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Purpose: Prostaglandin E2 (PGE2) is known to promote carcinogenesis and cancer progression in colon cancer. Enzymes involved in the metabolism of PGE2 include cyclooxygenase (COX)-2, microsomal prostaglandin E synthase-1 (mPGES-1), and 15-prostaglandin dehydrogenase (15-PGDH). The current study aims to determine how PGE2 is expressed by examining patients with colorectal cancer and evaluating colon cancer cells to gain insight into changes in relevant enzymes upon induction of PGE2.Methods: The concentration of PGE2 was measured in tumor tissues and adjacent normal mucosal tissues of 26 patients with colon cancer. The expression of COX-1, COX-2, mPGES-1, and 15-PGDH proteins was measured. The concentration of PGE2 in FET colon cancer cells was measured both in the initial status and after stimulation by tumor necrosis factor (TNF)-α. The expression levels of PGE2-related enzymes were measured as well.Results: There was no significant difference in the average concentration of PGE2, which was measured at 453.1 pg/mL in cancer tissues and 401.2 pg/mL in normal mucosa. Among PGE2-related enzymes, 15-PGDH was expressed at a lower level in tumor cells than in normal mucosa. In colon cancer cells, PGE2 was found to be upregulated upon stimulation by TNF-α, which led to strong induction of mPGES-1 without any change in the expression of COX-2 among the PGE2-related enzymes.Conclusion: These results demonstrated that PGE2 can be induced by stimuli such as TNF-α, and suggest that activation of mPGES-1 is more closely related than that of COX-2 in the induction of PGE2 on colon cancer.

Background: Transforming growth factor (TGF-β) pathway mediates suppression of anti-tumor immunity, and is associated with poor prognosis in triple-negative breast cancer (TNBC). Methods: In this study, we generated a humanized animal model by transplanting human peripheral blood mononuclear cells into immunodeficient mice followed by inoculation of MDA-MB-231 cells, and subsequently analyzed the role of TGF-β2 in the interaction between human T cells and human tumor cells. Results: Following reconstitution of the human immune system, inhibition of TGF-β signaling by TGF-β2 antisense oligodeoxynucleotide (TASO) resulted in accelerated tumor growth inhibition. TGF-β2 inhibition also resulted in downregulation of peripheral Foxp3+ regulatory T cells (Treg), whereas no effect was seen in the expression of CD8+ cytotoxic T cells. Analysis of the TASO-treated mice serum revealed elevated levels of human IFN-γ and reduced levels of human IL-10 and TGF-β2. Moreover, TGF-β2 inhibition resulted in increased CD8+ T cell infiltration, whereas the reduced infiltration of Tregs into the tumor partly resulted from decreased expression of CCL22. Decreased intra-tumoral Tregs facilitated the activation of cytotoxic T cells, associated with increased granzyme B expression. Conclusion: These results indicate that TASO potentiated T-cell mediated antitumor immunity, and it is proposed that TGF-β2 may be a promising target in the immunotherapeutic strategy of TNBC.

The overexpression of human epidermal growth factor receptor 2 (HER2) is recognized as a hallmark of several solid tumors, and the anti-HER2 monoclonal antibody and its engineered variants have been developed as therapeutic or diagnostic tools for HER2-overexpressing cancers. Here, we demonstrate the first example of extracellular production of an anti-HER2 single-chain variable fragment (scFv) in Escherichia coli via a non-peptide-guided secretion. The initial construct expressing an engineered green fluorescent protein-fused scFv was successful in extracellular secretion, but the expressed protein appeared to be readily truncated before the final purification. Alternatively, by adding Triton X-100 to the culture media, maltose-binding protein (MBP)-fused scFv could be secreted without significant truncation, and homogeneous purification of the intact protein was enabled. The affinity of the MBP-fused scFv to the extracellular domain of HER2 was confirmed by enzyme-linked immunosorbent assay, and the dissociation constant of the finally isolated scFv estimated by surface plasmon resonance was approximately 0.2 nM, which was superior to the other known anti-HER2 scFvs. Given that anti-HER2 scFv is an invaluable asset for developing various therapeutic or diagnostic agents for cancers, we expect that our method for the extracellular production will enable a better manufacturing process for its industrial application.

BACKGROUND Drain fluid amylase is commonly used as a predictor of pancreatic fistula after pancreaticoduodenectomy (PD). This study aimed to determine the ideal cut-off value of drain fluid amylase on postoperative day 1 (DFA1) for predicting pancreatic fistula after pancreaticogastrostomy (PG). METHODS Prospective data of 272 consecutive patients undergoing PG between 2010 and 2020 was collected and analysed to determine the postoperative pancreatic fistula (POPF) risk factors. RESULTS The incidence of POPF was 143 cases (52.6%). The median DFA1 in patients with POPF was significantly higher than that of patients with NO-POPF (5483 versus 311, P

In the search for new natural resources showing plant disease control effects, we found that the methanol extract of Polyalthia longifolia suppressed fungal disease development in plants. To identify the bioactive substances, the methanol extract of P. longifolia was extracted by organic solvents, and consequently, four new 2-oxo-clerodane diterpenes (1-4), a new 4(3 → 2)-abeo-clerodane diterpene (5), together with ten known compounds (6-16) were isolated and identified from the extracts. Of the new compounds, compound 2 showed a broad spectrum of antifungal activity with moderated minimum inhibitory concentration (MIC) values in a range of 50-100 μg/mL against tested fungal pathogens. Considering with the known compounds, compound 6 showed the most potent antifungal activity with an MIC value in the range of 6.3-12.5 μg/mL. When compound 6 was evaluated for an in vivo antifungal activity against rice blast, tomato late blight, and pepper anthracnose, compound 6 reduced the plant disease by at least 60% compared to the untreated control at concentrations of 250 and 500 μg/mL. Together, our results suggested that the methanol extract of twigs and leaves of P. longifolia and its major compound 6 could be used as a source for the development of eco-friendly plant protection agents.

Even though the endocrine-disrupting potential of perfluorooctanoic acid (PFOA) is well known, the mechanisms underlying its cellular and epigenetic toxicity at the critical stage of hypothalamic development are poorly understood. This is why we studied its effects on the embryonic mouse hypothalamic cell line N46 (mHypoE-N46) with a hope to shed more light on the mechanisms through which PFOA causes embryonic hypothalamic cell damage. To do that, we studied cell viability, global DNA methylation, and gene expression in cells exposed to PFOA. As the PFOA dose increased, cell viability decreased, while global DNA methylation increased. PFOA also significantly altered the expression of genes related to the apoptosis and cell cycle, neurotrophic genes, and the Tet, Dnmt, and Mecp2 genes. Our findings suggest that exposure to PFOA affects cell survival through the reprogramming of embryonic hypothalamic DNA methylation patterns and altering cell homeostasis genes. DNA methylation and changes in the Mecp2 gene expression induced by PFOA also imply wider ramifications, as they alter genes of other major mechanisms of the embryonic hypothalamus. Our study may therefore serve as a good starting point for further research into the mechanisms of PFOA effect of hypothalamic development.

To understand the mechanism of ring shakes in Dahurian larch (Larix gmelinii), the ring shake surface on the tangential section was observed and compared with the shear surface of green and air-dry wood. Macroscopically, the ring shakes occurred in the heartwood between the 20th and 40th growth ring. The ring shake surface exhibited an even and clean structure without the fluff. The shear surface of the green wood showed a larger amount of fluff compared to that of air-dry wood. In microscopy, ring shake failure occurred at the end of the latewood and/or the beginning of earlywood or within the earlywood zone. The ring shake surface was covered with a resinous substance, and the wood cells were observed after removing the resinous substance with ethanol. The tracheid walls in the ring shake and shear surface of green wood primarily exhibited intercell failure and rarely intrawall and transwall failures. In air-dry wood, the tracheid walls in the shear surface mostly exhibited intrawall and transwall failures. In the ring shake surface, there was hardly any failure in the epithelial and ray cells, thereby showing a distinct difference compared to the shear surface of the green and air-dry woods.

The use of prime editing-a gene-editing technique that induces small genetic changes without the need for donor DNA and without causing double strand breaks-to correct pathogenic mutations and phenotypes needs to be tested in animal models of human genetic diseases. Here we report the use of prime editors 2 and 3, delivered by hydrodynamic injection, in mice with the genetic liver disease hereditary tyrosinemia, and of prime editor 2, delivered by an adeno-associated virus vector, in mice with the genetic eye disease Leber congenital amaurosis. For each pathogenic mutation, we identified an optimal prime-editing guide RNA by using cells transduced with lentiviral libraries of guide-RNA-encoding sequences paired with the corresponding target sequences. The prime editors precisely corrected the disease-causing mutations and led to the amelioration of the disease phenotypes in the mice, without detectable off-target edits. Prime editing should be tested further in more animal models of genetic diseases.

Several endemic corona viruses (eCoVs) have been reported to be the most common etiologic agents for the seasonal common cold and also cause pneumonia. These eCoVs share extensive sequence homology with SARS-CoV-2, and immune responses to eCoVs can cross-react with SARS-CoV-2 antigens. Based on such cross-reactivity of antigens among eCoVs, the IgG antibodies against the spike protein (SP) of severe acute respiratory syndrome coronavirus (SARS-CoV) were isolated from pig serum using magnetic beads immobilized with SARS-CoV SP and a protein-A column. The selectivity of the isolated antibodies was tested using different types of antigens, such as SARS-CoV-2 nucleoprotein (NP), influenza A virus (Beijing type), influenza B virus (Tokio and Florida types), human hepatitis B virus surface antigen (HBsAg), and bovine serum albumin (BSA). From the selectivity test, the anti-SP antibodies isolated from pig serum had sufficient selectivity to other kinds of viral antigens, and the apparent binding constant of the isolated antibodies was approximately 1.5 × 10–8 M from the surface plasmon resonance (SPR) measurements. Finally, the isolated anti-SP antibodies were applied to the immunoassay of SP using competitive immunoassay configuration. The feasibility of the detection as well as the quantitative analysis of the SARS-CoV viral culture fluid was determined using four viral culture samples, namely, SARS-CoV, SARS-CoV-2, MERS-CoV, and CoV-229E.

Bio-composites containing kenaf and starch as the filler and matrix, respectively, and Polyvinyl alcohol (PVA) and Polyethylene glycol (PEG) as plasticizers were fabricated. The acetylation of hydrophilic kenaf increased the hydrophobic matrix and surfactant bonding in the complex, and the starch matrix increased the biodegradability. The physical, thermal, and biodegradability properties of composites comprising acetylated kenaf and starch (S), acetylated kenaf, starch, and PVA (S+PVA), and acetylated kenaf, starch, and PEG (S+PEG) were evaluated. The results showed that the acetylation of kenaf caused its surface to swell, improving the interfacial adhesion between kenaf and starch in the composites, whereas PVA and PEG did not enhance the physical properties of the composites. The addition of plasticizers caused a slight improvement in the thermal fluidity and stability of the acetylated kenaf composites. In addition, the composites buried in soil showed higher biodegradability than those buried in compost. The presence of moisture in the soil also increased the biodegradability by 80 %. The results of this study demonstrate the high potential of the acetylated kenaf composites as an alternative to synthetic polymer products. Moreover, considering their biodegradable nature, these composites can be applied in treatments and techniques that are focused on the safe disposal of plastic waste for the mitigation of environmental pollution.

Platycodon grandiflorum (balloon flower) root (Platycodi radix, PR) is used as a health supplement owing to its beneficial bioactive properties. In the present study, the anti-inflammatory, antioxidant, and whitening effects of deglycosylated platycosides (saponins) from PR biotransformed by pectinase from Aspergillus aculeatus were investigated. The bioactivities of the platycosides improved when the number of sugar moieties attached to the aglycone platycosides was decreased. The deglycosylated saponins exhibited higher lipoxygenase inhibitory activities (anti-inflammatory activities) than the precursor platycosides and the anti-inflammatory compound baicalein. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of the pectinase-treated PR extract was higher than that of the non-treated PR extract. The trolox-equivalent antioxidant capacity (TEAC) assay showed improved values as the saponins were hydrolyzed. The tyrosinase inhibitory activities (whitening effects) of deglycosylated platycosides were higher than those of the precursor platycosides. Furthermore, 3-O-β-D-glucopyranosyl platycosides showed higher anti-inflammatory, antioxidant, and whitening activities than their precursor glycosylated platycosides. Therefore, 3-O-β-D-glucopyranosyl platycosides may improve the beneficial effects of nutritional supplements and cosmetic products.

Color changes were tested and compared for heat-treated Paulownia tomentosa and Pinus koraiensis wood treated with hot oil or hot air for further utilization of these species. Hot oil and hot air treatments were conducted at 180, 200, and 220 °C for 1, 2, and 3 h. Heat-treated wood color changes were determined using the CIE-Lab color system. Weight changes of the wood before and after heat treatment were also determined. The weight of the oil heat-treated wood increased considerably but it decreased in air heat-treated wood. The oil heat-treated samples showed a greater decrease in lightness (L*) than air heat-treated samples. A significant change in L* was observed in Paulownia tomentosa. The red/green chromaticity (a*) of both wood samples increased at 180 and 200 °C and slightly decreased at 220 °C. The yellow/blue chromaticity (b*) in both wood samples increased at 180 °C, but it rapidly decreased with increasing treatment durations at 200 and 220 °C. The overall color change (ΔE*) in both heat treatments increased with increasing temperature, being higher in Paulownia tomentosa than in Pinus koraiensis. In conclusion, oil heat treatment reduced treatment duration and was a more effective method than air heat treatment in improving wood color.

Physical and mechanical properties were evaluated for bamboo-oriented strand boards (BOSB) prepared with combinations of two contrasting bamboo species and bonded with phenol formaldehyde resin under various compression ratios. The strands from the culms of Gigantochloa pseudoarundinacea and Dendrocalamus asper bamboo were steam-treated at a temperature of 126 °C and a pressure of 0.14 MPa for 1 h and then washed with a 1% NaOH solution. Three-layer dual-species bamboo-oriented strand boards with a shelling ratio of 25 to 50 to 25 (face to core to back) were manufactured with different compression ratios using an 8% phenol formaldehyde adhesive and 1% paraffin. The slenderness ratio and aspect ratio were evaluated by measuring 100 random strands to determine uniformity. The solidity profiles of the dual-species bamboo-oriented strand boards (thickness direction) were relatively uniform. The modulus of rupture, modulus of elasticity, and internal bond values of the dual-species bamboo-oriented strand boards increased as the compression ratio increased, but the water absorption and thickness swelling decreased. The dual-species bamboo-oriented strand boards prepared with compression ratios of 1.44 to 1.25 and 1.54 to 1.33 met all the requirements of CSA standard 0437 (2011). The optimum compression ratio for the preparation of dual-species bamboo-oriented strand boards was 1.44 to 1.25.

This study examined the activity and function of pig OCT4 enhancer in porcine reprogramming cells. Dual fluorescent protein reporter systems controlled by the upstream regulatory region of OCT4, which is one of the master regulators for pluripotency, are widely used in studies of the mechanism of pluripotency. We analyzed how this reporter system functions in fibroblast growth factor (FGF)- or leukemia inhibitory factor (LIF)-dependent reprogrammed porcine pluripotent stem cells using the previously established porcine-specific reporter system. Porcine embryonic fibroblasts were coinfected with the pOCT4-ΔPE-eGFP (distal enhancer [DE]-green fluorescent protein [GFP]) and pOCT4-ΔDE-DsRed2 (proximal enhancer [PE]-red fluorescent protein [RFP]) vectors, and GFP and RFP expression were verified during a DOX-dependent reprogramming process. We demonstrated that the porcine OCT4 DE and PE were activated in different expression patterns simultaneously as changes in the expression of pluripotent marker genes during the establishment of porcine-induced pluripotent stem cells (iPSCs). Porcine OCT4 upstream region-derived dual fluorescent protein reporter systems confirmed that porcine iPSCs are in primed state after reprogramming in FGF2- or LIF-containing media. This work demonstrates the applicability of porcine OCT4 upstream region-derived dual fluorescence reporter system, which may be applied to investigations of species-specific pluripotency in porcine-origin cells. These reporter systems may be useful tools for studies of porcine-specific pluripotency, early embryo development, and embryonic stem cells.

An increase in antibiotic usage is considered to contribute to the emergence of antimicrobial resistance. Although experts are counting on the antimicrobial stewardship programs to reduce antibiotic usage, their effect remains uncertain. In this study, we aimed to evaluate the impact of antibiotic usage and forecast the prevalence of hospital-acquired extended spectrum β-lactamase (ESBL)—producing Escherichia coli (E. coli) using time-series analysis. Antimicrobial culture information of E. coli was obtained using a text processing technique that helped extract free-text electronic health records from standardized data. The antimicrobial use density (AUD) of antibiotics of interest was used to estimate the quarterly antibiotic usage. Transfer function model was applied to forecast relationship between antibiotic usage and ESBL-producing E. coli. Of the 1938 hospital-acquired isolates, 831 isolates (42.9%) were ESBL-producing E. coli. Both the proportion of ESBL-producing E. coli and AUD increased over time. The transfer model predicted that ciprofloxacin AUD is related to the proportion of ESBL-producing E. coli two quarters later. In conclusion, excessive use of antibiotics was shown to affect the prevalence of resistant organisms in the future. Therefore, the control of antibiotics with antimicrobial stewardship programs should be considered to restrict antimicrobial resistance.

Objectives The aim of this study is to examine the effect of particulate autogenous tooth graft removed with organic matter and type I collagen addition on bone regeneration and to validate the possibility of useful allograft material for jaw defects. Material and methods Autogenous tooth bone maker (Korean Dental Solution® KOREA) made particulate autogenous tooth not including organic matter. We used to the developed tooth grafts for experiment. Cell adhesion test with hemacytometer and energy dispersive X-ray spectroscopy (Supra40 VP®, Carl Zeiss, Germany) analysis about the particulate autogenous tooth and type I collagen were performed. Rabbits were divided into three groups: bone graft with organic matter (OM) removing particulate autogenous tooth group, bone graft with OM removing particulate autogenous tooth and type I collagen group, and a control group. Bone grafting was performed in rabbit’s calvaria. The rabbits were sacrificed at different interval at 1, 2, 4, and 6 weeks after bone grafting for the histopathologic observation and observed the effect of bone regeneration by SEM, H-E & Masson stains, osteocalcin IHC staining. Result In vitro cytopathological study showed affinity for cells, cell attachment pattern, and cell proliferation in the order of control group, OM-removed and collagen-treated group, OM-removed particulate autogenous tooth group. The results of the degree of mineralization were opposite to those of the previous cell experimental results, and the OM-removed group, OM-removed group and collagen-treated group were relatively higher than the control group. Histopathologic analysis showed that vascularization and neonatal bone formation were higher in particulate autogenous tooth group with removing OM and with addition of collagen than control group and group of OM removed only. Immunohistochemical analysis showed that osteocalcin (OSC) expression was not observed in the control group, but at 4 weeks groups, OSC expression was observed the OM removed and OM-removed-collagen-treated particulate autogenous tooth, and the degree of expression was somewhat stronger in group of the OM removed and collagen additionally treated particulate autogenous tooth. Conclusion Particles that do not contain organic matter, the saint tooth, was responsible for sufficient bone graft material through the role of space maintenance and bone conduction, and further improved bone formation ability through additional collagen treatment. Therefore, research on various extracellular substrates and autologous bone grafting materials is necessary, and through this, it is possible to lay the foundation for a new type of autologous bone grafting material with excellent academic and technical utility.

Background The primary aim of this study was to determine the mean values for three of the most common parameters measured to assess hindfoot alignment in asymptomatic subjects: hindfoot alignment angle (HAA), hindfoot alignment ratio (HAR), and hindfoot moment arm (HMA). The secondary aim was to evaluate the mean value of each parameter according to age and sex. Methods We assessed 1128 asymptomatic subjects from January 2014 to June 2019. HAA, HAR and HMA were measured to evaluate the degree of hindfoot varus or valgus deviation on the hindfoot alignment view, described by Saltzman and el-Khoury. All subjects were divided into subgroups according to sex and age ( Results The overall mean HAA, HAR, and HMA were –4.07 ± 3.48°, 0.21 ± 0.15, and –6.12 ± 5.22 mm, respectively. Female subjects ≥45 years old had the largest valgus deviation (HAA, –7.08 ± 6.34°; HAR 0.09 ± 0.25; HMA, –10.58 ± 11.46 mm). Conclusions HAA, HAR, and HMA evaluation revealed that asymptomatic subjects had a hindfoot alignment with valgus deviation. Furthermore, the degree of valgus deviation was the largest in female subjects aged ≥45 years. We hope that the results of our study will be helpful to inform other researchers about the usefulness of these parameters as references.

Abnormal adipocyte growth, distinguished by an increase in cell numbers and cellular differentiation, is regarded as a major pathological characteristic of obesity. Thus, inhibition of adipogenic differentiation in adipocytes could prevent obesity. Recently, certain probiotic stains have been reported to regulate lipid metabolism in vitro and/or in vivo. In this backdrop, this study aimed to investigate basic probiotic properties and potential antiobesity characteristics of mouse 3T3-L1 preadipocytes. Six lactic acid bacteria (LAB) strains were prescreened for their cholesterol-lowering activity, antioxidant activity, and survival at low pH and in a solution containing bile salts. These six strains were investigated for antiadipogenic activity by employing 3T3-L1 mouse preadipocytes. 3T3-L1 cells were treated with selected strains during the differentiation process. Lactobacillus johnsonii 3121 and Lactobacillus rhamnosus 86 were found to be more capable of reducing triglyceride and lipid accumulation, as compared to control group, which are fully differentiated 3T3-L1 adipocytes. These strains also inhibited adipocyte differentiation by downregulating the adipogenic transcription factor in 3T3-L1 adipocytes. Taken together, these results indicate that L. johnsonni 3121 and L. rhamnosus 86 could potentially act as probiotic bacteria and prevent fat accumulation by regulating adipogenesis-related markers.

The sensory properties and flavor of sour cream are important factors that influence consumer acceptability. The present study aimed to isolate lactic acid bacteria with excellent diacetyl production ability and to optimize the fermentation conditions for sour cream manufacture. Lactococcus lactis ssp. cremoris was isolated as a lactic acid bacterium derived from raw milk. This strain showed the greatest diacetyl production among other strains and was named LRCC5306. Various culture conditions were optimized to improve the diacetyl production of LRCC5306. The highest diacetyl production was found to be at 105.04±2.06 mg/L, when 0.2% citric acid and 0.001% Fe2+ were added and cultured at 20°C for 15 h. Based on the optimal cultivation conditions, sour cream was manufactured using LRCC5306, with a viable count of 1.04×108 CFU/g and a diacetyl concentration of 106.56±1.53 mg/g. The electronic tongue system was used to compare the sensory properties of the sour cream; the fermented product exhibited sweetness and saltiness which was similar to that of an imported commercial product, but with slightly reduced bitterness and a significantly greater degree of sour taste. Therefore, our study shows that if cream is fermented using the LRCC5306, it is possible to produce sour cream with greatly improved sensory attractiveness, resulting in increased acceptance by consumers. Since this sour cream has a higher viable count of lactic acid bacteria, it is also anticipated that it will have a better probiotic effect.

This experiment was performed to verify whether dietary heat-killed Lactobacillus rhamnosus (LR) improves growth performance and modulates immune responses of weaned pigs. Ninety-six weaned pigs ([Landrace × Yorkshire] × Duroc; 6.95 ± 0.25 kg body weight [BW]; 28 d old) were randomly allocated to four treatments: 1) a basal diet without heat-killed LR (CON), 2) T1 (CON with 0.1% heat-killed LR), 3) T2 (CON with 0.2% heat-killed LR), and 4) T3 (CON with 0.4% heat-killed LR). Each treatment had six pens with four pigs (6 replicates per treatment) in a randomized completely block design. The heat-killed LR used in this study contained 1 × 109 FU/g of LR in a commercial product. Pigs were fed each treatment for four weeks using a two-phase feeding program to measure growth performance and frequency of diarrhea. During the last week of this study, all diets contained 0.2% chromic oxide as an indigestible marker. Fecal sampling was performed through rectal palpation for the consecutive three days after the four adaptation days to measure apparent total tract digestibility (ATTD) of dry matter, crude protein, and gross energy (GE). Blood sampling was also performed on day 1, 3, 7, and 14 after weaning to measure immune responses such as serum tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), C-reactive protein (CRP), and cortisol. The heat-killed LR increased (p < 0.05) growth rate, feed efficiency, and ATTD of GE for overall experimental period compared with CON, but reduced (p < 0.05) post-weaning diarrhea. In addition, pigs fed diets contained heat-killed had lower concentrations of serum TNF-α (d 7; p < 0.05), TGF-β1 (d 7; p < 0.10), and cortisol (d 3 and 7; p < 0.05) than pigs fed CON. In conclusion, dietary heat-killed LR improved growth rate, modified immune responses of weaned pigs, and alleviated post-weaning diarrhea.

This study aimed to assess the anti-inflammatory effect of Lactobacillus casei 3260 (LC) alone and LC-fermented Gleditsia sinensis thorn (GST) extract in mouse model of type II collagen induced rheumatoid arthritis (RA). In our previous work, we confirmed the anti-inflammatory effects of LC and GST against LPS-induced inflammation in vitro. In this study, LC and GST were fermented and their effects were assessed in an animal model of RA. Both LC and fermented GST (fGST) treatment reduced mice serum nitrite and total cholesterol and triggered myeloperoxidase (MPO) activity. In addition, both LC and fGST reduced inflammation-related serum biomarkers such as tumor necrosis factor-α, interleukin (IL)-6, IL-17, and IL-1β. As per the morphological analysis, both LC and fGST protected hind paw joints against RA, and its related mRNA markers improved. Finally, arthritis scores were measured as an indicator of RA of the whole experimental period; the scores suggested that both LC and fGST protect against collagen-induced RA-related inflammation in a mouse model.

A new hybrid non-ribosomal peptide-polyketide antibiotic (serratamid) for phytoprotection was isolated from the ethyl acetate layer of tryptic soy agar culture of the soil bacterium Serratia plymuthica C1 through bioassay-guided fractionation. Its chemical structure was elucidated using instrumental analyses, such as mass and nuclear magnetic resonance spectrometry. Serratamid showed antibacterial activity against 15 phytopathogenic bacteria, with minimum inhibitory concentration (MIC) values ranging from 0.244 to 31.25 μg/mL. In vitro, it displayed strong antibacterial activity against Ralstonia solanacearum and four Xanthomonas spp., with MIC values (0.244-0.488 μg/mL) superior to those of streptomycin sulfate, oxolinic acid, and oxytetracycline. Further, serratamid and the ethyl acetate layer of S. plymuthica C1 effectively reduced bacterial wilt caused by R. solanacearum on tomato seedlings and fire blight caused by Erwinia on apple fruits in a dose-dependent manner. These results suggest that serratamid is a promising candidate as a potent bactericide for controlling bacterial diseases.

This study was conducted to provide foundational anatomical information of three infrequently used wood species growing in tropical areas. Three species of the genus Syzygium, namely the clove tree, kupa, and spicate eugenia, were selected. The representative anatomical features of these species were classified using the International Association of Wood Anatomists (IAWA) anatomical feature list. The representative anatomical features of the clove tree included the distribution of small vessels with tangential diameters of approximately 60 µm in cross-surface, a dense spacing of vessels, the axial parenchyma in narrow bands or lines up to three cells wide, and the body ray cells procumbent with over four rows of upright and/or square marginal cells. The kupa showed axial parenchyma confluent and the body ray cells were procumbent with over four rows of upright and/or square marginal cells. In the spicate eugenia, the axial parenchyma was diffused in aggregate with exclusively uniseriate rays and the body ray cells were procumbent with one row of upright and/or square marginal cells. These three species were easily identified by optical microscopy via the anatomical features of the woods.

The anatomical features of three valuable commercial Gigantochloa bamboo species growing in Indonesia, including G. pseudoarundinacea, G. apus, and G. atroviolacea, were investigated by optical microscopy. The relative crystallinity and crystalline width of the culm of the bamboo species were examined by an X-ray diffraction method. These species contained vascular bundle of type III. Vascular bundle density was higher in the outer part of bamboo culm than in the inner. Fiber portion decreased from the outer part to the inner part and vice versa for the parenchyma and vessel portions. Fiber length of all species was higher in the outer part than the inner part of the culm. There was a significant difference in the fiber percentage between the bamboo species. Significant differences were also found in vessel diameter and parenchyma cell dimensions among the bamboo species. There was a slight difference in the crystalline properties between the outer and inner parts of the culm and among the bamboo species. All parameters showed a variation in the radial direction of the three bamboo culm but did not show a consistent tendency along the vertical direction.

Mytilus coruscus Gould, 1861 is a mussel species in the family Mytilidae, native to the Northwest Pacific Ocean, ranging from the East China Sea, the Yellow Sea, and as far as the Peter the Great Gulf in the East Sea. In Korea, this species has been heavily exploited for nutrient-rich food resources and experienced severe reduction in their population. The aim of this study was to investigate the genetic diversity and population structure and to provide baseline data to facilitate the conservation and sustainable use of the vulnerable species M. coruscus in South Korea. Mitochondrial DNA (mtDNA) cytochrome c oxidase I (COI) sequences of 91 adult individuals from four islands and one coastal localities in South Korea were sequenced. We then compared genetic diversity and haplotype data with previously published Chinese wild populations. Mytilus coruscus populations on Korean coasts were found to exhibit high genetic diversity despite concerns regarding recent population reduction. A total of 42 haplotypes were defined by 56 polymorphic sites. High-level genetic diversity was observed on four Island sites (Hd = 0.906–0.955, π = 0.0068–0.0090). The other seashore site represented relatively lower genetic diversity (Hd = 0.529, π = 0.0011) and was genetically differentiated from the others. In a previous study, wild populations on the East China Sea exhibited similarly high genetic diversity as that observed in our study. Additionally, Chinese M. coruscus populations exhibit a distinct regional haplotype distribution pattern while sharing six haplotypes with Korean populations. The results of this study provide insights that further the current understanding regarding the evolution of M. coruscus species and provides comprehensive genetic data to facilitate the development of an effective conservation strategy.

The objective of this study was to evaluate the effects of Lactobacillus acidophilus ATCC 43121 and L. fermentum MF27 on biochemical indices in the serum, cholesterol metabolism in the liver and mucin expression in the gallbladder in lithogenic diet (LD)-induced C57BL/6J mice to determine the preventive effects of lactobacilli on gallstone formation. By the end of 4 wk of the experimental period, mice fed on a LD with high-fat and high-cholesterol exhibited higher levels of total and low-density lipoprotein cholesterol in the serum compared to mice fed on control diet or LD with L. acidophilus ATCC 43121 (LD+P1; p

Objectives The optimal treatment option for carbapenem-resistant Acinetobacter baumannii (CRAB) is still limited. This study investigated the efficacy of three or more antibiotic types and regimens for treatment of CRAB infection in high CRAB endemic areas. Methods A multicentre retrospective study was conducted to evaluate the efficacy of treatment types and regimens of CRAB infections in 10 tertiary hospitals in the Republic of Korea. The outcomes comprised 7-day and 28-day mortality, and clinical and microbiological responses at 7 days, 28 days, and the end of treatment. Nephrotoxicity and hepatotoxicity were evaluated as drug adverse reactions. Results A total of 282 patients were included in the study. Among the CRAB strains, the two most susceptible antibiotics were colistin (99.6%) and minocycline (80.4%). A combination of colistin and carbapenem significantly reduced 7-day mortality, and a sulbactam-containing regimen significantly reduced 28-day mortality. Colistin monotherapy was significantly associated with increased 7-day and 28-day mortality. A minocycline-containing regimen showed the best microbiological responses at 7 days, 28 days, and the end of treatment. Colistin and tigecycline were associated with increased nephrotoxicity and hepatotoxicity, respectively. Subgroup analysis of patients with pneumonia showed similar results to the overall CRAB infection. Conclusions A combination of colistin and carbapenem and sulbactam-containing regimen may contribute improved mortality in CRAB infections. Colistin monotherapy should be considered cautiously in severe CRAB infections or CRAB pneumonia. A minocycline-containing regimen showed the best microbiological responses, and further studies may be needed to evaluate improved mortality.

Anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) nucleoprotein (NP) antibodies were isolated from pig sera using human SARS-CoV-2 NP-immobilized magnetic beads. The binding properties of the isolated antibodies against SARS-CoV-2 NP were tested via flow cytometry using SARS-CoV-2 NP-immobilized magnetic beads. A competitive immunoassay was developed for detecting SARS-CoV-2 NP as well as SARS-CoV-2 in the culture fluid using magnetic beads with immobilized anti-SARS-CoV-2 NP antibodies. Selectivity tests were carried out during the competitive immunoassay for SARS-CoV, MERS-CoV, and CoV strain 229E in the culture fluid.

Obesity is one of the major causes of the development of metabolic diseases, particularly cardiovascular diseases and type-2 diabetes mellitus. Increased lipid accumulation and abnormal adipocyte growth, which is an increase in cell numbers and differentiation, have been documented as major pathological characteristics of obesity. Thus, the inhibition of adipogenic differentiation prevents and suppresses obesity. Recently, specific probiotic strains have been known to regulate lipid metabolism in vitro and/or in vivo. Previously, we demonstrated that Lactobacillus johnsonni 3121 and Lactobacillus rhamnosus 86 could act as novel probiotic strains and reduce cholesterol levels. Moreover, both strains significantly reduced lipid accumulation and inhibited adipocyte differentiation by downregulating the adipogenic transcription factor in 3T3-L1 adipocytes. Therefore, L. johnsonni 3121 and L. rhamnosus 86 were selected for in vivo evaluation of their anti-obesity effects using a high-fat diet-induced obese mouse model. Daily oral administration of L. johnsonni 3121 and L. rhamnosus 86 for 12 weeks significantly improved serum lipid profile and downregulated the expression of genes related to adipogenesis and lipogenesis in epididymal white adipose tissue of high-fat diet fed obese mice (p

Covering: 2010 to 2020 Over the last few decades, Streptomyces have been extensively investigated for their ability to produce diverse bioactive secondary metabolites. Recent advances in Streptomyces research have been largely supported by improvements in high-throughput technology 'omics'. From genomics, numerous secondary metabolite biosynthetic gene clusters were predicted, increasing their genomic potential for novel bioactive compound discovery. Additional omics, including transcriptomics, translatomics, interactomics, proteomics and metabolomics, have been applied to obtain a system-level understanding spanning entire bioprocesses of Streptomyces, revealing highly interconnected and multi-layered regulatory networks for secondary metabolism. The comprehensive understanding derived from this systematic information accelerates the rational engineering of Streptomyces to enhance secondary metabolite production, integrated with the exploitation of the highly efficient 'Design-Build-Test-Learn' cycle in synthetic biology. In this review, we describe the current status of omics applications in Streptomyces research to better understand the organism and exploit its genetic potential for higher production of valuable secondary metabolites and novel secondary metabolite discovery.

Background/aim Intestinal mucositis with diarrhea is a dose-limiting toxicity of 5-fluorouracil (5-FU). M40403, a superoxide dismutase mimetic, was evaluated on whether it improves the mucositis with diarrhea. Materials and methods BALB/c mice were treated with daily intraperitoneal injections of 5-FU±M40403 for five consecutive days. Following treatment, light microscopy (apoptosis), electron microscopy (autophagy), and analyses for the expression of apoptosis/autophagy-related proteins were performed in analysing small intestinal samples. Body weight, diarrhea score, blood cytokine levels, complete blood count, and blood chemistries were measured. The in vivo anti-tumor activity of 5-FU±M40403 was also evaluated. Results M40403 improved 5-FU-induced intestinal mucositis (apoptosis and autophagy) and attenuated 5-FU-induced changes in the expression of apoptosis/autophagy-related proteins, weight loss, diarrhea score, and serum TNF-α levels. M40403 neither added further adverse effects nor compromised the anti-tumor activity during 5-FU treatment. Conclusion M40403 can be useful in improving 5-FU-induced intestinal mucositis with diarrhea.

Bursaphelenchus xylophilus, commonly known as the pine wood nematode (PWN), is one of the most destructive nematode species. It causes pine wilt, a slow progressive disease that results in economic loss worldwide. Here, we review the nematode detection methods, including morphological, molecular, chemical, and protein-based methods, and assess how the nematode’s distribution, virulence, incidence, and severity may be attenuated. Pathogenicity of the pine wood nematode is determined via its morphological and molecular characteristics. Many studies have used nucleic acid PCR amplification as a molecular-based technique, but there are often problems with DNA isolation. Currently, molecular-, chemical-, and protein-based analysis methods are used to diagnose emerging pine wilt diseases. It is important to quickly diagnose and treat symptomatic trees, but the asymptomatic trees also require quick diagnosis and removal. For this reason, morphological- and DNA-based methods should be combined with chemical- and protein-based approaches for quick and efficient detection.

Introduction Early allograft dysfunction (EAD) is known to be a prototype of graft failure and ultimately influences long-term graft failure or death. We hypothesized that pretransplant thrombogenicity evaluated by procoagulant and anticoagulant, von Willebrand factor (vWF), factor Ⅷ (FⅧ), protein C (PC) and their imbalance ratio of vWF-to-PC (vWFPCR) and FVIII-to-PC (FⅧPCR), is associated with EAD and 90-day graft failure after living-related liver transplantation (LDLT) and contributes to further exacerbation of graft dysfunction when coexists with systemic inflammation. Material and methods Of 1199 prospectively registered LDLT patients, 698 with measurements of each thrombogenicity parameters were analyzed. Risk factors for EAD development were searched and subsequent best cut-offs was calculated according to the receiver operator characteristic curve analysis. When comparing the outcome, multivariable regression analysis and inverse probability of treatment weighting (IPTW) of the propensity score were performed. Results The prevalence of EAD was 10.7% (n = 75/698) after LDLT. Of parameters, vWFPCR had highest predictivity potential of EAD with the best cut-off of 8.06. The relationship between vWFPCR≥8.06 showed significant association with EAD development (OR [95%CI], 2.55[1.28–5.09], P = 0.008) and 90-day graft failure (HR [95%CI], 2.24 [1–4.98], P = 0.043) after IPTW-adjustment. Furthermore, risk of EAD increased proportionally with increasing C-reactive protein as a continuous metric of systemic inflammation, and more steeply in those with higher thrombogenicity (i.e., higher vWFPCR). Adding vWFPCR to MELD score improved EAD risk prediction by 21.9%. Conclusions Pretransplant thrombogenicity assessed by imbalance of pro- and anticoagulant, was significantly associated with EAD and 90-day graft failure after LDLT and this association was worsened by systemic inflammation.

Different ionic liquids (ILs) and their mixtures with organic solvents (OSs) were investigated to determine their effects on pretreatment for enzymatic saccharification of pussy willow and Korean pine. Combinations of three ILs, namely (1-ethyl-3-methylimidazolium acetate ([EMIM]Ac), 1-butyl-3-methylimidazolium bromide ([BMIM]Br), and 1,3-dimethylimidazolium methyl sulfate ([MMIM]MeSO4)) and three OSs (N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), and dimethyl sulfoxide (DMSO)) were used. Acremonium cellulase and Optimash BG were used for enzymatic saccharification. The viscosity of ILs and their mixtures with OSs was reduced by adding and increasing the OS amount in mixtures. The viscosity of [BMIM]Br was considerably decreased by the addition of OSs. For both species, the water-soluble fractions (WSFs) obtained using pure ILs decreased with increasing OS content in mixtures. For all co-solvent systems, the WSFs for pussy willow were twice as large as those for Korean pine. For both species, the yields of glucose and xylose were higher for [EMIM]Ac and its mixtures with OSs than for [BMIM]Br, [MMIM]MeSO4, and their mixtures. However, only small differences between glycan and xylose yields among the products pretreated by [BMIM]Br, [MMIM]MeSO4, and their mixtures were observed. The overall xylose yields for pussy willow were higher than those for Korean pine for all pretreatments because xylan is the main hemicellulose component of hardwood.

Osteoporosis is a disease in which bone mineral density decreases due to abnormal activity of osteoclasts, and is commonly found in post-menopausal women who have decreased levels of female hormones. Sphingosylphosphorylcholine (SPC) is an important biological lipid that can be converted to sphingosine-1-phosphate (S1P) by autotaxin. S1P is known to be involved in osteoclast activation by stimulating osteoblasts, but bone regulation by SPC is not well understood. In this study, we found that SPC strongly inhibits RANKL-induced osteoclast differentiation. SPC-induced inhibitory effects on osteoclast differentiation were not affected by several antagonists of S1P receptors or pertussis toxin, suggesting cell surface receptor independency. However, SPC inhibited RANKL-induced calcineurin activation and subsequent NFATc1 activity, leading to decrease of the expression of Trap and Ctsk. Moreover, we found that bone loss in an experimental osteoporosis mouse model was recovered by SPC injection. SPC also blocked ovariectomy-induced body weight increase and Nfatc1 gene expression in mice. We also found that SPC inhibits RANKL-induced osteoclast differentiation in human macrophages. Since currently available treatments for osteoporosis, such as administration of female hormones or hormone receptor modulators, show serious side effects, SPC has potential as a new agent for osteoporosis treatment.

Aim In this study, we investigated the anti-osteoporotic effect of two fermented milk products (FMPs) fermented by Lactobacillus plantarum A41 and Lactobacillus fermentum SRK414 on a rat model of ovariectomy-induced post-menopausal primary osteoporosis. Methods and results The two Lactobacillus FMPs increased the bone volume and bone mineral density (BMD) in ovariectomized (OVX) rats, and normalized the bone biomarkers in the serum. Additionally, they altered the gene expression levels of bone metabolism-related markers. Furthermore, the two Lactobacillus FMPs down regulated bone apoptosis-related genes stimulated by ovariectomy. Interestingly, the Lactobacillus FMPs decreased the levels of inflammation markers in the serum, bone, ileum, and colon of the rats. Gut bacterial populations were also affected upon FMP treatment due to increase in the abundance of the genus Lactobacillus and Faecalibacterium prausnitzii. Conclusions Milk products fermented by L. plantarum A41 and L. fermentum SRK414 can exhibit anti-osteoporotic effects on post-menopausal osteoporosis via regulating the expression of bone metabolism-related markers. Significance and impact of study The two Lactobacillus FMPs used in the study can be an ideal method that has its potential of treating post-menopausal osteoporosis instead of drug treatments.

The radial variation of rays within the stems of Dahurian larch and Japanese larch growing in Korea was studied to obtain valuable information to identify the two species and determine wood quality. Uniseriate ray height, fusiform ray height, ray number, ray spacing, and epithelial cell number were investigated by optical microscopy. The heights of uniseriate and fusiform rays and epithelial cell numbers in Dahurian larch were lower than those in Japanese larch. Dahurian larch wood had greater ray number and ray spacing than Japanese larch wood. In both species, the heights of uniseriate and fusiform rays and epithelial cell number increased with increasing growth ring number but then stabilized from a certain growth ring number. However, ray number and ray spacing decreased with age but were stable toward the bark. There were significant differences in all ray properties between the two species. Furthermore, in both species, the number and spacing of rays showed a significant negative correlation with uniseriate ray height. The relationships between uniseriate and fusiform ray height, and between ray spacing and ray number were significantly positive. In conclusion, the results from this study provide basic information that can be used to identify these species, and the quality indices from ray properties will improve the effective utilization of the two woody species.

Many stresses induce the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum, a phenomenon known as ER stress. In response to ER stress, cells initiate a protective response, known as unfolded protein response (UPR), to maintain cellular homeostasis. The UPR sensor, inositol-requiring enzyme 1 (IRE1), catalyzes the cytoplasmic splicing of bZIP transcription factor-encoding mRNAs to activate the UPR signaling pathway. Recently, we reported that pretreatment of Arabidopsis thaliana plants with tunicamycin, an ER stress inducer, increased their susceptibility to bacterial pathogens; on the other hand, IRE1 deficient mutants were susceptible to Pseudomonas syringae pv. maculicola (Psm) and failed to induce salicylic acid (SA)-mediated systemic acquired resistance. However, the functional relationship of IRE1 with the pathogen and TM treatment remains unknown. In the present study, we showed that bacterial pathogen-associated molecular patterns (PAMPs) induced IRE1 expression; however, PAMP-triggered immunity (PTI) response such as callose deposition, PR1 protein accumulation, or Pst DC3000 hrcC growth was not altered in ire1 mutants. We observed that IRE1 enhanced plant immunity against the bacterial pathogen P. syringae pv. tomato DC3000 (Pst DC3000) under ER stress. Moreover, TM-pretreated ire1 mutants were more susceptible to the avirulent strain Pst DC3000 (AvrRpt2) and showed greater cell death than wild-type plants during effector-triggered immunity (ETI). Additionally, Pst DC3000 (AvrRpt2)-mediated RIN4 degradation was reduced in ire1 mutants under TM-induced ER stress. Collectively, our results reveal that IRE1 plays a pivotal role in the immune signaling pathway to activate plant immunity against virulent and avirulent bacterial strains under ER stress.

Background Cholinergic interneurons (ChINs) in the nucleus accumbens (NAc) play critical roles in processing information related to reward. However, the contribution of ChINs to the emergence of addiction-like behaviors and its underlying molecular mechanisms remain elusive. Methods We employed cocaine self-administration to identify two mouse subpopulations: susceptible and resilient to cocaine seeking. We compared the subpopulations for physiological responses with single-unit recording of NAc ChINs, and for gene expression levels with RNA sequencing of ChINs sorted using fluorescence-activated cell sorting. To provide evidence for a causal relationship, we manipulated the expression level of dopamine D2 receptor (DRD2) in ChINs in a cell type–specific manner. Using optogenetic activation combined with a double whole-cell recording, the effect of ChIN-specific DRD2 manipulation on each synaptic input was assessed in NAc medium spiny neurons in a pathway-specific manner. Results Susceptible mice showed higher levels of nosepoke responses under a progressive ratio schedule, and impairment in extinction and punishment procedures. DRD2 was highly abundant in the NAc ChINs of susceptible mice. Elevated abundance of DRD2 in NAc ChINs was sufficient and necessary to express high cocaine motivation, putatively through reduction of ChIN activity during cocaine exposure. DRD2 overexpression in ChINs mimicked cocaine-induced effects on the dendritic spine density and the ratios of excitatory inputs between two distinct medium spiny neuron cell types, while DRD2 depletion precluded cocaine-induced synaptic plasticity. Conclusions These findings provide a molecular mechanism for dopaminergic control of NAc ChINs that can control the susceptibility to cocaine-seeking behavior.

This study aimed to investigate the effects of glycated milk casein (Gc) fermented with Lactobacillus rhamnosus 4B15 (FGc) on the intestinal microbiota and physiological and behavioral properties in mice under chronic stress. Mice were administered Gc or FGc for 10 weeks and then exposed to unpredictable chronic mild stress (UCMS) for 7 weeks. FGc administration restored alterations of gut microbiota induced by UCMS. Moreover, FGc significantly reduced the stress-induced increase in serum corticosterone and decrease in serotonin levels. Anxiety-like behaviors induced by UCMS were also significantly decreased in the FGc group. UCMS-induced dysregulation of gene and protein expression related to neuroendocrine function, neuronal development, and inflammation, and gut-blood-brain barrier function was controlled by FGc pre-treatment. These results strongly suggest the protective effects of FGc targeting of intestinal microbiota for abnormal brain activity, which is consistent with the view that FGc plays an important role in regulating stress-related gut-brain axis disorders.

Anti-coronavirusdisease-2019 (COVID-19; anti-severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2)) antibodies against nucleoprotein (NP) were purified from pig sera. Following the separation of the antibody fraction using a protein-A column, the final yield of the purified antibodies against SARS-CoV-2 NPs was estimated to be 0.26 ± 0.05 % (absolute amount of 143.4 ± 25.2 ng, n=5) from 1 mL of pig sera. The binding activities of the isolated antibodies were confirmed using immunoassay and immunostaining. Based on the specific binding activity to NPs, a quantitative assay was performed using a surface plasmon resonance (SPR) biosensor. From the doseresponse curve, the binding constant (Kd) was calculated to be 185 pM and the limit of detection was estimated to be 1.02 pM. The SPR biosensor with the isolated antibodies against SARS-CoV-2 NPs was applied for the detection of SARS-CoV-2, MERS-CoV, and CoV strain 229E in culture fluid.

Specialized proresolving mediators (SPMs), such as resolvins and maresins, resolve inflammation and protect against infection at trace amounts generated by neutrophils and macrophages in humans. Th...

Nuclear protein HMGB1 is secreted in response to various stimuli and functions as a danger-associated molecular pattern. Extracellular HMGB1 induces inflammation, cytokine production, and immune cell recruitment via activation of various receptors. As HMGB1 does not contain an endoplasmic reticulum-targeting signal peptide, HMGB1 is secreted via the endoplasmic reticulum-Golgi independently via an unconventional secretion pathway. However, the mechanism underlying HMGB1 secretion remains largely unknown. Here, we investigated the role of secretory autophagy machinery and vesicular trafficking in HMGB1 secretion. We observed that HSP90AA1 (heat shock protein 90 alpha family class A member 1), a stress-inducible protein, regulates the translocation of HMGB1 from the nucleus to the cytoplasm and its secretion through direct interaction. Additionally, geldanamycin, an HSP90AA1 inhibitor, reduced HMGB1 secretion. GORASP2/GRASP55 (golgi reassembly stacking protein 2), ARF1Q71L (ADP ribosylation factor 1), and SAR1AT39N (secretion associated Ras related GTPase 1A), which promoted unconventional protein secretion, increased HMGB1 secretion. HMGB1 secretion was inhibited by an early autophagy inhibitor and diminished in ATG5-deficient cells even when GORASP2 was overexpressed. In contrast, a late autophagy inhibitor increased HMGB1 secretion under the same conditions. The multivesicular body formation inhibitor GW4869 dramatically decreased HMGB1 secretion under HMGB1 secretion-inducing conditions. Thus, we demonstrated that secretory autophagy and multivesicular body formation mediate HMGB1 secretion.

Acne is a chronic skin disease that typically occurs in the teens and twenties, and its symptoms vary according to age, sex, diet, and lifestyle. The condition is characterized by hyperproliferation of keratinocytes in the epidermis, sebum overproduction, excessive growth of Propionibacterium acnes, and P. acnes-induced skin inflammation. Interleukin (IL)-1α and IL-6 are predominant in the inflammatory lesions of acne vulgaris. These cytokines induce an inflammatory reaction in the skin in the presence of pathogens or stresses. Moreover, IL-1α accelerates the production of keratin 16, which is typically expressed in wounded or aberrant skin, leading to abnormalities in architecture and hyperkeratinization. Orobol (3',4',5,7-tetrahydroxyisoflavone) is a metabolite of genistein that inhibited the P. acnes-induced increases in IL-6 and IL-1α levels in human keratinocytes (HaCaTs) more effectively compared with salicylic acid. In addition, orobol decreased the IL-1α and IL-6 mRNA levels and inhibited the phosphorylation of inhibitor of kappa-B kinase, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, and mitogen-activated protein kinase induced by P. acnes. Finally, the expression of Ki67 was decreased by orobol. Thus, orobol ameliorated the inflammation and hyperkeratinization induced by heat-killed P. acnes and thus has potential for use in functional foods and cosmetics.

Pectobacterium carotovorum subsp. carotovorum (Pcc) causes bacterial soft rot on a wide range of crops worldwide, especially in countries with warm and humid climates. This study was conducted to establish an efficient screening method for resistant cultivars of Chinese cabbage to bacterial soft rot. Resistance degrees of 65 commercial Chinese cabbage cultivars to the Pcc KACC 10225 isolate were investigated. For further study, three Chinse cabbage cultivars (Taebong, Hadaejangkun, CR Alchan) showing different level of resistance to the bacterium were selected. The development of bacterial soft rot on the cultivars was tested according to several conditions such as growth stage of Chinse cabbage seedling, inoculum concentration, and incubation temperature after inoculation. On the basis of the results, we suggest that an efficient screening method for resistant Chinses cabbage to Pcc is to inoculate twenty one-day-old seedlings with a bacterial suspension of Pcc at a concentration of 1×107 cfu/ml, and to incubate the plants in a dew chamber at 25°C for 24 hr and then to cultivate in a growth room at 25°C and 80% relative humidity with 12-hr light per day.