Water-treated Group Research Articles

<i>In Vivo</i> antiplasmodial and schizont inhibition activity of methanol stem bark extract of <i>Ficus vallis-choude</i>

Ficus vallis-choudae has been traditionally utilized for treating malaria, pain, jaundice, headaches, and convulsions. This study aimed to assess the antiplasmodial activity of the plant's methanol stem bark extract (FvMSE) both in vitro and in vivo. Preliminary phytochemical analysis was conducted, and the oral median lethal dose (LD50) was estimated following the OECD protocol. The in vitro antiplasmodial activity was evaluated using the schizont inhibition model as outlined by Trager and Jensen. For the in vivo assessment, mice infected with chloroquine-sensitive Plasmodium berghei were used in curative, suppressive, and prophylactic experimental models. Phytochemical screening identified the presence of saponins, flavonoids, tannins, alkaloids, terpenoids, steroids, and cardiac glycosides. The oral LD50 of FvMSE was found to be above 5000 mg/kg. The extract exhibited significant chemosuppressive activity (p<0.05) at doses of 1000, 500, and 250 mg/kg, reducing parasite density compared to the distilled water-treated group. In the prophylactic model, the extract significantly decreased (p<0.05) parasite counts in all treated groups compared to the distilled water-treated group, although its activity was lower than that of the standard drug pyrimethamine. The curative study results demonstrated that FvMSE significantly reduced (p<0.05) parasite densities compared to the distilled water-treated group. Additionally, FvMSE significantly (p<0.05) reduced the mean number of schizonts compared to the negative control, similar to the effects observed with standard drugs chloroquine and artesunate. These findings support the traditional use of Ficus vallis-choudae in treating malaria.

Network analysis of metabolomics, transcriptome and hormones reveals propionic acid-mediated novel survival strategy against drought in wheat.

Propionic acid (PA), a low-molecular-weight organic acid, is crucial to plant life metabolism. However, the regulatory mechanism of PA-mediated drought resistance in wheat remains largely unknown. Herein, we reported on a regulatory network of PA-mediated drought resistance in wheat using integrated transcriptome and metabolomics analysis and verified genes associated with drought resistance. Compared to the water-treated group, the application of PA alleviated the damage of drought by increasing plant water content, antioxidant enzyme activities and decreasing the malondialdehyde level (MDA). Transcriptome and metabolomics analysis revealed that PA triggered upregulation of key genes and metabolites, including TaBCAT, TaALDH6A1, TaALDH7A1, TaCHI, TaFLS, chrysin, and galangin, which were involved in valine, leucine and isoleucine degradation or flavonoid biosynthesis, respectively. In addition, the expression of genes encoding auxin-related transcription factors (TFs) strikingly increased, such as auxin/indoleacetic acid (AUX/IAA) and auxin response factor (ARF). Moreover, PA activated abscisic acid (ABA) and indole-3-acetic acid (IAA) signalling pathways. Taken together, our findings suggest that PA promotes energy metabolism and antioxidant activities to confer wheat drought resistance by introducing comprehensive and systemic effects of valine, leucine and isoleucine degradation flavonoid biosynthesis. Furthermore, activated AUX/IAA and ARF TFs might serve vital roles in drought resistance via modulating IAA signalling. This study provides novel insights into PA-mediated crop resistance and the improvement of the agroecological environment.

GhGASA14 regulates the flowering time of upland cotton in response to GA3.

The silencing of GhGASA14 and the identification of superior allelic variation in its coding region indicate that GhGASA14 may positively regulate flowering and the response to GA3. Gibberellic acid-stimulated Arabidopsis (GASA), a member of the gibberellin-regulated short amino acid family, has been extensively investigated in several plant species and found to be critical for plant growth and development. However, research on this topic in cotton has been limited. In this study, we identified 38 GhGASAs that were dispersed across 18 chromosomes in upland cotton, and all of these genes had a GASA core domain. Transcriptome expression patterns and qRT-PCR results revealed that GhGASA9 and GhGASA14 exhibited upregulated expression not only in the floral organs but also in the leaves of early-maturing cultivars. The two genes were functionally characterized by virus-induced gene silencing (VIGS), and the budding and flowering times after silencing the target genes were later than those of the control (TRV:00). Compared with that in the water-treated group (MOCK), the flowering period of the different fruiting branches in the GA3-treated group was more concentrated. Interestingly, allelic variation was detected in the coding sequence of GhGASA14 between early-maturing and late-maturing accessions, and the frequency of this favorable allele was greater in high-latitude cotton cultivars than in low-latitude ones. Additionally, a significant linear relationship was observed between the expression level of GhGASA14 and flowering time among the 12 upland cotton accessions. Taken together, these results indicated that GhGASA14 may positively regulate flowering time and respond to GA3. These findings could lead to the use of valuable genetic resources for breeding early-maturing cotton cultivars in the future.

A soy protein enzymatic digest mitigates Nrf2-related oxidative stress and attenuates depression-like behavior in a mouse model of sub-chronic restraint stress

Continuous oxidative stress conditions have been identified as a major cause of various neuropsychiatric disorders, including depression. The present study investigated the potential antidepressant-like effects of a soy protein enzymatic digest (SPD) containing soy-deprestatin, which is a soy-derived peptide with reported antidepressant-like effects, as well as its ability to mitigate oxidative stress in the brain caused by sub-chronic restraint stress. Mice were divided into two groups: a control group and restraint stress group. The restraint stress group was further divided into two groups administered water or SPD. After repeated short-time restraints over five days, we evaluated immobility times in the tail suspension test, and antioxidant enzyme activities, glutathione levels, oxidative stress maker levels, and the gene expression levels of Nrf2 and antioxidant enzymes in the brain. The results obtained showed that the oral administration of SPD reduced immobility times in mice exposed to restraint stress. In comparisons with the water-treated restraint group, the administration of SPD restored superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities and glutathione levels and prevented restraint stress-induced increases in malondialdehyde, carbonyl protein, and 8-OHdG levels in the restraint stress group. In addition, high expression levels of Nrf2, HO-1, NQO-1 and GCLC were observed in the SPD-treated restraint group. These results suggest that SPD attenuated repeated restraint stress-induced depression-like behaviors by mitigating oxidative stress through the activation of the Nrf2 signaling pathway.

Multiscale viscoelasticity response for bamboo after partial hemicellulose removal treatment

Hemicellulose degradation can decrease the hygroscopicity and result in an improvement of dimensional stability for nature materials. The mechanical properties has always been used as an indicator of hemicellulose degradation, but lack of an indicator that can be reflects the additive effects of treatment condition and the effects of time. This work aimed to use multiscale viscoelasticity response to evaluate the coupled effects of physical/chemical treatment and loading time. Different conditions (hot water, acidic and saturated steam) were tested on bamboo. Macroscopic creep of bamboo slices and microscopic creep behavior of cell wall were determined. The relationship between gradient structure and viscoelasticity has been obtained. The outer slice, i.e., bamboo green, had best strength and flexural toughness. Middle slice exhibits significant viscoelasticity response. Inner slice, also called bamboo yellow, exhibits little viscoelasticity response but bad strength. The relationship between treatment conditions and macroscopic/microscopic creep also has been obtained. At macro scale, the acid group exhibits significant viscoelasticity response, while the water group and steam group exhibit more elasticity response, especially for water groups. At micro scale, the steam-treated and acid-treated group are all showed significant viscoelasticity response, while the water-treated group had lowest relative creep. This paper could be a reasonable selection support of bamboo materials for stiffness or flexible products.

Investigation of In Vitro Effectiveness of Polymeric Nanoparticles Containing Clinoptilolit on Cryptosporidium Parvum

Cryptosporidium species, which do not have a definite prevention and treatment protocol, are pathogenic protozoans that cause diarrhoea in humans and many animal species. This study aimed to demonstrate the in vitro efficacy of clinoptilolite polymer nanoparticle, which has known antidiarrheal effects. DNA isolation was made for species identification of Cryptosporidium oocysts obtained from faeces samples from naturally infected calves and lambs. RFPL analysis was performed in typing. For this purpose, nested PCR and SrpI, VspI and MboII enzymes were used. The coverslip surface was covered with 80% CaCo-2 cells and infected with 1x109 C. parvum. Nanoparticles containing 250, 500, 750 and 1000 μg/mL clinoptilolite were applied to infected cells. Percent of infection rate was calculated by counting under a fluorescent microscope following incubation. While the infection rate was 23.46% in the water-treated control cell group, the percentage infection rates in the clinoptilolite-containing nanoparticle treated group were respectively 15.60%, 8.13%, 10.33% and 13.46%. Inhibition percentages were determined as 33.54%, 65.56%, 55.99% and 42.66%, respectively. As a result, it was observed that the nanoparticle containing clinoptilolite had anticriptocidal activity in infection with C. parvum in Caco-2 cells. In addition, it was observed that the efficacy was dose-dependent, and the IC50 value was the most appropriate value at 750 and 1000 μg/mL doses.

Effect of entomopathogenic fungus Beauveria bassiana on the growth characteristics and metabolism of black soldier fly larvae

Beauveria bassiana is an entomopathogenic fungus widely used in agriculture to reduce populations of various pests. However, when agricultural waste is utilized for organic recycling, B. bassiana has the potential to impact recycling performance, by affecting the survival, and body mass of decomposing organisms (such as insect's larvae). Additionally, in natural conditions where decayed organic matter contains a high load of different entomopathogenic organisms, larval growth may be affected when consumed or in contact. In a laboratory study, we aimed to comprehend the effects of B. bassiana on the growth characteristics and larval metabolism of the black soldier fly larvae, which is a known decomposing insect. The experiments used both feeding (mixing the spores with the diet, hereafter BF) and contact treatments (by dipping the larva in the spores solution, hereafter BD), and were compared to a water-treated control group. The BF treatment significantly reduced larval body weight, adult emergence, and adult weight compared to both the control and the BD treatment. Furthermore, an analysis of hemolymph metabolites, categorized by class, indicated a higher accumulation of metabolites belonging to the purine and purine derivative classes, as well as carboxylic acids and their derivatives, including peptides and oligopeptides, indicating potential disruption of protein synthesis or degradation caused by the BF treatment. Pathway enrichment analysis showed significant alterations in purine metabolism and D-Arginine and D-ornithine metabolism compared to the control. Taurine and hypotaurine metabolism were significantly altered in the BD treatment compared to the control but not significantly enriched in the BF treatment. Our results suggest that the BF treatment impairs protein synthesis or degradation, affecting larval growth characteristics. Future studies should explore innate immunity-related gene expression and antimicrobial peptide production in BSF larvae to understand their immunity to pathogens.

Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters.

The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat at 5 mg/kg twice daily was able to prevent the airborne transmission of SARS-CoV-2 from infected to uninfected Syrian Golden hamsters. SARS-CoV-2 RNA was detectable in the throat swabs of the water-treated control group 4 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, throat swabs from the intranasal nafamostat-treated hamsters remained SARS-CoV-2 RNA negative for the full 4 days of cohabitation. Significantly lower SARS-CoV-2 RNA concentrations were seen in the nasal turbinates of the nafamostat-treated group compared to the control (p = 0.001). A plaque assay quantified a significantly lower concentration of infectious SARS-CoV-2 in the lungs of the nafamostat-treated group compared to the control (p = 0.035). When taken collectively with the pathological changes observed in the lungs and nasal mucosa, these data are strongly supportive of the utility of intranasally delivered nafamostat for the prevention of SARS-CoV-2 infection.

Reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acid

Nimesulide (NIM) is a nonsteroid anti-inflammatory drug which acts as a selective cyclooxygenase 2 inhibitor and is widely used for acute pain treatment. In medical practice, a large amount of data has been collected describing the effect of NIM on the body, while a hepatotoxic side effect of the drug has been found. The exact mechanisms of such NIM-induced hepatotoxicity largely remain unknown but likely involve the intermediate reaction of its metabolism. Reduction of the hepatotoxic side effect of NIM is an actual problem for pharmacology. The aim of the present research was to evaluate the hepatotoxicity of the mechanochemically obtained composition of NIM with glycyrrhizic acid disodium salt (Na2GA) compared to pure NIM and a physical mixture of NIM with Na2GA. Material and methods. CD-1 mice were orally administered for 14 days: 1 group – mechanochemical composition NIM/Na2GA (1:10, m/m) at a dose of 1650 mg/kg; 2 group – physical mixture of NIM with Na2GA (1:10, m/m) at a dose of 1650 mg/kg; 3 group – pure NIM at a dose of 600 mg/kg (which pharmacokinetically corresponds to 1650 mg/kg of NIM/Na2GA); 4 group – vehicle (distilled water). The liver damage was assessed using histological studies and enzymatic activity of the alanine aminotransferase and aspartate aminotransferase in blood serum. Results. Histological analysis did not detect any changes in the liver of NIM/Na2GA-treated animals in comparison with a water-treated group. On the opposite, NIM given alone or as a physical mixture with Na2GA induced severe hepatotoxicity in experimental mice. Biochemical analysis of the blood serum revealed that mechanochemical NIM/Na2GA composition significantly reduced activity of the alanine aminotransferase (about 1.5 times) and aspartate aminotransferase (1.3 times) as compared with the pure NIM. Conclusions. The results obtained indicate a high potential for the practical application of the NIM/Na2GA mechanochemical composition.

Abrogation of Acute Inflammation in ICR Mice with Topical Administration of Philippine Stingless Bee (Tetragonula biroi Friese) Honey

Pharmacognosy Research,2023,15,2,258-266.DOI:10.5530/pres.15.2.028Published:February 2023Type:Original Article Authors:Mark Joseph Maranan Desamero, Mikaela Bernadette Andres Rabino, Maria Angelica Rimas Tayao, Mary Jasmin Cabillon Ang, Jussiaea Valente Bariuan, Roxanne Posilero Gapasin, Therese Marie Avena Collantes, Melissa Marie Risos Rondina, Cherry Pambid Fernandez-Colorado, Cleofas Rodriguez Cervancia, and Maria Amelita Celino Estacio Author(s) affiliations:Mark Joseph Maranan Desamero1,2,*, Mikaela Bernadette Andres Rabino1, Maria Angelica Rimas Tayao1, Mary Jasmin Cabillon Ang1, Jussiaea Valente Bariuan1,2, Roxanne Posilero Gapasin1,2, Therese Marie Avena Collantes3, Melissa Marie Risos Rondina4, Cherry Pambid Fernandez-Colorado3, Cleofas Rodriguez Cervancia2,5, Maria Amelita Celino Estacio1,2 1Department of Basic Veterinary Sciences, College of Veterinary Medicine, University of the Philippines Los Baños, Laguna, PHILIPPINES. 2UPLB Bee Program, University of the Philippines Los Baños, Laguna, PHILIPPINES. 3Department of Veterinary Paraclinical Sciences, College of Veterinary Medicine, University of the Philippines Los Baños, Laguna, PHILIPPINES. 4Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of the Philippines Los Baños, Laguna, PHILIPPINES. 5Institute of Biological Sciences, College of Arts and Sciences, University of the Philippines Los Baños, Laguna, PHILIPPINES Abstract:Background: Honey, a sweet sugar-rich bee-derived product, has been widely recognized in the realm of Ayurveda and Pharmacognosy for the treatment of various inflammatory conditions including inflammatory bowel disease, asthma, arthritis, and gastric ulcer. However, the anti-inflammatory effect of Philippine honey obtained from local stingless bees remains unexplored and poorly investigated. Hence, this study delved on the anti-inflammatory potential of topically applied Philippine stingless bee honey (PSH) using the λ-Carrageenan-induced mouse model of paw edema. Materials and Methods: A total of 30, male ICR mice of six weeks of age were randomly divided into the following groups (n=10 per group) as follows: Distilled water-, 1% Diclofenac sodium-, and Honey-treated group. All treatments were administered immediately after Carrageenan injection and then every 8 hr during the 24-hr test duration. Results: Repeated topical application of PSH significantly attenuated the gross hind paw swelling observed at the onset of the 6 hr post-induction (pi) until the 24 hr pi with Carrageenan in contrast to the Distilled water-treated group. This corresponded histologically to a marked reduction in dermal thickness, dermal edema, and leukocytic infiltration. Whereas, at the cytokine level, this correlated to significant suppression of the circulating blood levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6. Conclusion: Based on these results, honey from the Philippine stingless bees shows convincing anti-inflammatory activity which is partly mediated through the regulation of the expression of inflammation-associated cytokines. Keywords:Anti-inflammatory, Honey, IL-1β, IL-6, Philippine stingless bees, TNF-α.View:PDF (1.75 MB)

Improved production and antioxidant activity of exopolysaccharides by submerged culture of Lentinula edodes by the addition of lignocellulose

The objective of this study was to investigate the effect of addition of four different lignocellulose (water-treated corn straw, water-treated xylosma sawdust, alkali-treated corn straw and alkali-treated xylosma sawdust) on the production and antioxidant activity of exopolysaccharides by Lentinula edodes. To evaluate the antioxidant activity of polysaccharides, the analyses of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging activity, lipid peroxidation inhibition rate and erythrocyte hemolysis inhibition rate were carried out. The result clearly indicated that the exo-polysaccharide production and antioxidant activity by L.edodes mycelium was enhanced in varying degrees via the decomposition of lignocellulose. The yield of exo-polysaccharide in alkali-treated corn straw group was the highest (0.351g/L), which was 31.06% higher than that in control group after 5 days of submerged fermentation. High DPPH radical scavenging activity was observed in water-treated xylosma sawdust group, which decreased with the extension of fermentation time (23.15%-44.06%). Alkali-treated groups performed better than water-treated groups in terms of lipid peroxidation inhibitory activity. As for hemolysis inhibition activity toward erythrocytes, xylosma sawdust groups showed stronger oxidation resistance than corn straw groups.

Citrus unshiu Peel Attenuates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice due to Modulation of the PI3K/Akt Signaling Pathway and MAPK and NF-κB.

Aim Citrus unshiu peel has been used to treat various diseases in traditional East Asian medicine including Korea, and many studies have been reported regarding inflammatory diseases including ulcerative colitis (UC). However, the underlying mechanism by which Citrus unshiu peel modulates inflammation in UC remains unclear. Therefore, this study aimed to evaluate the therapeutic effect and underlying mechanism of Citrus unshiu peel water extract (CUP) for UC. Methods The experiment for UC was conducted with 8-week-old male Balb/c mice. After 1 week of adaptation, acute colitis was induced in all groups except the normal group by 5% DSS dissolved in drinking water for 1 week. Balb/c mice were divided into 5 groups (n = 8/group): control group (Control), distilled water-treated group (DSS), 100 mg/kg sulfasalazine-treated group (SASP), 100 mg/kg CUP-treated group (CUPL), and 200 mg/kg CUP-treated group (CUPH). The efficacy of CUP on UC was evaluated by biochemical analyses such as ROS and MPO in serum and MDA in tissues, and expression of proteins related to inflammation and apoptosis was evaluated through Western blot. Results As a result of confirming the macroscopic changes and H&E staining in colon tissues to confirm the preventive and therapeutic effects of CU, decrease in colon length and inflammatory lesions were inhibited in the CUP-treated group compared to the DSS group. In addition, as a result of serum ROS and tissue MDA analysis and oxidative stress-related protein analysis, it was significantly decreased in the CUP-administered group compared to the control group. In addition, treatment with CUP not only inactivated MAPK, p-IκBα, and NF-κBp65 by blocking the PI3K/Akt pathway but also significantly reduced the expression of inflammatory cytokines. Conclusion These results show that CUP not only suppresses oxidative stress in UC but also regulates inflammation-related proteins and apoptotic proteins by regulating the PI3K/Akt signaling pathway, suggesting that it has the potential as a material for developing new natural therapeutic agents for UC.

Effect of Extract-Added Water Derived from Deep-Sea Water with Different Hardness on Cognitive Function, Motor Ability and Serum Indexes of Obese Mice.

Deep-sea water (DSW) contains multiple minerals and is widely used as drinking water, for cosmetic purposes, and as seasoning. In this study, several types of extract-added water with different levels of hardness (200, 300, 500) were prepared from DSW collected off the coast of Muroto City, Kochi Prefecture. We administrated it to obese mice for two months and tested it for several effects. Although there was no anti-obesity effect for any hardness level in obese mice, the cognitive functions of each DSW-extract-added water-treated group were significantly improved compared to control obese mice in the water maze test. Time-to-fall by the rota-rod test was also dramatically improved in the DSW-extract-added water-treated groups. The levels of triglycerides and blood urea nitrogen were significantly decreased in DSW-extract-added water-treated obese mice. However, these results did not depend on the hardness. Hardness levels of 200 or 300 of DSW-extract-added water had greater effects on cognitive function and serum scores compared to a level of 500. We analyzed DSW using inductively coupled plasma atomic emission spectroscopy and inductively coupled plasma mass spectrometry. High concentrations of magnesium and potassium were detected, but sodium was not detected at very high concentrations. Although the detailed mechanisms of its effects are not yet understood, chronic intake of DSW-extract-added water may have a beneficial effect on health.

Correlation of Antifungal Activities and Nonribosomal Peptide Synthetase Gene Expression of Bacillus siamensis 1021

Members of the genus Bacillus were biocontrol agents against various phytopathogenic fungi. Several factors affected the regulation and production of nonribosomal peptides (NRPs) in Bacillus species. The aim of this study was to examine how culture media infl uenced the antagonistic activities and gene expression of Bacillus siamensis 1021. The bacterial supernatant from potato dextrose broth (PDB) exhibited higher inhibitory effects against mycelia of Pyricularia oryzae and Colletotrichum fructicola, when compared with those from nutrient broth (NB) and minimal salt medium (MSM). However, the biocontrol activities of these supernatants were not signifi cantly different when they were tested against P. oryzae and C. fructicola conidia. Additionally, the bacterial supernatant from PDB signifi cantly reduced the disease severity caused by P. oryzae in rice seedlings when compared with the water-treated control group. The genome of strain 1021 was sequenced, and biosynthetic gene clusters of nonribosomal peptides surfactin, fengycin and bacillibactin were identifi ed. Effects of PDB, NB and MSM media on expression levels of core biosynthetic genes of surfactin (srfAA), fengycin (fenC) and bacillibactin (dhbE) gene clusters were determined by reverse-transcription quantitative PCR. fenC expression was signifi cantly increased in PDB and corresponded with the antagonistic activities against fungal mycelia. Conversely, expression of the regulatory genes comA and codY in PDB were highly reduced in PDB, indicating their negative relation with fenC expression. This expression analysis indirectly suggested that fengycin was potentially the bioactive compound of B. siamensis 1021 against P. oryzae and C. fructicola

METRONIDAZOLE INDUCES SIGNIFICANT PATHOLOGICAL ALTERATIONS IN THE MALE REPRODUCTIVE SYSTEM OF MICE

The present study was aimed to investigate the possible effects caused by the antibiotic, metronidazole, on the histology of the testis and the morphology of the sperms of mice. To achieve this, adult male albino Swiss Mice were orally administrated with 0.1 ml (100 mg\ kg ) of the commercially used metronidazole (Flagyl) for 60 consecutive days. The results showed significant decreases (p<0.05) in the mean weight of body and testis in the treated mice as compared to the distilled water-treated control group. The treatment also caused several histopathological changes in the testis which included necrosis, congestion, hemorrhage, edema, germ cell downfall and rupture in the seminiferous tubules. The tests of the sperm morphology revealed a number of deformations as a result of the treatment, such as the appearance of headless, bend, broken-tailed, hook-tailed, and two-headed sperms, as well as sperms with cytoplasmic droplets. We conclude that from these results that orally administered Metronidazole exerts negative effects on the male reproductive system of mice .

Evidence that the gut microbiota regulates progression of neurodegeneration in a mouse model of tauopathy, in a sex‐ and ApoE isoform‐dependent manner

Alzheimer's disease (AD) is a fatal progressive neurodegenerative disease. Mounting evidence supports that an unbalanced gut microbiota (GM) is linked to amyloid-β deposition potentially by disrupting neuroinflammation and metabolic homeostasis. However, the contribution of the GM to tau-mediated neurodegeneration is poorly characterized. Furthermore, recent studies have reported that the configuration of the GM is also affected by ApoE isoforms, which is the strongest genetic risk factor for late-onset AD. Here, we explore the hypothesis that the GM regulates tau-mediated neurodegeneration in a sex- and ApoE isoform- dependent manner, using a mouse model of tauopathy.Male and female P301S tau transgenic mice were crossed with human ApoE knock-in mice (ApoE3 or ApoE4) or ApoE knockout mice (EKO) to generate P301S::ApoE3/E3, ApoE4/E4, or P301S/EKO mice, termed TE3F, TE4F, and TEKO, respectively. The GM in each group was perturbed by gastric gavage of a combination of antibiotics (ABX) from post-natal day 16-22; controls were gavaged with water (H2O). Mice were housed in a specific pathogen-free facility and fed a standard mouse chow diet ad libitum until they were euthanized at 9 months of age. In addition, a separate group of male and female TE4F mice were housed under germ-free conditions. Collected brains were sectioned, stained with 0.1% Sudan black and used to measure volumes of regions of interest.In males, TE3F and TE4F mice treated with H2O showed significant hippocampal atrophy compared to P301S mice lacking a functional ApoE gene (TEKO). However, TE3F mice treated with a short-term ABX showed significantly milder hippocampal atrophy compared to the water-treated group (p < 0.001, t-test). ABX treatment of TE4F animals was also associated with milder atrophy, although the effect did not reach statistical significance (p = 0.09, t-test). There were no effects in TEKO mice treated with ABX. Remarkably, these phenotypic effects of ABX treatment were not observed in females. Moreover, germ-free TE4F mice showed a marked decrease in brain atrophy compared to conventionally-raised animals; this was true for both sexes.Our results indicate that tau-mediated neurodegeneration occurs in a ApoE- dependent manner and is influenced by the gut microbiota and gender.

Remineralizing efficacy of fluoride in the presence of oral microcosm biofilms

ObjectivesThe oral biofilm structure or composition can affect the penetration of remineralizing agents. Therefore, this study evaluated the remineralizing efficacy of fluoride using a pH-cycling model with oral microcosm biofilms. MethodsArtificial carious lesions were formed in 80 bovine incisors. The pH-cycling conditions with or without oral microcosm biofilms were applied to 40 specimens each. The pH-cycling scheme was repeated for 12 days. Fluorescence loss (ΔF,%) of early carious lesions was measured for all specimens using a quantitative light-induced fluorescence-digital camera, before and after fluoride application. Biofilms on specimens were further analyzed for red fluorescence intensity (red/green ratios) and colony-forming unit counts. The effects of pH-cycling conditions and treatments on changes in ΔF (ΔΔF) and the effects of interactions between factors were analyzed using two-way analysis of variance. ResultsThe fluoride-treated group with oral biofilms had an approximately 0.89-fold lower ΔΔF than the fluoride-treated group without oral biofilms (p < 0.0001). When oral biofilms were absent, the fluoride-treated group showed a 1.31-fold greater ΔΔF compared to that in the distilled water-treated group (p < 0.0001). When oral biofilms were present, the fluoride-treated group showed a 1.14-fold greater ΔΔF compared to that in the distilled water-treated group; however, this difference was not statistically significant. ConclusionsThere was a significant difference in fluoride remineralizing efficacy based on the presence of biofilms on early carious lesions. Therefore, fluoride remineralization assessment in the absence of oral biofilms could lead to an overestimation of efficacy. Clinical SignificanceFluoride application might not have a robust remineralization effect on early carious lesions in the presence of a mature biofilm on the tooth surface.

How does ultrasound influence the thermal stability of wood?

This study elucidates the mechanism of the influence of ultrasonic treatment on wood pyrolysis and the details of the thermal stability changes of samples treated with ultrasonic alkali are explained. Four groups of samples were designed to clarify this scientific question, including the control group, the ultrasonic water-treated group, the alkali-treated group and the ultrasonic alkali-treated group. The extractives contents (organic extractives and hot water extractives) were determined, the crystal region, the functional groups of chemical components, the distribution of chemical components, and the thermal stability of wood were investigated using X-ray diffraction, Fourier-transform infrared spectroscopy, confocal Raman microscopy, and thermogravimetric analysis, respectively. The results suggested that all the treatments reduced the extractives contents, increased the relative crystallinity, destroyed the structure of hemicellulose and lignin, and affected the thermal stability of wood, to different degrees. Ultrasonic time and alkali concentration were shown to be two important indexes. Ultrasound can enhance the treatment effects of low concentration alkali (0.1 %), but in a highly concentrated alkali environment, the auxiliary effect is not obvious. Ultrasonic treatment reduced the intensity of lignin in the whole cell wall region, while alkali treatment followed a more systematic process as the solvent permeated from the S layer to CCML. The initial degradation temperature T0 was not only related to the extractives content but also to the concentrations of hemicellulose and lignin in the sample. The hemicellulose degradation temperature T1 and cellulose degradation temperature T2 changed with changes in T0. A detailed understanding of the spatial and temporal variations of the major components in the rigid cell wall during the pretreatment process will help to develop more effective pretreatment strategies, which is crucial for the efficient optimization of the process.

Claustral colony founding does not prevent sensitivity to the detrimental effects of azole fungicides on the fecundity of ants

Azole fungicides (benzimidazoles, triazoles and imidazoles) are among the most widely used agrochemicals in the world. Unfortunately, azole fungicides are increasingly recognized for playing the role of endocrine disruptors in non-target organisms. Previously, the fecundity of ants with semi-claustral colony founding was found to be severely decreased in response to field-realistic concentrations of azole fungicides. However, during claustral colony founding, the ant queens do not feed and could therefore be protected against effects of agrochemicals applied during the colony founding. In the present study, we hypothesized that claustral colony founding is associated with a lower risk of oral exposure of ant queens to azole fungicides. We exposed queens of a common farmland ant species with claustral colony founding, Lasius niger, to four azole fungicides (epoxiconazole, flusilazole, prochloraz and thiophanate-methyl) that are commonly used in foliar applications and analyzed the differences in fecundity between fungicide-treated groups and the control water-treated group. We found that oral exposure to all four tested formulations of azole fungicides decreased the fecundity of L. niger queens. The decreases in fecundity ranged from 30.5% (epoxiconazole) to 40.3% (prochloraz), although the concentrations of fungicides used were several times lower than the minimum effective concentrations used to eliminate the target fungi by foliar applications of examined fungicides on various crops. Ants with both claustral and semi-claustral colony founding are highly vulnerable to field-realistic concentrations of azole fungicides that are sprayed in foliar applications. Azole fungicides substantially decrease the fitness of ant queens and may explain part of the recently observed decreases in farmland insect abundance and diversity.

Influence of a novel pH-cycling model using dental microcosm biofilm on the remineralizing efficacy of fluoride in early carious lesions.

To evaluate the remineralizing efficacy of fluoride in early carious lesions using a novel microbial pH-cycling model that combines the chemical pH-cycling model with dental microcosm biofilms. Artificial carious lesions were formed in 48 bovine incisors. The chemical and microbial pH-cycling models were applied to 24 specimens, respectively; the latter was applied after formation of dental microcosm biofilms for 6days, based on the human saliva inoculation. The pH-cycling schedule was repeated for 12days. All specimens were evaluated for fluorescence loss (ΔF) using quantitative light-induced fluorescence-digital before and after the pH-cycling. Specimen biofilms were further analyzed for red/green values (R/G ratios) and colony-forming units (CFUs). One-way analysis of variance and Tukey's post hoc analysis were used to analyze change in fluorescence loss (ΔΔF) according to the pH-cycling model and treatment. When the chemical pH-cycling and microbial pH-cycling models were used, ΔΔF was 1.36 (p = 0.008) and 1.17 (p > 0.05) times higher, respectively, in the fluoride-treated group than that in the distilled water-treated group. In the microbial pH-cycling model, R/G ratios and CFU counts of biofilms were not significantly different between treatments (p > 0.05). No significant difference was observed in the remineralizing efficacy of fluoride according to the presence of dental biofilms covering early carious lesions. The remineralizing efficacy of fluoride could be overestimated in the absence of dental biofilms. Therefore, for accurate evaluation of the clinical value of remineralizing agents, dental biofilms should be included in in vitro tests.