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Mucormycosis (MCM) is a rare fungal disorder that has recently been increased in parallel with novel COVID-19 infection. MCM with COVID-19 is extremely lethal, particularly in immunocompromised individuals. The collection of available scientific information helps in the management of this co-infection, but still, the main question on COVID-19, whether it is occasional, participatory, concurrent, or coincidental needs to be addressed. Several case reports of these co-infections have been explained as causal associations, but the direct contribution in immunocompromised individuals remains to be explored completely. This review aims to provide an update that serves as a guide for the diagnosis and treatment of MCM patients’ co-infection with COVID-19. The initial report has suggested that COVID-19 patients might be susceptible to developing invasive fungal infections by different species, including MCM as a co-infection. In spite of this, co-infection has been explored only in severe cases with common triangles: diabetes, diabetes ketoacidosis, and corticosteroids. Pathogenic mechanisms in the aggressiveness of MCM infection involves the reduction of phagocytic activity, attainable quantities of ferritin attributed with transferrin in diabetic ketoacidosis, and fungal heme oxygenase, which enhances iron absorption for its metabolism. Therefore, severe COVID-19 cases are associated with increased risk factors of invasive fungal co-infections. In addition, COVID-19 infection leads to reduction in cluster of differentiation, especially CD4+ and CD8+ T cell counts, which may be highly implicated in fungal co-infections. Thus, the progress in MCM management is dependent on a different strategy, including reduction or stopping of implicit predisposing factors, early intake of active antifungal drugs at appropriate doses, and complete elimination via surgical debridement of infected tissues.

Honey has been used as a traditional remedy for various health benefits. This study investigated the potential of honey against the onset of autoimmune diabetes and its associated secondary complications in type 1 diabetic (T1D) experimental animals. Autoimmune diabetes was induced in Sprague Dawley rats, and at the same time, the rats were treated with honey or metformin. Sandwich ELISAs were used to estimate blood glucose, hemoglobin A1C (HbA1c), total cholesterol, and triglycerides. Histopathological examinations determined the T1D-induced lesions on kidneys, pancreas, cornea, and retina. Treatment of rats with honey during the course of T1D induction showed a significant reduction in fasting-blood-glucose and HbA1c (p < 0.01), and total lipid profile was also improved (p < 0.05). Not only these, but honey also reduced the T1D-induced lesions in the kidney, pancreas, and cornea/retina (p < 0.05). Metformin showed similar effects and was used as a positive control. In conclusion, honey showed therapeutic potential against the onset of autoimmune diabetes, as it reduces blood glucose/HbA1c and improves the lipid profile by reducing the plasma levels of total cholesterol, low-density lipoproteins (LDL), very low-density lipoprotein (VLDL), and triglycerides. Moreover, it also showed protective potential against the development of diabetic nephropathy, pancreatitis, and retinopathy.

Abstract Background Mast cells and basophils are multifunctional effector cells and contain plentiful secretary granules in their cytoplasm. These cell types are involved in several inflammatory and immune events and are known to produce an array of mediators including a broad spectrum of cytokines. Pomegranate fruit is rich in anthocyanins and hydrolysable tannins; a group of polyphenolic compounds shown to be potent antioxidant with anti-inflammatory activity. However, no studies have been undertaken to investigate whether a polyphenol-rich pomegranate fruit extract (POMx) inhibits the inflammatory activity of activated human mast cells and basophils. The aim of this study was to examine whether POMx modulates inflammatory reactions using human basophilic cell line KU812. Methods KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus calcium inophore A23187 (PMACI). The inhibitory effect of POMx on pro-inflammatory cytokine gene expression and production by stimulated KU812 cells was measured by quantitative RT-PCR, and cytokine-specific ELISA assays, respectively. Western blotting was used to analyze the effect of POMx on the activation of mitogen-activated protein kinases (MAPKs), and the nuclear factor (NF)-κB in PMACI stimulated KU812 cells. Effect on the activity of NF-κB was determined using Luciferase reporter assay. Significance of differences from control values were analyzed by means of standard statistical methods. Results POMx significantly decreased PMACI stimulated inflammatory gene expression and production of interleukin (IL)-6 and IL-8 in KU812 cells. The inhibitory effect of POMx on the pro-inflammatory cytokines was MAPK subgroups c-jun N-terminal kinase (JNK)- and extracellular-regulated kinase (ERK) dependent. In addition, POMx suppressed the NF-κB activation induced by PMACI by inhibiting IκB-degradation in human basophil cells. POMx also suppressed the powerful induction of NF-κB promoter-mediated luciferase activity in transiently transfected KU812 cells. Conclusion These novel pharmacological actions of POMx provide new suggestion that POMx or POMx-derived compounds may be of therapeutic use for the treatment of inflammatory diseases by suppressing mast cells/basophils activation.

Abstract Several recent studies have documented that supplementation with pomegranate fruit extract inhibits inflammatory symptoms in vivo. However, the molecular basis of the observed effects has not been fully revealed. Although previous studies have documented the inhibition of nitric oxide and cyclooxygenase (COX) activity in vitro by plant and fruit extracts added directly into the culture medium but whether concentrations of bioactive compounds sufficient enough to exert such inhibitory effects in vivo can be achieved through oral consumption has not been reported. In the present study we determined the effect of rabbit plasma obtained after ingestion of a polyphenol rich extract of pomegranate fruit (PFE) on COX enzyme activity ex vivo and the IL-1β-induced production of NO and PGE2 in chondrocytes in vitro. Plasma samples collected before and 2 hr after supplementation with PFE were tested. Plasma samples collected after oral ingestion of PFE were found to inhibit the IL-1β-induced PGE2 and NO production in chondrocytes. These same plasma samples also inhibited both COX-1 and COX-2 enzyme activity ex vivo but the effect was more pronounced on the enzyme activity of COX-2 enzyme. Taken together these results provide additional evidence of the bioavailability and bioactivity of compounds present in pomegranate fruit after oral ingestion. Furthermore, these studies suggest that PFE-derived bioavailable compounds may exert an anti-inflammatory effect by inhibiting the inflammatory cytokine-induced production of PGE2 and NO in vivo.

This article explores the therapeutic potential of catalase, an enzyme found in living organisms, in mitigating oxidative stress and preventing oxidative damage to cells and tissues. It discusses the mechanisms of catalase activity, its applications in treating oxidative stress-related diseases, and future perspectives for harnessing its therapeutic potential. The article highlights the importance of understanding catalase's role in cellular physiology and its potential as a therapeutic agent. Additionally, a document of references related to catalase and its role in various diseases and therapeutic applications is provided, including studies on oxidative stress and neurodegenerative diseases, catalase deficiency and metabolic processes, and the potential use of catalase in kidney injury, cardiovascular diseases, and cancer. Delivery strategies and clinical trials involving catalase are also mentioned. [Extracted from the article]

This article explores the field of cancer genetics and epigenetics, emphasizing the importance of understanding the genetic and epigenetic mechanisms of cancer for effective treatment. It discusses various research topics within this field, such as the role of MTAP deficiency, manipulation of ERBB2 mRNA sequences, and the use of ferroptosis as a biomarker and treatment for ovarian cancers. The article also mentions the association of MTHFR gene polymorphisms with prostate cancer risk, noting that this influence is specific to certain populations. Overall, the article highlights the need for further research to identify biomarkers, mechanisms of cancer development, and drug resistance, and emphasizes the potential of precision diagnostics and treatments in cancer care. [Extracted from the article]

This article explores the challenges and potential of using superoxide dismutase (SOD) as a therapeutic agent in various fields. SOD is an important enzyme in the antioxidant defense system and has applications in medicine, biotechnology, and cosmetology. However, there are obstacles to the clinical translation of SOD-based therapies, such as formulation, delivery, and efficacy. The article suggests that by addressing these challenges and taking advantage of emerging opportunities, the full potential of SOD can be harnessed for improving human health. [Extracted from the article]

Objective: Triple-negative breast cancer (TNBC) is a very aggressive form of cancer that grows and spreads very fast and generally relapses. Therapeutic options of TNBC are limited and still need to be explored completely. Gold nanoparticles conjugated with citrate (citrate-AuNPs) are reported to have anticancer potential; however, their role in regulating microRNAs (miRNAs) in TNBC has never been investigated. This study investigated the potential of citrate- AuNPs against tumorigenic inflammation viamodulation ofmiRNAs in TNBC cells. Methods: Gold nanoparticles were chemically synthesized using the trisodiumcitrate method and were characterized by UV-Vis spectrophotometry and dynamic light scattering studies. Targetscan bioinformatics was used to analyze miRNA target genes. Levels of miRNA and mRNA were quantified using TaqMan assays. The pairing of miRNA in 3'untranslated region (3'UTR) of mRNA was validated by luciferase reporter clone, containing the entire 3'UTR of mRNA, and findings were further re-validated via transfection with miRNA inhibitors. Results: Newly synthesized citrate-AuNPs were highly stable, with a mean size was 28.3 nm. The data determined that hsa-miR155-5p is a direct regulator of SOCS1 (suppressor-of-cytokine-signaling) expression and citrate-AuNPs inhibits SOCS1 mRNA/protein expression via modulating hsa-miR155-5p expression. Transfection of TNBC MDA-MB-231 cells with anti-miR155-5p markedly increased SOCS1 expression (p<0.001), while citrate-AuNPs treatment significantly inhibited anti-miR155-5p transfection-induced SOCS1 expression (p<0.05). These findings were validated by IFN-g-stimulated MDA-MB-231 cells. Moreover, the data also determined that citrate-AuNPs also inhibit IFN-ginduced NF-kB p65/p50 activation in MDA-MB-231 cells transfected with antihsa- miR155-5p. [ABSTRACT FROM AUTHOR]

This article provides an overview of the management of allergic disorders in Saudi Arabia, focusing on challenges and future perspectives. It discusses the increasing prevalence of allergic disorders in the country, including asthma, allergic rhinitis, atopic dermatitis, and food allergies. The article highlights the need for effective preventive strategies and explores the current management strategies and treatment options available. However, the Saudi Arabian government faces challenges such as limited awareness and education, a shortage of specialized healthcare providers, limited accessibility to healthcare services, and the cost of treatment and medications. The article suggests future perspectives, including increasing public awareness, investing in training programs for healthcare professionals, and strengthening the primary healthcare system. It emphasizes the importance of research and collaboration to develop effective prevention and management strategies for allergic disorders in Saudi Arabia. [Extracted from the article]