Ameliorative potential of eriocitrin against cadmium instigated hepatotoxicity in rats via regulating Nrf2/keap1 pathway.

BACKGROUND: Cadmium (Cd) is a hazardous heavy metal that adversely affects the vital body organs particularly liver. Eriocitrin (ERCN) is a plant-based flavonoid that is well-known for its wide range of pharmacological potential. This research trial was aimed to determine the ameliorative potential of ERCN against Cd provoked hepatotoxicity in rats. METHODOLOGY: Twenty-four rats (Rattus norvegicus) were apportioned into control, Cd treated (5 mg/kg), Cd (5 mg/kg) + ERCN (25 mg/kg) and only ERCN (25 mg/kg) administrated group. Expressions of Nrf2/Keap1 pathway and apoptotic markers were assessed through qRT-PCR. The levels of inflammatory and liver function markers were evaluated by using standard ELISA kits. KEY FINDINGS: Cd exposure reduced the expression of Nrf2 and anti-oxidant genes as well as the activity of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione (GSH) contents while escalating the expression of Keap1. Furthermore, Cd intoxication augmented malondialdehyde (MDA) and reactive oxygen species (ROS) levels in hepatic tissues. Exposure to Cd resulted in a notable elevation in the levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST). Cd administration upregulated nuclear factor-kappa B (NF-κB), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels as well as cyclooxygenase-2 (COX-2) activity. Furthermore, Cd administration upsurged Bax and Caspase-3 expression while reducing the expression of Bcl-2. Moreover, Cd intoxication disrupted the normal architecture of hepatic tissues. However, supplementation of ERCN significantly (p < 0.05) ameliorated the aforementioned disruptions induced by Cd intoxication. CONCLUSION: ERCN treatment remarkably ameliorated the hepatic tissues owing to its antioxidant, anti-inflammatory, and anti-apoptotic potentials. These findings underscore the therapeutic potential of ERCN to counteract the adverse effects of environmental pollutants on hepatic tissues.

Isolation and characterization of novel cadmium-resistant Escherichia fergusonii ZSF-15 from industrial effluent for flocculant production and antioxidant enzyme activity.

Cadmium (Cd) is a highly toxic metal that frequently contaminates our environment. In this study, the bioflocculant-producing, cadmium-resistant Escherichia fergusonii ZSF-15 was characterized from Paharang drain, Bawa Chak, Faisalabad, Pakistan. The Cd-resistant E. fergusonii was used to determine the bioflocculant production using yeast-peptone-glycerol medium (pH 6.5) supplemented with 50 mg L-1 of Cd. The culture was incubated for 3 days at 37 °C in a rotary shaker at 120 rpm. The fermentation broth was centrifuged at 4000 g for 10 min after the incubation period. The maximum flocculating activity by isolate ZSF-15 was found to be 71.4% after 48 h of incubation. According to the Fourier transform infrared spectroscopy analysis, the bioflocculant produced by strain ZSF-15 was comprised of typical polysaccharide and protein, i.e. hydroxyl, carboxyl, and amino groups. The strain ZSF-15 exhibited bioflocculant activity at range of pH (6-8) and temperature (35-50℃). Maximum flocculation activity (i.e. 71%) was observed at 47℃, whereas 63% flocculation production was observed at pH 8. In the present study, antioxidant enzyme profile of ZSF-15 was also evaluated under cadmium stress. A significant increase in antioxidant enzymes including superoxide dismutase (118%) and ascorbate peroxidase (28%) was observed, whereas contents of catalase (86%), glutathione transferase (13%), and peroxidase (8%) were decreased as compared to control.

Molecular detection of bacterial zoonotic abortive agents from ruminants in Turkey.

Abortions in cattle and sheep are one of the major causes of economic losses worldwide. Brucella spp. are the most common infectious agent associated with these abortions. However, abortions caused by bacteria such as Listeria spp., Leptospira spp., Campylobacter spp. and Mycoplasma spp. are usually overlooked due to their sporadic nature and their status as non-priority abortion agents. In our study, we investigated the bacteria associated with abortion cases in cattle and sheep using PCR. For this purpose, we collected vaginal swab samples (n: 110) of aborted cattle and sheep, as well as stomach content samples (n: 69) of aborted calves and lambs from various cities in Turkey. The samples were analysed by bacteria-specific PCR to detect Campylobacter fetus, Leptospira spp., Listeria spp., Mycoplasma spp., and Yersinia spp. PCR analyses revealed that the investigated bacterial agents were present in 18.85% and 19.3% of the cattle and sheep samples, respectively, with an overall percentage of 18.99%. While the overall positivity rate for C. fetus, Leptospira spp., and Mycoplasma spp. was 2.79%, 10.06%, and 4.47%, respectively, the positivity rate for co-infection with Leptospira spp. and C. fetus was 1.68%. All samples were found to be negative for Yersinia spp. and Listeria spp. The high C. fetus positivity rate detected in sheep and in the stomach contents was statistically significant (p < 0.05). However, the difference in positivity rates between the cities, hosts, co-infections and causative agents was statistically insignificant (p > 0.05). This study provides preliminary data on the significant involvement of C. fetus, Leptospira spp. and Mycoplasma spp. in cattle and sheep abortions in Turkey indicating that they should not be overlooked in diagnosis. In addition, further research is needed to investigate the zoonotic potential of these pathogens for public health in Turkey.

In-silico analysis of potential anticancer drug for NEK7 and PPP1CA proteins overexpressed in pancreatic ductal adenocarcinoma.

NIMA-related kinase 7 (NEK7) and phosphoprotein phosphatase-1 catalytic subunit alpha (PPP1CA) are the most common proteins overexpressed in pancreatic ductal adenocarcinoma, which is the most common type of pancreatic cancer. The goal of the current study was to identify a possible NEK7 and PPP1CA therapeutic inhibitor. For this investigation, 5000 compounds were retrieved from the IMPPAT library of phytochemicals, which were docked with our respective target proteins. Also, a reference compound, gemcitabine, which is a Food and Drug Administration (FDA) approved drug, was docked with the target proteins. The binding energy of the reference compound for both the targeted proteins was -6.5 kcal/mol. The common ligand with the lowest binding energy for both targets is boeravinone B (PubChem ID: 14018348) with -9.2 kcal/mol of NEK7 and -7.6 kcal/mol for PPP1CA. The compound was further investigated through density function theory (DFT) and molecular dynamic simulation analysis. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding analysis indicated the stability of the boeravinone B with the target proteins (NEK7 and PPP1CA).Communicated by Ramaswamy H. Sarma.

Characterization and in-vitro plant-based control of hindgut bacteria isolated from Odontotermes obesus Rambur (Termitidae) and Heterotermes indicola Wasmann (Rhinotermitidae).

Termites cause a serious menace to wooden structures all over the world. They rely mostly on entozoic fauna residing in their hindgut for the digestion of cellulosic and hemicellulosic materials. One of the ways to control termites is through their gut symbionts. The present study was designed to characterize the hindgut bacteria isolated from Odontotermes obesus and Heterotermes indicola. Furthermore, the growth inhibitory effect of eight tropical plant extracts was investigated to find out potential control agents for these bacterial isolates. The characterization of bacteria was carried out based on their morphology, Gram staining, biochemical and amplification of 16SrRNA gene. Amplified products were sequenced to confirm their relationship with bacterial isolates from termites of other regions. The growth inhibitory effect of ethanolic leaf extracts of eight plants was evaluated in an invitro agar well diffusion method. Qualitative and quantitative phytochemical analysis of the most effective plant was carried out to learn about bioactive agents. The results confirmed the presence of five bacteria from each termite species. The Bacillus cereus, Escherichia coli, and Lysinibacillus fusiformis were common to both termites whereas Lysinibacillus xylanilyticus and Lysinibacillus macrolides were found in O. obesus only and H. indicola harbor Bacillus subtilis and Shigella sonnei in addition to common three ones. Among the plant extracts of Carica papaya, Eucalyptus camaldulensis, Osmium basilicum, Grevillea robusta, Eucalyptus globulus, Pongamia pinnata, Mentha longifolia, and Melia azedarach, the G. robusta > E. camaldulensis > O. basilicum were found to have growth inhibitory effects with increasing concentrations from 100 to 2000 µg/mL. The biodiversity of the bacterial fauna is important for the biological control of termites. Leaf extracts of these medicinal plants can be used to control termite infestation in an environment-friendly manner to save huge economic loss.

Evaluation of Kappa-carrageenan supplementation in extender for post-thaw Kajli ram sperm quality.

Cryopreservation is one of the reliable techniques for long-term storage of sperm. The success of this technique depends on the choice of cryoprotectant; therefore, a plethora of literature has reported the effects of different cryoprotective agents so far. Kappa-carrageenan (κ-carrageenan) is a hydrocolloid polysaccharide extracted from red marine seaweed. Its unique property makes it a promising option as a non-colligative cryoprotectant. The current study aims to evaluate the cryoprotective effect of k-carrageenan along with glycerol on ram sperm quality both after equilibration and freezing. Nine Kajli rams were utilized in this experiment for semen collection through an artificial vagina maintained at 42°C. Qualified samples were diluted in tris egg yolk glycerol (TEYG) extender containing different concentrations of k-carrageenan as 0 mg/mL (control), 0.2, 0.5, 0.8 and 1 mg/mL. Post-thaw assessment was done at 37°C after 24 h of storage, which showed a significant improvement (p < .05) in sperm viability, motility, membrane and acrosome integrity in an extender containing k-carrageenan at a concentration of 0.5 mg/mL compared to control. It is concluded from the current study that the combination of glycerol and 0.5 mg/mL concentration of k-carrageenan improved the sperm post-thaw quality.

A review on toxicity of nanomaterials in agriculture: Current scenario and future prospects.

Phytonanotechnology plays a crucial part in the production of good quality and high-yield food. It can also alter the plant's production systems, hence permitting the efficient, controlled and stable release of agrochemicals such as fertilizers and pesticides. An advanced understanding of nanomaterials interaction with plant responses like localization and uptake, etc. could transfigure the production of crops with high disease resistance and efficient nutrients utilization. In agriculture, the use of nanomaterials has gained acceptance due to their wide-range applications. However, their toxicity and bioavailability are the major hurdles for their massive employment. Undoubtedly, nanoparticles positively influence seeds germination, growth and development, stress management and post-harvest handling of vegetables and fruits. These nanoparticles may also cause toxicity in plants through oxidative stress by generation of excessive reactive oxygen species thus affecting the cellular biomolecules and targeting different channels. Nanoparticles have shown to exert various effects on plants that are mainly affected by various attributes such as physicochemical features of nanomaterials, coating materials for nanoparticles, type of plant, growth stages and growth medium for plants. This article discusses the interaction, accretion and toxicity of nanomaterials in plants. The factors inducing nanotoxicity and the mechanisms followed by nanomaterials causing toxicity are also instructed. At the end, detoxification mechanism of plant is also presented.

Determination of heavy metals (Pb, Cr, As, Hg, and Cd) into the body organs of selected fish, water, sediment, and soil samples from Head Punjnad and Head Taunsa, Punjab, Pakistan.

The present study was conducted on Head Punjnad (HP) and Head Taunsa (HT) to evaluate the contamination of Pb, Cr, As, Hg, and Cd in water, soil, sediment, fish as a whole and fish organs. Fish, water, soil and sediment samples were collected from different sites of HT and HP on a monthly basis for 8 months. Heavy metals in water, soil, and sediment were determined by a polarized Zeeman atomic absorption spectrophotometer and in fish and fish organs by an atomic absorption spectrophotometer. Contamination of Cd, Hg, and As was significantly (P<0.05) higher in water of HP as compared to HT, while Cr showed a non-significant (P>0.05) difference at HP and HT. Pb was significantly (P<0.05) higher in water of HT as compared to HP. In the case of soil, Cd, Hg, and Pb were higher at HT as compared to HP, while As and Cr were significantly (P<0.05) higher at HP as compared to HT. In sediment, contamination of Cd, Hg, and As were significantly (P<0.05) higher at HP as compared to HT, while the Cr difference was non-significant (P>0.05) but Pb showed a significantly (P<0.05) higher value at HT than HP. Cd accumulation in different fish species was recorded as R. rita ˃O. niloticus ˃C. marulius ˃S. sarwari ˃C. idella ˃C. catla ˃N. notopterus ˃E. vacha ˃L. rohita ˃C. carpio, respectively. Hg as O. niloticus ˃S. sarwari ˃R. rita ˃C. marulius ˃C. catla ˃N. notopterus ˃E. vacha ˃L. rohita ˃C. carpio ˃C. idella, respectively. As as O. niloticus ˃R. rita ˃S. sarwari ˃C. marulius ˃C. catla ˃C. carpio ˃N. notopterus ˃C. idella ˃E. vacha ˃L. rohita, respectively. Cr accumulation recorded as L. rohita ˃C. idella ˃O. niloticus ˃C. marulius ˃E. vacha ˃R. rita ˃C. catla ˃C. carpio ˃S. sarwari ˃N. notopterus, respectively. Pb accumulation in different fish species was recorded as C. idella ˃C. carpio ˃N. notopterus ˃L. rohita ˃O. niloticus ˃C. marulius ˃R. rita ˃S. sarwari ˃E. vacha ˃C. catla, respectively. Cd accumulation in different organs was recorded as kidney ˃liver ˃gills ˃muscle ˃skin ˃scale. Hg accumulation in different organs was recorded as kidney ˃gills ˃liver ˃skin ˃muscle ˃scale. As accumulation in different organs was recorded as kidney ˃liver ˃gills ˃muscle ˃skin ˃scale. Cr accumulation in different organs was recorded as gills ˃ liver ˃skin ˃muscle ˃kidney ˃scale. Pb accumulation in different organs was recorded as gills˃ kidney˃ skin˃ liver˃ muscle˃ scale.

The role of bixin as antioxidant, anti-inflammatory, anticancer, and skin protecting natural product extracted from Bixa orellana L.

Since long, medicinal plants or herbs are being used in different traditional treatment systems as therapeutic agents to treat a variety of illnesses. Bixa orellana L., an medicinal plant (family: Bixaceae), is an Ayurvedic herb used to treat dyslipidemia, diarrhoea, and hepatitis since ancient times. B. orellana L., seeds contain an orange-red coloured component known as bixin (C25H30O4), which constitutes 80% of the extract.Chemically, bixin is a natural apocarotenoid, biosynthesized through the oxidative degradation of C40 carotenoids. Bixin helps to regulate the Nrf2/MyD88/TLR4 and TGF-1/PPAR-/Smad3 pathways, which further give it antifibrosis, antioxidant, and anti-inflammatory properties. This current review article presents a comprehensive review of bixin as an anti-inflammatory, antioxidant, anticancer,and skin protecting natural product. In addition, the biosynthesis and molecular target of bixin, along with bixin extraction techniques, are also presented.

Synthesis and characterization of peanut hull modified chitosan beads.

The incorporation of plant materials is an effective method to improve the stability of chitosan beads, as it further increases the adsorption of toxic dyes and metals from aqueous systems. In the present study, chitosan gels were impregnated with a novel type of powder as the groundnut hull powder in order to form composite beads by using a simple droplet-based microfluidic system. The beads were then characterised through various techniques such as SEM, TGA, FTIR, and XRD. Microscopic imaging revealed a change in the surface morphology of the composite beads, which became rough and wrinkled with more valley-like features and irregular cracks. FTIR data suggest that the impregnation of groundnut hull powder led to an increase in functional groups. The thermal analysis allowed for the assessment of composite bead hydration contents and indicated the presence of groundnut hull entrapped in the loaded beads, which was corroborated by vibrational spectroscopy. XRD analysis allows us to conclude that there is an involvement of groundnut hull in the chitosan gels, and the consequence of that is the formation of amorphous beads, which would make them suitable for the adsorption of toxic dyes and metals from water systems.

Comparative analysis of phyto-fabricated chitosan, copper oxide, and chitosan-based CuO nanoparticles: antibacterial potential against Acinetobacter baumannii isolates and anticancer activity against HepG2 cell lines.

The aim of this study was to provide a comparative analysis of chitosan (CH), copper oxide (CuO), and chitosan-based copper oxide (CH-CuO) nanoparticles for their application in the healthcare sector. The nanoparticles were synthesized by a green approach using the extract of Trianthema portulacastrum. The synthesized nanoparticles were characterized using different techniques, such as the synthesis of the particles, which was confirmed by UV-visible spectrometry that showed absorbance at 300 nm, 255 nm, and 275 nm for the CH, CuO, and CH-CuO nanoparticles, respectively. The spherical morphology of the nanoparticles and the presence of active functional groups was validated by SEM, TEM, and FTIR analysis. The crystalline nature of the particles was verified by XRD spectrum, and the average crystallite sizes of 33.54 nm, 20.13 nm, and 24.14 nm were obtained, respectively. The characterized nanoparticles were evaluated for their in vitro antibacterial and antibiofilm potential against Acinetobacter baumannii isolates, where potent activities were exhibited by the nanoparticles. The bioassay for antioxidant activity also confirmed DPPH scavenging activity for all the nanoparticles. This study also evaluated anticancer activities of the CH, CuO, and CH-CuO nanoparticles against HepG2 cell lines, where maximum inhibitions of 54, 75, and 84% were recorded, respectively. The anticancer activity was also confirmed by phase contrast microscopy, where the treated cells exhibited deformed morphologies. This study demonstrates the potential of the CH-CuO nanoparticle as an effective antibacterial agent, having with its antibiofilm activity, and in cancer treatment.

Pinostrobin alleviates testicular and spermatological damage induced by polystyrene microplastics in adult albino rats.

BACKGROUND: Polystyrene microplastics (PS-MPs) have become major environmental pollutants that adversely effects multiple organs specifically testicles. Pinostrobin (PN) is an important flavonoid which, shows several pharmacological potentials. PURPOSE: The current study was designed to elucidate the mitigative effects of PN against PS-MPs induced testicular toxicities in rats. METHODS: 48 male albino rats were randomly distributed into 4 groups, control, PS-MPs group (0.01 mg/kg), PS-MPs + PN group (0.01 mg/kg of PS-MPs; 40 mg/kg of PN) and PN group (40 mg/kg). RESULTS: PS-MPs intoxication substantially lessened the activities of glutathione peroxidase (GPx), glutathione reductase (GSR), superoxide dismutase (SOD) along with catalase (CAT) while, raised the level of malondialdehyde (MDA) as well as reactive oxygen species (ROS). Additionally, PS-MPs reduced luteinizing hormone (LH), plasma testosterone, follicle-stimulating hormone (FSH) concentration, sperm motility, sperm count, expression of steroidogenic enzymes and Bcl-2 (anti-apoptotic protein) along with the count of spermatogenic cells. While, dead sperm count, sperm abnormalities (tail, neck and head), Bax and caspase-3 (apoptotic proteins) expression along with histopathological anomalies were elevated. Moreover, PS-MPs exposure increased the level of inflammatory markers. However, PN treatment considerably decreased oxidative stress (OS) by reducing ROS as well as increased sperm motility and alleviated all the damages induced by the PS-MPs. CONCLUSION: Therefore, it is concluded that PN may prove a potential therapeutic candidate to restore all the PS-MPs-induced testicular toxicities.

A Comprehensive Review on Pharmacological Activities of Pachypodol: A Bioactive Compound of an Aromatic Medicinal Plant Pogostemon Cablin Benth.

As is well known, plant products have been increasingly utilized in the pharmaceutical industry in recent years. By combining conventional techniques and modern methodology, the future of phytomedicines appears promising. Pogostemon Cablin (patchouli) is an important herb used frequently in the fragrance industries and has various therapeutic benefits. Traditional medicine has long used the essential oil of patchouli (P. cablin) as a flavoring agent recognized by the FDA. This is a gold mine for battling pathogens in China and India. In recent years, this plant has seen a significant surge in use, and approximately 90% of the world's patchouli oil is produced by Indonesia. In traditional therapies, it is used for the treatment of colds, fever, vomiting, headaches, and stomachaches. Patchouli oil is used in curing many diseases and in aromatherapy to treat depression and stress, soothe nerves, regulate appetite, and enhance sexual attraction. More than 140 substances, including alcohols, terpenoids, flavonoids, organic acids, phytosterols, lignins, aldehydes, alkaloids, and glycosides, have been identified in P. cablin. Pachypodol (C18H16O7) is an important bioactive compound found in P. cablin. Pachypodol (C18H16O7) and many other biologically essential chemicals have been separated from the leaves of P. cablin and many other medicinally significant plants using repeated column chromatography on silica gel. Pachypodol's bioactive potential has been shown by a variety of assays and methodologies. It has been found to have a number of biological activities, including anti-inflammatory, antioxidant, anti-mutagenic, antimicrobial, antidepressant, anticancer, antiemetic, antiviral, and cytotoxic ones. The current study, which is based on the currently available scientific literature, intends to close the knowledge gap regarding the pharmacological effects of patchouli essential oil and pachypodol, a key bioactive molecule found in this plant.

A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in Mice.

The development of new vaccine adjuvants represents a key approach to improvingi the immune responses to recombinant vaccine antigens. Emulsion adjuvants, such as AS03 and MF59, in combination with influenza vaccines, have allowed antigen dose sparing, greater breadth of responses and fewer immunizations. It has been demonstrated previously that emulsion adjuvants can be prepared using a simple, low-shear process of self-emulsification (SE). The role of alpha tocopherol as an immune potentiator in emulsion adjuvants is clear from the success of AS03 in pandemic responses, both to influenza and COVID-19. Although it was a significant formulation challenge to include alpha tocopherol in an emulsion prepared by a low-shear process, the resultant self-emulsifying adjuvant system (SE-AS) showed a comparable effect to the established AS03 when used with a quadrivalent influenza vaccine (QIV). In this paper, we first optimized the SE-AS with alpha tocopherol to create SE-AS44, which allowed the emulsion to be sterile-filtered. Then, we compared the in vitro cell activation cytokine profile of SE-AS44 with the self-emulsifying adjuvant 160 (SEA160), a squalene-only adjuvant. In addition, we evaluated SE-AS44 and SEA160 competitively, in combination with a recombinant cytomegalovirus (CMV) pentamer antigen mouse.

Bringing an end to the silence: identifying priorities and solutions to addressing the mental health consequences of child marriage.

Despite its inclusion in Sustainable Development Goal 5 to end all harmful gendered practices by 2030, child, early and forced marriages continue to be a pervasive problem globally. While there is consistent evidence on the physical health consequences of child marriage, there is a lack of evidence and inquiry into the mental health consequence. We completed a change-oriented Delphi study to establish consensus on priority areas of research and intervention in relation to the mental health consequences of child, early and forced marriages. Invited experts (n = 11), survivors (n = 27) and professionals (n = 30) participated in our Delphi. Four rounds of data collection included: a blended in-person and online workshop with invited experts, an online mixed-methods questionnaire, focus groups in Zimbabwe with women who are survivors of child marriage and a repeat questionnaire sent to the first round of experts. Quantitative data were analysed using descriptive statistics and ranking methods, consistent with other Delphi studies. Qualitative data were analysed using thematic network analysis. Findings coalesced around three areas: perspectives on the relationship between mental health and child marriage, policy actions and treatment-driven solutions. Consensus was reached on 16 items across these areas which included the need to prioritize psychosocial and social interventions to improve mental health outcomes for women and girls in existing marriages. They also called for new approaches to advocacy to drive awareness of this issue in policy circles. Implications for future practice are discussed.

Tracking the footsteps of Francisella tularensis: Bacteriological and serological monitoring in epidemic areas in Ankara.

The study aimed to detect Francisella tularensis (F. tularensis) in water samples and to investigate the seroreactivity of sheep to tularemia in endemic areas where human tularemia cases have been reported in Ankara, Turkey. For the isolation of F. tularensis, 50 water samples were collected from rural areas of 5 regions of Ankara (Turkey) and selectively cultured on Francis medium supplemented with 8-9 % sheep blood and antibiotics (100 IU/ml penicillin G, 100 mg/L cycloheximide, 80,000 U/L polymixin B). No F. tularensis isolate was cultivated from the water samples. To determine the seroreactivity of sheep to tularemia, 1006 sheep blood samples were collected from the regions, where human tularemia is endemic. A microagglutination test (MAT) identified significant antibody titers, ranging from 1/20-1/640 in 181 (17.99 %) of the investigated sheep sera. Further investigation is required in order to evaluate and confirm a possible epidemiologic relationship between human outbreaks and probable role of sheep or other sources.

Nonclinical Safety Assessment of Lipid Nanoparticle-and Emulsion-Based Self-Amplifying mRNA Vaccines in Rats.

Vaccines containing mRNA with the capacity to self-amplify represent an alternative to the mRNA vaccines that came to prominence during the COVID-19 pandemic. To gain further insights on the safety profile of self-amplifying mRNA- (SAM-) vaccines, this preclinical toxicology study in rats evaluated the effect of (i) the type of delivery system (lipid nanoparticle [LNP] vs cationic nano-emulsion [CNE]); (ii) antigen-encoding sequence (rabies glycoprotein G vs SARS-CoV-2 Spike); and (iii) RNA amplification. Further analyses also evaluated gene expression in peripheral blood after vaccination, and the biodistribution of vaccine RNA. The SAM vaccines administered as two doses 2-weeks apart had acceptable safety profiles in rats, with respect to clinical signs, blood biochemistry, and macroscopic and microscopic pathology. A transient increase in ALT/AST ratio occurred only in female rats and in the absence of muscle and liver damage was dependent on RNA amplification and appeared related to the greater quantities of vaccine RNA in the muscle and livers of female rats vs male rats. The RNA and delivery-vehicle components, but not the nature of the antigen-coding sequence or the requirement for RNA amplification, affected aspects of the stimulation of innate-immune activity, which was consistent with the transient activation of type I and type II interferon signaling. The delivery vehicle, LNP, differed from CNE as vaccine RNA in CNE compositions appeared independently to stimulate innate-immune activity at 4 hours after vaccination. Our analysis supports further studies to assess whether these differences in innate-immune activity affect safety and efficacy of the SAM vaccine.

Fisetin Attenuates Arsenic-Induced Hepatic Damage by Improving Biochemical, Inflammatory, Apoptotic, and Histological Profile: In Vivo and In Silico Approach.

Arsenic (As) is a toxic metalloid and human carcinogen that may cause hepatotoxicity. Fisetin (3, 3', 4', 7-tetrahydroxyflavone) is a phytoflavonoid, which shows diverse therapeutic activities. This study aimed to examine the remedial potential of fisetin against As-instigated hepatotoxicity in adult male rats. To accomplish this aim, albino rats (N = 48) were evenly classified into 4 groups: control group, As (10 mg/kg) group, fisetin (2.5 mg/kg) + As (10 mg/kg) group, and fisetin (2.5 mg/kg) group. After one month of treatment, biochemical assay, total protein content (TPC), hepatic serum enzymes, inflammatory as well as pro- or anti-apoptotic markers, and histopathological profile of hepatic tissues were estimated. As administration disordered the biochemical profile by decreasing activities of antioxidant enzymes i.e., catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), and glutathione (GSH) content while escalating the levels of reactive oxygen species (ROS), and thiobarbituric acid reactive substances (TBARS). TPC was also considerably reduced after exposure to As. Furthermore, As markedly raised the levels of liver serum enzymes such as aspartate transaminase (AST), alkaline phosphatase (ALP), and alanine transaminase (ALT) as well as the levels of inflammatory markers, i.e., nuclear factor- κB (NF-κB), tumor necrosis- α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and cyclo-oxygenase-2 (COX-2) activity. Besides, it lowered the level of antiapoptotic markers (Bcl-2) and upregulated the levels of proapoptotic markers (Bax, Caspase-3, and Caspase-9). Additionally, As exposure led to histopathological damage in hepatic tissues. However, fisetin administration remarkably alleviated all the depicted hepatic damages. For further verification, the screening of several dock complexes was performed by using the GOLD 5.3.0 version. Based on docking fitness and GOLD score, the ranking order of receptor proteins with fisetin compound is superoxide dismutase, interleukin, aspartate aminotransferase, alkaline phosphatase, TNF-alpha, alanine transaminase, cyclo-oxygenase 2, antiapoptotic, and glutathione reductase. Out of these three receptor proteins superoxide dismutase, interleukin, and aspartate aminotransferase showed the best interaction with the fisetin compound. In vivo and in silico outcomes of the current study demonstrated that fisetin could potentially ameliorate As-instigated hepatotoxicity.

Ecofriendly phytosynthesized zirconium oxide nanoparticles as antibiofilm and quorum quenching agents against Acinetobacter baumannii.

The worldwide increase of multi-drug resistance has directed the researchers to focus on ecofriendly ways of nanoparticles synthesis with effective antivirulence properties. Here, we report the antibiofilm and quorum quenching (QQ) potential of zirconium oxide nanoparticles (ZrO2 NPs) synthesized from aqueous ginger extract against multi-drug resistant (MDR) Acinetobacter baumannii. The results indicated that ZrO2 NPs were of tetragonal shape with average diameter of 16 nm. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values for A. baumannii were 15.6 and 62.5 µg/ml, respectively, as revealed by broth microdilution assay. Exposure of bacterial cells to ZrO2 NPs resulted in reactive oxygen species (ROS) generation which in turn led to cellular membrane disruption as observed by an increase in leakage of cellular contents, such as proteins, sugars, and DNA. The antibiofilm activity was evaluated by microtiter plate assay and the results revealed that the percentage inhibition of biofilm was found to be 14.3-80.6%. ZrO2 NPs also obstructed the chemical composition of biofilms matrix by reducing the proteins and carbohydrate contents. Molecular docking studies of ZrO2 NPs with four proteins (2NAZ, 4HKG, 5D6H, and 5HM6) involved in biofilm formation of A. baumannii revealed the interaction of zirconium with target proteins. These findings suggested the in vitro efficacy of phytosynthesized ZrO2 NPs as antibiofilm and QQ agents that can be exploited in the development of alternative therapeutic options against MDR A. baumannii.

Effect of nucleated cell count and cryopreservation on engraftment post autologous stem cell transplant.

Using 753 collections from 426 adult haematology patients, we conducted a retrospective, analysis into the effects of overnight storage and nucleated cell counts (NCC) on viable, CD34+ (vCD34+) recovery and engraftment kinetics post autologous stem cell, transplant (ASCT) with peripheral blood stem cells (PBSC). There were significant, differences in vCD34 + recovery ( P < 0.01) after cryopreservation associated with, the fresh NCC of ≥ 300 × 10 6 /mL in products stored overnight, but no association, with time to platelet or neutrophil engraftment post-ASCT was observed for these, products. There was no association of vCD34+ numbers or engraftment kinetics with cryopreserved NCC with either below or greater than the local recommended concentration of 400 × 106 /mL of product. However, there was significant difference in engraftment kinetics in relation to the viable CD34+ dose given at ASCT, in relation to the time to early engraftment and the amount of platelet support given during the engraftment period post-ASCT. We conclude the vCD34+ dose at ASCT is of great importance to early engraftment kinetics and that NCC is an important factor during overnight storage, but not for cryopreservation of PBSC. In light of our findings, we recommend that apheresis products collected in a closed system can safely be stored undiluted overnight.