Potential promising anticancer applications of ß-glucans: a review.

ß-Glucans are valuable functional polysaccharides distributed in nature, especially in the cell walls of fungi, yeasts, bacteria, and cereals. The unique features of ß-glucans, such as water solubility, viscosity, molecular weight, and so on, have rendered them to be broadly applied in various food systems as well as in medicine to improve human health. Moreover, inhibition of cancer development could be achieved by an increase in immune system activity via ß-glucans. ß-glucans, which are part of a class of naturally occurring substances known as biological response modifiers (BRMs), have also shown evidence of being anti-tumorogenic, anti-cytotoxic, and anti-mutagenic. These properties make them attractive candidates for use as pharmaceutical health promoters. Along these lines, they could activate particular proteins or receptors, like lactosylceramide (LacCer), Dickin-1, complement receptor 3 (CR3), scavenge receptors (SR), and the toll-like receptor (TLR). This would cause the release of cytokines, which would then activate other antitumor immune cells, like macrophages stimulating neutrophils and monocytes. These cells are biased toward pro-inflammatory cytokine synthesis and phagocytosis enhancing the elicited immunological responses. So, to consider the importance of ß-glucans, the present review introduces the structure characteristics, biological activity, and antitumor functions of fungal ß-glucans, as well as their application.

Macrophage-Based Therapeutic Strategies in Hematologic Malignancies.

Macrophages are types of immune cells, with ambivalent functions in tumor growth, which depend on the specific environment in which they reside. Tumor-associated macrophages (TAMs) are a diverse population of immunosuppressive myeloid cells that play significant roles in several malignancies. TAM infiltration in malignancies has been linked to a poor prognosis and limited response to treatments, including those using checkpoint inhibitors. Understanding the precise mechanisms through which macrophages contribute to tumor growth is an active area of research as targeting these cells may offer potential therapeutic approaches for cancer treatment. Numerous investigations have focused on anti-TAM-based methods that try to eliminate, rewire, or target the functional mediators released by these cells. Considering the importance of these strategies in the reversion of tumor resistance to conventional therapies and immune modulatory vaccination could be an appealing approach for the immunosuppressive targeting of myeloid cells in the tumor microenvironment (TME). The combination of reprogramming and TAM depletion is a special feature of this approach compared to other clinical strategies. Thus, the present review aims to comprehensively overview the pleiotropic activities of TAMs and their involvement in various stages of cancer development as a potent drug target, with a focus on hematologic tumors.

Neurological manifestations of SARS-CoV-2 infections: towards quantum dots based management approaches.

Developing numerous nanotechnological designed tools to monitor the existence of SARS-CoV-2, and modifying its interactions address the global needs for efficient remedies required for the management of COVID-19. Herein, through a multidisciplinary outlook encompassing different fields such as the pathophysiology of SARS-CoV-2, analysis of symptoms, and statistics of neurological complications caused by SARS-CoV-2 infection in the central and peripheral nervous systems have been testified. The anosmia (51.1%) and ageusia (45.5%) are reported the most frequent neurological manifestation. Cerebrovascular disease and encephalopathy were mainly related to severe clinical cases. In addition, we focus especially on the various concerned physiological routes, including BBB dysfunction, which transpired due to SARS-CoV-2 infection, direct and indirect effects of the virus on the brain, and also, the plausible mechanisms of viral entry to the nerve system. We also outline the characterisation, and the ongoing pharmaceutical applications of quantum dots as smart nanocarriers crossing the blood-brain barrier and their importance in neurological diseases, mainly SARS-CoV-2 related manifestations Moreover, the market status, six clinical trials recruiting quantum dots, and the challenges limiting the clinical application of QDs are highlighted.

Neurological disorders of COVID-19: insights to applications of natural products from plants and microorganisms.

In addition to the typical respiratory manifestations, various disorders including involvement of the nerve system have been detected in COVID-19 ranging from 22 to 36%. Although growing records are focusing on neurological aspects of COVID-19, the pathophysiological mechanisms and related therapeutic methods remain obscure. Considering the increased concerns of SARS-CoV-2 potential for more serious neuroinvasion conditions, the present review attempts to focus on the neuroprotective effects of natural compounds as the principle source of therapeutics inhibiting multiple steps of the SARS-CoV-2 infection cycle. The great majority of the natural products with anti-SARS-CoV-2 activity mainly inhibit the attachment, entry and gene expression rather than the replication, assembly, or release. Although microbial-derived natural products comprise 38.5% of the known natural products with neuroprotective effects following viral infection, the neuroprotective potential of the majority of microorganisms is still undiscovered. Among natural products, chrysin, huperzine A, ginsenoside Rg1, pterostilbene, and terrein have shown potent in vitro neuroprotective activity and can be promising for new or repurpose drugs for neurological complications of SARS-CoV-2.

Current understanding of epigenetics role in melanoma treatment and resistance.

Melanoma is the most aggressive form of skin cancer resulting from genetic mutations in melanocytes. Several factors have been considered to be involved in melanoma progression, including genetic alteration, processes of damaged DNA repair, and changes in mechanisms of cell growth and proliferation. Epigenetics is the other factor with a crucial role in melanoma development. Epigenetic changes have become novel targets for treating patients suffering from melanoma. These changes can alter the expression of microRNAs and their interaction with target genes, which involves cell growth, differentiation, or even death. Given these circumstances, we conducted the present review to discuss the melanoma risk factors and represent the current knowledge about the factors related to its etiopathogenesis. Moreover, various epigenetic pathways, which are involved in melanoma progression, treatment, and chemo-resistance, as well as employed epigenetic factors as a solution to the problems, will be discussed in detail.

Recent Advances in Glioma Cancer Treatment: Conventional and Epigenetic Realms.

Glioblastoma (GBM) is the most typical and aggressive form of primary brain tumor in adults, with a poor prognosis. Successful glioma treatment is hampered by ineffective medication distribution across the blood-brain barrier (BBB) and the emergence of drug resistance. Although a few FDA-approved multimodal treatments are available for glioblastoma, most patients still have poor prognoses. Targeting epigenetic variables, immunotherapy, gene therapy, and different vaccine- and peptide-based treatments are some innovative approaches to improve anti-glioma treatment efficacy. Following the identification of lymphatics in the central nervous system, immunotherapy offers a potential method with the potency to permeate the blood-brain barrier. This review will discuss the rationale, tactics, benefits, and drawbacks of current glioma therapy options in clinical and preclinical investigations.

The Role of Cell Organelles in Rheumatoid Arthritis with Focus on Exosomes.

Auto-immune diseases involved at least 25% of the population in wealthy countries. Several factors including genetic, epigenetic, and environmental elements are implicated in development of Rheumatoid Arthritis as an autoimmune disease. Autoantibodies cause synovial inflammation and arthritis, if left untreated or being under continual external stimulation, could result in chronic inflammation, joint injury, and disability. T- and B-cells, signaling molecules, proinflammatory mediators, and synovium-specific targets are among the new therapeutic targets. Exosomes could be employed as therapeutic vectors in the treatment of autoimmune diseases. Herein, the role of cell organelle particularly exosomes in Rheumatoid Arthritis had discussed and some therapeutic applications of exosome highlighted.

Fruit wrapping kraft coated paper promotes the isolation of actinobacteria using ex situ and in situ methods.

Designing novel isolation methods could enhance the diversification of the available bacterial strains to biotechnology. In this study, the new ex situ and in situ cultivation methods are introduced for the isolation of actinobacteria. In the ex situ experiments, the soil suspension was spread on the isolation media located above some ordinary papers in immediate contact with the slurry of soil substrate and incubated for 16 weeks. The paper was wholly immersed in the cave soil for in situ cultivations, and the containers were buried under layers of soil in Hampoeil cave for 10 weeks. Fruit wrapping kraft coated paper, with 68.8% recovery of isolates, was a better choice in isolation of actinobacteria than other studied filter paper. Based on the molecular identification results, 19% of the isolates obtained from the in situ cultivation method had less than 98.5% similarity to known taxa of actinobacteria and potentially may represent new species. In contrast, in the standard cultivation method, 1.3% of the isolates had less than 98.5% similarity 16Sr RNA gene. This data shows that the introduced cultivation method is a promising technique for isolating less culturable or new actinobacteria.

The potential of endoscopic ultrasound sonography (EUS)-elastography in determining the stage of pancreatic tumor.

AIM: The current study was designed to evaluate the role of semi-quantitative EUS- elastography (strain ratio) in staging malignant pancreatic lesions. BACKGROUND: Pancreatic cancer is considered one of the most lethal malignancies with a survival rate of only 5% worldwide. Pancreatic lesions include a wide range of diagnoses from benign to malignant forms. Biopsy and pathological study are the gold standard for the differentiation of malignant lesions and staging of tumors. Recently, endoscopic ultrasound sonography (EUS) elastography has been noticed as a non-invasive diagnosis modality. Nevertheless, no evidence of its potential to determine different stages of malignant tumors is available. METHODS: This prospective study included 81 adult patients with a confirmed diagnosis of malignant pancreatic lesion in different clarified stages. All diagnoses were confirmed after endoscopic ultrasound sonography via pathological investigation of surgical specimens or needle biopsies. The results of EUS-elastography based on tumor size (T staging), involved lymph nodes (N staging), and metastasis (M staging) were compared with the gold standard. RESULTS: The mean age of patients was 60.11±13.57 years. The mean SR elastography value was 52.78±48.97. Elastography could not significantly discriminate T stage, N stage, or M stage of tumors (p=0.57, p=0.92, p=0.11, respectively). Moreover, the Spearman rank correlation coefficients for the correlation between T staging, N staging, M staging and SR elastography were not significant (p=0.40, p=0.94, p=0.39, respectively). CONCLUSION: The non-invasive modality EUS-elastography cannot replace the gold standard in staging tumors; however, EUS-elastography seemed to differentiate benign lesions from malignant ones.

Prominent and emerging anti-diabetic molecular targets.

Diabetes is on the rise across the globe affecting more than 463 million people and crucially increasing morbidities of diabetes-associated diseases. Urgent and immense actions are needed to improve diabetes prevention and treatment. Regarding the correlation of diabetes with many associated diseases, inhibition of the disease progression is more crucial than controlling symptoms. Currently, anti-diabetic drugs are accompanied by undesirable side-effects and target confined types of biomolecules. Thus, extensive research is demanding to identify novel disease mechanisms and molecular targets as probable candidates for effective treatment of diabetes. This review discusses the conventional molecule targets that have been applied for their therapeutic rationale in treatment of diabetes. Further, the emerging and prospective molecular targets for the future focus of library screenings are presented.

Hypothetical targets and plausible drugs of coronavirus infection caused by SARS-CoV-2.

The world is confronting a dire situation due to the recent pandemic of the novel coronavirus disease (SARS-CoV-2) with the mortality rate passed over 470,000. Attaining efficient drugs evolve in parallel to the understanding of the SARS-CoV-2 pathogenesis. The current drugs in the pipeline and some plausible drugs are overviewed in this paper. Although different types of anti-viral targets are applicable for SARS-CoV-2 drug screenings, the more promising targets can be considered as 3C-like main protease (3Cl protease) and RNA polymerase. The remdesivir could be considered the closest bifunctional drug to the provisional clinical administration for SARS-CoV-2. The known molecular targets of the SARS-CoV-2 include fourteen targets, while four molecules of angiotensin-converting enzyme 2 (ACE2), cathepsin L, 3Cl protease and RNA-dependent RNA polymerase (RdRp) are suggested as more promising potential targets. Accordingly, dual-acting drugs as an encouraging solution in drug discovery are suggested. Emphasizing the potential route of SARS-CoV-2 infection and virus entry-related factors like integrins, cathepsin and ACE2 seems valuable. The potential molecular targets of each phase of the SARS-CoV-2 life cycle are discussed and highlighted in this paper. Much progress in understanding the SARS-CoV-2 and molecular details of its life cycle followed by the identification of new therapeutic targets are needed to lead us to an efficient approach in anti-SARS-CoV-2 drug discovery.

Unusual gastrointestinal manifestations of COVID-19: two case reports.

As of December 2019, a new strain of coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was discovered in Wuhan, China, following an epidemic of a fast-spreading viral respiratory disease, later called Coronavirus Disease 2019 (COVID-19), which then lead to the present pandemic the world has come to know. Patients who tested positive for COVID-19 are mostly asymptomatic or present with mild self-limiting symptoms. While GI symptoms occur with less prevalence, they are increasingly being reported. A diagnosis of Covid-19 has increased dramatically in patients presenting with gastrointestinal symptoms suggesting that GI symptoms should be taken into serious consideration with patient diagnosis. Case 1: A 65-year-old man presented to the hospital emergency room with abdominal pain, Murphy's sign and chills without fever, subsequently diagnosed as acute acalculous cholecystitis with a positive COVID-19 rRT-PCR. Case 2: A 78-year-old woman presented to the hospital emergency room complaining of severe positional epigastric pain precipitated by lying supine, chills with no fever, being later diagnosed as acute pancreatitis and a positive COVID-19 rRT-PCR. It has become evident that the ACE2 receptor plays a significant role as the entry site into human cells for the virus. This receptor is generally expressed in respiratory cells, as well as the gastrointestinal tract, corresponding with extrapulmonary manifestations of COVID-19. Studies concluded that the origin of gastrointestinal symptoms could be caused by the interaction of the SARS-CoV-2 virus with cells through the ACE2 receptor. The findings of the present study support this theory, as both patients presented with symptoms regarding tissues with high ACE2 expression.

The synergistic impact of NSAIDs and aggressive hydration therapy on the rate of post-ERCP pancreatitis in high -risk and low -risk patients.

AIM: The main complication of Endoscopic retrograde cholangiopancreatography (ERCP) is post-ERCP pancreatitis (PEP). BACKGROUND: Based on demographic characteristics and underlying issues and ERCP indication, patients are categorized as high risk or low risk. There have been no studies on the synergistic effects of NSAIDS and hydration therapy, separately sorted by the risk assessment of PEP in different groups of patients. METHODS: This study included 281 eligible participants after exclusion. According to demographic characteristics and co-morbidities, the patients were divided to high risk and low risk. The high-risk group was divided randomly into two subgroups and both of them received NSAIDs (100 mg rectal Diclofenac). One group received standard hydration (1.5mg/kg/hr), another the other received aggressive hydration (3mg/kg/h). The low-risk group received standard hydration. One of its subgroups received NSAIDs, while others did not. The efficacy of these preventions was compared across 4 subgroups. RESULTS: The mean age was 59.85±17.17. Eight hours after ERCP, the amylase and lipase were significantly higher in the high-risk group with standard hydration (P=0.00). Amylase, lipase 8 hours, between two low risk subgroups, NSAIDs had no significant effect (P=0.38, P=0.95, respectively). After adjustment based on cannulation, manipulation and duration of time, the results had no change (P=0.64, P=0.19, P=0.61). CONCLUSION: The aggressive hydration could significantly decrease the risk of PEP. However, the low-risk group was exposed to the lowest risk of PEP. NSAIDs could not help to decrease the rate PEP in the low-risk groups alone. Overall, it seems hydration and NSAIDs therapy had synergistic outcome in high-risk patients.

Development of a Single Stranded DNA Aptamer as a Molecular Probe for LNCap Cells Using Cell-SELEX.

BACKGROUND: Nowadays, highly specific aptamers generated by cell SELEX technology (systematic evolution of ligands by exponential enrichment) are being applied for early detection of cancer cells. Prostate Specific Membrane Antigen (PSMA), over expressed in prostate cancer, is a highly specific marker and therefore can be used for diagnosis of the prostate cancer cells. The aim of the present study was to select single-stranded DNA aptamers against LNCap cells highly expressing PSMA, using cell-SELEX method which can be used as a diagnostic tool for the detection of prostate cancer cells. METHODS: After 10 rounds of cell-SELEX, DNA aptamers were isolated against PSMA using LNCaP cells as a target and PC-3 cell lines for counter SELEX. Five DNA aptamers with more than 70% affinity were selected up on flow cytometry analysis of positive clones. RESULTS: Dissociation constants of two selected sequences (A12-B1) were estimated in the range of 33.78±3.77 and 57.49±2.214 pmol, respectively. Conserved secondary structures of A12 and B1 sequences suggest the necessity of these structures for binding with high affinity to native PSMA. Comparison of the secondary structures of our isolated aptamers and aptamer A10 obtained by protein SELEX showed similar stem-loop structures which could be responsible for the recognition of PSMA on LNCap cell surface. CONCLUSION: Our results indicated that selected aptamers may turn out to be ideal candidates for the development of a detection tool and also can be used in targeted drug delivery for future smart drugs.