed more ACE inhibitory potential than catechin in both domains. They were selective on the nACE domain, especially compound 5. Also, the compound 5 & 6 had the highest binding affinity toward active site of nACE, cACE, AT1R, ACE2, and TNF-α receptors. Meanwhile, compound 3 showed more activity to inhibit TXA2. Drug likeness and ADMET analysis showed that the compounds passed the criteria of drug likeness and Lipinski rules. The current study depicted that P. reptans root showed cardioprotective effect in COVID-19 infection and manipulation of angiotensin II-induced side effects.

Psychometric Assessment of the Persian Translation of the Interpersonal Mindfulness Scale With Undergraduate Students.

Interpersonal mindfulness is a construct that significantly contributes to social interaction. To date, no validated measure assessing interpersonal mindfulness has been developed in Iran. Therefore, the aim of this study was to translate and validate the Interpersonal Mindfulness Scale (IMS) among Iranian undergraduate students. Participants in the study (370 undergraduate students; 220 females) from the Azad University completed the translated IMS, the Five Facet Mindfulness Questionnaire, and the Inventory of Interpersonal Problems Scale. The translated measure demonstrated acceptable face validity. All items had acceptable content validity and were deemed essential to the scale. The results of a Confirmatory Factor Analysis (CFA) confirmed a scale with four subscales (presence, awareness of self and others, non-judgmental acceptance, and non-reactivity), with acceptable internal consistency. The findings support the psychometric properties of the Persian translated Interpersonal Mindfulness Scale, which could be used to measure interpersonal mindfulness among undergraduate students in Iran.

Role of Acute Myeloid Leukemia (AML)-Derived exosomes in tumor progression and survival.

Acute myeloid leukemia (AML) is a quickly aggressive hematopoietic disorder that progress due to the accumulation and clonal expansion of immature myeloid cells. Despite the latest developments in AML treatment, repeated relapses and drug resistance remain one of the major challenges in treatment of leukemia. Currently, it is well known that the components of the tumor microenvironment such as cellular and non-cellular elements play a critical function in treatment failures of AML, also they are most common cause of complications including suppression of hematopoiesis. Exosomes are membrane-bound extracellular vesicles (EVs) that transfer signaling molecules and have attracted a large amount of attention due to their important role in inter-cellular communication in health and disease. Exosomes participate in the survival and chemoresistance of many leukemia through transferring their rich cargos of molecules including miRNAs, growth factors, and cytokines. The key producers of exosomes that mainly participate to AML pathogenesis are bone marrow mesenchymal stem cell (BMSCs) and AML cell themselves. These cells release an enormous number of exosomes that affect several target cells such as natural killer (NK) and hematopoietic stem cells to the development of leukemia proliferation and progression. In the present study, a comprehensive review of the literature has been done to briefly discuss the biology of exosomes and highlight the role of exosomes derived from AML in the progress of acute myeloid leukemia.

Immunotherapy of inflammatory bowel disease (IBD) through mesenchymal stem cells.

Many pathophysiologic pathways and immune-pathologic etiologies are addressed as Inflammatory bowel disease (IBD) causes. Moreover, dysfunction of the immune system leads to inflammatory responses against intestinal components that boost disease severity. The use of routine treatments has limitations. Besides, patients may experience drug resistance. Therefore, the use of novel and effective therapies is essential. Relying on the immune regulatory functions of Mesenchymal Stem Cells (MSCs), researchers have suggested possible benefits of MSCs administration for IBD, both in experimental and clinical studies. Experimental animal models of IBD have shown effects of MSCs, MSC-derived exosomal micro RNAs, and MSC-based drug delivery systems on the regulation of the immune system (Th17 suppression versus T-regular cell biased responses). These studies have suggested MSCs' benefits on intestinal integrity, improved smooth cell function, and tissue repair. On the other hand, various clinical trials have been registered for MSCs application in IBD patients that show reliable safety in humans. Most clinical trials have used MSCs of bone marrow, umbilical cord, and adipose tissue that have been administered by intravenous or intra-tissue injection. Studies have evaluated clinical outcomes, patient symptoms, or healing processes; while immunological studies in the clinical era are missing. As we reviewed, huge shreds of experimental shreds of evidence have led to the inception of multiple clinical trials in phase I/II, showing promising results for IBD treatment. We suggest that further clinical investigation should be more focused on in-vitro/in-vivo assessed outcomes as well as the immunological endpoints to have more reliable results with more support for laboratory evidence.