A promising impact of oral administration of noscapine against imiquimod-induced psoriasis-like skin lesions.

Objective: Psoriasis is a chronic inflammatory autoimmune disease. The effectiveness of noscapine has been employed as a helpful treatment for various disorders and subjected to recent theoretical breakthroughs. Materials and Methods: Psoriasis-like lesions were induced by topical application of 5% imiquimod (IMQ) (10 mg/cm2 of skin) in male Balb/c mice and then medicated with a single oral dose of methotrexate (MET) as a positive control or daily oral treatment of noscapine (5, 15 and 45 mg/kg). In this way, skin inflammation intensity, psoriatic itchiness, psoriasis area severity index (PASI) score, ear length, thickness, and organ weight were daily measured. At the end of the study, histological and immunohistochemical and enzyme-linked immunosorbent assays (ELISA, for pro-/anti-inflammatory factors) were performed in each ear. Results: IMQ caused psoriasis-like lesions. Noscapine markedly alleviated macroscopic parameters, namely ear thickness, ear length, skin inflammation, itching, and organ weight, as well as microscopic parameters including, pathology and Ki67 and p53, and tissue immunological mediators, such as tumour necrosis factor (TNF-α), interleukin (IL)-10, transforming growth factor (TGF-ß), interferon-γ (IFN-γ), IL-6, IL-17, and IL-23p19 in the psoriatic skin in a concentration manner (p<0.05-<0.001). Conclusion: Therefore, noscapine with good pharmacological properties has considerable effects on psoriasis inflammation.

A Review of Routine Laboratory Biomarkers for the Detection of Severe COVID-19 Disease.

As the COVID-19 pandemic continues, there is an urgent need to identify clinical and laboratory predictors of disease severity and prognosis. Once the coronavirus enters the cell, it triggers additional events via different signaling pathways. Cellular and molecular deregulation evoked by coronavirus infection can manifest as changes in laboratory findings. Understanding the relationship between laboratory biomarkers and COVID-19 outcomes would help in developing a risk-stratified approach to the treatment of patients with this disease. The purpose of this review is to investigate the role of hematological (white blood cell (WBC), lymphocyte, and neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet, and red blood cell (RBC) count), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and lactate dehydrogenase (LDH)), and biochemical (Albumin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, D-dimer, total Cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) biomarkers in the pathogenesis of COVID-19 disease and how their levels vary according to disease severity.

Resveratrol-Mediated Gold-Nanoceria Synthesis as Green Nanomedicine for Phytotherapy of Hepatocellular Carcinoma.

BACKGROUND: In the present study, resveratrol was used to prepare complexes of cerium and nanoceria, also coated with gold (CeO2@Au core-shells) to improve the surface interactions in physiological conditions. METHODS: The CeO2@Au core-shells were characterized using powder X-ray diffraction (PXRD), Fourier transforms infrared spectroscopy (FTIR), transmission electron microscope (TEM) analysis, dynamic light scattering (DLS) and ζ potential. RESULTS: The experiment was led to the successful synthesis of nanosized CeO2@Au core-shells, although agglomeration of particles caused the distribution of the larger particles. The TEM analysis demonstrated the particles sizes ranged from 20 nm to 170 nm. Moreover, the PXRD analysis showed that both nanoceria and gold with the same crystal systems and space groups. To investigate the anticancer activity of the CeO2@Au core-shells, the cytotoxicity of the nanoparticles was investigated against liver cancerous cell lines (HepG2). CONCLUSIONS: The results indicated biosynthesized NCs have significant cellular toxicity properties against HepG2 and could be utilized in hepatocarcinoma therapy. Further in vivo investigations is proposed to be designed to assess anti-cancer and safety effects of fabricated nanocomposites.

Topical Formulation of Noscapine, a Benzylisoquinoline Alkaloid, Ameliorates Imiquimod-Induced Psoriasis-Like Skin Lesions.

Psoriasis is considered an autoimmune inflammatory disease. The disease is spread and diagnosed by the infiltration of inflammatory mediators and cells into the epidermis. Recent theoretical developments have focused on the effectiveness of noscapine (NOS) as a potential alkaloid for being used as a valuable treatment for different diseases. In the present study, psoriasis-like dermatitis was induced on the right ear pinna surface of male Balb/c mice by topical application of imiquimod (IMQ) for ten consecutive days, which was treated with noscapine (0.3, 1, 3, and 10% w/v) or clobetasol (0.05% w/v) as a positive control. The levels of ear length, thickness, severity of skin inflammation, psoriatic itch, psoriasis area severity index (PASI) score, and body weight were measured daily. On the 10th day of study, each ear was investigated for inflammation, fibrosis, proliferation, and apoptosis using histopathological (H&E and Masson's trichrome staining) and immunohistochemistry (Ki67 and p53 staining) assays. Furthermore, the levels of inflammatory biomarkers were characterized by an enzyme-linked immunosorbent assay (ELISA). The results confirmed IMQ-induced psoriasis for five consecutive days. In contrast, noscapine significantly reduced the ear length, thickness, severity of skin inflammation, psoriatic itch and body weight, tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), interferon-gamma (IFN-γ), interleukin 6 (IL-6), IL-17, and IL-23p19 in a concentration-dependent manner (P < 0.001-0.05 for all cases). Overall, topical noscapine significantly ameliorated both the macroscopical and microscopical features of psoriasis. However, further clinical investigations are required to translate the effects to clinics.

Bacterial biofilms and their resistance mechanisms: a brief look at treatment with natural agents.

Biofilm is a complex community of microorganisms residing within a polysaccharide and/or protein matrix. Biofilm can be produced by several microorganisms, including various bacteria and fungi. Nowadays, the resistance of biofilm-growing cells to antimicrobials originated from the structural nature of biofilms, and phenotypic alteration of sessile cells is becoming a global issue. Bacterial biofilms are important in various aspects of human health, including chronic infections, dental plaque, and infection of indwelling medical devices such as catheters. They are also a major problem in other industries, including oil recovery, drinking water distribution, papermaking, metalworking, and food processing. Estimates indicate that more than 80% of infectious diseases are biofilm-derived. The aim of this study is to describe mechanisms of antibiotic resistance to provide a better perspective on how to manage it. Moreover, the current strategies for biofilm inhibition were described. Considering that plants are a valuable source of abundant natural chemicals to create prophylactic and therapeutic medicines against biofilm-based infections, significant natural compounds with anti-biofilm properties were highlighted. Finally, natural anti-biofilm compounds under clinical trial evaluation were summarized to provide a background for more extensive researches and assist in opening a new window to novel treatments.

From plants to antimicrobials: Natural products against bacterial membranes.

Bacterial membrane barrier provides a cytoplasmic environment for organelles of bacteria. The membrane is composed of lipid compounds containing phosphatide protein and a minimal amount of sugars, and is responsible for intercellular transfers of chemicals. Several antimicrobials have been found that affect bacterial cytoplasmic membranes. These compounds generally disrupt the organization of the membrane or perforate it. By destroying the membrane, the drugs can permeate and replace the effective macromolecules necessary for cell life. Furthermore, they can disrupt electrical gradients of the cells through impairment of the membrane integrity. In recent years, considering the spread of microbial resistance and the side effects of antibiotics, natural antimicrobial compounds have been studied by researchers extensively. These molecules are the best alternative for controlling bacterial infections and reducing drug resistance due to the lack of severe side effects, low cost of production, and biocompatibility. Better understanding of the natural compounds' mechanisms against bacteria provides improved strategies for antimicrobial therapies. In this review, natural products with antibacterial activities focusing on membrane damaging mechanisms were described. However, further high-quality research studies are needed to confirm the clinical efficacy of these natural products.

Biological and pharmacological activities of noscapine: Focusing on its receptors and mechanisms.

Noscapine has been mentioned as one of the effective drugs with potential therapeutic applications. With few side effects and amazing capabilities, noscapine can be considered different from other opioids-like structure compounds. Since 1930, extensive studies have been conducted in the field of pharmacological treatments from against malaria to control cough and cancer treatment. Furthermore, recent studies have shown that noscapine and some analogues, like 9-bromonoscapine, amino noscapine, and 9-nitronoscapine, can be used to treat polycystic ovaries syndrome, stroke, and other diseases. Given the numerous results presented in this field and the role of different receptors in the therapeutic effects of noscapine, we aimed to review the properties, therapeutic effects, and the role of receptors in the treatment of noscapine.

Bio-indicators in cadmium toxicity: Role of HSP27 and HSP70.

Heat shock proteins (HSPs) are a family of proteins that are expressed by cells in reply to stressors. The changes in concentration of HSPs could be utilized as a bio-indicator of oxidative stress caused by heavy metal. Exposure to the different heavy metals may induce or reduce the expression of different HSPs. The exposure to cadmium ion (Cd2+) could increase HSP70 and HSP27 over 2- to 10-fold or even more. The in vitro and in vivo models indicate that the HSP70 family is more sensitive to Cd intoxication than other HSPs. The analyses of other HSPs along with HSP70, especially HSP27, could also be useful to obtain more accurate results. In this regard, this review focuses on examining the literature to bold the futuristic uses of HSPs as bio-indicators in the initial assessment of Cd exposure risks in defined environments.

Astrocytes and Inflammasome: A Possible Crosstalk in Neurological Diseases.

Inflammasome research has primarily focused on neurological tissue, particularly on damaged tissue. Most current neurological literature involves in vivo and in vitro studies utilizing astroglia, as astroglia express the cytoskeletal glial fibrillary acidic protein (GFAP), which is used as a hallmark of neuropathological disorders. Research suggests that astrocytes respond to all forms of neurological damage or disease through reactive astrogliosis. Additionally, there is a consensus among scientists that inflammasomes play an important role in neuroinflammation. This review focuses on the latest developments in inflammasome biology, describing the current understanding of how inflammasomes can be triggered in the brain and summarizing the literature on the relevance of inflammasome NLR in prevalent neurological diseases.

Boosting the autophagy-lysosomal pathway by phytochemicals: A potential therapeutic strategy against Alzheimer's disease.

The lysosome is a membrane-enclosed organelle in eukaryotic cells, which has basic pattern recognition for nutrient-dependent signal transduction. In Alzheimer's disease, the already declining autophagy-lysosomal function is exacerbated by an increased need for clearance of damaged proteins and organelles in aged cells. Recent evidence suggests that numerous diseases are linked to impaired autophagy upstream of lysosomes. In this way, a comprehensive survey on the pathophysiology of the disease seems necessary. Hence, in the first section of this review, we will discuss the ultimate findings in lysosomal signaling functions and how they affect cellular metabolism and trafficking under neurodegenerative conditions, specifically Alzheimer's disease. In the second section, we focus on how natural products and their derivatives are involved in the regulation of inflammation and lysosomal dysfunction pathways, including how these should be considered a crucial target for Alzheimer's disease therapeutics.

Cedrol protects against chronic constriction injury-induced neuropathic pain through inhibiting oxidative stress and inflammation.

Injured somatosensory nervous system cause neuropathic pain which is quite difficult to treat using current approaches. It is therefore important to find new therapeutic options. We have analyzed cedrol effect on chronic constriction injury (CCI) induced neuropathic pain in rats. The mechanical and thermal hypersensitivity were evaluated using the von Frey filament, radiant heat and acetone drop methods. The changes in the levels of biomarkers of oxidative stress including malondialdehyde (MDA) and total thiol (SH), as well as inflammatory mediators including Tumour Necrosis Factor alpha (TNF-α) and Interleukin 6 (IL-6) were estimated in the lumbar portion (L4-L6) of neuropathic rats. Administration of cedrol attenuated the CCI-induced mechanical and thermal hypersensitivity. CCI produced an increase in MDA along with a reduction in SH levels in the spinal cord of the CCI rats. Reduced levels of SH were restored by cedrol. Also, the levels of MDA were reduced in the cedrol-treated CCI rats compared to the untreated CCI rats. Besides, level of TNF-α and IL-6 increased in the spinal cord of CCI group and cedrol could reverse it. The current study showed that cedrol attenuates neuropathic pain in CCI rats by inhibition of inflammatory response and attenuation of oxidative stress.

The role of orphan G protein-coupled receptors in the modulation of pain: A review.

G protein-coupled receptors (GPCRs) comprise a large number of receptors. Orphan GPCRs are divided into six families. These groups contain orphan receptors for which the endogenous ligands are unclear. They have various physiological effects in the body and have the potential to be used in the treatment of different diseases. Considering their important role in the central and peripheral nervous system, their role in the treatment of pain has been the subject of some recent studies. At present, there are effective therapeutics for the treatment of pain including opioid medications and non-steroidal anti-inflammatory drugs. However, the side effects of these drugs and the risks of tolerance and dependence remain a major problem. In addition, neuropathic pain is a condition that does not respond to currently available analgesic medications well. In the present review article, we aimed to review the most recent findings regarding the role of orphan GPCRs in the treatment of pain. Accordingly, based on the preclinical findings, the role of GPR3, GPR7, GPR8, GPR18, GPR30, GPR35, GPR40, GPR55, GPR74, and GPR147 in the treatment of pain was discussed. The present study highlights the role of orphan GPCRs in the modulation of pain and implies that these receptors are potential new targets for finding better and more efficient therapeutics for the management of pain particularly neuropathic pain.

Detection of genes involved in biofilm formation in Staphylococcus aureus isolates.

Staphylococcus aureus is one of the Gram-positive pathogens causing a wide range of nosocomial infections. The present study investigates genotypic and phenotypic aspects involved in biofilm formation in methicillin-resistant Staphylococcus aureus strains isolated from nosocomial infections in Isfahan. A total of 110 S. aureus strains were collected from three major hospitals in Isfahan, the center of Iran. The antibiotic resistance pattern, phenotypes, and biofilm formation genes were studied using Congo red agar (CRA) and multiplex PCR (M-PCR). We found that 103 out of 110 samples (93.6%) were MRSA. The highest frequency of resistance was found to penicillin (89%), ciprofloxacin (87.4%), and erythromycin (86.1%). Phenotypic results showed that 53.5% were high biofilm producers, while 33.3% and 13.2% were intermediate and low biofilm producers, respectively. icaC (69.3%) had the highest frequency in comparison to other intercellular adhesion (ica) genes, icaD (54.8%) was second most common. The results show that the adherence or attachment ability and biofilm production are important for enhancing virulence factors among isolates of S. aureus strains.