Epstein-Barr virus: the mastermind of immune chaos.

The Epstein-Barr virus (EBV) is a ubiquitous human pathogen linked to various diseases, including infectious mononucleosis and multiple types of cancer. To control and eliminate EBV, the host's immune system deploys its most potent defenses, including pattern recognition receptors, Natural Killer cells, CD8+ and CD4+ T cells, among others. The interaction between EBV and the human immune system is complex and multifaceted. EBV employs a variety of strategies to evade detection and elimination by both the innate and adaptive immune systems. This demonstrates EBV's mastery of navigating the complexities of the immunological landscape. Further investigation into these complex mechanisms is imperative to advance the development of enhanced therapeutic approaches with heightened efficacy. This review provides a comprehensive overview of various mechanisms known to date, employed by the EBV to elude the immune response, while establishing enduring latent infections or instigate its lytic replication.

Pharmacological assessment of the antineoplastic and immunomodulatory properties of a new spiroindolone derivative (7',8'-Dimethoxy-1',3'-dimethyl-1,2,3',4'-tetrahydrospiro[indole-3,5'-pyrazolo[3,4-c]isoquinolin]-2-one) in chronic myeloid leukemia.

The discovery and development of effective novel compounds is paramount in oncology for improving cancer therapy. In this study, we developed a new derivative of spiroindolone (7',8'-Dimethoxy-1',3'-dimethyl-1,2,3',4'-tetrahydrospiro[indole-3,5'- pyrazolo[3,4-c]isoquinolin]-2-one) and evaluated its anticancer- and immunomodulatory potential in a vitro model of chronic leukemia. We utilized the chronic leukemia cell line K562, as well as non-cancerous peripheral blood mononuclear cells (PBMC) and Vero cells (kidney epithelium of Cercopithecus aethiops). We assessed the cytotoxicity of the compound using the MTT assay, and performed cell cycle assays to determine its impact on different stages of the cell cycle. To evaluate its antineoplastic activity, we conducted a colony formation test to measure the effect of the compound on the clonal growth of cancer cells. Furthermore, we evaluated the immunomodulatory activity of the compound by measuring the levels of pro and anti-inflammatory cytokines. The study findings demonstrate that the spiroindolone-derived compound exerted noteworthy cytotoxic effects against K562 cells, with an IC50 value of 25.27 µg/mL. Additionally, it was observed that the compound inhibited the clonal proliferation of K562 cells while displaying minimal toxicity to normal cells. The compound exhibited its antiproliferative activity by inducing G2/M cell cycle arrest, preventing the entry of K562 cells into mitosis. Notably, the compound demonstrated an immunomodulatory effect by upregulating the production of cytokines IL-6 and IL-12/23p40. In conclusion, the spiroindolone-derived compound evaluated in this study has demonstrated significant potential as a therapeutic agent for the treatment of chronic myeloid leukemia. Further investigations are warranted to explore its clinical applications.

Cytotoxic and immunomodulatory potential of a novel [2-(4-(2,5-dimethyl-1H-pyrrol-1-yl)-1H-pyrazol-3-yl)pyridine] in myeloid leukemia.

Cancer ranks among the leading causes of mortality worldwide. However, the efficacy of commercially available anticancer drugs is compromised by the emerging challenge of drug resistance. This study aimed to investigate the anticancer and immunomodulatory potential of a recently developed a novel [2-(4-(2,5-dimethyl-1 H-pyrrol-1-yl)- 1 H-pyrazol-3-yl) pyridine]. The cytotoxic potential of the compound was assessed using the MTT assay on both cancerous HL60 (acute myeloid leukemia) and K562 (chronic myeloid leukemia) cell lines, as well as non-cancerous Vero cells and human peripheral blood mononuclear cells (PBMCs). A clonogenic assay was employed to evaluate the anticancer efficacy of the compound, while flow cytometry was utilized to investigate its effect on cell cycle arrest. Furthermore, the immunomodulatory potential of the compound was assessed by quantifying inflammatory and anti-inflammatory biomarkers in the supernatant of PBMCs previously treated with the compound. Our study revealed that the novel pyridine ensemble exhibits selective cytotoxicity against HL60 (IC50 = 25.93 µg/mL) and K562 (IC50 = 10.42 µg/mL) cell lines, while displaying no significant cytotoxic effect on non-cancerous cells. In addition, the compound induced a decrease of 18% and 19% in the overall activity of COX-1 and COX-2, respectively. Concurrently, it upregulated the expression of cytokines including IL4, IL6, IL10, and IL12/23p40, while downregulating INFγ expression. These findings suggest that the compound has the potential to serve as a promising candidate for the treatment of acute and chronic myeloid leukemias due to its effective antiproliferative and immunomodulatory activities, without causing cytotoxicity in non-cancerous cells.

Persistence of SARS-CoV-2 Antigens in the Nasal Mucosa of Eight Patients with Inflammatory Rhinopathy for over 80 Days following Mild COVID-19 Diagnosis.

The nasal mucosa is the main gateway for entry, replication and elimination of the SARS-CoV-2 virus, the pathogen that causes severe acute respiratory syndrome (COVID-19). The presence of the virus in the epithelium causes damage to the nasal mucosa and compromises mucociliary clearance. The aim of this study was to investigate the presence of SARS-CoV-2 viral antigens in the nasal mucociliary mucosa of patients with a history of mild COVID-19 and persistent inflammatory rhinopathy. We evaluated eight adults without previous nasal diseases and with a history of COVID-19 and persistent olfactory dysfunction for more than 80 days after diagnosis of SARS-CoV-2 infection. Samples of the nasal mucosa were collected via brushing of the middle nasal concha. The detection of viral antigens was performed using immunofluorescence through confocal microscopy. Viral antigens were detected in the nasal mucosa of all patients. Persistent anosmia was observed in four patients. Our findings suggest that persistent SARS-CoV-2 antigens in the nasal mucosa of mild COVID-19 patients may lead to inflammatory rhinopathy and prolonged or relapsing anosmia. This study sheds light on the potential mechanisms underlying persistent symptoms of COVID-19 and highlights the importance of monitoring patients with persistent anosmia and nasal-related symptoms.

Phenolic Composition, Wound Healing, Antinociceptive, and Anticancer Effects of Caralluma europaea Extracts.

Caralluma europaea (Guss.) is an important medicinal plant widely used in Morocco for various traditional purposes. Our work aimed to evaluate the phenolic composition, wound healing, antinociceptive, and anticancer activities of C. europaea extracts. Moreover, this study assessed the beneficial effect of C. europaea phytocompounds on the TRADD, cyclooxegenase-2, Wnt/ß-catenin, and tyrosine kinase signaling pathways. The wound healing effect of C. europaea formulations against skin burn was evaluated for 21 days. The cytotoxic effect of the C. europaea extracts was evaluated against human leukemic (K562 and HL60) and liver cancer cell lines (Huh-7) using the MTT test. All the phytoconstituents identified by UHPLC in the polyphenols were docked for their inhibitory power on protein casein kinase-1, glycogen synthase kinase-3-ß, cyclooxegenase-2, tyrosine kinase, and TRADD. Luteolin and kaempferol are the main compounds identified in C. europaea polyphenols. The group treated with polyphenols showed the greatest wound contractions and all tested extracts presented a significant antinociceptive effect. Polyphenols showed a remarkable antitumoral activity against the K562, HL60 and Huh-7 cell lines. Saponins exerted an important cytotoxic effect against the Huh-7 cell line, whereas no cytotoxicity was observed for the hydroethanolic and flavonoids extracts. Hesperetin and trimethoxyflavone presented the highest docking G-score on tyrosine kinase and cyclooxygenase, respectively.

Antileukemic, Antioxidant, Anti-Inflammatory and Healing Activities Induced by a Polyphenol-Enriched Fraction Extracted from Leaves of Myrtus communis L.

Natural products have offered a number of exciting approaches in cancer treatment over the years. In this study, we investigated the prophylactic and therapeutic effects of the polyphenol-enriched fraction extracted from Myrtus communis (PEMC) on acute and chronic leukemia. According to the UHPLC-MSn, the fraction is rich in flavonoids. Protective activity of the PEMC was assessed by evaluating the antioxidant, anti-inflammatory, wound healing, and hemolysis potential in a series of in vivo and in vitro assays, while the therapeutic approach consisted of the evaluation of cytotoxic activity of the PEMC against HL60 and K562 leukemia cell lines. Safety of the fraction was also evaluated on a non-cancerous Vero cell line and by an acute toxicity test performed in mice. The PEMC demonstrated a significant anti-inflammatory and healing potential. The activities found at the dose of 100 mg/kg were better than those observed using a reference drug. The PEMC demonstrated a significant antioxidant effect and a specific cytotoxicity towards HL60 (IC50 = 19.87 µM) and K562 (IC50 = 29.64 µM) cell lines being non-toxic to the Vero cell line. No hemolytic activity was observed in vitro and no toxicity effect was found in mice. Thus, the PEMC has a pharmacological potential as both preventive and therapeutic agent. However, further research is necessary to propose its mechanism of action.

Clinico-epidemiological and sociodemographic profile of patients with hemophilia in the Brazilian Amazon: High prevalence of hepatitis C infection and its possible corrrelation with inhibitor development.

Hemophilia is a recessive genetic disease caused by a mutation on the X chromosome that has been linked to a high risk of transfusion-transmitted infections, especially sexually transmitted infections. The purpose of this retrospective study was to characterize the clinical and epidemiological profile and describe the prevalence of sexually transmitted viral infections in patients with hemophilia in the Northern Brazilian state of Amazonas. We assessed clinical, laboratory and sociodemographic data of hemophiliac patients (n = 311) for the period 2011-2019. The majority of the study population was composed of people with a low level of education aged 21-30 years old. The prevalence of HCV, HBV, and HTLV-1/2 infections among the study population were 10.52, 0.52, and 1.05%, respectively. No HIV infection was found among the patients. Between 2011 and 2015 the prevalence of HCV increased by over 100% and the incidence peaked in 2013. The severe hemophilia was associated with the presence of inhibitor factor (Odds Ratio [OD] 9.83; 95% IC: 3.41-27.62, p < 0.0001) or target joint (OD 6.59; 95% IC: 3.27-13.34, p < 0.0001). The presence of inhibitor was positive and significantly correlated with HCV infection (r = 1.00, p < 0.0001). Our results showed that HCV infection is highly prevalent in patients with hemophilia and might be involved in the development of inhibitors. Thus, these data provide new insights into the clinical and epidemiological profile of patients suffering from hemophilia in the Northern Brazilian state of Amazonas.

Distinct plasma chemokines and cytokines signatures in Leishmania guyanensis-infected patients with cutaneous leishmaniasis.

The immunopathology associated with Leishmaniasis is a consequence of inflammation. Upon infection with Leishmania, the type of host-immune response is determinant for the clinical manifestations that can lead to either self-healing or chronic disease. Multiple pathways may determine disease severity. A comparison of systemic immune profiles in patients with cutaneous leishmaniasis caused by L. guyanensis and healthy individuals with the same socio-epidemiological characteristics coming from the same endemic areas as the patients is performed to identify particular immune profile and pathways associated with the progression of disease development. Twenty-seven plasma soluble circulating factors were evaluated between the groups by univariate and multivariate analysis. The following biomarkers pairs IL-17/IL-9 (ρ=0,829), IL-17/IL-12 (ρ=0,786), IL-6/IL-1ra (ρ=0,785), IL-6/IL-12 (ρ=0,780), IL-1ß/G-CSF (ρ=0,758) and IL-17/MIP-1ß (ρ=0,754) showed the highest correlation mean among the patient while only INF-γ/IL-4 (ρ=0.740), 17/MIP-1ß (ρ=0,712) and IL-17/IL-9 (ρ=0,707) exhibited positive correlation among the control group. The cytokine IL-17 and IL1ß presented the greater number of positive pair correlation among the patients. The linear combinations of biomarkers displayed IP-10, IL-2 and RANTES as the variables with the higher discriminatory activity in the patient group compared to PDGF, IL-1ra and eotaxin among the control subjects. IP-10, IL-2, IL-1ß, RANTES and IL-17 seem to be predictive value of progression to the development of disease among the Lg-infected individuals.

Increased Serum Levels of Growth-Differentiation Factor 3 (GDF3) and Inflammasome-Related Markers in Pregnant Women during Acute Zika Virus Infection.

The systemic inflammatory response elicited by acute Zika virus (ZIKV) infection during pregnancy plays a key role in the clinical outcomes in mothers and congenitally infected offspring. The present study aimed to evaluate the serum levels of GDF-3 and inflammasome-related markers in pregnant women during acute ZIKV infection. Serum samples from pregnant (n = 18) and non-pregnant (n = 22) women with acute ZIKV infection were assessed for NLRP3, IL-1ß, IL-18, and GDF3 markers through an enzyme-linked immunosorbent assay. ZIKV-negative pregnant (n = 18) and non-pregnant women (n = 15) were used as control groups. All serum markers were highly elevated in the ZIKV-infected groups in comparison with control groups (p < 0.0001). Among the ZIKV-infected groups, the serum markers were significantly augmented in the pregnant women in comparison with non-pregnant women (NLRP3 p < 0.001; IL-1ß, IL-18, and GDF3 p < 0.0001). The IL-18 marker was found at significantly higher levels (p < 0.05) in the third trimester of pregnancy. Bivariate and multivariate analyses showed a strong positive correlation between GDF3 and NLRP3 markers among ZIKV-infected pregnant women (r = 0.91, p < 0.0001). The findings indicated that acute ZIKV infection during pregnancy induces the overexpression of GDF-3 and inflammasome-related markers, which may contribute to congenital disorders and harmful pregnancy outcomes.

Bacillus subtilis spores as delivery system for nasal Plasmodium falciparum circumsporozoite surface protein immunization in a murine model.

Malaria remains a widespread public health problem in tropical and subtropical regions around the world, and there is still no vaccine available for full protection. In recent years, it has been observed that spores of Bacillus subtillis can act as a vaccine carrier and adjuvant, promoting an elevated humoral response after co-administration with antigens either coupled or integrated to their surface. In our study, B. subtillis spores from the KO7 strain were used to couple the recombinant CSP protein of P. falciparum (rPfCSP), and the nasal humoral-induced immune response in Balb/C mice was evaluated. Our results demonstrate that the spores coupled to rPfCSP increase the immunogenicity of the antigen, which induces high levels of serum IgG, and with balanced Th1/Th2 immune response, being detected antibodies in serum samples for 250 days. Therefore, the use of B. subtilis spores appears to be promising for use as an adjuvant in a vaccine formulation.

Seroprevalence of Epstein-Barr virus and cytomegalovirus infections in Presidente Figueiredo, Amazonas, Brazil.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections affect around 95% of the world's population. In Brazil, there are few epidemiological reports related to EBV and CMV infection, especially in the western Amazon region. This study aimed to estimate the seroprevalence of EBV and CMV infection in individuals residents in Presidente Figueiredo, Amazonas, Brazil. Blood samples of 443 individuals were tested for the presence of anti-EBV and anti-CMV IgG antibodies through an enzyme-linked immunosorbent assay. EBV (95.9%; 95% CI: 0.94;0.98), CMV (96.8%; 95% CI: 0.95;0.98) and CMV/EBV (93%;95% CI: 0.91-0.95) coinfection were highly prevalent in the study population. Children (1 to 5 years) not attending school were less susceptible to EBV (OR 0.15; 95% CI: 0.05-0.52; p = 0.017) and CMV infections (OR 0.05; 95% CI: 0.02 - 0.17; p < 0.0001). Teenagers at high school showed increased susceptibility to CMV infection (OR 4.65; 95%CI: 1.43-15.08; p = .013) and EBV/CMV co-infection (OR 3.04; 95%CI: 1.44-6.45; p = 0.005). The seroprevalence of CMV and EBV infections were preeminent and tend to increase with age in the study population. Either attendance to a daycare facility or primary school before the age of 5 years may increase the susceptibility to EBV or CMV infection.

Trends in unsuitability for blood donation in the Brazilian Amazon.

Introduction: Sociodemographic and behavioral factors are usually associated with the unsuitability to donate blood. Understanding the reasons behind the exclusion of blood bags is crucial for reducing donor deferral rates. This study aimed to characterize the profile of unsuitable donors in the Blood Center of the northern Brazilian state of Amazonas. Methods: This is a retrospective study, based on documentary analysis of electronic medical records obtained in the Hematology and Hemotherapy Foundation of the state of Amazonas. This study included all individuals with complete medical records (n = 87,463) who tried to donate blood between 2017 and 2019. Results: The overall rate of donor unsuitability was 19.12% (n = 16,627) and the main reason was poor nutritional status (15.17%), followed by chronic health problems (11.40%), risky sexual behavior (9.5%) and exposure to risk (8.83%). High blood pressure figured as the leading cause of unsuitability among chronic health conditions (85.19%), while having sex with multiple partners (92.63%) was the main sexual risk behavior. The risk of exposure to malaria was responsible for 99.45% of unsuitability among those who were unsuitable due to exposure to risk factors. Deferral rates were associated with increasing age and replacement donation, which was the predominant type of donation. Women had the highest rates of unsuitability, mainly during the first donation (37.04%). Discussion: This study provides the first known profile of blood donor unsuitability in the Brazilian Amazon and raises awareness of the region-specific needs that must be met to reduce blood donor unsuitability.

A new Kunitz trypsin inhibitor from Erythrina poeppigiana exhibits antimicrobial and antibiofilm properties against bacteria.

Erythrina poeppigiana belongs to Fabaceae family (subfamily Papillionoideae) and is commonly found in tropical and subtropical regions in Brazil. Herein, we described the purification and characterization of a new Kunitz-type inhibitor, obtained from E. poeppigiana seeds (EpTI). EpTI is composed by three isoforms of identical amino-terminal sequences with a molecular weight ranging from 17 to 20 kDa. The physicochemical features showed by EpTI are common to Kunitz inhibitors, including the dissociation constant (13.1 nM), stability against thermal (37-100 °C) and pH (2-10) ranging, and the presence of disulfide bonds stabilizing its reactive site. Furthermore, we investigated the antimicrobial, anti-adhesion, and anti-biofilm properties of EpTI against Gram-positive and negative bacteria. The inhibitor showed antimicrobial activity with a minimum inhibitory concentration (MIC, 5-10 µM) and minimum bactericidal concentration (MBC) of 10 µM for Enterobacter aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, Staphylococcus aureus, and Staphylococcus haemolyticus. The combination of EpTI with ciprofloxacin showed a marked synergistic effect, reducing the antibiotic concentration by 150%. The increase in crystal violet uptake for S. aureus and K. pneumoniae strains was approximately 30% and 50%, respectively, suggesting that the bacteria plasma membrane is targeted by EpTI. Treatment with EpTI at 1x and 10 x MIC significantly reduced the biofilm formation and prompted the disruption of a mature biofilm. At MIC/2, EpTI decreased the bacterial adhesion to polystyrene surface within 2 h. Finally, EpTI showed low toxicity in animal model Galleria mellonella. Given its antimicrobial and anti-biofilm properties, the EpTI sequence might be used to design novel drug prototypes.

Prevalence and Recurrence Rates of Cytomegalovirus Infection Among Patients With Hematological Diseases in the Western Brazilian Amazon: A Cross-Sectional Study.

Cytomegalovirus (CMV) is a worldwide distributed pathogen that may cause serious complications in patients with hematological diseases. This study aimed to serologically characterize CMV infection in patients suffering from hematological diseases in Amazonas state, Brazil. Serum samples from 323 patients were tested for the presence of anti-CMV IgM or IgG antibodies using an enzyme-linked immunosorbent assay. Positive samples for IgM were submitted to the IgG avidity test to differentiate primary infection from recurrent infection. An epidemiological questionnaire was administered to collect the sociodemographic information of the study population. The overall prevalence of CMV infection verified in this study was 91.3%. The highest rates were found in patients suffering from platelet disorders (94.5%), anemia (93.3%), or leukemia (91%). The study population was predominantly composed of individuals with low socioeconomic status. Blood transfusions were more common in patients with anemia or leukemia, but this variable was not correlated with the seropositivity for CMV infection. Measurement of IgG avidity in patients positive for anti-CMV IgM demonstrated a recurrent infection rate of 5.2% (17/323). Over 80% of recurrent infections occurred in patients with acute lymphocytic leukemia (ALL) or anemia. Our findings indicated that CMV infection is highly prevalent in patients from the western Brazilian Amazon who have hematological diseases. The prevalence observed progressively rose with increasing age, whereas anemia or ALL figured as risk factors for the recurrence of CMV infection.

Increased vulnerability to SARS-CoV-2 infection among indigenous people living in the urban area of Manaus.

The COVID-19 pandemic threatens indigenous peoples living in suburban areas of large Brazilian cities and has thus far intensified their pre-existing socio-economic inequalities. We evaluated the epidemiological situation of SARS-CoV-2 infection among residents of the biggest urban multiethnic indigenous community of the Amazonas state, Brazil. Blood samples of 280 indigenous people living in the surrounding area of Manaus were tested for the presence of anti-SARS-CoV-2 IgA or IgG antibodies. The risk factors and sociodemographic information were assessed through an epidemiological questionnaire. We found a total positivity rate of 64.64% (95% CI 59.01-70.28) for SARS-CoV-2 infection. IgA and IgG were detected in 55.71% (95% CI 49.89-61.54) and 60.71% (95% CI 54.98-66.45) of the individuals, respectively. Over 80% of positive individuals were positive for both IgA and IgG.No significant difference in positivity rates between genders or age groups was observed. Moreover, the age group ≥ 60 years old showed the highest antibody ratios (IgA mean ratio = 3.080 ± 1.623; IgG mean ratio = 4.221 ± 1.832), while the age groups 13-19 and 20-29 showed the lowest IgA (mean ratio = 2.268 ± 0.919) and IgG ratios (mean ratio = 2.207 ± 1.246), respectively. Individuals leaving the home more frequently were at higher risk of infection (Odds ratio (OD) 2.61; 95% CI 1.00-1.49; p = 0.048). Five or more individuals per household increased fivefold the risk of virus transmission (OR 2.56; 95% CI 1.09-6.01; p = 0.019). The disproportionate dissemination of SARS-CoV-2 infection observed among the study population might be driven by typical cultural behavior and socioeconomic inequalities. Despite the pandemic threat, this population is not being targeted by public policies and appears to be chronically invisible to the Brazilian authorities.

Nutritional and Bioactive Properties of an Amazon Wild Oyster Culinary-Medicinal Mushroom, Pleurotus ostreatus (Agaricomycetes): Contributions to Functional Food and Human Health.

A wild Amazonian strain of Pleurotus ostreatus (Jacq.: Fr.) P. Kumm. was cultivated using local agroindustrial wastes-açai seeds (AS) and elephant grass straw (EGS)-as substrates and evaluated for its nutritional composition and bioactivities. Basidiomata presented higher contents of protein (27.19%) and dietary fiber (18.57%) when grown on AS, while lipids (2.26%), nonfiber carbohydrates (53.21%), and metabolizable energy (304.02 kcal/100 g) were higher on EGS substrate. Methanolic extracts of P. ostreatus grown on AS also provided a higher phenolic content (31.24 mg gallic acid equivalents/g extract) and greater antioxidant activity, scavenging 82.60% and 91.13% of DPPH· and ABTS·+ radicals, respectively, while chelating ability of Fe2+ was higher on EGS mushroom extracts (74.34%). Hemagglutinating activity of 1,997 HA U/mg protein was observed solely in the aqueous extracts of AS-grown mushrooms. Higher proteolytic activity was observed in aqueous extracts from mushrooms grown on EGS (219.10 U/mg protein), and their saline extract was the sole one with fibrinolytic activity (3.14 mm2). Both substrates and extractions yielded similar activity of protease inhibitors, with higher inhibition of serine than cysteine proteases. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis profiling showed protein bands related to lectins, proteases, fibrinolytic enzymes, and protease inhibitors. Thus, this wild Amazonian strain has great nutritional potential and produces biomolecules that can contribute to important applications in food, health, and industry.

Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds.

Leukemia is a group of hematological neoplastic disorders linked to high mortality rates worldwide, but increasing resistance has led to the therapeutic failure of conventional chemotherapy. This study aimed to evaluate in vitro the antileukemic activity and potential mechanism of action of a polyphenolic extract obtained from the seeds of Coriandrum sativum L. (CSP). A methylthiazoletetrazolium assay was performed to assess the CSP cytotoxicity on chronic (K562) and acute (HL60) myeloid leukemia cell lines and on normal Vero cell line. CSP toxicity was also evaluated in vivo using the OECD 423 acute toxicity model on Swiss albino mice. The results demonstrated a remarkable antitumoral activity against K562 and HL60 cell lines (IC50 = 16.86 µM and 11.75 µM, respectively) although no cytotoxicity was observed for the Vero cells or mice. A silico study was performed on the following receptors that are highly implicated in the development of leukemia: ABL kinase, ABL1, BCL2, and FLT3. The molecular docking demonstrated a high affinity interaction between the principal CSP components and the receptors. Our findings demonstrated that CSP extract has remarkable antileukemic activity, which is mainly mediated by the flavonoids, catechins, and rutin, all of which showed the highest binding affinity for the targeted receptors. This study revealed a promising active compound alternative research-oriented biopharmacists to explore.

Epidemiological and Liver Biomarkers Profile of Epstein-Barr Virus Infection and Its Coinfection with Cytomegalovirus in Patients with Hematological Diseases.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are viruses globally distributed that have been associated with the development and prognosis of many pathologies, including hematological diseases. This study aimed to characterize the epidemiological profile of EBV infection and the infection-correlated hepatic manifestations in patients with hematological diseases of the northern Brazilian state of Amazonas. A total of 228 patients were serologically tested for the presence of anti-EBV and anti-CMV IgG antibodies through an enzyme-linked immunosorbent assay. The coinfection with CMV, sociodemographic and laboratory records of all patients were also assessed. The overall prevalence observed among the study population for EBV infection and EBV/CMV coinfection was 85.09% (95% CI: 0.80-0.90) and 78.51% (95% CI: 0.73-0.84), respectively. The age group 31-40 years old were more susceptible to EBV/CMV coinfection (95% CI: 1.59-93.41, p = 0.011), while young people aged 1-10 years old were less affected for both EBV infection (CI 95%; 0.66-0.91, p = 0.001) and EBV/CMV coinfection (95% CI: 0.52-0.81, p < 0.0001). High serum levels of the liver biomarker ferritin were associated with EBV infection (95% CI: 1.03-1.54, p = 0.031) and EBV/CMV coinfection (95% CI: 1.02-1.70, p = 0.038). Our findings indicated that the elevated prevalence of EBV infection is not associated with the hematological diseases or transfusion rates, but with the socioeconomic status of the study population. Also, this study suggests that the EBV infection and its coinfection with CMV are related to the increase of serum ferritin levels.

COVID-19 in Amazonas, Brazil, was driven by the persistence of endemic lineages and P.1 emergence.

The northern state of Amazonas is among the regions in Brazil most heavily affected by the COVID-19 epidemic and has experienced two exponentially growing waves, in early and late 2020. Through a genomic epidemiology study based on 250 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from different Amazonas municipalities sampled between March 2020 and January 2021, we reveal that the first exponential growth phase was driven mostly by the dissemination of lineage B.1.195, which was gradually replaced by lineage B.1.1.28 between May and June 2020. The second wave coincides with the emergence of the variant of concern (VOC) P.1, which evolved from a local B.1.1.28 clade in late November 2020 and replaced the parental lineage in <2 months. Our findings support the conclusion that successive lineage replacements in Amazonas were driven by a complex combination of variable levels of social distancing measures and the emergence of a more transmissible VOC P.1 virus. These data provide insights to understanding the mechanisms underlying the COVID-19 epidemic waves and the risk of dissemination of SARS-CoV-2 VOC P.1 in Brazil and, potentially, worldwide.

HTLV-2 infection in Manaus, Brazil: first description of HTLV-2c subtype in an urban area of the Western Amazon region

Abstract INTRODUCTION: We investigated the prevalence of human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) infection in patients with hematological diseases from the western Amazon region of Brazil. METHODS: Samples from 306 patients were submitted for the molecular diagnosis of HTLV-1/2 infection by real time PCR (qPCR), with amplification, sequencing, and phylogenetic analysis of the long terminal repeat (LTR) region. RESULTS: A 29-year-old male carrier of sickle cell anemia with a history of multiple blood transfusions was diagnosed with the HTLV-2c subtype. CONCLUSIONS: This study describes the first known occurrence of HTLV-2c in the urban area of Brazil's western Amazon region.