Dermatological manifestations of tick-borne viral infections found in the United States.

Tick-borne diseases (TBDs) are bacterial, viral, and parasitic diseases transmitted by ticks. Viral TBDs have increased in prevalence over the last decade with many new pathogenic viruses being discovered. Doxycycline is often empirically prescribed by clinicians to treat symptomatic patients following tick bites due to suspicions of bacterial TBDs such as Rocky Mountain spotted fever, anaplasmosis, and ehrlichiosis. However, viral TBDs are included in the differential diagnosis if patients do not clinically improve following antibiotic therapy. Several viral TBDs present with dermatological manifestations. Recognizing the differences in clinical presentations of TBDs, particularly of newly emerging viral TBDs in the United States, can help physicians identify the viral TBD, and possibly rule out viral illnesses with different clinical presentations. Therefore, this review discusses clinical manifestations, with an emphasis on dermatologic manifestations of Heartland Virus, Bourbon Virus, Powassan Virus, Deer Tick Virus and Colorado Tick Fever Virus. KEY POINTS: Viral tick-borne diseases have increased in prevalence over the last decade and often have similar clinical manifestations to other tick-borne diseases, including bacterial infections. Here, we review the dermatologic manifestations of Heartland Virus (HRTV), Bourbon Virus (BRBV), Powassan Virus (POWV), Deer Tick Virus (DTV) and Colorado Tick Fever Virus (CTFV) that are important for clinicians.

Neurological Complications of COVID-19: Underlying Mechanisms and Management.

COVID-19 is a severe respiratory disease caused by the newly identified human coronavirus (HCoV) Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The virus was discovered in December 2019, and in March 2020, the disease was declared a global pandemic by the World Health Organization (WHO) due to a high number of cases. Although SARS-CoV-2 primarily affects the respiratory system, several studies have reported neurological complications in COVID-19 patients. Headache, dizziness, loss of taste and smell, encephalitis, encephalopathy, and cerebrovascular diseases are the most common neurological complications that are associated with COVID-19. In addition, seizures, neuromuscular junctions' disorders, and Guillain-Barré syndrome were reported as complications of COVID-19, as well as neurodegenerative and demyelinating disorders. However, the management of these conditions remains a challenge. In this review, we discuss the prevalence, pathogenesis, and mechanisms of these neurological sequelae that are secondary to SARS-CoV-2 infection. We aim to update neurologists and healthcare workers on the possible neurological complications associated with COVID-19 and the management of these disease conditions.

Catechins: Therapeutic Perspectives in COVID-19-Associated Acute Kidney Injury.

Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5-46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities.

IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells.

IL-11 has been detected in inflamed joints; however, its role in the pathogenesis of arthritis is not yet clear. Studies were conducted to characterize the expression and functional significance of IL-11 and IL-11Rα in rheumatoid arthritis (RA). IL-11 levels were elevated in RA synovial fluid (SF) compared to osteoarthritis (OA) SF and plasma from RA, OA and normal individuals (NLs). Morphologic studies established that IL-11 was detected in lining fibroblasts and macrophages in addition to sublining endothelial cells and macrophages at higher levels in RA compared to NL synovial tissues. Since IL-11Rα was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11Rα strongly provoked fibroblast infiltration into RA joint, while cell proliferation was unaffected by this process. Secretion of IL-8 and VEGF from IL-11 activated RA fibroblasts was responsible for the indirect effect of IL-11 on endothelial cell transmigration and tube formation. Moreover, IL-11 blockade impaired RA SF capacity to elicit endothelial cell transmigration and tube formation. We conclude that IL-11 binding to endothelial IL-11Rα can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization.

Differential impact of obesity on the pathogenesis of RA or preclinical models is contingent on the disease status.

OBJECTIVE: Studies were performed to uncover the significance of obesity in rheumatoid arthritis (RA) and preclinical models. METHODS: Preclinical arthritis models were used to examine the impact of obesity on disease onset and remission. Conditioned media from RA adipose tissues were used to investigate the mechanism contributing to joint neutrophil influx and M1 macrophage differentiation observed in early and remission phases of arthritis. RESULTS: We report that mice fed with high fat diet (HFD) have an earlier onset of collagen-induced arthritis (CIA) compared with mice on regular diet. However, the differences in CIA joint swelling between the two diet groups are lost once disease is established. We found that early arthritis triggered by obesity is due to elevated joint MIP2/interleukin-8 levels detected in CIA as well as in the RA and mouse adipose tissues and the effect of this chemokine on neutrophil recruitment. Although active disease progression is similarly affected in both diet groups, arthritis resolution is accelerated in lean mice while joint inflammation is sustained in obese mice. We document that HFD can prolong toll-like receptor (TLR)4-induced arthritis by increasing joint monocyte migration and further remodelling the recruited cells into M1 macrophages. Consistently, we show that adipose condition media can transform RA and wild-type naïve myeloid cells into M1 macrophages; however, this function is impaired by TLR4 blockade or deficiency. CONCLUSIONS: We conclude that despite established disease being unaffected by obesity, the early and the resolution phases of RA are impacted by obesity through different mechanisms.

Ebola virus outbreak, updates on current therapeutic strategies.

Filoviruses are enveloped negative-sense single-stranded RNA viruses, which include Ebola and Marburg viruses, known to cause hemorrhagic fever in humans with a case fatality of up to 90%. There have been several Ebola virus outbreaks since the first outbreak in the Democratic Republic of Congo in 1976 of which, the recent 2013-2015 epidemic in Guinea, Liberia, and Sierra Leone is the largest in recorded history. Within a few months of the start of the outbreak in December 2013, thousands of infected cases were reported with a significant number of deaths. As of March 2015, according to the Centers for Disease Control and Prevention, there have been nearly 25,000 suspected cases, with 15,000 confirmed by laboratory testing, and over 10,000 deaths. The large number of cases and the high mortality rate, combined with the lack of effective Food and Drug Administration-approved treatments, necessitate the development of potent and safe therapeutic measures to combat the current and future outbreaks. Since the beginning of the outbreak, there have been considerable efforts to develop and characterize protective measures including vaccines and antiviral small molecules, and some have proven effective in vitro and in animal models. Most recently, a cocktail of monoclonal antibodies has been shown to be highly effective in protecting non-human primates from Ebola virus infection. In this review, we will discuss what is known about the nature of the virus, phylogenetic classification, genomic organization and replication, disease transmission, and viral entry and highlight the current approaches and efforts, in the development of therapeutics, to control the outbreak.

A Podocyte-Based Automated Screening Assay Identifies Protective Small Molecules.

Podocyte injury and loss mark an early step in the pathogenesis of various glomerular diseases, making these cells excellent targets for therapeutics. However, cell-based high-throughput screening assays for the rational development of podocyte-directed therapeutics are currently lacking. Here, we describe a novel high-content screening-based phenotypic assay that analyzes thousands of podocytes per assay condition in 96-well plates to quantitatively measure dose-dependent changes in multiple cellular features. Our assay consistently produced a Z' value >0.44, making it suitable for compound screening. On screening with >2100 pharmacologically active agents, we identified 24 small molecules that protected podocytes against injury in vitro (1% hit rate). Among the identified hits, we confirmed an ß1-integrin agonist, pyrintegrin, as a podocyte-protective agent. Treatment with pyrintegrin prevented damage-induced decreases in F-actin stress fibers, focal adhesions, and active ß1-integrin levels in cultured cells. In vivo, administration of pyrintegrin protected mice from LPS-induced podocyte foot process effacement and proteinuria. Analysis of the murine glomeruli showed that LPS administration reduced the levels of active ß1 integrin in the podocytes, which was prevented by cotreatment with pyrintegrin. In rats, pyrintegrin reduced peak proteinuria caused by puromycin aminonucleoside-induced nephropathy. Our findings identify pyrintegrin as a potential therapeutic candidate and show the use of podocyte-based screening assays for identifying novel therapeutics for proteinuric kidney diseases.

The pathogenic role of angiogenesis in rheumatoid arthritis.

Angiogenesis is the formation of new capillaries from pre-existing vasculature, which plays a critical role in the pathogenesis of several inflammatory autoimmune diseases such as rheumatoid arthritis (RA), spondyloarthropathies, psoriasis, systemic lupus erythematosus, systemic sclerosis, and atherosclerosis. In RA, excessive migration of circulating leukocytes into the inflamed joint necessitates formation of new blood vessels to provide nutrients and oxygen to the hypertrophic joint. The dominance of the pro-angiogenic factors over the endogenous angiostatic mediators triggers angiogenesis. In this review article, we highlight the underlying mechanisms by which cells present in the RA synovial tissue are modulated to secrete pro-angiogenic factors. We focus on the significance of pro-angiogenic factors such as growth factors, hypoxia-inducible factors, cytokines, chemokines, matrix metalloproteinases, and adhesion molecules on RA pathogenesis. As pro-angiogenic factors are primarily produced from RA synovial tissue macrophages and fibroblasts, we emphasize the key role of RA synovial tissue lining layer in maintaining synovitis through neovascularization. Lastly, we summarize the specific approaches utilized to target angiogenesis. We conclude that the formation of new blood vessels plays an indispensable role in RA progression. However, since the function of several pro-angiogenic mediators is cross regulated, discovering novel approaches to target multiple cascades or selecting an upstream cascade that impairs the activity of a number of pro-angiogenic factors may provide a promising strategy for RA therapy.

Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay.

UNLABELLED: Severe acute respiratory syndrome coronavirus (SARS-CoV) and Ebola, Hendra, and Nipah viruses are members of different viral families and are known causative agents of fatal viral diseases. These viruses depend on cathepsin L for entry into their target cells. The viral glycoproteins need to be primed by protease cleavage, rendering them active for fusion with the host cell membrane. In this study, we developed a novel high-throughput screening assay based on peptides, derived from the glycoproteins of the aforementioned viruses, which contain the cathepsin L cleavage site. We screened a library of 5,000 small molecules and discovered a small molecule that can inhibit the cathepsin L cleavage of all viral peptides with minimal inhibition of cleavage of a host protein-derived peptide (pro-neuropeptide Y). The small molecule inhibited the entry of all pseudotyped viruses in vitro and the cleavage of SARS-CoV spike glycoprotein in an in vitro cleavage assay. In addition, the Hendra and Nipah virus fusion glycoproteins were not cleaved in the presence of the small molecule in a cell-based cleavage assay. Furthermore, we demonstrate that the small molecule is a mixed inhibitor of cathepsin L. Our broad-spectrum antiviral small molecule appears to be an ideal candidate for future optimization and development into a potent antiviral against SARS-CoV and Ebola, Hendra, and Nipah viruses. IMPORTANCE: We developed a novel high-throughput screening assay to identify small molecules that can prevent cathepsin L cleavage of viral glycoproteins derived from SARS-CoV and Ebola, Hendra, and Nipah viruses that are required for their entry into the host cell. We identified a novel broad-spectrum small molecule that could block cathepsin L-mediated cleavage and thus inhibit the entry of pseudotypes bearing the glycoprotein derived from SARS-CoV or Ebola, Hendra, or Nipah virus. The small molecule can be further optimized and developed into a potent broad-spectrum antiviral drug.

GM-CSF: An immune modulatory cytokine that can suppress autoimmunity.

GM-CSF was originally identified as a colony stimulating factor (CSF) because of its ability to induce granulocyte and macrophage populations from precursor cells. Multiple studies have demonstrated that GM-CSF is also an immune-modulatory cytokine, capable of affecting not only the phenotype of myeloid lineage cells, but also T-cell activation through various myeloid intermediaries. This property has been implicated in the sustenance of several autoimmune diseases like arthritis and multiple sclerosis. In contrast, several studies using animal models have shown that GM-CSF is also capable of suppressing many autoimmune diseases such as Crohn's disease, Type-1 diabetes, Myasthenia gravis and experimental autoimmune thyroiditis. Knockout mouse studies have suggested that the role of GM-CSF in maintaining granulocyte and macrophage populations in the physiological steady state is largely redundant. Instead, its immune-modulatory role plays a significant role in the development or resolution of autoimmune diseases. This is mediated either through the differentiation of precursor cells into specialized non-steady state granulocytes, macrophages and dendritic cells, or through the modulation of the phenotype of mature myeloid cells. Thus, outside of myelopoiesis, GM-CSF has a profound role in regulating the immune response and maintaining immunological tolerance.

A novel pancreatic ß-cell targeting bispecific-antibody (BsAb) can prevent the development of type 1 diabetes in NOD mice.

To prepare a novel Bispecific Antibody (BsAb) as a potential targeted therapy for T1D, we produced a "functionally inert" monoclonal antibody (mAb) against Glucose transporter-2 (GLUT-2) expressed on ß-cells to serve as an anchoring antibody. The therapeutic arm is an agonistic mAb against Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), a negative regulator of T-cell activation expressed on activated CD4+ T-cells. A BsAb was prepared by chemically coupling an anti-GLUT2 mAb to an agonistic anti-CTLA-4 mAb. This BsAb was able to bind to GLUT2 and CTLA-4 in vitro, and to pancreatic islets, both in vitro and in vivo. We tested the safety and efficacy of this BsAb by treating Non-Obese Diabetes (NOD) mice and found that it could delay the onset of diabetes with no apparent undesirable side effects. Thus, engagement of CTLA-4 on activated T cells from target tissue can be an effective way to treat type-1 diabetes.

In silico and in vivo evaluation of the anti-cryptosporidial activity of eugenol.

Background: Cryptosporidiosis is an opportunistic parasitic disease widely distributed worldwide. Although Cryptosporidium sp. causes asymptomatic infection in healthy people, it may lead to severe illness in immunocompromised individuals. Limited effective therapeutic alternatives are available against cryptosporidiosis in this category of patients. So, there is an urgent need for therapeutic alternatives for cryptosporidiosis. Recently, the potential uses of Eugenol (EUG) have been considered a promising novel treatment for bacterial and parasitic infections. Consequently, it is suggested to investigate the effect of EUG as an option for the treatment of cryptosporidiosis. Materials and methods: The in silico bioinformatics analysis was used to predict and determine the binding affinities and intermolecular interactions of EUG and Nitazoxanide (NTZ) toward several Cryptosporidium parvum (C. parvum) lowa II target proteins. For animal study, five groups of immunosuppressed Swiss albino mice (10 mice each) were used. Group I was left uninfected (control), and four groups were infected with 1,000 oocysts of Cryptosporidium sp. The first infected group was left untreated. The remaining three infected groups received NTZ, EUG, and EUG + NTZ, respectively, on the 6th day post-infection (dpi). All mice were sacrificed 30 dpi. The efficacy of the used formulas was assessed by counting the number of C. parvum oocysts excreted in stool of infected mice, histopathological examination of the ileum and liver tissues and determination of the expression of iNOS in the ileum of mice in different animal groups. Results: treatment with EUG resulted in a significant reduction in the number of oocysts secreted in stool when compared to infected untreated mice. In addition, oocyst excretion was significantly reduced in mice received a combination therapy of EUG and NTZ when compared with those received NTZ alone. EUG succeeded in reverting the histopathological alterations induced by Cryptosporidium infection either alone or in combination with NTZ. Moreover, mice received EUG showed marked reduction of the expression of iNOS in ileal tissues. Conclusion: Based on the results, the present study signified a basis for utilizing EUG as an affordable, safe, and alternative therapy combined with NTZ in the management of cryptosporidiosis.

Corrigendum: In silico and in vivo evaluation of the anti-cryptosporidial activity of eugenol.

[This corrects the article DOI: 10.3389/fvets.2024.1374116.].

Analysis of Student Perceptions of a Newly Developed Integrative System Course Model.

Background: During Spring 2021, we piloted a course model that integrated the immune system and HEENT (head, eyes, ears, nose, and throat) by concurrently presenting them in the context of clinical cases. Immune system topics (e.g., infection, cancer) were tied to their manifestations in the HEENT system, and concepts from both systems were consolidated in weekly case-based learning and small group discussion (CBL/SGD) sessions. Methods: To evaluate students' perceptions of the effectiveness of this model, we administered to the class a voluntary survey containing closed- and open-ended items; conducted a focus group of 10 students selected via convenience sampling; and employed a mixed approach to analyze the resulting data, including multiple qualitative methods. Results: Thirty-nine of 74 students completed the survey (53% response rate). In response to the item related to overall effectiveness of using CBL/SGD for system integration, nearly half (48.72%) of these students rated the overall effectiveness as average. Constant comparison analysis of the qualitative data revealed three major themes-student satisfaction with integration of immunology and HEENT, content and time involved in CBL/SGD, and suggestions for improvement-and classical content analysis revealed the relative importance of these themes. Participants held positive and negative perceptions, expressed concerns regarding CBL/SGD (e.g., its helpfulness, complexity), and made suggestions for improvement of integration. Conclusions: Using multiple methods allowed us to gain a deeper understanding of students' perceptions of the new course model, and we have taken actions to improve course quality in the future.

Essential Oils: Chemistry and Pharmacological Activities.

In this review, we provide an overview of the current understanding of the main mechanisms of pharmacological action of essential oils and their components in various biological systems. A brief introduction on essential oil chemistry is presented to better understand the relationship of chemical aspects with the bioactivity of these products. Next, the antioxidant, anti-inflammatory, antitumor, and antimicrobial activities are discussed. The mechanisms of action against various types of viruses are also addressed. The data show that the multiplicity of pharmacological properties of essential oils occurs due to the chemical diversity in their composition and their ability to interfere with biological processes at cellular and multicellular levels via interaction with various biological targets. Therefore, these natural products can be a promising source for the development of new drugs.

Molecular Characterization of Fasciola hepatica in Sheep Based on DNA Sequences of Ribosomal ITS-1.

Introduction: World Health Organization (WHO) considers Fascioliasis as a neglected tropical disease that requires global efforts for disease control. Data from the genetic characterization of Fasciola population shed light on the spread of infections among animals which could help in the development of effective parasite control. The aim of the present work was to genetically characterize Fasciola adult worms isolated from sheep in Saudi Arabia by sequence analysis of ITS-1 region. Methods: A total of 12,653 slaughtered sheep in Jeddah city, Saudi Arabia were examined for the presence of Fasciola spp. adult worms. The ITS-1 region of all parasites was amplified and sequenced. Results: Overall, 12 variants DNA sequences were obtained. The variance of isolates ranged from 0.00771 to 0.34405. BLAST search showed that all obtained sequences were Fasciola hepatica and had >99.3% similarity with F. hepatica isolates from Spain and USA (from different hosts other than sheep). Phylogenetic analysis showed that Fasciola isolates were closely related to isolates from different countries. Discussion: The current study showed that F. hepatica was the only spp. isolated from sheep in Jeddah. Further studies from different localities in Saudi Arabia are needed to help in the development of disease control.

Lemongrass essential oil and its major constituent citral isomers modulate adipogenic gene expression in 3T3-L1 cells.

Obesity is a predisposing factor to diseases such as diabetes mellitus, hypertension, and coronary artery disease. Lemongrass essential oil (LEO), from Cymbopogon flexuosus, possesses numerous therapeutic properties including modulation of obesity in vivo. This experiment investigated the effect of LEO and its major components citral (3,7-dimethyl-2,6-octadienal), citral dimethyl acetal (1,1-dimethoxy-3,7-dimethylocta-2,6-diene), and citral diethyl acetal (1,1-diethoxy-3,7-dimethylocta-2,6-diene) in modulation of adipogenesis and genetic expression in adipocytes. Adipogenesis was induced from murine 3T3-L1 preadipocytes procured from ATCC and maintained in Dulbecco's modified Eagle's medium (DMEM) enriched with calf serum. Differentiation was conducted using DMEM enriched with 10% fetal bovine serum, Dexamethasone 0.25 µM, 3-isobutyl-methylxanthine 0.5 mM, and insulin 10 mg/ml for 2 days, followed by 5 days of insulin 10 mg/ml alone. Samples were subjected to experimental treatments at a concentration of 2.5 × 10-3 . Intracellular triglycerides were quantified and photomicrographs were obtained following Oil red O (ORO) staining procedure. Total ribonucleic acid was extracted and expression of genes effecting in lipid metabolism were quantitated using real-time polymerase chain reaction. ORO staining procedure and spectrophotometric analysis demonstrated decreased lipid accumulation following treatments. LEO and its major constituents significantly inhibited expression of sterol response binding protein 2, cluster of differentiation 36, fatty acid binding protein 4, and peripilin. These results indicate modulation of lipid accumulation through decreased lipid uptake, increased lipolysis, decreased differentiation, and downregulated lipid biosynthesis. This investigation suggests that LEO and its constituents exert effects on adipocyte metabolism and are important for understanding metabolic disease. Further investigation is required to elucidate the degree that each mechanism implicated contributes to the observed effect.

Identification and Genetic Characterization of Blastocystis Species in Patients from Makkah, Saudi Arabia.

Background: Blastocystis species (sp.) are gastrointestinal protozoan parasites with high prevalence rates worldwide. Blastocystis sp. show extensive genetic diversity with 17 different subtypes (STs) described to date. A few studies have investigated the prevalence and STs of Blastocystis sp. in Makkah, Saudi Arabia. Therefore, we aimed in this study to identify and characterize subtypes of Blastocystis sp. in the City of Makkah, Saudi Arabia. Methods: Stool samples were collected from 140 patients who presented to King Abdulaziz Hospital, Hera General Hospital and Modern Medical Center in Saudi Arabia. Different microscopic examination methods of patients' stools and molecular analyses (using primers targeting SSU rRNA gene) were performed to identify and characterize STs of Blastocystis sp. Results: Our microscopic examination of stool samples showed that 96/140 patients (68.6%) had Blastocystis sp. infection. Clinical examination of infected patients revealed that 81 patients were symptomatic, whereas 15 were asymptomatic. Next, we isolated DNA from Blastocystis sp.-positive stool samples followed by PCR amplification of small-subunit ribosomal RNA (SSU rRNA) gene and sequence analysis. Our sequence analysis showed that subtype 3 (ST3) was the most prevalent (53.13%) followed by subtype 1 (ST1) (45.83%), whereas subtype 2 (ST2) was the least prevalent (1.04%). Moreover, our results showed that all three STs resulted in more symptomatic than asymptomatic cases. Finally, we identified novel haplotypes which comprised of 8 ST3, 6 ST1, and one ST2 haplotypes. Conclusion: Our identification of several haplotypes in patients' stools confirms the genetic diversity of Blastocystis sp. and may explain the reported low host specificity and differential pathogenicity of Blastocystis sp. We believe that additional molecular epidemiological and genomic studies are needed to understand the prevalence and pathogenicity of different subtypes in humans and animal hosts.

Renoprotective Effects of Luteolin: Therapeutic Potential for COVID-19-Associated Acute Kidney Injuries.

Acute kidney injury (AKI) has been increasingly reported in critically-ill COVID-19 patients. Moreover, there was significant positive correlation between COVID-19 deaths and renal disorders in hospitalized COVID-19 patients with underlying comorbidities who required renal replacement therapy. It has suggested that death in COVID-19 patients with AKI is 3-fold higher than in COVID-19 patients without AKI. The pathophysiology of COVID-19-associated AKI could be attributed to unspecific mechanisms, as well as COVID-19-specific mechanisms such as direct cellular injury, an imbalanced renin-angiotensin-aldosterone system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. To date, there is no specific treatment for COVID-19 and its associated AKI. Luteolin is a natural compound with multiple pharmacological activities, including anticoronavirus, as well as renoprotective activities against kidney injury induced by sepsis, renal ischemia and diverse nephrotoxic agents. Therefore, in this review, we mechanistically discuss the anti-SARS-CoV-2 and renoprotective activities of luteolin, which highlight its therapeutic potential in COVID-19-AKI patients.

Identification and Genetic Characterization of Fasciola hepatica Isolated from Cattle in Jeddah, Saudi Arabia Based on Sequence Analysis of Mitochondrial (COI) Gene.

Background: In Saudi Arabia, more than US$ 0.2 million annual losses are caused by liver condemnations due to fascioliasis. Data obtained from the genetic characterization of Fasciola population sheds light on parasite transmission which could eventually help in development of effective parasite control measures. So, the aim of this study was to investigate the genetic diversity of Fasciola spp. isolated from cattle in Saudi Arabia by sequence analyses of COI gene. Materials and Methods: A total of 325 cows slaughtered at the central municipal abattoir in Jeddah city, Jeddah Province, Saudi Arabia were examined for fascioliasis in the period from 1st of June to 1st of July 2020. DNA was extracted from adult Fasciola worms and used for PCR and DNA sequence using a primer pair targeting COI gene. Analysis of the obtained sequences was done using BLAST search and phylogenetic analysis. Results: Bovine fascioliasis was diagnosed in 18 out of 325 cattle (5.5%). Forty-eight flukes were extracted from infected animals and DNA was successfully amplified from all flukes. Overall 12 different DNA sequences were obtained. BLAST search showed that all obtained sequences were F. hepatica and had >97% similarity with F. hepatica isolates from Tanzania, Europe and Iran. Phylogenetic analysis of the obtained sequences showed that Fasciola isolates from the current study were clustered in one subclade closely related to isolates from North and South Africa and Italy. Conclusion: Reports on the molecular characterization of Fasciola spp. in Saudi Arabia are limited. In the current study, our findings showed that F. hepatica was the only Fasciola species parasitizing cattle in Jeddah city, Saudi Arabia. Further studies using a large number of samples from different localities in Saudi Arabia are needed to provide data that will help the development of control measures against fascioliasis.