Host-specific growth responses of Larix kaempferi and Quercus acutissima to Asian gypsy moth defoliation in central Korea.

As the risk of gypsy moth outbreaks that have detrimental effects on forest ecosystem in the Northern Hemisphere increase due to climate change, a quantitative evaluation of the impact of gypsy moth defoliation is needed to support the adaptive forest management. To evaluate the host-specific impact of gypsy moth defoliation, radial growth and annual carbon accumulation were compared for one severely defoliated (Larix kaempferi (Lamb.) Carrière) and one moderate defoliated (Quercus acutissima Carruth.) host, in defoliated and non-defoliated site using tree-ring analysis. Finally, the resilience indices of radial growth variables were calculated to assess the ability of sampled trees to withstand defoliation. Gypsy moth defoliation mainly decreased latewood width and caused reduction in annual carbon absorption more than 40% for both tree species. However, L. kaempferi, showed the reduced growth until the year following defoliation, while Q. acutissima, showed no lagged growth depression and rapid growth recover. The findings show how each species reacts differently to gypsy moth defoliation and highlight the need of managing forests in a way that takes resilient tree species into account.

Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disorder characterized by the loss of upper and lower motor neurons, resulting in debilitating muscle weakness and atrophy. Currently, there are no effective treatments available for ALS, posing significant challenges in managing the disease that affects approximately two individuals per 100,000 people annually. To address the urgent need for effective ALS treatments, we conducted a drug repurposing study using a combination of bioinformatics tools and molecular docking techniques. We analyzed sporadic ALS-related genes from the GEO database and identified key signaling pathways involved in sporadic ALS pathogenesis through pathway analysis using DAVID. Subsequently, we utilized the Clue Connectivity Map to identify potential drug candidates and performed molecular docking using AutoDock Vina to evaluate the binding affinity of short-listed drugs to key sporadic ALS-related genes. Our study identified Cefaclor, Diphenidol, Flubendazole, Fluticasone, Lestaurtinib, Nadolol, Phenamil, Temozolomide, and Tolterodine as potential drug candidates for repurposing in sporadic ALS treatment. Notably, Lestaurtinib demonstrated high binding affinity toward multiple proteins, suggesting its potential as a broad-spectrum therapeutic agent for sporadic ALS. Additionally, docking analysis revealed NOS3 as the gene that interacts with all the short-listed drugs, suggesting its possible involvement in the mechanisms underlying the therapeutic potential of these drugs in sporadic ALS. Overall, our study provides a systematic framework for identifying potential drug candidates for sporadic ALS therapy and highlights the potential of drug repurposing as a promising strategy for discovering new therapies for neurodegenerative diseases.

Ultrathin Graphene Oxide-Based Nanocomposite Membranes for Water Purification.

Two-dimensional graphene oxide (GO)-based lamellar membranes have been widely developed for desalination, water purification, gas separation, and pervaporation. However, membranes with a well-organized multilayer structure and controlled pore size remain a challenge. Herein, an easy and efficient method is used to fabricate MoO2@GO and WO3@GO nanocomposite membranes with controlled structure and interlayer spacing. Such membranes show good separation for salt and heavy metal ions due to the intensive stacking interaction and electrostatic attraction. The as-prepared composite membranes showed high rejection rates (˃70%) toward small metal ions such as sodium (Na+) and magnesium (Mg2+) ions. In addition, both membranes also showed high rejection rates ˃99% for nickel (Ni2+) and lead (Pb2+) ions with good water permeability of 275 ± 10 L m-2 h-1 bar-1. We believe that our fabricated membranes will have a bright future in next generation desalination and water purification membranes.

SperoPredictor: An Integrated Machine Learning and Molecular Docking-Based Drug Repurposing Framework With Use Case of COVID-19.

The global spread of the SARS coronavirus 2 (SARS-CoV-2), its manifestation in human hosts as a contagious disease, and its variants have induced a pandemic resulting in the deaths of over 6,000,000 people. Extensive efforts have been devoted to drug research to cure and refrain the spread of COVID-19, but only one drug has received FDA approval yet. Traditional drug discovery is inefficient, costly, and unable to react to pandemic threats. Drug repurposing represents an effective strategy for drug discovery and reduces the time and cost compared to de novo drug discovery. In this study, a generic drug repurposing framework (SperoPredictor) has been developed which systematically integrates the various types of drugs and disease data and takes the advantage of machine learning (Random Forest, Tree Ensemble, and Gradient Boosted Trees) to repurpose potential drug candidates against any disease of interest. Drug and disease data for FDA-approved drugs (n = 2,865), containing four drug features and three disease features, were collected from chemical and biological databases and integrated with the form of drug-disease association tables. The resulting dataset was split into 70% for training, 15% for testing, and the remaining 15% for validation. The testing and validation accuracies of the models were 99.3% for Random Forest and 99.03% for Tree Ensemble. In practice, SperoPredictor identified 25 potential drug candidates against 6 human host-target proteomes identified from a systematic review of journals. Literature-based validation indicated 12 of 25 predicted drugs (48%) have been already used for COVID-19 followed by molecular docking and re-docking which indicated 4 of 13 drugs (30%) as potential candidates against COVID-19 to be pre-clinically and clinically validated. Finally, SperoPredictor results illustrated the ability of the platform to be rapidly deployed to repurpose the drugs as a rapid response to emergent situations (like COVID-19 and other pandemics).

Quantifying the importance of day length in process-based models for the prediction of temperate spring flowering phenology.

Owing to climate change and frequent extreme weather events, changes in spring flowering phenology have been observed in temperate forests. The flowering time response to climate change is divergent among species and is difficult to predict due to the complexity of flowering mechanisms. To compare the effects of spring warming, winter chilling, and day length on spring flowering time, we evaluated eight process-based models (two types of forcing models, two types of chilling-forcing models, and four models with the effect of day length added to the aforementioned four models). We used flowering data of seven temperate species (Cornus officinalis, Rhododendron mucronulatum, Forsythia koreana, Prunus yedoensis, Rhododendron yedoense f. poukhanense, Rhododendron schlippenbachii, and Robinia pseudoacacia) observed in nine different arboretums in South Korea over 9 years. Generally, the forcing model performed better than the sequential chilling-forcing model, regardless of the species. The performance gap between the models was reduced when day length term was included in model, but the chilling-forcing model did not outperform the forcing model. The effect of day length on flowering time differed depending on the species. Prunus yedoensis, which had a particularly low warming sensitivity compared to other species, was more dependent on day length than other species. On the other hand, day length had little effect on the flowering time of Robinia pseudoacacia and Cornus officinalis, mostly found in the early successional stage. These findings imply that the effect of chilling on flowering time would be minor for the seven species inhabiting the warm-temperate forest, and the effect of day length on flowering time was species-specific and dependent on species' temperature (warming) sensitivity and life strategy. In the future warm climate, the flowering time of day length sensitive species would not advance significantly, which may result in a phenological mismatch and endanger their life.

Study of the Anticancer Potential of Plant Extracts Using Liver Tumor Microphysiological System.

BACKGROUND: Plants have been considered a vital source of modern pharmaceutics since the paleolithic age. Contemporary chemotherapeutic drugs for cancer therapy are chemical entities sourced from plants. However, synthetic drugs or their derivatives come with severe to moderate side effects for human health. Hence, the quest to explore and discover plant-based novel anticancer drugs is ongoing. Anticancer activities are the primary method to estimate the potential and efficacy of an extract or compound for drug discovery. However, traditional in vitro anticancer activity assays often show poor efficacy due to the lack of in-vivo-like cellular environment. In comparison, the animal-based in vivo assays lack human genetic makeup and have ethical concerns. AIM: This study aimed to overcome the limitations of traditional cell-culture-based anticancer assays and find the most suitable assay for anticancer activity of plant extracts. We first reported utilizing a liver tumor microphysiological system in the anticancer effect assessment of plant extracts. METHODOLOGY: Methanolic extracts of Acer cappadocicum Gled were used to assess anticancer activity against liver tumor microphysiological system (MPS), and cell viability, liver function tests, and antioxidant enzyme activities were performed. Additionally, an embedded transepithelial electrical resistance sensor was utilized for the real-time monitoring of the liver tumor MPS. The results were also compared with the traditional cell culture model. RESULTS: The study demonstrated the superiority of the TEER sensor-based liver tumor MPS by its better anticancer activity based on cell viability and biomarker analysis compared to the traditional in vitro cell culture model. The anticancer effects of the plant extracts were successfully observed in real time, and methanolic extracts of Acer cappadocicum Gled increased the alanine transaminase and aspartate aminotransferase secretion, which may reveal the different mechanisms of these extracts and suggest a clue for the future molecular study of the anticancer pathways. CONCLUSION: Our results show that the liver tumor microphysiological system could be a better platform for plant-based anticancer activity assessment than traditional cell culture models.

Quisqualis indica extract ameliorates low urinary tract symptoms in testosterone propionate-induced benign prostatic hyperplasia rats.

Benign prostate hyperplasia (BPH) is a common disease in old-age males, accounting for approximately 77% of morbidity within the age range of 40 to 70 years. It has been shown that morbidity increases with social graying. Quisqualis indica linn (QI) has been used to treat inflammation, stomach pain, and digestion problems. In this study, we evaluated the symptom-regulating effects of QI extract on a testosterone-induced BPH rat model. After inducing BPH in rats using testosterone propionate (TP) injection, we assessed basal intraurethral pressure (IUP) and increments of IUP elicited by electrical field stimulation (5 V, 5, 10, or 20 Hz) or phenylephrine (Phe) (0.01, 0.03, 0.1 mg/kg IV). To induce BPH, 8-week-old rats were subjected to a daily subcutaneous TP (3 mg/kg) injection for 4 weeks. Finasteride (Fina) (10 mg/kg PO) was administered to the rats in the first treatment, while QI (150 mg/kg PO) was administered to those in the second group. Blood pressure was measured together with IUP, after which low urinary tract (LUT), ventral prostate (VP), testicle, and corpus spongiosum were isolated and weighed. Basal IUPs for the Fina- and QI-treated groups were 87.6 and 86.8%, respectively. LUT and VP organ weights in the QI group were lower than those in the Fina group. However, the QI group showed significantly reduced electrical stimulated or Phe-induced IUP increment compared to the Fina and BPH groups. These results proved that QI can be beneficial for BPH symptoms by inhibiting 5α-reductase and consequently decreasing prostate and releasing urinary pressure.

Abundance and Distribution of Korean Flower Flies (Diptera: Syrphidae): Dominant Influence of Latitude on Regional Distribution.

Studies on abundance and distribution at different scales are rare. We examined whether the abundance of flower flies at a site in South Korea was related to the national occupancy and global distribution (distributional extent or range size) and whether the national occupancy was related to global distribution. In global distribution, the influence of two dimensions (latitude and longitude) was analyzed separately. Flower flies were collected by malaise and pitfall traps at a forest gap in South Korea. Data regarding national occupancy and global distribution were obtained from a Korean Flower Fly Atlas. We collected 46 species from the field survey and obtained a list of 119 species from the Korean Flower Fly Atlas. Our results showed that abundance at a site was positively correlated with national occupancy, but not global distribution, and the national occupancy was positively correlated with global distribution, mainly by the latitudinal range size. Finally, our results indicated that the regional distribution of flower flies was influenced by its one-dimensional global distribution.

A fluorescent lateral flow biosensor for the quantitative detection of Vaspin using upconverting nanoparticles.

Vaspin is a protein present in human serum that can cause type-2 diabetes, obesity, and other cardiovascular diseases. We report fluorescent upconverting nanoparticles (UCNPs)-based lateral flow biosensor for ultrasensitive detection of Vaspin. A pair (primary and secondary) of cognate aptamers was used that has duo binding with Vaspin. UCNPs with a diameter of around 100 nm were used as a tag to label a detection probe (secondary aptamer). A primary aptamer (capture probe) was immobilized on the test zone. Sandwich type hybridization reactions among the conjugate probe, target Vaspin, and primary aptamer were performed on the lateral flow biosensor. In the presence of target Vaspin, UCNPs were captured on the test zone of the biosensor and the fluorescent intensity of the captured UCNPs was measured through a colorimetric app under NIR. Fluorescence intensity indicates the quantity of Vaspin present in the sample. A range of Vaspin concentration across 0.1-55 ng ml-1 with a Limit of detection (LOD) 39 pg ml-1 was tested through this UCNPs based LFSA with high sensitivity, reproducibility and repeatability, whereas it's actual range in human blood is from 0.1 to 7 ng ml-1. Therefore, this research provides a well-suited lateral flow strip with an ultrasensitive and low-cost approach for the early diagnosis of type-2 diabetes and this could be applied to any targets with a duo of aptamers generated.

Effect of Veratrum maackii on Testosterone Propionate-Induced Benign Prostatic Hyperplasia in Rats.

Veratrum maackii (VM), a perennial plant in the Melanthiaceae family, has anti-hypertensive, anti-cholinergic, anti-asthmatic, anti-tussive, anti-fungal, anti-melanogenesis, and anti-tumor activities. Here, we investigated the therapeutic effect of VM on benign prostatic hyperplasia (BPH) in human normal prostate cell line (WPMY-1) and a testosterone propionate-induced BPH animal model. WPMY-1 cells were treated with VM (1-10 µg/mL) and testosterone propionate (100 nM). BPH in rats was generated via daily subcutaneous injections of testosterone propionate (3 mg/kg) dissolved in corn oil, for 4 weeks. VM (150 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the testosterone propionate. All rats were sacrificed and the prostates were dissected, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Immunoblotting experiments indicated that WPMY-1 cells treated testosterone propionate had increased expression of prostate specific antigen (PSA) and androgen receptor (AR), and treatment with VM or finasteride blocked this effect. In rat model, VM significantly reduced prostate weight, prostatic hyperplasia, prostatic levels of dihydrotestosterone (DHT), and expression of proliferation markers such as proliferating cell nuclear antigen (PCNA) and cyclin D1, but increased the expression of pro-apoptotic Bcl-2-associated X protein (Bax) and the cleavage of caspase-3. VM administration also suppressed the testosterone propionate-induced activation of nuclear factor-kappaB (NF-κB). Our results indicate that VM effectively represses the development of testosterone propionate-induced BPH, suggesting it may be a useful treatment agent for BPH.

Standardized Seed Extract of Quisqualis indica (HU-033) Attenuates Testosterone Propionate-Induced Benign Prostatic Hyperplasia via α1-Adrenergic Receptors and Androgen/Estrogen Signaling.

Benign prostatic hyperplasia (BPH) is an age-related disease characterized by prostatic enlargement and is the most common urologic symptoms in elderly men 60 years of age and older. Previously, we documented that 70% ethanol (EtOH) seed extract of Quisqualis indica (QI) attenuates pathological condition of testosterone propionate (TP)-induced BPH rat model via modulation of proliferation and apoptosis of prostate cells. Based on this potential of QI, we produced standardized seed extract of QI (HU-033) in order to prove further mechanisms. In this study, we aimed to suggest further mechanisms underlying the relationship between BPH and HU-033. Through not only cellular and nuclear receptor functional assays, but TP-mediated BPH rat model treated with HU-033, we demonstrated that HU-033 exerted antagonist effect on α1A- and α1D-adrenergic receptors in vitro and inhibitory effect on protein expression of androgen receptor and estrogen receptor alpha in vivo. Taken together, these results suggest that HU-033 is a novel candidate for the management of BPH.

pH-sensitive tangeretin-ZnO quantum dots exert apoptotic and anti-metastatic effects in metastatic lung cancer cell line.

Most cancer patients die as a consequence of distant metastases, which are frequently unresponsive to cancer therapy. This study focuses on the anti-tumorigenic and anti-metastatic properties of tangeretin-zinc oxide quantum dots (Tan-ZnO QDs) against the NCI-H358 cell line. Tan-ZnO QDs are pH-sensitive and capitalize on the acidic pH maintained in the tumor microenvironment; therefore, targeted drug delivery is directed specifically to cancer cells, leaving the normal cells less affected. Tan was loaded into synthesized ZnO QDs, and drug loading was analyzed using Fourier transform infrared (FTIR) spectroscopy and ultraviolet-visible (UV-Vis) spectrometry. Crystalline phase and particle size were measured using transmission electron microscopy (TEM) and X-ray diffraction (XRD). Drug release was evaluated in buffered solutions with differing pH for up to 15 h. The results confirmed stable drug release (80%) in an acidic pH. Tan-ZnO QDs induced significant cytotoxicity in NCI-H358 metastatic cells, while not markedly affecting HK-2 human normal cells. Morphology of treated H358 cells analyzed via atomic force microscopy (AFM) showed an increased surface roughness and pores. Further, the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells increased after treatment with Tan-ZnO QDs. DNA fragmentation was also induced after treatment with increasing concentrations of Tan-ZnO QDs in H358 cells. We also confirmed regulation of apoptosis via expression levels of Bax and Bcl-2 proteins; G2/M phase cell cycle arrest was observed. Additionally, cell proliferation and migration drastically decreased, and cell invasion and migration, hallmarks of metastasis, were significantly inhibited in H358 cells. Matrix metalloproteinase (MMP)2 and MMP9, markers of metastasis, as well as vascular endothelial growth factor (VEGF), a marker of angiogenesis, were significantly downregulated upon treatment with Tan-ZnO QDs. In conclusion, our novel formulation destabilized H358 cells by using its acidic tumor microenvironment, thereby regulating cell apoptosis, proliferation, and metastatic properties.

Quisqualis indica Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis.

Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks. The rats in treatment group were orally gavaged with QI (150 mg/kg) together with the TP injection. In-vitro studies showed that TP-induced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, dihydrotestosterone (DHT) concentration and 5α-reductase type 2 mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3ß (GSK3ß) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.

Synthesis and evaluation of the cytotoxic and anti-proliferative properties of ZnO quantum dots against MCF-7 and MDA-MB-231 human breast cancer cells.

Current trends in therapeutic research are the application of nanomaterial carriers for cancer therapy. One such molecule, ZnO, originally used in diagnosis and as a drug carrier, is gaining importance for its biological properties. Here, we report for the first time, the scope of ZnO QDs for enhanced cytotoxicity against MCF-7 and metastatic MDA-MB-231 human breast cancer cells. Unlike other ZnO nanostructures, ZnO QDs are dispersed and small sized (8-10nm) which is believed to greatly increase the cellular uptake. Furthermore, the acidic tumor microenvironment attracts ZnO QDs enhancing targeted therapy while leaving normal cells less affected. Results from MTT assay demonstrated that ZnO QDs induced cytotoxicity to MCF-7 and metastatic MDA-MB-231 breast cancer cells at very low concentrations (10 and 15µg/ml) as compared to other reported ZnO nanostructures. HEK-293 cells showed less toxicity at these concentrations. Confocal microscope images from DAPI staining and TUNEL assay demonstrated that ZnO QDs induced nuclear fragmentation and apoptosis in MCF-7 and MDA-MB-231. FACS results suggested ZnO QDs treatment induced cell cycle arrest at the G0/G1 phase in these cells. ZnO QDs drastically decreased the proliferation and migration of MCF-7 and MDA-MB-231 as seen from the results of the clonogenic and wound healing assays respectively. Furthermore, our data suggested that ZnO QDs regulated apoptosis via Bax and Bcl-2 proteins as validated by immunofluorescence and western blot. Taken together, our findings demonstrate that these ultra-small sized ZnO QDs destabilize cancer cells by using its acidic tumor microenvironment thereby inducing apoptosis and controlling the cell proliferation and migration at low dosages.

Resistive Switching in All-Printed, Flexible and Hybrid MoS2-PVA Nanocomposite based Memristive Device Fabricated by Reverse Offset.

Owing to the increasing interest in the nonvolatile memory devices, resistive switching based on hybrid nanocomposite of a 2D material, molybdenum disulphide (MoS2) and polyvinyl alcohol (PVA) is explored in this work. As a proof of concept, we have demonstrated the fabrication of a memory device with the configuration of PET/Ag/MoS2-PVA/Ag via an all printed, hybrid, and state of the art fabrication approach. Bottom Ag electrodes, active layer of hybrid MoS2-PVA nanocomposite and top Ag electrode are deposited by reverse offset, electrohydrodynamic (EHD) atomization and electrohydrodynamic (EHD) patterning respectively. The fabricated device displayed characteristic bistable, nonvolatile and rewritable resistive switching behavior at a low operating voltage. A decent off/on ratio, high retention time, and large endurance of 1.28 × 102, 105 sec and 1000 voltage sweeps were recorded respectively. Double logarithmic curve satisfy the trap controlled space charge limited current (TCSCLC) model in high resistance state (HRS) and ohmic model in low resistance state (LRS). Bendability test at various bending diameters (50-2 mm) for 1500 cycles was carried out to show the mechanical robustness of fabricated device.

Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity.

Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [(14)C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects.

Topical application of Scutellaria baicalensis suppresses 2,4-dinitrochlorobenzene-induced contact dermatitis.

Allergic contact dermatitis (ACD) is a prototypic T-cell-mediated cutaneous inflammatory response. In the present study we describe the anti-allergic effect of topically applied Scutellaria bacalensis aqueous extract (WSBE) in suppressing 2,4-dinitrochlorobenzene (DNCB)-induced ACD in BALB/c mice. Topically applied WSBE attenuated the epidermal thickness and mast cell infiltration into the skin in DNCB-induced contact dermatitis. Furthermore, WSBE suppressed DNCB-induced production of serum IgE as well as IL-4, IFN-γ, and TNF-α in the skin. Topical application of WSBE also ameliorated the significant decrease in dermal glutathione and superoxide dismutase levels. Moreover, present results demonstrated that the baicalin, bioactive compound of WSBE, was able to penetrate into the skin following topical application, which was confirmed by the HPLC analysis using rat model. Taken together, topical application of WSBE exerts beneficial effects in contact dermatitis model, suggesting that WSBE might be a candidate for the treatment of contact dermatitis.

A polymethoxy flavonoids-rich Citrus aurantium extract ameliorates ethanol-induced liver injury through modulation of AMPK and Nrf2-related signals in a binge drinking mouse model.

Nobiletin and tangeretin are polymethoxy flavonoids (PMFs), found in rich quantities in the peel of citrus fruits. In the present study, we assessed the biological effect of the PMFs on liver damage using a mouse model of binge drinking. First, we extracted PMFs from the peels of Citrus aurantium to make Citrus aurantium extract (CAE). Male C57BL/6 mice were orally treated with silymarin and CAE (50, 100, and 200 mg/kg) for 3 days prior to ethanol (5 g/kg, total of 3 doses) oral gavage. Liver injury was observed in the ethanol alone group, as evidenced by increases in serum hepatic enzymes and histopathologic alteration, as well as by hepatic oxidative status disruption. CAE improved serum marker and hepatic structure and restored oxidative status by enhancing antioxidant enzyme levels and by reducing lipid peroxidation levels. In addition, CAE evidently suppressed inflammation and apoptosis in the livers of mice administered with ethanol, by 85% (tumor necrosis factor-α) and 44% compared to the control group, respectively. Furthermore, CAE activated lipid metabolism related signals and enhanced phosphorylation of AMP-activated protein kinase (AMPK) and nuclear factor E2-related factor 2 (Nrf2) with several cytoprotective proteins including heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, and γ-glutamylcysteine synthetase. Taken together, the present study demonstrated that, CAE possesses antioxidant, anti-inflammatory, and antiapoptotic activity against ethanol-induced liver injury.

Characterization of betaine aldehyde dehydrogenase (BetB) as an essential virulence factor of Brucella abortus.

The pathogenic mechanisms of Brucellosis used to adapt to the harsh intracellular environment of the host cell are not fully understood. The present study investigated the in vitro and in vivo characteristics of B. abortus betaine aldehyde dehydrogenase (BetB) (Gene Bank ID: 006932) using a betB deletion mutant constructed from virulent B. abortus 544. In test under stress conditions, including osmotic- and acid stress-resistance, the betB mutant had a lower osmotic-resistance than B. abortus wild-type. In addition, the betB mutant showed higher internalization rates compared to the wild-type strain; however, it also displayed replication failures in HeLa cells and RAW 264.7 macrophages. During internalization, compared to the wild-type strain, the betB mutant was more adherent to the host surface and showed enhanced phosphorylation of protein kinases, two processes that promote phagocytic activity, in host cells. During intracellular trafficking, colocalization of B. abortus-containing phagosomes with LAMP-1 was elevated in betB mutant-infected cells compared to the wild-type cells. In mice, the betB mutant was predominantly cleared from spleens compared to the wild-type strain after 2 weeks post-infection, and the vaccination test with the live betB mutant showed effective protection against challenge infection with the virulent wild-type strain. These findings suggested that the B. abortus betB gene substantially affects the phagocytic pathway in human phagocytes and in host cells in mice. Furthermore, this study highlights the potential use of the B. abortus betB mutant as a live vaccine for the control of brucellosis.

Assessment of dermal safety of Scutellaria baicalensis aqueous extract topical application on skin hypersensitivity.

Scutellaria baicalensis has been used as a traditional herbal medicine for bronchitis, hepatitis, and allergic diseases. The root of Scutellaria baicalensis contains active flavonoid components, including baicalin, baicalein, wogonoside, and wogonin, which have pharmaceutical properties. In the present study, the antiallergic properties of a standardized aqueous extract of S. baicalensis were evaluated, and the skin toxicity of its dermal application was also determined. The in vivo and in vitro assays were performed by using the ß-hexosaminidase assay in rat basophilic leukemia cells (RBL-2H3) and cutaneous skin reaction in BALB/c mice, respectively. In addition, the acute dermal irritation/corrosion test was carried out in New Zealand white rabbits, and the skin sensitization test was conducted by Buhler's method in Hartley guinea pigs to estimate the safety of the standardized aqueous extract of S. baicalensis for topical application. ß-Hexosaminidase release in RBL-2H3 was markedly decreased following treatment with the standardized aqueous extract of S. baicalensis. It also ameliorated antigen-induced ear swelling compared with the control group in BALB/c mice. In the toxicological studies, it did not induce any dermal irritation/corrosion in rabbits or skin sensitization in guinea pigs. Although still limited, these results concerning the toxicological effects of S. baicalensis could be an initial step toward the topical application of S. baicalensis extracts on hypersensitive skin.