Medicinal Mushroom Supplements in Cancer: A Systematic Review of Clinical Studies.

PURPOSE OF REVIEW: Patients seek clinical guidance on mushroom supplements that can be given alongside conventional treatments, but most research on such fungi has been preclinical. The current systematic review focused on clinical studies of mushrooms in cancer care conducted in the past 10 years. We searched Medline (Ovid), Embase (Ovid), Scopus (Wiley), and Cochrane Library to identify all mushroom studies conducted in humans published from January 2010 through December 2020. Two authors independently assessed papers for inclusion. RECENT FINDINGS: Of 136 clinical studies identified by screening 2349, 39 met inclusion criteria. The studies included 12 different mushroom preparations. A survival benefit was reported using Huaier granules (Trametes robiniophila Murr) in 2 hepatocellular carcinoma studies and 1 breast cancer study. A survival benefit was also found in 4 gastric cancer studies using polysaccharide-K (polysaccharide-Kureha; PSK) in the adjuvant setting. Eleven studies reported a positive immunological response. Quality-of-life (QoL) improvement and/or reduced symptom burden was reported in 14 studies using various mushroom supplements. Most studies reported adverse effects of grade 2 or lower, mainly nausea, vomiting, diarrhea, and muscle pain. Limitations included small sample size and not using randomized controlled trial design. Many of the reviewed studies were small and observational. Most showed favorable effects of mushroom supplements in reducing the toxicity of chemotherapy, improving QoL, favorable cytokine response, and possibly better clinical outcomes. Nevertheless, the evidence is inconclusive to recommend the routine use of mushrooms for cancer patients. More trials are needed to explore mushroom use during and after cancer treatment.

A peek behind the curtain in the diagnosis and management of COVID­19­Associated Mucormycosis (CAM).

Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is responsible for a high mortality rate due to its unique and severe host-pathogen interactions. Critically ill or immunocompromised COVID-19 patients are more prone to suffer from aggressive mycoses. Probable victims include those with uncontrolled diabetes mellitus (DM), metabolic acidosis, prolonged neutropenia, increased ferritin levels, hypoxia, and prolonged hospitalization with/without mechanical ventilators and corticosteroids administration. The current review aims to outline the journey of patients with CAM as well as the advantages and disadvantages of the currently available diagnostic techniques. It also discussed the current status of treatment options and caveats in the management of mucormycosis. Multidisciplinary team, early diagnosis, controlling the predisposing condition(s), complete surgical debridement, effective antifungal therapies (e.g., amphotericin B, isavuconazole, and posaconazole), and implementing antifungal stewardship programs are imperative in CAM cases.

Rise of the natural red pigment 'prodigiosin' as an immunomodulator in cancer.

Cancer is a heterogeneous disease with multifaceted drug resistance mechanisms (e.g., tumour microenvironment [TME], tumour heterogeneity, and immune evasion). Natural products are interesting repository of bioactive molecules, especially those with anticancer activities. Prodigiosin, a red pigment produced by Serratia marcescens, possesses inherent anticancer characteristics, showing interesting antitumour activities in different cancers (e.g., breast, gastric) with low or without harmful effects on normal cells. The present review discusses the potential role of prodigiosin in modulating and reprogramming the metabolism of the various immune cells in the TME, such as T and B lymphocytes, tumour-associated macrophages (TAMs), natural killer (NK) cells, and tumour-associated dendritic cells (TADCs), and myeloid-derived suppressor cells (MDSCs) which in turn might introduce as an immunomodulator in cancer therapy.

Disengaging the COVID-19 Clutch as a Discerning Eye Over the Inflammatory Circuit During SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the cytokine release syndrome (CRS) and leads to multiorgan dysfunction. Mitochondrial dynamics are fundamental to protect against environmental insults, but they are highly susceptible to viral infections. Defective mitochondria are potential sources of reactive oxygen species (ROS). Infection with SARS-CoV-2 damages mitochondria, alters autophagy, reduces nitric oxide (NO), and increases both nicotinamide adenine dinucleotide phosphate oxidases (NOX) and ROS. Patients with coronavirus disease 2019 (COVID-19) exhibited activated toll-like receptors (TLRs) and the Nucleotide-binding and oligomerization domain (NOD-), leucine-rich repeat (LRR-), pyrin domain-containing protein 3 (NLRP3) inflammasome. The activation of TLRs and NLRP3 by SARS-CoV-2 induces interleukin 6 (IL-6), IL-1ß, IL-18, and lactate dehydrogenase (LDH). Herein, we outline the inflammatory circuit of COVID-19 and what occurs behind the scene, the interplay of NOX/ROS and their role in hypoxia and thrombosis, and the important role of ROS scavengers to reduce COVID-19-related inflammation.

Theophylline-encapsulated Nile Tilapia fish scale-based collagen nanoparticles effectively target the lungs of male Sprague-Dawley rats.

Nile Tilapia fish scale collagen has high biodegradability, excellent biocompatibility, and low antigenicity. We assessed both the encapsulation efficiency of theophylline into Nile Tilapia fish scale-based collagen nanoparticles and their stability as a pulmonary drug delivery system in male Sprague-Dawley rats. The present study has demonstrated the successful encapsulation of theophylline into the synthesised nanoparticles as shown by spectrophotometric analysis, light microscope, scanning electron microscope, transmission electron microscope, and dynamic light scattering. The antibacterial activity of the nanoparticles improves with increasing their concentrations. Intratracheal treatment of rats using theophylline-encapsulated nanoparticles reduced the levels of creatinine, alanine transaminase, and aspartate transaminase, compared to the control group. Nevertheless, nanoparticles combined with theophylline exhibited no effects on cholesterol and triglycerides levels. Histopathological examination revealed typical uniform and diffuse thickening of the alveolar walls with capillary oedema in treated rats. We concluded that the synthesised collagen nanoparticles appropriately target the lungs of male Sprague-Dawley rats when delivered via a nebuliser, showing good tolerability to lung cells. However, dose ratio of collagen nanoparticles to theophylline needs further evaluation. The nanoprecipitation method may be optimised to involve poorly water-soluble inhaled drugs, and avoid the drawbacks of traditional drug delivery.

The role of 5-lipoxygenase in the pathophysiology of COVID-19 and its therapeutic implications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, known as coronavirus disease 2019 (COVID-19) causes cytokine release syndrome (CRS), leading to acute respiratory distress syndrome (ARDS), acute kidney and cardiac injury, liver dysfunction, and multiorgan failure. Although several studies have discussed the role of 5-lipoxygenase (5-LOX) in viral infections, such as influenzae and SARS, it remains unexplored in the pathophysiology of COVID-19. 5-LOX acts on free arachidonic acid (AA) to form proinflammatory leukotrienes (LTs). Of note, numerous cells involved with COVID-19 (e.g., inflammatory and smooth muscle cells, platelets, and vascular endothelium) widely express leukotriene receptors. Moreover, 5-LOX metabolites induce the release of cytokines (e.g., tumour necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and interleukin-1ß [IL-1ß]) and express tissue factor on cell membranes and activate plasmin. Since macrophages, monocytes, neutrophils, and eosinophils can express lipoxygenases, activation of 5-LOX and the subsequent release of LTs may contribute to the severity of COVID-19. This review sheds light on the potential implications of 5-LOX in SARS-CoV-2-mediated infection and the anticipated therapeutic role of 5-LOX inhibitors.

Prodigiosin/PU-H71 as a novel potential combined therapy for triple negative breast cancer (TNBC): preclinical insights.

Prodigiosin, a secondary metabolite red pigment produced by Serratia marcescens, has an interesting apoptotic efficacy against cancer cell lines with low or no toxicity on normal cells. HSP90α is known as a crucial and multimodal target in the treatment of TNBC. Our research attempts to assess the therapeutic potential of prodigiosin/PU-H71 combination on MDA-MB-231 cell line. The transcription and protein expression levels of different signalling pathways were assessed. Treatment of TNBC cells with both drugs resulted in a decrease of the number of adherent cells with apoptotic effects. Prodigiosin/PU-H71 combination increased the levels of caspases 3,8 and 9 and decreased the levels of mTOR expression. Additionally, there was a remarkable decrease of HSP90α transcription and expression levels upon treatment with combined therapy. Also, EGFR and VEGF expression levels decreased. This is the first study to show that prodigiosin/PU-H71 combination had potent cytotoxicity on MDA-MB-231 cells; proving to play a paramount role in interfering with key signalling pathways in TNBC. Interestingly, prodigiosin might be a potential anticancer agent to increase the sensitivity of TNBC cells to apoptosis. This study provides a new basis for upcoming studies to overcome drug resistance in TNBC cells.

Budget impact analysis for dapagliflozin in type 2 diabetes in Egypt.

Introduction: Type 2 diabetes mellitus (T2DM) is a major health problem in Egypt with a high impact on morbidity, mortality, and healthcare resources. This study evaluated the budget impact and the long-term consequences of dapagliflozin versus other conventional medications, as monotherapy, from both the societal and health insurance perspectives in Egypt.Methods: A static budget impact model was developed to estimate the financial consequences of adopting dapagliflozin on the healthcare payer budget. We measured the direct medical costs of dapagliflozin (new scenario) as monotherapy, compared to metformin, insulin, sulphonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinedione, and repaglinide (old scenarios) over a time horizon of 3 years. Myocardial infarction (MI), ischemic stroke, hospitalization for heart failure (HHF), and initiation of renal replacement therapy (RRT) rates were captured from DECLARE TIMI 58 trial. One-way sensitivity analyses were conducted.Results: The budget impact model estimated 2,053,908 patients eligible for treatment with dapagliflozin from a societal perspective and 1,207,698 patients from the health insurance (HI) perspective. The new scenario allows for an initial savings of EGP121 million in the first year, which increased to EGP243 and EGP365 million in the second and third years, respectively. The total cumulative savings from a societal perspective were estimated at EGP731 million. Dapagliflozin allows for savings of EGP71, EGP143, and EGP215 million in the first, second and third years respectively, from the HI perspective, with total cumulative savings of EGP430 million over the 3 years.Conclusion: Treating T2DM patients using dapagliflozin instead of conventional medications, maximizes patients' benefits and decreases total costs due to drug cost offsets from fewer cardiovascular and renal events. The adoption of dapagliflozin is a budget-saving treatment option, resulting in substantial population-level health gains due to reduced event rate and cost savings from the perspective of the national healthcare system.