COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches.

Extensive research in countries with high sociodemographic indices (SDIs) to date has shown that coronavirus disease 2019 (COVID-19) may be directly associated with more severe outcomes among patients living with haematological disorders and malignancies (HDMs). Because individuals with moderate to severe immunodeficiency are likely to undergo persistent infections, shed virus particles for prolonged periods, and lack an inflammatory or abortive phase, this represents an overall risk of morbidity and mortality from COVID-19. In cases suffering from HDMs, further investigation is needed to achieve a better understanding of triviruses and a group of related variants in patients with anemia and HDMs, as well as their treatment through vaccines, drugs, and other methods. Against this background, the present study aimed to delineate the relationship between HDMs and the novel COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides, effective treatment options for HDM cases were further explored to address this epidemic and its variants. Therefore, learning about how COVID-19 manifests in these patients, along with exploiting the most appropriate treatments, may lead to the development of treatment and care strategies by clinicians and researchers to help patients recover faster. Video Abstract.

Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases.

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in the genome of this virus. S, M, H, and E proteins are structural proteins, and NSPs include accessory and replicase proteins. The structural and NSP components of SARS-CoV-2 play an important role in its infectivity, and some of them may be important in the pathogenesis of chronic diseases, including cancer, coagulation disorders, neurodegenerative disorders, and cardiovascular diseases. The SARS-CoV-2 proteins interact with targets such as angiotensin-converting enzyme 2 (ACE2) receptor. In addition, SARS-CoV-2 can stimulate pathological intracellular signaling pathways by triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, and Eph receptors, which play important roles in the progression of neurodegenerative diseases like Alzheimer's disease, epilepsy, and multiple sclerosis, and multiple cancers such as glioblastoma, lung malignancies, and leukemias. Several compounds such as polyphenols, doxazosin, baricitinib, and ruxolitinib could inhibit these interactions. It has been demonstrated that the SARS-CoV-2 spike protein has a stronger affinity for human ACE2 than the spike protein of SARS-CoV, leading the current study to hypothesize that the newly produced variant Omicron receptor-binding domain (RBD) binds to human ACE2 more strongly than the primary strain. SARS and Middle East respiratory syndrome (MERS) viruses against structural and NSPs have become resistant to previous vaccines. Therefore, the review of recent studies and the performance of current vaccines and their effects on COVID-19 and related diseases has become a vital need to deal with the current conditions. This review examines the potential role of these SARS-CoV-2 proteins in the initiation of chronic diseases, and it is anticipated that these proteins could serve as components of an effective vaccine or treatment for COVID-19 and related diseases. Video Abstract.

Folic Acid-Adorned Curcumin-Loaded Iron Oxide Nanoparticles for Cervical Cancer.

Cancer is a deadly disease that has long plagued humans and has become more prevalent in recent years. The common treatment modalities for this disease have always faced many problems and complications, and this has led to the discovery of strategies for cancer diagnosis and treatment. The use of magnetic nanoparticles in the past two decades has had a significant impact on this. One of the objectives of the present study is to introduce the special properties of these nanoparticles and how they are structured to load and transport drugs to tumors. In this study, iron oxide (Fe3O4) nanoparticles with 6 nm sizes were coated with hyperbranched polyglycerol (HPG) and folic acid (FA). The functionalized nanoparticles (10-20 nm) were less likely to aggregate compared to non-functionalized nanoparticles. HPG@Fe3O4 and FA@HPG@Fe3O4 nanoparticles were compared in drug loading procedures with curcumin. HPG@Fe3O4 and FA@HPG@Fe3O4 nanoparticles' maximal drug-loading capacities were determined to be 82 and 88%, respectively. HeLa cells and mouse L929 fibroblasts treated with nanoparticles took up more FA@HPG@Fe3O4 nanoparticles than HPG@Fe3O4 nanoparticles. The FA@HPG@Fe3O4 nanoparticles produced in the current investigation have potential as anticancer drug delivery systems. For the purpose of diagnosis, incubation of HeLa cells with nanoparticles decreased MRI signal enhancement's percentage and the largest alteration was observed after incubation with FA@HPG@Fe3O4 nanoparticles.

Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems.

Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discussed.

PADI4 Polymorphisms in Iranian Patients with Rheumatoid Arthritis.

AIM: Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects many tissues and organs, but majorly attacks synovial joints. Beyond the major histocompatibility complex (MHC) genes, Peptidyl arginine deiminase type IV (PADI4) has been suggested to be associated with RA susceptibility. Evidence regarding the association of PADI4 single nucleotide polymorphisms (SNP) and RA is controversial, thus we conducted this large-scale case-control study to assess the association of rs874881 and rs11203367 PADI4 SNPs with susceptibility to RA. MATERIALS AND METHODS: Study population (including 665 RA patients and 392 sex-, age-, and ethnicity-matched healthy controls) were enrolled from Rheumatology Research Center of Tehran University of Medical Sciences, Shariati hospital. RESULTS: Allele or genotype frequencies of the investigated PADI4 SNPs were not different between RA patients and healthy subjects; genotypes (expressed as odds ratios) of rs11203367 [TT 0.98 (0.68-1.4), CT 0.93 (0.71-1.24), P value > 0.05] and rs874881 [CC 1.02 (0.71-1.46), CG (0.70-1.39), p value > 0.05] did not affect RA risk. Disease severity score DAS28, RF and anti-CCP antibodies of RA patients were not different between various genotypes of PADI4 SNPs. CONCLUSIONS: These findings were similar for haplotypes and diplotypes of rs11203367 and rs874881 PADI4 SNPs. In conclusion, in this case-control study with sufficient sample size to detect associations, we observed that PADI4 SNPS rs11203367 and rs874881 do not significantly determine RA susceptibility; which is in line with studies of some European populations. It seems RA pathogenesis might be different among various ethnicities, which encourage us to consider these differences in developing therapeutic interventions for management of patients.

Association of Killer Cell Immunoglobulin- Like Receptor Genes in Iranian Patients with Rheumatoid Arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by persistent synovitis, ultimately leading to cartilage and bone degeneration. Natural Killer cells and CD28 null T-cells are suspected as role players in RA pathogenesis. These cells are similar in feature and function, as they both exert their cytotoxic effect via Killer Cell Immunoglobulin- Like Receptors (KIR) on their surface. KIR genes have either an inhibitory or activating effect depending on their intracytoplasmic structure. Herein we genotyped 16 KIR genes, 3 pseudo genes and 6 HLA class І genes as their corresponding ligands in RA patients and control subjects. METHODS: In this case-control study, KIR and HLA genes were genotyped in 400 RA patients and 372 matched healthy controls using sequence-specific primers (SSP-PCR). Differences in the frequency of genes and haplotypes were determined by χ² test. RESULTS: KIR2DL2, 2DL5a, 2DL5b and activating KIR: KIR2DS5 and 3DS1 were all protective against RA. KIR2DL5 removal from a full Inhibitory KIR haplotype converted the mild protection (OR = 0.56) to a powerful predisposition to RA (OR = 16.47). Inhibitory haplotype No. 7 comprising KIR2DL5 in the absence of KIR2DL1 and KIR2DL3 confers a 14-fold protective effect against RA. CONCLUSION: Individuals carrying the inhibitory KIR haplotype No. 6 have a high potential risk for developing RA.

Effects of Nanoparticles on the Environment and Outdoor Workplaces.

Today, most parts of different nanotechnologies are growing and developing without any special rules and regulations. This could result in undesirable changes in the environment and affect workers in indoor and outdoor workplaces. Carbon-based nanoparticles, such as fullerenes, nanotubes, the oxides of metals such as iron and titanium, and natural inorganic compounds, including asbestos and quartz, can have biological effects on the environment and human health. The risk assessment of such nanoparticles requires evaluation of their mobility, reactivity, environmental toxicity, and stability. With the increasing use of nanoparticles for commercial and industrial purposes, the debate becomes whether the numerous benefits of nanoparticles can overcome the economic costs, environmental impacts, and unknown risks resulting from their use. To date, few studies have been conducted on the toxic and environmental effects that result from direct and indirect exposure to nanoparticles, and there are no clear standards to determine their effects. Lack of technical information in this regard has provided an appropriate context for supporters and opponents of nanoparticles to present contradictory and ill-considered results. Such an uncertain atmosphere has caused increased concerns about the effects of nanoparticles. Therefore, adequate studies to determine the exact, real risks of the use of nanoparticles are required. The information resulting from these studies can be useful in minimizing the environmental hazards that could arise from the use of nanoparticles. Thus, this paper briefly explains the classification of environmental nanoparticles and how to deal with their formation, diffusion, environmental fate and impacts, and our exposure to them.