Significant Protection Research Articles

Effect of single-dose, live, attenuated dengue vaccine in children with or without previous dengue on risk of subsequent, virologically confirmed dengue in Cebu, the Philippines: a longitudinal, prospective, population-based cohort study

A three-dose dengue vaccine (CYD-TDV) was licensed for use in children aged 9 years and older starting in 2015 in several dengue-endemic countries. In 2016, the Philippine Department of Health implemented a dengue vaccination programme, which was discontinued because of safety concerns. We assessed the relative risk of developing virologically confirmed dengue among children who did or did not receive a single dose of CYD-TDV by previous dengue virus (DENV) infections at baseline classified as none, one, and two or more infections. In this longitudinal, prospective, population-based cohort study, we enrolled healthy children (aged 9-14 years) residing in Bogo or Balamban, Cebu, Philippines, between May 2, and June 2, 2017, before a mass dengue vaccination campaign, via the Rural Health Unit in Bogo and three Rural Health Units in Balamban. We collected demographic information and sera for baseline DENV serostatus and conducted active surveillance for acute febrile illness. Children who developed acute febrile illness were identified, clinical data were collected, and blood was drawn for confirmation of dengue by RT-PCR. The primary outcome was the relative risk of developing virologically confirmed dengue among children who received or did not receive a single dose of CYD-TDV by DENV serostatus at baseline. A single dose of CYD-TDV did not confer protection against virologically confirmed dengue in children who had none or one previous DENV infection at baseline. One dose conferred significant protection against hospital admission for virologically confirmed dengue among participants who had two or more previous DENV infections at baseline during the first 3 years (70%, 95% CI 20-88; p=0·017) and the entire follow-up period (67%, 19-87; p=0·016). The risk of developing virologically confirmed dengue after a single dose of CYD-TDV varied by baseline DENV serostatus. Since the study assessed the effect of only a single dose, the findings cannot inform decisions on vaccination by public health officers. However, the findings have implications for children who receive an incomplete vaccination regimen and these results should prompt more detailed analyses in future trials on dengue vaccines. The Philippine Department of Health, Hanako Foundation, WHO, Swedish International Development Cooperation Agency, International Vaccine Institute, University of North Carolina, and US National Institute of Allergy and Infectious Diseases.

Extracellular vesicles secreted from mesenchymal stem cells ameliorate renal ischemia reperfusion injury by delivering miR-100-5p targeting FKBP5/AKT axis

The incidence of acute kidney injury (AKI) due to ischemia–reperfusion (IR) injury is increasing. There is no effective treatment for AKI, and because of this clinical challenge, AKI often progresses to chronic kidney disease, which is closely associated with poor patient outcomes and high mortality rates. Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUCMSC-sEVs) play increasingly vital roles in protecting tissue function from the effects of various harmful stimuli owing to their specific biological features. In this study, we found that miR-100-5p was enriched in hUCMSC-sEVs, and miR-100-5p targeted FKBP5 and inhibited HK-2 cell apoptosis by activating the AKT pathway. HK-2 cells that were exposed to IR injury were cocultured with hUCMSC-sEVs, leading to an increase in miR-100-5p levels, a decrease in FKBP5 levels, and an increase in AKT phosphorylation at Ser 473 (AKT-473 phosphorylation). Notably, these effects were significantly reversed by transfecting hUCMSCs with an miR-100-5p inhibitor. Moreover, miR-100-5p targeted FKBP5, as confirmed by a dual luciferase reporter assay. In vivo, intravenous infusion of hUCMSC-sEVs into mice suffering from IR injury resulted in significant apoptosis inhibition, functional maintenance and renal histological protection, which in turn decreased FKBP5 expression levels. Overall, this study revealed an effect of hUCMSC-sEVs on inhibiting apoptosis; hUCMSC-sEVs reduced renal IR injury by delivering miR-100-5p to HK-2 cells, targeting FKBP5 and thereby promoting AKT-473 phosphorylation to activate the AKT pathway. This study provides novel insights into the role of hUCMSC-sEVs in the treatment of AKI.

Refined risk assessment and differentiated protection of lightning damage in distribution network lines considering the underlying surface environment

The distribution line is widely distributed and the span of pole-towers is small. However, the existing lightning positioning system has limited positioning accuracy, and the lightning strike coordinates it locates have certain deviations for the distribution network. The lightning hazard risk divided by lightning density is not sufficient to support the differentiated lightning protection transformation of the distribution network. The environment of the underlying surface where the pole-tower is located has a significant impact on lightning activity, so this paper combines terrain, climate, lightning current characteristics, and historical lightning trip data to finely evaluate the lightning risk level in the distribution line pole-tower area. This paper provides a detailed analysis of the relationship between different underlying surface environments and lightning current characteristics and utilizes the entropy weight method to construct a comprehensive lightning disaster risk index, then evaluates the risk level of lightning disaster in different regions, and corrects it through lightning fault data. Overlaying the risk level of the area and the distribution map of the pole-tower foundation coordinates, it will obtain the distribution of lightning hazard-pregnant risk at the pole-tower area, which would contribute to guiding the differentiated lightning protection transformation of the line. Compared to traditional unified lightning protection renovation methods, differentiated lightning protection methods that integrate factors such as pole-tower structure, wire type, and lightning risk level can achieve significant lightning protection effects at a lower economic cost. Taking Nanchang City as an example, risk assessment and lightning protection renovation were conducted on 21 distribution lines. The average number of lightning trips per year is 55 before the renovation, but it is only 4 after the renovation, which the number of lightning trips significantly reduce. This verifies the effectiveness of using lightning hazard-pregnant assessment results to guide differentiated lightning protection methods.

Comparative analysis of the efficacy of vaccines using structural protein subunits of the severe fever with thrombocytopenia syndrome virus.

The severe fever with thrombocytopenia syndrome virus (SFTSV) represents a significant emerging health threat as a tick-borne pathogen that causes SFTS, with mortality rates ranging between 10 and 30%. Despite the considerable risk presented by SFTSV, an effective vaccine has yet to be developed. Our study assessed the efficacy of recombinant protein vaccines, focusing on the purified nucleocapsid protein (NP) and surface glycoproteins (Gn and Gc), against SFTSV in both singular and combined formulations. Individual vaccinations with NP or Gn subunits yielded partial protection in type I interferon receptor-knockout (IFNAR-KO) mice, with survival rates of 66.7 and 16.7%, respectively, whereas Gc vaccination did not confer significant protection, resulting in 100% mortality similar to that of the unvaccinated control group. Notably, NP vaccination substantially enhanced antigen-specific T cell responses, and Gc vaccination exhibited strong neutralizing activity against SFTSV. Among the combined recombinant protein formulations (Gn + NP, Gc + NP, and Gn + Gc + NP) tested, the Gc + NP combination provided the highest survival rate (85.7%) following challenge with a lethal dose of SFTSV, highlighting its potential as a vaccine candidate. Longitudinal studies showed that antibody levels in both wild type C57BL/6 and IFNAR-KO mice peaked between 2 and 3 months post-vaccination and declined over time. A notable decrease in NP-specific CD8+ T cell responses was observed 6 months post-vaccination in C57BL/6 mice, while NP-specific CD4+ T cell responses persisted up to 12 months. By 12 months post-vaccination, all IFNAR-KO mice vaccinated with single subunit antigens succumbed to the virus, suggesting that effective protection against SFTS may rely on antibody responses to subunit antigens and/or CD8+ T cell activity. These findings underscore the necessity of an optimized SFTS vaccine that combines protective antigens with an adjuvant system to ensure durable humoral and cellular immunity.

Bioinformatic, Biochemical, and Immunological Mining of MHC Class I Restricted T Cell Epitopes for a Marburg Nucleoprotein Microparticle Vaccine.

The Marburg virus (MARV), the virus responsible for Marburg hemorrhagic fever (MHF), is considered a top-priority pathogen for vaccine development. Recent outbreaks in Equatorial Africa have highlighted the urgency of MARV because of its high fatality rate and historical concerns about potential weaponization. Currently, there are no licensed vaccines for MARV. Existing vaccine candidates rely on attenuated recombinant vesicular stomatitis virus carrying MARV glycoprotein (VSVΔG) or the chimpanzee replication-defective adenovirus 3 vector ChAd3-MARV. Although these platforms provide significant protection in animal models, they face challenges because of their limited thermal stability and the need for cold storage during deployment in resource-poor areas. An alternative approach involves using adjuvanted poly (lactic-co-glycolic acid) (PLGA) microparticles loaded with synthetic peptides representing MHC class I-restricted T cell epitopes. This vaccine platform has demonstrated effectiveness in protecting against SARS-CoV-2 and EBoV disease in animal models and has the advantage of not requiring cold storage and remaining stable at room temperature for over six months. This report outlines the design, manufacturing, and in vivo immunogenicity testing of PLGA microparticle human vaccines designed to prevent Marburg hemorrhagic fever.

Comparison of Attainment and Protective Effects of Lupus Low Disease Activity State in Patients With Newly Diagnosed Versus Established Systemic Lupus Erythematosus.

To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE). Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare. Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up. LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).

Useful Role of a New Generation of Dexamethasone, Vitamin E and Human Serum Albumin Microparticles in the Prevention of Excitotoxicity Injury in Retinal Ocular Diseases.

Excitotoxicity has been linked to the pathogenesis of several serious degenerative ocular diseases. Long-term overactivation of the NMDA receptor by glutamate in retinal ganglion cells (RGCs) results in degeneration, apoptosis and loss of function leading to blindness. NMDA receptor antagonists have been proposed as a pharmacological blockage of glutamate excitotoxicity. However, an inhibition of the pathway activated by glutamate receptors has intolerable side effects. An interesting pharmacological alternative would be the use of antiapoptotic compounds as RGCs' neuroprotective active substances. Several mechanisms have been proposed to explain neuroprotection, including anti-inflammatory and scavenging activities. Here, the role of dexamethasone in neuroprotection was studied. For this purpose, original controlled release systems composed of microparticles containing dexamethasone with or without vitamin E and human serum albumin (HSA) were designed. The particles were prepared by the solid-in-oil-in-water (S/O/W) emulsion-evaporation technique. After properly characterization of the particles, they were intravitreally injected into an rat model of acute ocular excitotoxicity injury. The functionality of the retina was determined by electroretinography and RGCs were counted after cell immunohistochemistry. These microparticulate systems showed the ability to maintain normal electroretinal activity and promoted significant protection of RGCs. Through this proof of concept, we demonstrated that dexamethasone could be a useful anti-inflammatory agent to avoid the progression of degenerative ocular diseases. Furthermore, when administered in controlled release systems that provide low concentrations during prolonged periods of time, not only can the patient's comfort be increased but the cytotoxicity of the drugs can also be avoided.

The effect of dapagliflozin on anemia in elderly patients with heart failure by bioinformatics analysis.

Anemia associated with heart failure is frequent and can exacerbate the symptoms of heart failure. Dapagliflozin is the first SGLT-2 inhibitor with significant cardiovascular protection. However, the effect of dapagliflozin on anemia in elderly patients with heart failure is unknown. We aimed to study the effect of dapagliflozin on anemia in elderly patients with heart failure by bioinformatics analysis. The target genes were determined, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network and modules were constructed. The dapagliflozin-targets network in anemia and heart failure was constructed. Molecular docking experiments between dapagliflozin and its key target AKT1 were performed. We found 1 dapagliflozin related target gene and 2 disease related genes. Totally, 134 target genes of dapagliflozin on anemia in elderly patients with heart failure were determined. The pathways may involve lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, hepatitis B, insulin signaling pathway, fluid shear stress and atherosclerosis, neurotrophin signaling pathway, insulin resistance, toxoplasmosis, colorectal cancer, and EGFR tyrosine kinase inhibitor resistance. The hub genes in network were AKT1, TP53, GAPDH, TNF, CASP3, EGFR, and MAPK3. The structure of dapagliflozin and AKT1 molecular docking was exhibited. The hub genes in network were AKT1, TP53, GAPDH, TNF, CASP3, EGFR, and MAPK3. The structure of dapagliflozin and AKT1 molecular docking was exhibited.

CheV enhances the virulence of Salmonella Enteritidis, and the Chev-deleted Salmonella vaccine provides immunity in mice

BackgroundSalmonella enteritidis (SE) is a major zoonotic pathogen and causes infections in a variety of hosts. The development of novel vaccines for SE is necessary to eradicate this pathogen. Genetically engineered attenuated live vaccines are more immunogenic and safer. Thus, to develop a live attenuated Salmonella vaccine, we constructed a cheV gene deletion strain of SE (named ΔcheV) and investigated the role of cheV in the virulence of SE. First, the ability to resist environmental stress in vitro, biofilm formation capacity, drug resistance and motility of ΔcheV were analyzed. Secondly, the bacterial adhesion, invasion, intracellular survival assays were performed by cell model. Using a mouse infection model, an in vivo virulence assessment was conducted. To further evaluate the mechanisms implicated by the reduced virulence, qPCR analysis was utilized to examine the expression of the strain’s major virulence genes. Finally, the immune protection rate of ΔcheV was evaluated using a mouse model.ResultsCompared to C50336, the ΔcheV had significantly reduced survival ability under acidic, alkaline and thermal stress conditions, but there was no significant difference in survival under oxidative stress conditions. There was also no significant change in biofilm formation ability, drug resistance and motility. It was found that the adhesion ability of ΔcheV to Caco-2 cells remained unchanged, but the invasion ability and survival rate in RAW264.7 cells were significantly reduced. The challenge assay results showed that the LD50 values of C50336 and ΔcheV were 6.3 × 105 CFU and 1.25 × 107 CFU, respectively. After the deletion of the cheV gene, the expression levels of fimD, flgG, csgA, csgD, hflK, lrp, sipA, sipB, pipB, invH, mgtC, sodC, rfbH, xthA and mrr1 genes were significantly reduced. The live attenuated ΔcheV provided 100% protection in mice against SE infection.ConclusionAll the results confirmed that the deletion of the cheV gene reduces the virulence of SE and provides significant immune protection in mice, indicating that ΔcheV could be potential candidates to be explored as live-attenuated vaccines.

Analysis of polyphenols, anthocyanins and toxic elements in Açaí Juice (Euterpe oleracea Mart.): Quantification and in vivo assessment of the antioxidant capacity of clarified Açaí juice

This study aims to measure the concentration of total polyphenols, anthocyanins and inorganic contaminants (Al, Pb and Ni) in samples of açaí juice collected in the municipalities of Pará and evaluate the in vivo antioxidant capacity of purified açaí juice. Total polyphenols and anthocyanins were determined by UV/Vis spectrophotometry, while inorganic contaminants were measured using Graphite Furnace Atomization Atomic Absorption Spectrometry (GF-AAS) and Flame Atomic Absorption Spectrometry (F-AAS) after microwave-assisted digestion. The in vivo study lasted five days and involved 16 rats divided into four groups. The antioxidant capacity was evaluated through the formation of peroxyl free radicals (ACAP) in rat liver tissue. The average concentrations (mg GAE/DE) of total phenolic compounds averaged 27.34, with individual values ranging from 13.28 to 56.58. The average concentration (mg ANTO/g) of anthocyanins was 7.6, with individual concentrations ranging from 5.52 to 9.75. Contaminant concentrations (mg/kg) ranged from 1.82 to 11.74 for Al, 0.04 to 0.53 for Pb and 0.18 to 0.78 for Ni. The levels of Pb found in the samples may represent a concern to health. Al and Pb induced oxidative stress in the liver tissue, but Euterpe oleracea clarified juice (EOCJ) led to significant antioxidant protection. Animals treated with the highest dose of EOCJ (2.07 g/kg body weight) experienced an approximately five-fold reduction in ACAP compared to the group exposed to the metals (Al and Pb). The findings suggest the need to monitor inorganic contaminants in açaí products as well as the potential benefits of antioxidant compounds against the liver toxicity of Al and Pb.

Using L. minor and C. elegans to assess the ecotoxicity of real-life contaminated soil samples and their remediation by clay- and carbon-based sorbents

Toxic substances, such as polycyclic aromatic hydrocarbons (PAHs) and heavy metals, can accumulate in soil, posing a risk to human health and the environment. To reduce the risk of exposure, rapid identification and remediation of potentially hazardous soils is necessary. Adsorption of contaminants by activated carbons and clay materials is commonly utilized to decrease the bioavailability of chemicals in soil and environmental toxicity in vitro, and this study aims to determine their efficacy in real-life soil samples. Two ecotoxicological models (Lemna minor and Caenorhabditis elegans) were used to test residential soil samples, known to contain an average of 5.3, 262, and 9.6 ppm of PAHs, lead, and mercury, for potential toxicity. Toxicity testing of these soils indicated that 86% and 58% of soils caused ≤50% inhibition of growth and survival of L. minor and C. elegans, respectively. Importantly, 3 soil samples caused ≥90% inhibition of growth in both models, and the toxicity was positively correlated with levels of heavy metals. These toxic soil samples were prioritized for remediation using activated carbon and SM-Tyrosine sorbents, which have been shown to immobilize PAHs and heavy metals, respectively. The inclusion of low levels of SM-Tyrosine protected the growth and survival of L. minor and C. elegans by 83% and 78%, respectively from the polluted soil samples while activated carbon offered no significant protection. These results also indicated that heavy metals were the driver of toxicity in the samples. Results from this study demonstrate that adsorption technologies are effective strategies for remediating complex, real-life soil samples contaminated with hazardous pollutants and protecting natural soil and groundwater resources and habitats. The results highlight the applicability of these ecotoxicological models as rapid screening tools for monitoring soil quality and verifying the efficacy of remediation practices.

Potent, selective and reversible hMAO-B inhibition by benzalphthalides: Synthesis, enzymatic and cellular evaluations and virtual docking and predictive studies

Monoaminooxidases (MAOs) are important targets for drugs used in the treatment of neurological and psychiatric disorders and particularly on Parkinson's Disease (PD). Compounds containing a trans-stilbenoid skeleton have demonstrated good selective and reversible MAO-B inhibition. Here, twenty-two (Z)-3-benzylidenephthalides (benzalphthalides, BPHs) displaying a trans-stilbenoid skeleton have been synthesised and evaluated as inhibitors of the MAO-A and MAO-B isoforms. Some BPHs have selectively inhibited MAO-B, with IC50 values ranging from sub-nM to μM. The most potent compound with IC50 = 0.6 nM was the 3′,4′-dichloro-BPH 16, which showed highly selective and reversible MAO-B inhibitory activity. Furthermore, the most selective BPHs displayed a significant protection against the apoptosis, and mitochondrial toxic effects induced by 6-hydroxydopamine (6OHDA) on SH-SY5Y cells, used as a cellular model of PD. The results of virtual binding studies on the most potent compounds docked in MAO-B and MAO-A were in agreement with the potencies and selectivity indexes found experimentally. Additionally, related to toxicity risks, drug-likeness and ADME properties, the predictions found for the most relevant BPHs in this research were within those ranges established for drug candidates.

MRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea.

Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8*) or expressed P2-VP8* as a fusion protein with lumazine synthase (LS-P2-VP8*) to allow the formation and secretion of protein particles that present VP8* on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8*-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8*-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8*-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8* compared to the P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines.

Elevated Serum Levels of SARS-CoV-2 Anti-Spike S1 RBD IgM, IgG, and IgA in Pfizer-BioNTech Vaccinated, COVID-19 Infected, and COVID-19 Infected after Pfizer-BioNTech Vaccinated Individuals after One Month

Background: While protective immunity against some viruses, such as coronaviruses, is relatively short-lived, healing from acute infections of many different viruses, such as those caused by yellow fever, polio, measles, and smallpox, can give cell-mediated and humoral immunity for a lifetime. The main element in the long-term prevention of reinfection by most viruses might be due to the specific antibodies generated by plasma cells. Aim: This study aims to estimate the levels of SARS-CoV-2 Anti-Spike S1 RBD IgM, IgA, and IgG in serum among people in Baghdad after one month of receiving the Pfizer-BioNTech vaccine, infected with the SARS-CoV-2 virus after vaccination and COVID-19 infected patients respectively. Methods: A total of 120 volunteers were enrolled in this study, which was conducted between the 1st of November 2022 and the 13th of January 2023, and they were divided into four groups, each group containing 30 individuals. The study groups were categorized after one month into vaccinated with the Pfizer-BioNTech vaccine (BNT162b2), infected with SARS-CoV-2 after Pfizer vaccination, COVID-19 patients, and control. Results: The study presented a significant difference where (P value &lt; 0.05) in the serum levels of Anti-Spike S1 RBD IgM, IgA, and IgG for all groups compared to the control. Serum levels of S1 RBD IgM Anti-Spike of SARS-CoV-2 in all groups were significantly increased (P value &gt;0.05) compared to each other. For Anti-Spike S1 RBD IgA and IgG, there was no significant difference (P value &gt;0.05) between the COVID-19-infected patients group and those infected by SARS-CoV-2 after the Pfizer vaccination group. Positive correlations were found among Anti-Spike S1 RBD IgM, IgA, and IgG levels in the serum. Conclusions: Natural infection by SARS-CoV-2 or vaccination with Pfizer-BioNTech (BNT162b2) provides significant humoral Immunological protection.

Ziziphus rugosa Leaf: Pharmacognostical Characters and Anti-Inflammatory Properties against Carrageenan-Induced Paw Edema

Ziziphus rugosa belongs to the family Rhamnaceae, which includes many flowering species, primarily trees and shrubs, and sometimes vines. This study aims to describe the pharmacognostic characteristics and potential anti-inflammatory properties of Z. rugosa leaf. The pharmacognostical and preliminary phytochemical studies were performed following standard procedures. Acetone, ethanol, and aqueous extracts were screened for anti-inflammatory potential using the carrageenan-induced paw edema model. Ziziphus rugosa was identified by its evergreen nature, recurved hooks, and drupe-type fruits. Leaves are elliptic/rounded with cordate base exhibiting a dark green glossy upper surface and pubescent lower surface. The leaf exhibited a dorsiventral nature in the transverse section, covering trichomes, collenchyma, sclerenchyma patch, and calcium oxalate crystals as key histological characters. Anamocytic stomata, covering trichomes, crystals, and fragments of vessels, are the imperative elements in powder. The extracts contain carbohydrates, alkaloids, glycosides, tannins, saponins, phenolic compounds, proteins, and flavonoids. The acetone extract at 400 and 200 mg/kg displays a maximum inflammation inhibition of 56.96% and 48.77% among the extracts, and the standard diclofenac sodium inhibits inflammation by 65.61% at 24 hours. The altered liver superoxide dismutase, glutathione, and malondialdehyde levels in the positive control group are significantly near normal in the treatment groups. The histopathological studies of treated animals show significant protection against paw and liver tissue damage. Pharmacognostical study outcomes aid in the identification of species along with ascertaining standardization parameters. Further fractionation of acetone extract followed by isolating compounds responsible for the anti-inflammatory activity would provide an alternative to managing inflammation.

Pertussis Vaccines Scarcely Provide Protection against Bordetella parapertussis Infection in Children-A Systematic Review and Meta-Analysis.

Pertussis, or whooping cough, is a global public health concern. Pertussis vaccines have demonstrated good protection against Bordetella pertussis infections, but their effectiveness against Bordetella parapertussis remains debated due to conflicting study outcomes. A systematic review and meta-analysis were conducted to assess the effectiveness of pertussis vaccines in protecting children against B. parapertussis infection. A comprehensive search of PubMed, Web of Science, and Scopus databases was conducted, and randomized controlled trials (RCTs) and observational studies that met inclusion criteria were included in the analysis. The meta-analysis, involving 46,533 participants, revealed no significant protective effect of pertussis vaccination against B. parapertussis infection (risk ratio: 1.10, 95% confidence interval: 0.83 to 1.44). Subgroup analyses by vaccine type and study design revealed no significant protection. The dearth of recent data and a limited pool of eligible studies, particularly RCTs, underscore a critical gap that warrants future research in the domain. These findings offer crucial insights into the lack of effectiveness of pertussis vaccines against B. parapertussis. Given the rising incidence of cases and outbreaks, coupled with the lack of cross-protection by the existing vaccines, there is an urgent need to develop vaccines that include specific antigens to protect against B. parapertussis.

Protective effects of Helicteres isora L. fruit extract on phenylhydrazine-induced hemolytic anemia in rats

BackgroundAnemia is a serious global public health problem that affects young children and pregnant women with an increased risk of maternal and child mortality. Helicteres isora L. (Family: Malvaceae) has significant antioxidant properties responsible for its medicinal properties. The present study was conducted to investigate the protective effects of aqueous fruit extract of Helicteres isora L. (AEHI) on phenylhydrazine-induced hemolytic anemia in rats. MethodsThe fruits of Helicteres isora L. (H. isora L.) were extracted with distilled water to obtain the AEHI. The AEHI was subjected to preliminary phytochemical analysis, iron estimation and in-vitro antioxidant assay. The HPTLC fingerprinting followed by HR-LCMS analysis of the isolated HPTLC fraction of AEHI was carried out to investigate the phytoconstitutents. Male Wistar albino rats were administered phenylhydrazine (40 mg/kg, i.p.) for two consecutive days to induce anemia. The effects of AEHI were investigated at three oral doses viz. 250, 500 and 750 mg/kg once daily for 13 days by estimating blood parameters and pathological changes in the liver, heart, spleen, kidney, lungs and bone marrow. ResultsThe phytochemical analysis showed the presence of alkaloids, tannins, phenolic compounds, carbohydrates and steroids in the AEHI. The iron content of AEHI was found to be 208 µg/ml. In-vitro antioxidant assays, the IC50 value of AEHI was found to be 90.01 µg/ml. Phenylhydrazine administration caused a significant decrease in red blood cells, hemoglobin, and hematocrit levels. These decreased levels were significantly improved by AEHI in a dose-dependent manner. Pathological changes in the liver, heart, spleen, kidney, lungs and bone marrow were prevented by AEHI treatment. ConclusionIt is concluded that the AEHI provides significant protection against phenylhydrazine-induced hemolytic anemia.

Protection of prior SARS-CoV-2 infection, COVID-19 boosters, and hybrid immunity against Omicron severe illness: A population-based cohort study of five million residents in Canada.

Evidence on protection of different patterns of infection- and vaccine-acquired immunity against Omicron-associated severe illness is useful in planning booster vaccination strategies. We examined protection of prior SARS-CoV-2 infection, a third or a fourth COVID-19 vaccine dose, and hybrid immunity against Omicron-associated severe illness. This population-based cohort study followed five million individuals with at least one SARS-CoV-2 RT-PCR test before November 21, 2021 until an Omicron-associatedhospitalization or death. We used Cox regression models to estimate risks of Omicron-associated hospitalization and a composite severe outcome (hospitalized and death), among individuals with infection- and/or vaccination-acquired immunity. Individuals who were unvaccinated and had no history of a prior infection severed as the reference group. Both adjusted hazard ratios (HR) and corresponding protection (one minus adjusted HR), with 95% confidence intervals (CIs), were reported. Three doses provided 94% (95%CI 93-95) and 93% (95%CI 91-94) protection against Omicron-associated hospitalization at 2-3 and ≥3 months post-vaccination respectively, similar to the protection conferred by three doses and a prior infection (2-3 months: 99%, 95%CI 97-100; ≥3 months: 97%, 95%CI 92-99) and four doses (1 month: 87%, 95%CI 79-92; 1-2 months: 96%, 95%CI 92-98). In individuals ≥65 years old, protection of four doses increased to 95% (95%CI 91-98) at 1-2 months, significantly higher than that of three doses over the follow-up period. Similar results were observed with the composite severe outcome. At least three antigenic exposures, achieved by vaccination or infection, confers significant protection against Omicron-associated hospitalization and death in all age groups. Our findings support a third dose for the overall population, regardless of prior infection status, and a fourth dose for the elderly to maintain high level of immunity and substantially reduce risk of severe illness at individual level.

Netrin1-carrying magnetic microspheres with magnetic field activate neurotrophin factors to guide neuronal outgrowth in vitro and in vivo

Nerve injuries often result in the failure of functional synapses connections, primarily due to the absence of neurotrophic factors and guidance at the injury sites. In response to this challenge, an effective approach involving magnetic microspheres carrying axonal guidance cue (Netrin1) was presented. These microspheres were prepared using Fe3O4 and PLGA via electrospray. Netrin1 was incorporated into structural particles that could be oriented in a magnetic field and released at the injury sites. In this study, oriented and longer axons were observed in the cortical neurons after 10 μg/mL magnetic microspheres (MMSs) treatment. Under an applied magnetic field of 5 mT, Netrin1-carrying magnetic microspheres (N@MMSs) demonstrated a more significant increase in cell viability, mitochondrial membrane potential, mRNA expressions of BDNF and NGF compared to MMSs. These findings were assessed using the cell counting kit-8, tetramethyl rhodamine fluorescence, and real time PCR assay, respectively. Furthermore, N@MMSs demonstrated significant protection against glutamate-induced neuronal oxidative toxicity, as evaluated by mitochondrial respiratory function and glycolysis stress using the Seahorse Extracellular Flux analyzer. Subsequently, N@MMSs and a magnetic field were applied to adult mice after sciatic nerve injury. Behavior analysiss, including the open field test, indicated that N@MMSs typically increased motor activity under the magnetic field and significantly decreased paw licking latency on the 14th day. Finally, both BDNF and NGF expressions increased compared to the injury group. In conclusion, N@MMSs show promise as alternative particles for nerve regeneration.

Technical note: A method for calculating offsets to ozone depletion and climate impacts of ozone-depleting substances

Abstract. By phasing out production and consumption of most ozone-depleting substances (ODSs), the Montreal Protocol on Substances that Deplete the Ozone Layer (Montreal Protocol) has avoided consequences of increased ultraviolet (UV) radiation and will restore stratospheric ozone to pre-1980 conditions by mid-century, assuming compliance with the phaseout. However, several studies have documented an unexpected increase in emissions and suggested unreported production of trichlorofluoromethane (CFC-11) and potentially other ODSs after 2012 despite production phaseouts under the Montreal Protocol. Furthermore, because most ODSs are powerful greenhouse gases (GHGs), there are significant climate protection benefits in collecting and destroying the substantial quantities of historically allowed production of chemicals under the Montreal Protocol that are contained in existing equipment and products and referred to as ODS “banks”. This technical note presents a framework for considering offsets to ozone depletion, climate forcing, and other environmental impacts arising from occurrences of unexpected emissions and unreported production of Montreal Protocol controlled substances, as recently experienced and likely to be experienced again. We also show how this methodology could be applied to the destruction of banks of controlled ODSs and GHGs or to halon or other production allowed under a Montreal Protocol Essential Use Exemption or Critical Use Exemption. Further, we roughly estimate the magnitude of offset each type of action could provide for ozone depletion, climate, and other environmental impacts that Montreal Protocol Parties agree warrant remedial action.