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Abstract: Given the importance of COVID-19-induced ARDS, recently, researchers have strived to determine underlying mechanisms involved in the inflammatory responses. In this regard, inflammasomes possess a distinct priority for cytokine storm occurrence and, subsequently, ARDS progression in ill patients with SARS-CoV-2 infection. In this minireview, the characteristics of known inflammasome inhibitors and designed research in this field were concretely deciphered.

Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes acute inflammation due to extensive replication of the virus in the epithelial cells of the upper and lower respiratory system. The mammalian target of rapamycin (mTOR) is a l signalling protein with critical functions in cell growth, metabolism, and proliferation. It is known for its regulatory functions in protein synthesis and angiogenesis cascades. The structure of mTOR consists of two distinct complexes (mTORC1 and mTORC2) with diverse functions at different levels of the signalling pathway. By activating mRNA translation, the mTORC1 plays a key role in regulating protein synthesis and cellular growth. On the other hand, the functions of mTORC2 are mainly associated with cell proliferation and survival. By using an appropriate inhibitor at the right time, mTOR modulation could provide immunosuppressive opportunities as antirejection regimens in organ transplantation as well as in the treatment of autoimmune diseases and solid tumours. The mTOR also has an important role in the inflammatory process. Inhibitors of mTOR might indeed be promising agents in the treatment of viral infections. They have further been successfully used in patients with severe influenza A/H1N1 pneumonia and acute respiratory failure. The officially accepted mTOR inhibitors that have undergone clinical testing are sirolimus, everolimus, temsirolimus, and tacrolimus. Thus, further studies on mTOR inhibitors for SARS-CoV-2 infection or COVID-19 therapy are well merited.

In this review, we discussed the biological targets of carnitine, its effects on immune function, and how L-carnitine supplementation may help critically ill patients. L-carnitine is a potent antioxidant. L-carnitine depletion has been observed in prolonged intensive care unit (ICU) stays, while L-carnitine supplementation has beneficial effects in health promotion and regulation of immunity. It is essential for the uptake of fatty acids into mitochondria. By inhibiting the ubiquitin-proteasome system, down-regulating the apelin receptor in cardiac tissue, and reducing β-oxidation of fatty acid, carnitine may decrease vasopressor requirement in septic shock and improve clinical outcomes of this group of patients. We also reviewed animal and clinical studies that have been recruited for evaluating the beneficial effects of L-carnitine in the management of sepsis/ septic shock. Additional clinical data are required to evaluate the optimal daily dose and duration of L-carnitine supplementation.

Organic chemistry plays a vital role in the pharmaceutical industry. Knowledge of organic compounds is used to inform research and further the discovery and development of new medicines. Likewise, organic chemistry is fundamental to understanding biological reactions, mechanisms and all life sciences in general. Basic Chemistry for Life Science Students and Professionals is an ideal introduction to organic chemistry in the context of the life sciences and pharmacy related disciplines; utilising drug molecules to illustrate the chemical basis of their efficacy and interaction with biological targets. This book builds upon the basic concepts of organic chemistry to develop the reader’s understanding of the importance of organic chemistry to the life sciences from natural product sources, their synthesis, and approaches to drug discovery. Ideal for undergraduate students in the natural sciences, this book is also an excellent primer for postgraduates in a variety of disciplines including forensic science and allied-health programmes as well as professionals working in related fields seeking a comprehensive introduction to organic chemistry in the context of pharmaceuticals.

Besides the common symptoms in COVID-19, it has been thought to be a more imperative measure to identify the extraordinary manifestations of the illness, which would be more helpful to improve clinical management. In the current report, a 39-year-old woman and a 44-year-old man showed reactive cervical and preauricular lymphadenopathies, respectively, upon a range of the common symptoms of the disease. Interestingly, none of them showed the symptoms of lower respiratory tract infection as well. Notably, a herpes-like skin lesion was also observed on the right lower eyelid in one of the positive patients.

Currently, the world is facing a pandemic of the new coronavirus SARS-CoV-2 that causes COVID-19. Identifying key targets in the viral infection lifecycle is urgently needed for designing therapeutic strategies to combat the virus. Furin is a subtilisin-like proprotein convertase with diverse cellular functions. Emerging evidence suggests that furin plays a critical role in the activation and/or infectivity of SARS-CoV-2. In this perspective, we discuss the potential role of furin in the entry SARS-CoV-2 into host cells. Furthermore, we evaluate available peptide and non-peptide furin inhibitors and potential outcomes, including immune responses.

The central dogma of molecular biology explains the flow of genetic information from DNA to functional products such as proteins. In most cases, a linear relationship with a high correlation coefficient exists between the concentration of mRNA, the middle man, and the functional product. Untranslated regions (UTRs) of RNA form a considerable base pairing that contributes to the secondary and tertiary structures of mRNA. The interaction between the mRNA secondary structures (cis-elements), RNA-binding proteins (RBP) and miRs (trans-element) are critical determinants of mRNAs' fate and stability. Among different viral families, the positive sense (+) RNA viruses use the simplest possible strategy of replication and expression, as the same molecule functions both as a genome and mRNA. Additionally, nucleotide composition and codon usage of +RNA viruses are the closest to human codon adaptation index (CAI). Since the origin of replication of viral intermediate RNA molecules is at the 3'-end of the genome, the 3'UTR plays a role in viral RNA replication. Moreover, the messenger role of RNA likely places functional demands on the 3'UTR to serve a role typical of cellular mRNA. This article reviews the effect of 3'UTR of RNA viruses with positive sense and genomes on mRNA stability and translation improvement. A range of animal (e.g., Dengue, Sindbis, Corona and Polio) and plant (Barley yellow dwarf, Brome mosaic, Turnip crinkle, Tobacco mosaic, Cowpea mosaic and Alfalfa mosaic) viruses are examined to highlight the role of 3'UTR in viral survival and as a potential target for pharmaceutical applications.

Mitochondria are ubiquitous membrane-bound organelles that not only play a key role in maintaining cellular energy homeostasis and metabolism but also in signaling and apoptosis. Aryl hydrocarbons receptors (AhRs) are ligand-activated transcription factors that recognize a wide variety of xenobiotics, including polyaromatic hydrocarbons and dioxins, and activate diverse detoxification pathways. These receptors are also activated by natural dietary compounds and endogenous metabolites. In addition, AhRs can modulate the expression of a diverse array of genes related to mitochondrial biogenesis and function. The aim of the present review is to analyze scientific data available on the AhR signaling pathway and its interaction with the intracellular signaling pathways involved in mitochondrial functions, especially those related to cell cycle progression and apoptosis. Various evidence have reported the crosstalk between the AhR signaling pathway and the nuclear factor κB (NF-κB), tyrosine kinase receptor signaling and mitogen-activated protein kinases (MAPKs). The AhR signaling pathway seems to promote cell cycle progression in the absence of exogenous ligands, whereas the presence of exogenous ligands induces cell cycle arrest. However, its effects on apoptosis are controversial since activation or overexpression of AhR has been observed to induce or inhibit apoptosis depending on the cell type. Regarding the mitochondria, although activation by endogenous ligands is related to mitochondrial dysfunction, the effects of endogenous ligands are not well understood but point towards antiapoptotic effects and inducers of mitochondrial biogenesis.

Arglabin (l(R),10(S)-epoxy-5(S),5(S),7(S)-guaia-3(4),ll(13)-dien-6,12-olide), is a natural sesquiterpene γ-lactone which was first isolated from Artemisia glabella. The compound has been shown to possess anti-inflammatory activity through inhibition of the NLR Family pyrin domain-containing 3 (NLRP3) inflammasome and production of proinflammatory cytokines including interleukin (IL)-1β and IL-18. A more hydrophilic derivative of the compound also exhibited antitumor activity in the breast, colon, ovarian, and lung cancer. Some other synthetic derivatives of the compound have also been synthesized with antitumor, cytotoxic, antibacterial, and antifungal activities. Since both NLRP3 inflammasome and cytokine storm are associated with the pathogenesis of COVID-19 and its lethality, compounds like arglabin might have therapeutic potential to attenuate the inflammasome-induced acute respiratory distress syndrome and/or the cytokine storm associated with COVID-19.

Primary pediatric tumors are the most common solid tumors in children. There are limited reports on the management and outcome of these tumors in the developing countries. In recent years, advances have been done in the diagnosis, treatment, and outcome of these tumors. The aim of this study was to evaluate the histopathology, characteristics, and outcome of primary pediatric tumors in Iran. This retrospective study examines primary brain tumors in children below 14 years of age who have undergone surgery. Histopathological characteristics according to WHO 2017 classification, age, sex, tumor resection rate, and patient outcome were extracted and studied. The results of the study were compared with the results of similar reports from neighboring countries and other parts of the world. In this study, 199 primary pediatric tumors were examined. Out of 199 cases, 114 cases were males, and 85 cases were females, and the male/female ratio was 1.34. The most common tumor group in this study was astrocytic tumors (68.3%) and the most common tumor was pilocytic astrocytoma (22.1%). In terms of malignancy, 50.7% of tumors were benign, and 49.3% were malignant. Total resection was done in 46% and subtotal resection in 35%. The mortality rate was found 19.2%. Among the remaining cases during follow-up, 76.6% had a good outcome without neurological deficits or mild disability and 23.4% had moderate to severe disability. The results of the study in terms of pathology and demographic characteristics were mainly similar to other reports. The mean age of patients was lower, and the patients’ outcome was better than the other countries in the region.

Neurodegenerative disorders, particularly in the elderly population, represent one of the most pressing social and health-care problems in the world. Besides the well-established role of both oxidative stress and inflammation, alterations of the immune response have been found to be closely linked to the development of neurodegenerative diseases. Interestingly, various scientific evidence reported that an altered gut microbiota composition may contribute to the development of neuroinflammatory disorders. This leads to the proposal of the concept of the gut-brain-immune axis. In this scenario, polyphenols play a pivotal role due to their ability to exert neuroprotective, immunomodulatory and microbiota-remodeling activities. In the present review, we summarized the available literature to provide a scientific evidence regarding this neuroprotective and immunomodulatory effects and the interaction with gut microbiota of polyphenols and, the main signaling pathways involved that can explain their potential therapeutic application in neurodegenerative diseases.

The existing drug treatments for trypanosomiases are limited and suffer from shortcomings due to their toxicity and the emergence of resistant parasites. Developing anti-trypanosomal compounds based on natural products is a promising way of fighting trypanosomiases.This study aims to identify through scientific review a large variety of medicinal plants (anti-trypanosomal) used worldwide and scientifically shown to display anti-trypanosomal effects.To collect data, the anti-trypanosomal activities of Africa, Asia, the Middle East, South America, North America, Europe and Oceania medicinal plants have been checked by considering the published paper.Based on collected data, 77 natural molecules were reported in the literature. Of which 59 were from the African region, 11 from Asia, 3 from Europe and 4 from Latin America. These active components belong to alkaloids, triterpenoids, lactone, quinoids, flavonoids, iridoids, lignans, steroids, lipids, oxygenated heterocycles, benzenoids, proteins, coumarins, phenylpropanoids and peptides. We also specified the prosperous plants with unique anti-trypanosomal activities.However, there is a need for further studies on the ability of the isolated compounds to ameliorate the trypanosome-induced pathological alterations and also the elucidation of their modes of actions and activities against other trypanosome species.

To examine the preventive effects of Aloe vera in colorectal cancer patients undergoing radiotherapy. Twenty colorectal cancer patients, who received radiation, were randomized to receive Aloe vera 3% or placebo ointment, 1 g twice daily for 6 weeks. At weekly visits, acute radiation proctitis (ARP) was evaluated by Radiation Therapy Oncology Group and clinical presentation criteria as the primary endpoint. We also evaluated secondary endpoints of quality of life, psychosocial status, by applying Hospital Anxiety-Depression (HAD) Scale and laboratory measures of quantitative measurement of C-reactive protein (CRP) as a marker for systemic inflammation. There was a significant improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (p = 0.029, median score: 0.5 vs. 0.001). The overall primary and secondary outcomes favored Aloe group, while the measures of toxicity did not achieve a statistical significant difference. The lifestyle score improved significantly with A. vera (p = 004), and they also had a lower depression score in HAD scale (p = 0.008). Furthermore, quantitative CRP decreased significantly during the course of treatment with Aloe vera. The use of topical formulation of Aloe vera 3% diminishes the severity of ARP in colorectal cancer patients.

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and sub-clinical studies are currently undertaken to find a gold-standard therapeutic regimen with high efficacy and low side effect. Based on the published scientific evidence published to date, we summarized herein the effects of different potential therapies and up-to-date clinical trials. The review is intended to help readers aware of potentially effective COVID-19 treatment and provide useful references for future studies. Electronic supplementary material The online version of this article (10.1007/s43440-020-00152-9) contains supplementary material, which is available to authorized users.

Background Lignans are large group of polyphenols that are formed by the coupling of two coniferyl alcohol residues. Based on their origin, lignans are broadly grouped into plant lignans such as isolariciresinol, secoisolariciresinol diglucoside, lariciresinol, and matairesinol; and mammalian lignans such as enterodiol and enterolactone. Based on the oxidation level of the lignan skeleton, they are also categorized into numerous groups such as dibenzylfuran, dibenzylbutyrolactol, dihydroxybenzylbutane, arylnaphtalene and aryltetraline lactone derivatives. Depending on structural type and concentration, numerous dietary lignans have been shown to possess biological activities including protective effect against diseases such as hormone-dependent tumors and cardiovascular diseases. Also, they display antioxidant properties in tissues and organs including the liver and the brain, lignans are found in most fiber-rich seeds such as sesame and pumpkin, and grains including barley, wheat, oats and rye. Scope and approach This paper focus on the metabolism in humans, and recent studies on the antioxidant and possible prooxidant effects of lignans at three levels: in vitro, in vivo in animals and clinical studies. Key Findings and Conclusions: Most of the studies investigating the antioxidant effect of lignans were in vitro and animal models and only five clinical trials were found; one evaluating the effect of enterolactone on low-density lipoprotein (LDL) peroxidation and four investigating the effects of plant lignans including flaxseed lignan components, secoisolariciresinol and sesamin on lipid peroxidation. So, lignans seem to be a valuable source for identifying new molecules for preventing various diseases especially cardiovascular disorders. Since most of studies are preclinical, however, further clinical trials are required to achieve more conclusive results.

Infection by human Coronaviruses (CoVs) such as HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1generally results in moderate to severe respiratory and intestinal infections in humans The deadly human CoVs emerging in the last two decades however became the cause of great global concern The severe acute respiratory syndrome (SARS) SARS-CoV, Middle East respiratory syndrome (MERS) (MERS-CoV) and the current SARS-CoV-2 that causes COVID-19 are related respiratory infections with high degree of mortality With currently no available vaccine or approved therapy for COVID-19, the development of directly acting antiviral drugs becomes a sensible strategy Viral infections, like many other disease conditions have been frequently managed using traditional medicine COVID-19 and SARS-CoV-2 infections have also been treated with preparations from traditional Chinese medicine although their efficacy has not yet been well documented Several antiviral agents have also been reported from natural sources and these could provide good opportunity for developing products and therapies that might be applicable in managing COVID-19 In this review, we discuss natural antiviral products that target the various infection stages of the different viruses’ including CoV, which may be useful for direct management of COVID-19 or provide insights for the development of effective therapies

Interest in alkylamide, as a class of compound, has grown tremendously in recent years. This interest is due to the many presumed benefits in food, cosmetics, and medicine. This review focuses on the different alkylamides naturally occurring in many plant species. Several methods have been employed for their identification as well as isolation and several in vitro and in vivo studies have revealed their therapeutic effects in various diseases. In general, alkylamides have been reported to have several biological activities and pharmacological effects which include immunomodulatory, antithrombotic, antimicrobial, antiviral, antioxidant, anti-inflammatory, analgesic, anticancer, antidiabetic, and antiprotozoal activities. Moreover, many studies have reported on their mechanisms of action, structure-activity relationship, pharmacokinetics, and toxicity. We herein present an updated report on the chemistry and pharmacology of alkylamides of natural origin.

By using the streptozotocin- (STZ-) induced cytotoxicity in β-TC3 cells as an assay model, a bioassay-guided fractionation study was employed to isolate and characterize the potential antidiabetic principles of roots of Prosopis farcta. A combination of open column chromatography on reverse-phase silica gel using a water-ethanol gradient (10 : 90 to 100 : 0) followed by HPLC-based fractionation led to an active compound that appears to be composed of carbohydrate/sugar. When cell viability under STZ was reduced to 49.8 ± 4% (mean ± SD), treatment with the active compound at the concentration of 0.5 mg/mL either as a coadministration or a pretreatment improved the viability to 93 ± 1.9% and 91.5 ± 7%, respectively. The reduction in the mitochondrial membrane potential by STZ (47.34 ± 8.9% of control) was similarly recovered to 84.5 ± 4.3 (coadministration) and 88 ± 5.5% (pretreatment) by the active fraction. The bioassay-guided fractionation, β-cell protective effect, and increased glucose consumption (up to 1.49-fold increase) in hepatocytes by the extracts and active fraction are also discussed.

BackgroundIn late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for coronavirus disease (COVID-19), was identified as the new pathogen to lead pneumonia in Wuhan, China, which has spread all over the world and developed into a pandemic. Despite the over 1 year of pandemic, due to the lack of an effective treatment plan, the morbidity and mortality of COVID-19 remains high. Efforts are underway to find the optimal management for this viral disease.Main bodySARS-CoV-2 could simultaneously affect multiple organs with variable degrees of severity, from mild to critical disease. Overproduction of pro-inflammatory mediators, exacerbated cellular and humoral immune responses, and coagulopathy such as Pulmonary Intravascular Coagulopathy (PIC) contributes to cell injuries. Considering the pathophysiology of the disease and multiple microthrombi developments in COVID-19, thrombolytic medications seem to play a role in the management of the disease. Beyond the anticoagulation, the exact role of thrombolytic medications in the management of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) is not explicit. This review focuses on current progress in underlying mechanisms of COVID-19-associated pulmonary intravascular coagulopathy, the historical use of thrombolytic drugs in the management of ARDS, and pharmacotherapy considerations of thrombolytic therapy, their possible benefits, and pitfalls in COVID-19-associated ARDS.ConclusionsInhaled or intravenous administration of thrombolytics appears to be a salvage therapy for severe ARDS associated with COVID-19 by prompt attenuation of lung injury. Considering the pathogenesis of COVID-19-related ARDS and mechanism of action of thrombolytic agents, thrombolytics appear attractive options in stable patients without contraindications.

Carnosic acid (CA) and carnosol (CAR) are two major diterpenes of the rosemary plant (Rosmarinus officinalis). They possess a phenolic structural moiety and are endowed with the power to remove cellular reactive oxygen species (ROS) either through direct scavenging reaction or indirectly through upregulation of antioxidant defences. Hand in hand with these activities are their multiple biological effects and therapeutic potential orchestrated through modulating various signalling pathways of inflammation, including the NF-κB, MAPK, Nrf2, SIRT1, STAT3 and NLRP3 inflammasomes, among others. Consequently, they ameliorate the expression of pro-inflammatory cytokines (e.g., TNF-α, IL-1 and IL-6), adhesion molecules, chemokines and prostaglandins. These anti-inflammatory mechanisms of action as a therapeutic link to various effects of these compounds, as in many other natural products, are scrutinised.

The isolation of phlorizin from the bark of an apple tree in 1835 led to a flurry of research on its inhibitory effect on glucose transporters in the intestine and kidney. Using phlorizin as a prototype drug, antidiabetic agents with more selective inhibitory activity towards glucose transport at the kidney have subsequently been developed. In contrast, its hydrolysis product in the body, phloretin, which is also found in the apple plant, has weak antidiabetic properties. Phloretin, however, displays a range of pharmacological effects including antibacterial, anticancer, and cellular and organ protective properties both in vitro and in vivo. In this communication, the molecular basis of its anti-inflammatory mechanisms that attribute to its pharmacological effects is scrutinised. These include inhibiting the signalling pathways of inflammatory mediators’ expression that support its suppressive effect in immune cells overactivation, obesity-induced inflammation, arthritis, endothelial, myocardial, hepatic, renal and lung injury, and inflammation in the gut, skin, and nervous system, among others.

Colchicine has shown clinical benefits in the management of COVID-19 via its anti-inflammatory effect. However, the exact role of colchicine in COVID-19 patients is unknown. The current clinical trial was performed on 202 patients with moderate to severe COVID-19. Patients were randomly assigned in a 1:1 ratio to receive up to a 3-day course of 0.5 mg colchicine followed by a 12-day course of 1 mg colchicine in combination with standard care or a 15-day course of standard care. Among 202 randomized patients, 153 completed the study and received colchicine/standard care or continued standard care (M age, 54.72 [SD, 15.03] years; 93 [63.1%] men). On day 14, patients in the colchicine/standard care group had significantly higher odds of a better clinical status distribution on chest CT evaluation (p = .048). Based on NYHA classification, the percentage change of dyspnea on day 14 between groups was statistically significant (p = .026), indicating a mean of 31.94% change in the intervention group when compared with 19.95% in the control group. According to this study, colchicine can improve clinical outcomes and reduce pulmonary infiltration in COVID-19 patients if contraindications and precautions are considered and it is prescribed at the right time and in appropriate cases.

Abstract: Hypothetical proteins (HPs) are non-predicted sequences that are identified only by open reading frames in sequenced genomes, but their protein products remain uncharacterized by any experimental means. The genome of every species consists of HPs that are involved in various cellular processes and signaling pathways. Annotation of HPs is important as they play a key role in disease mechanisms, drug designing, vaccine production, antibiotic production, and host adaptation. In the case of bacteria, 25-50% of the genome comprises HPs, which are involved in metabolic pathways and pathogenesis. The characterization of bacterial HPs helps to identify virulent proteins that are involved in pathogenesis. This can be done using in-silico studies, which provide sequence analogs, physiochemical properties, cellular or subcellular localization, structure and function validation, and protein-protein interactions. The most diverse types of virulent proteins are exotoxins, endotoxins, and adherent virulent factors that are encoded by virulent genes present on the chromosomal DNA of the bacteria. This review evaluates virulent HPs of pathogenic bacteria, such as Staphylococcus aureus, Chlamydia trachomatis, Fusobacterium nucleatum, and Yersinia pestis. The potential of these HPs as a drug target in bacteria-caused infectious diseases, along with the mode of action and treatment approaches, has been discussed.

Recently, the medications used for the severe form of the coronavirus disease-19 (COVID-19) therapy are of particular interest. In this sense, it has been supposed that anti-VEGF compounds would be good candidates in the face of "cytokine storm" and intussuscepted angiogenesis due to having an appreciable anti-inflammatory effect. Therefore, they can be subjected to therapeutic protocols to manage acute respiratory distress syndrome (ARDS). Since the compelling evidence emphasized that VEGFs contribute to the inflammatory process and play a mainstay role in disease pathogenesis, in this review, we aimed to highlight the VEGF's plausible participation in the cytokine storm exacerbation in COVID-19. Next, the recent clinical advances regarding the anti-VEGF medications, including humanized monoclonal antibody, immunosuppressant, a tyrosine kinase inhibitor, and a cytokine inhibitor, have been addressed in the setting of COVID-19 treatment in critically ill patients. Together, retrieving the increased level of VEGF subsets, as well as antagonizing VEGF related receptors, could be helpful for the treatment of COVID-19, especially in those suffering from ARDS.

Rutin is a unique antioxidant flavonoid that is mainly found in fruit, vegetables, cereals, and many other plant-based human diets. This review aims to highlight the in vitro anticancer properties of rutin including combination therapeutic strategies. Literature resources were gathered through PubMed, Scopus, Web of Science, and Google Scholar databases that cover the period of 1995–2021. Rutin is demonstrated to inhibit the proliferation of breast, colon, lung, and prostate cancers and other tumors. Furthermore, rutin alone or in combination with other therapeutic agents has been shown to regulate several signalling pathways involving the Ras/Raf and PI3K/Akt, MAPK, and TGF-β2/Smad2/3Akt/PTEN, etc., which are related to the processes of carcinogenesis and induction of apoptosis. The combination of rutin with other chemotherapy drugs may benefit on prevention of tumor cells by decreasing drug resistance and chemotherapy side effects. Moreover, rutin induces apoptosis synergistically with the therapeutic agent. More in vivo and clinical data are however needed to evaluate the true potential of rutin as an anticancer agent as an adjuvant. The present review highlights the effects of rutin which can be a promising candidate in combination with other antitumor drugs or alone for cancer treatment in vitro. Also, rutin can lead to decrease in drug resistance and chemotherapeutic side effects.

Neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington disease, amyotrophic lateral sclerosis, and prion disease affect any part of the brain. The complete mechanism of ND is unknown, but there are some molecular mechanism and chemical process. Natural compounds have better compatibility with the human body along with lesser side effects. Moreover, several studies showed that various natural compounds have significant neuroprotective, potent antioxidant, and anti-inflammatory properties, which are effective for treating the different type of ND. In ND, natural compounds act by various mechanisms such as preventing the generation of reactive oxygen species (ROS), eliminating destructed biomolecules before their accumulation affects cell metabolism, and improving the disease conditions. But due to the presence of the blood-brain barrier (BBB) layer and unfavorable pharmacokinetic properties of natural compounds, their delivery into the brain is limited. To minimize this problem and enhance drug delivery into the brain with an effective therapeutic dose, there is a need to develop a practical novel approach. The various studies showed that nanoformulations and microneedles (MN) containing natural compounds such as quercetin, curcumin, resveratrol, chrysin, piperine, ferulic acid, huperzine A, berberine, baicalein, hesperetin, and retinoic acid effectively improved many ND. In this review, the effect of such natural drug-loaded nanoformulation and MN patches on ND management is discussed, along with their merits and demerits. This review aims to introduce different novel approaches for enhancing natural drug delivery into the brain to manage various neurodegenerative diseases.

Wound is defined as any injury to the body such as damage to the epidermis of the skin and disturbance to its normal anatomy and function. Since ancient times, the importance of wound healing has been recognized, and many efforts have been made to develop novel wound dressings made of the best material for rapid and effective wound healing. Medicinal plants play a great role in the wound healing process. In recent decades, many studies have focused on the development of novel wound dressings that incorporate medicinal plant extracts or their purified active compounds, which are potential alternatives to conventional wound dressings. Several studies have also investigated the mechanism of action of various herbal medicines in wound healing process. This paper attempts to highlight and review the mechanistic perspective of wound healing mediated by plant-based natural products. The findings showed that herbal medicines act through multiple mechanisms and are involved in various stages of wound healing. Some herbal medicines increase the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) which play important role in stimulation of re-epithelialization, angiogenesis, formation of granulation tissue, and collagen fiber deposition. Some other wound dressing containing herbal medicines act as inhibitor of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) protein expression thereby inducing antioxidant and anti-inflammatory properties in various phases of the wound healing process. Besides the growing public interest in traditional and alternative medicine, the use of herbal medicine and natural products for wound healing has many advantages over conventional medicines, including greater effectiveness due to diverse mechanisms of action, antibacterial activity, and safety in long-term wound dressing usage.

Various interferon (IFN)-inducible transmembrane (IFITM) proteins are known to be expressed in human tissues though only IFITM 1–3 are inducible by IFN. Numerous studies have shown that activation of IFITM3 could suppress infection by influenza and coronaviruses such as the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In view of the potential application of IFITM proteins’ induction to target SARS-CoV-2 infection that causes COVID-19, this article layout insights into the known antiviral mechanisms and therapeutic agents related to IFITM. Blocking viral entry through various mechanisms and the potential application of the FDA approved immunosuppressant agent, mycophenolic acid, as inducer of IFITM3 are among those discussed., Highlights • Interferon -inducible transmembrane (IFITM) proteins are readily expressed in human tissues. • IFITM proteins block viral entry into host cells through diverse mechanisms. • IFITM3 suppress infection by influenza and coronaviruses such as MERS-CoV. • Combination therapy with mycophenolic acid and IFN can be used for treatment of covid19.

The discovery of new drugs for treating the new coronavirus (SARS-CoV-2) or repurposing those already in use for other viral infections is possible through understanding of the viral replication cycle and pathogenicity. This article highlights the advantage of targeting one of the non-structural proteins, helicase (nsp13), over other SARS-CoV-2 proteins. Highlighting the experience gained from targeting Nsp13 in similar coronaviruses (SARS-CoV and MERS) and known inhibitors, the article calls for research on helicase inhibitors as potential COVID-19 therapy.

Background Levamisole has shown clinical benefits in the management of COVID-19 via its immunomodulatory effect. However, the exact role of Levamisole effect in clinical status of COVID-19 patients is unknown. We aimed to evaluate the efficacy of Levamisole on clinical status of patients with COVID-19 during their course of the disease. Methods This prospective, double-blind, randomized controlled clinical trial was performed in adult patients with mild to moderate COVID-19 (room-air oxygen saturation > 94%) from late April 2020 to mid-August 2020. Patients were randomly assigned to receive a 3-day course of Levamisole or placebo in combination with routine standard of care. Results With 25 patients in each arm, 50 patients with COVID-19 were enrolled in the study. Most of the study participants were men (60%). On days 3 and 14, patients in Levamisole group had significantly better cough status distribution when compared to the placebo group (P-value = 0.034 and 0.005, respectively). Moreover, there was significant differences between the two groups in dyspnea at follow-up intervals of 7 (P-value = 0.015) and 14 (P-value = 0.010) days after receiving the interventions. However, no significant difference in fever status was observed on days 1, 3, 7, and 14 in both groups (P-value > 0.05). Conclusion The results of the current study suggest that Levamisole may improve most of clinical status of patients with COVID-19. The patients receiving Levamisole had significantly better chance of clinical status including cough and dyspnea on day 14 when compared to the placebo. However, the effect-size of this finding has uncertain clinical importance. Trial registration The trial was registered as IRCT20190810044500N7 (19/09/2020).

Berberine, the main bioactive component of many medicinal plants belonging to various genera such as Berberis, Coptis, and Hydrastis is a multifunctional compound. Among the numerous interesting biological properties of berberine is broad antimicrobial activity including a range of Gram-positive and Gram-negative bacteria. With the aim of identifying berberine analogues possibly endowed with higher lead-likeness and easier synthetic access, the molecular simplification approach was applied to the secondary metabolite and a series of analogues were prepared and screened for their antimicrobial activity against Gram-positive and Gram-negative bacterial test species. Rewardingly, the berberine simplified analogues displayed 2–20-fold higher potency with respect to berberine. Since our berberine simplified analogues may be easily synthesized and are characterized by lower molecular weight than the parent compound, they are further functionalizable and should be more suitable for oral administration. Molecular docking simulations suggested FtsZ, a well-known protein involved in bacterial cell division, as a possible target.

Objective: To assess the patient’s satisfaction rate during two distinct registry procedures in the emergency department. Methods: A cross-sectional study was conducted in educational hospitals with a high volume of patient’s admission in Tabriz-Iran and Erzurum-Turkey. In this study, we used a Press Ganey questionnaire as a data collection tool that was filled out with patients or their companions before discharging or referred to other areas (wards). Finally, data were analyzed by using SPSS software version 16. Results: The included patients were from three-admission time courses includes morning, evening, and night shifts. The present study results indicated that the total satisfaction score was two scores higher than the classic one (p

The novel coronavirus 2019-nCoV (SARS-CoV-2) infection that emerged in China in December 2019 has rapidly spread to become a global pandemic. This article summarizes the potential benefits of erythropoietin (EPO) in alleviating SARS-CoV-2 pathogenesis which is now called COVID-19. As with other coronavirus infection, the lethality of COVID-19 is associated with respiratory dysfunction due to overexpression of proinflammatory cytokines induced by the host immune responses. The resulting cytokine storm leads to the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Erythropoietin, well known for its role in the regulation of erythropoiesis, may have protective effects against ALI/ARDS induced by viral and other pathogens. EPO exerts antiapoptotic and cytoprotective properties under various pathological conditions. With a high safety profile, EPO promotes the production of endothelial progenitor cells and reduce inflammatory processes through inhibition of the nuclear factor-κB (NF-κB) and JAK-STAT3 signaling pathways. Thus, it may be considered as a safe drug candidate for COVID-19 patients if given at the early stage of the disease. The potential effects of erythropoietin on different aspects of ALI/ARDS associated with SARS-CoV-2 infection are reviewed.

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.

Since the first human infection of SARS‐CoV‐2 was reported in the Hubei (Wuhan) province of China, the world has been facing a relentless degree of socioeconomic and medical crisis. The disease of SARS‐CoV‐2 infection which is now called the COVID‐19 pandemic has spread to several countries across the globe (Nicastri et al., 2020). This article is protected by copyright. All rights reserved.

This article summarizes the effects of sivelestat on ALI/ARDS or ARDS with coagulopathy, both of which are frequently seen in patients with COVID-19. The emergence of the novel 2019-nCoV infection has been a global pandemic. The following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane library, Pubmed, Medline, EMBASE from 1980 through March 2020. COVID-19 patients are more susceptible to thromboembolic diseases including DIC. In this connection, various studies have emphasized on the role of neutrophil elastase (NE) in the development of DIC in patients with ARDS and sepsis. It has been shown that NE inhibition by sivelestat mitigates ALI through amelioration of alveolar epithelium and vascular endothelium injuries as well as reversing the activated neutrophil-mediated increased vascular permeability. Sivelestat is a selective NE inhibitor has not been evaluated for its possible therapeutic effects against SARS-CoV-2 infection and/or COVID-19. Nevertheless, based on its promising beneficial effects in underlying complications of COVID-19, sivelestat could be considered as a promising treatment for the management of ALI/ARDS or coagulopathy in patients with COVID-19.

Benign prostatic hyperplasia (BPH) is the most prevalent disease of the prostate in elderly men. SinceThe oil was extracted using the cold-pressing method. Fifty rats were divided into five groups of 10 each as follows: Group 1 orally (p.o.) received normal saline; groups 2-5 were castrated and subcutaneously received 5 mg/kg testosterone propionate for four weeks. Group 2, namely, BPH model, underwent no further treatment, Groups 3 and 4 were treated with 400 mg/kg and 800 mg/kgOur results showed that oral treatment with 400 and 800 mg/kgThe study demonstrated that the oil seed exerted anti-BPH effects which may be associated with its antioxidant properties

The global spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes COVID-19 has become a source of grave medical and socioeconomic concern to human society. Since its first appearance in the Wuhan region of China in December 2019, the most effective measures of managing the spread of SARS-CoV-2 infection have been social distancing and lockdown of human activity; the level of which has not been seen in our generations. Effective control of the viral infection and COVID-19 will ultimately depend on the development of either a vaccine or therapeutic agents. This article highlights the progresses made so far in these strategies by assessing key targets associated with the viral replication cycle. The key viral proteins and enzymes that could be targeted by new and repurposed drugs are discussed.