Systemic antibiotics cause deterioration of emphysema associated with exaggerated inflammation and autophagy.

The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it is unclear whether dysbiosis caused by antibiotics can affect disease progression. Here, we tried to elucidate the effect of systemic antibiotics on smoking-exposed emphysema models. In this study, the antibiotic mixture caused more alveolar destruction and airspace expansion in the smoking group than in the smoking only or control groups. This emphysema aggravation as a result of antibiotic exposure was associated with increased levels of inflammatory cells, IL-6, IFNγ and protein concentrations in bronchoalveolar lavage fluid. Proteomics analysis indicated that autophagy could be involved in antibiotic-associated emphysema aggravation, and increased protein levels of LC3B, atg3, and atg7 were identified by Western blotting. In microbiome and metabolome analyses, the composition of the gut microbiota was different with smoking and antibiotic exposure, and the levels of short-chain fatty acids (SCFAs), including acetate and propionate, were reduced by antibiotic exposure. SCFA administration restored emphysema development with reduced inflammatory cells, IL-6, and IFNγ and decreased LC3B, atg3, and atg7 levels. In conclusion, antibiotics can aggravate emphysema, and inflammation and autophagy may be associated with this aggravation. This study provides important insight into the systemic impact of microbial dysbiosis and the therapeutic potential of utilizing the gut microbiota in emphysema.

COVID-19 Vaccine Acceptance during Pregnancy and Influencing Factors in South Korea.

Pregnant women were excluded from vaccination against Coronavirus 2019 (COVID-19) until September 2021 in South Korea. Although vaccination for pregnant women started in October 2021, vaccine acceptance in pregnant women is yet unknown. This cross-sectional study aimed to investigate COVID-19 vaccine acceptance during pregnancy and influencing factors. An anonymous survey was distributed in obstetrics departments to all pregnant or postpartum women, during the prenatal or postpartum visit. The proportion of self-reported COVID-19 vaccination during pregnancy among 436 women was 26.6%. Pregnancy-related independent factors influencing maternal COVID-19 vaccination were "received vaccine information about from obstetrics and gynecology (OBGYN) doctors" (OR 3.41, 95% CI 2.05-5.65), "cohabitant COVID-19 vaccination" (OR 2.43, 95% CI 1.06-5.59), and "second trimester" (OR 7.35, 95% CI 1.54-35.15). In women who did not want to get vaccinated, the most common reason for COVID-19 vaccination hesitancy was concern that COVID-19 vaccine might affect the fetus (91.7%, 243/266), followed by distrust in COVID-19 vaccine effectiveness (42.6%, 113/266). This study showed that providing information about maternal COVID-19 vaccination, especially by OBGYN doctors, is crucial for increasing vaccination coverage in pregnant women. Providing updated evidence of COVID-19 vaccine efficacy and safety in pregnant women may be also helpful for increasing vaccine acceptance.

The microbiome of lung cancer tissue and its association with pathological and clinical parameters.

Lung cancer is the primary cause of cancer-related deaths worldwide. Recently, although the microbiome has emerged as the key modulator of the carcinogenesis, it has not been evaluated in lung cancer. Here, we evaluated the microbial composition of lung cancer tissues according to the histologic type and genetic mutation, compared it with that of the adjacent normal lung tissues, and investigated the association between the lung microbiome and clinical parameters. We collected lung tissue samples from 162 patients with non-small cell lung cancer (NSCLC, 162 cancer and 54 adjacent normal tissues), surgically resected between January 2018 and December 2019, and analyzed their microbiome using 16S rRNA gene amplicon sequencing, the QIIME2 pipeline, and statistical analyses. NSCLC tissues had significantly lower alpha diversity than the normal tissues, and their microbial composition differed according to the histologic type and cancer genetic mutation. The genera Romboutsia, Novosphingobium, Acinetobacter, and Prevotella were significantly overrepresented in NSCLC tissues. Alpha diversity steadily declined from a normal to a more advanced stage, and microbial compositional differences were noted along with recurrence. Stenotrophomonas was the most predominant genus in the NSCLC tissues of patients with recurrence. The pathways related to the tricarboxylic acid cycle and L-glutamate and L-glutamine biosynthesis were predominant in adenocarcinoma, whereas those related to purine and pyrimidine nucleotide degradation and formaldehyde assimilation were predominant in squamous cell carcinoma. Our findings suggest that the altered lung cancer microbial composition might be associated with cancer initiation and/or progression.

A split face study on the effect of an anti-acne product containing fermentation products of Enterococcus faecalis CBT SL-5 on skin microbiome modification and acne improvement.

Antibiotic-resistant Cutibacterium acnes and dysbiosis of the skin microbiome are of increasing concern in acne treatment. Enterococcus faecalis, a widely used probiotic, has shown benefits for acne treatment by exerting antimicrobial activity against C. acnes. Therefore, this study aimed to investigate the efficacy and safety of an E. faecalis CBT SL-5-extract-containing lotion in patients with mild-to-moderate acne. Twenty patients were enrolled in this randomized, placebo-controlled, split-face comparative study. Patients were treated with E. faecalis lotion on one side of the face and a vehicle lotion on the other side for 4 weeks. The efficacy outcome measures included improvement in the investigators' assessment of acne severity, patient satisfaction, changes in skin parameters and diversity of the skin microbiome. The investigators' assessment score was significantly improved on the test side compared to the control side, after 2 weeks (p = 0.009) and 6 weeks (p < 0.0005). However, TEWL and skin hydration were not significantly different between the two groups. The phylogenetic diversity of the skin microbiota decreased over time in the skin samples of test side. In conclusion, E. faecalis CBT SL-5 extract can be a feasible and well-tolerated option for improving acne severity and skin microbiome dysbiosis in mild-to-moderate acne patients.

Inhibition of RANKL-induced osteoclast differentiation through the downregulation of c-Fos and NFATc1 by Eremochloa ophiuroides (centipedegrass) extract.

Osteoclasts, derived from hematopoietic stem cells, are specialized macrophages and have a homeostatic role in skeletal modeling and remodeling with bone-forming osteoblasts. However, excessive osteoclast activity induces bone diseases, including osteoporosis, periodontitis and rheumatoid arthritis. Natural substances have received attention as therapeutic drugs in human diseases. In the current study, cells isolated from mouse bone marrow, and a mouse model, were used to determine the effect of centipedegrass extract (CGE) on osteoclasts. Multiple concentrations of CGE were administered to bone marrow cells for 24­72 hours and, for the in vivo study, mice were treated with CGE for 8 days. The effects of CGE on transcription and translation of osteoclast-associated molecules were then determined using reverse transcription-polymerase chain reaction and immunoblotting, respectively. In the present study it was shown that CGE extracted from Eremochloa ophiuroides (centipedegrass) inhibited receptor activator of nuclear factor κ­B ligand (RANKL)­mediated osteoclast differentiation in bone marrow macrophages, without cytotoxicity, in a dose­dependent manner. CGE decreased the expression levels of osteoclast­specific genes, including matrix metalloproteinase­9, osteoclast­associated immunoglobulin­like receptor and cathepsin K, however, CGE had no inhibitory effect on the expression levels of mitogen­activated protein kinases, nuclear factor­κB and Akt. Furthermore, the protein and RNA levels of RANKL­induced c­Fos and nuclear factor of activated T-cell cytoplasmic 1 were suppressed by CGE. These results indicated that CGE may serve as a useful drug in the prevention of bone loss.

Total Aortic Arch Revascularization with Extra-anatomic Bypass for Takayasu Arteritis.

Total arch replacement with median sternotomy and hypothermic circulatory arrest is described for Takayasu arteritis (TA) with aortic arch and supra-aortic trunk involvement.(1,2) We report aortic arch revascularization using extra-anatomic bypass through partial sternotomy, without cardiopulmonary bypass, in a TA patient. Avoidance of cardiopulmonary bypass may enhance outcomes and represent an attractive approach to arch revascularization in TA.

Centipedegrass extract induces apoptosis through the activation of caspases and the downregulation of PI3K/Akt and MAPK phosphorylation in leukemia cells.

Acute lymphoblastic leukemia (ALL), which involves the blood and bone marrow, is the most common type of cancer in children younger than 5 years of age. Previous studies have investigated the effects of centipedegrass extract (CGE), which is mainly composed of maysin and its derivatives, and have demonstrated that it has various biological activities, including antioxidant and anti­inflammatory activities, pancreatic lipase inhibitory activity, anti-adipogenic activity and insecticidal activity. To the best of our knowledge, this study is the first to investigate the anticancer effects of CGE in ALL cell lines and to elucidate the mechanisms underlying these effects. Cell viability was measured by thiazolyl blue tetrazolium blue (MTT) assay. Apoptosis, cell cycle progression and mitochondrial membrane potential (∆Ψm) were determined by flow cytometry. The effects of CGE on the phosphatidylinositol 3­kinase (PI3K)/Akt pathway and mitogen­activated protein kinases (MAPKs) were assessed by immunoblotting. PI3K, MAPK and caspase inhibitors were used to further confirm the molecular mechanisms involved. Our results clearly demonstrated that the proliferation of the ALL cells was significantly inhibited by CGE in a dose­dependent manner. Apoptosis was accompanied by the induction of significant G1 cell cycle arrest. The resulting alteration of the ∆Ψm increased the activity of caspase­3/7. The induction of apoptosis was enhanced by the combined treatment of CGE with a PI3K inhibitor or an extracellular signal-regulated kinase (ERK) inhibitor, whereas the CGE­induced apoptosis was inhibited in the presence of caspase inhibitors, such as z­VAD­fmk and z­IETD­fmk. Furthermore, CGE inhibited PI3K activity by decreasing the levels of phosphorylated (p­)Akt, p­BAD, and Bcl­2 together with the levels of MAPKs, including p­ERK and p­JNK, but demonstrated no effects on p38 MAPK. Thus, our data suggest that CGE may be a novel natural compound with potential for use as an antitumor agent in ALL.

Molecular mechanism of apoptosis induction in skin cancer cells by the centipedegrass extract.

BACKGROUND: Centipedegrass extract (CGE) is mainly composed of maysin and its derivatives, which are recognized internationally as natural compounds. Compared to other flavonoids, maysin has a unique structure in that mannose is bound to the flavonoid backbone. CGE exhibits some biological properties in that it can function as an anti-oxidant, anti-inflammatory, anti-adipogenic, and insecticidal. Whether CGE has other biological functions, such as anti-cancer activity, is unknown. METHODS: B16F1 (mouse) and SKMEL-5 (human) cells were treated with CGE, and their subsequent survival was determined using MTT assay. We performed a cell cycle analysis using propidium iodide (PI), and detected apoptosis using double staining with annexin V-FITC/PI. In addition, we examined mitochondrial membrane potentials using flow cytometry, as well as signaling mechanisms with an immunoblotting analysis. RESULTS: CGE inhibited skin cancer cell growth by arresting the cell cycle in the G2/M phase, and increased both early and late apoptotic cell populations without affecting normal cells. Furthermore, we observed mitochondrial transmembrane depolarization, increased cytochrome-c release, caspase-3 and caspase-7 activation, and increased poly ADP-ribose polymerase degradation. CGE also downregulated activation of p-AKT, p-glycogen synthase kinase-3ß (GSK-3ß), and p-BAD in a time-dependent manner. LY294002 inhibition of phosphoinositide 3-kinase (PI3K) significantly sensitized skin cancer cells, which led to an increase in CGE-induced apoptosis. CONCLUSIONS: CGE controlled skin cancer cell growth by inhibiting the PI3K/AKT/GSK-3ß signaling pathway and activating the effector caspases. This study is the first to demonstrate anti-cancer properties for CGE, and that CGE may be an effective therapeutic agent for treating skin cancer.

Hispidulin attenuates bone resorption and osteoclastogenesis via the RANKL-induced NF-κB and NFATc1 pathways.

Hispidulin, a flavonoid that is known to have anti-inflammatory and anti-oxidant effects, attenuates osteoclastogenesis and bone resorption. To investigate the molecular mechanism of its inhibitory effect on osteoclastogenesis, we employed the receptor activator of the nuclear factor κB (NF-κB) ligand (RANKL)-induced murine monocyte/macrophage RAW 264.7 cells and bone marrow-derived macrophages (BMMs) for osteoclastic differentiation in vitro. The inhibitory effect on in vitro osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and by measuring the expression levels of osteoclast-specific genes such as matrix metalloproteinase 9 (MMP9), TRAP and cathepsin K. Similarly, hispidulin significantly inhibited osteoclast activity in RAW 264.7 cell as well as stimulated the ALP activity of MC3T3E1 cells. Furthermore, the in vivo suppressive effect on bone loss was assessed quantitatively in a lipopolysaccharide (LPS)-induced mouse model using microcomputational tomography (µCT) and histochemical analyses. Hispidulin was found to inhibit RANKL-induced activation of Jun N-terminal kinase (JNK) and p38, in addition to NF-κB in vitro experiment. Additionally, hispidulin decreased NFATc1 transcriptional activity in RANKL-induced osteoclastogenesis. This study identifies hispidulin as a potent inhibitor of osteoclastogenesis and bone resorption and provides evidence for its therapeutic potential to treat diseases involving abnormal bone lysis.

Anti-angiogenic and anti-tumor activity of Bavachinin by targeting hypoxia-inducible factor-1α.

Hypoxia-inducible factor-1 (HIF-1) consists of two subunits, the HIF-1ß, which is constitutively expressed, and HIF-1α, which is oxygen-responsive. HIF-1α is over-expressed in response to hypoxia, increasing transcriptional activity linked to tumor progression, angiogenesis, metastasis, and invasion. This study aimed to demonstrate that the natural compound, Bavachinin, has potent anti-angiogenic activity in vitro and in vivo. Bavachinin inhibited increases in HIF-1α activity in human KB carcinoma (HeLa cell derivative) and human HOS osteosarcoma cells under hypoxia in a concentration-dependent manner, probably by enhancing the interaction between von Hippel-Lindau (VHL) and HIF-1α. Furthermore, Bavachinin decreased transcription of genes associated with angiogenesis and energy metabolism that are regulated by HIF-1, such as vascular endothelial growth factors (VEGF), Glut 1 and Hexokinase 2. Bavachinin also inhibited tube formation in human umbilical vein endothelial cells (HUVECs) as well as in vitro migration of KB cells. In vivo studies showed that injecting Bavachinin thrice weekly for four weeks significantly reduced tumor volume and CD31 expression in nude mice with KB xenografts. These data indicate that Bavachinin could be used as a therapeutic agent for inhibiting tumor angiogenesis.

Isopsoralen Induces Differentiation of Prechondrogenic ATDC5 Cells via Activation of MAP Kinases and BMP-2 Signaling Pathways.

Endochondral bone formation is the process by which mesenchymal cells condense to become chondrocytes, which ultimately form new bone. The process of chondrogenic differentiation and hypertrophy is critical for bone formation and as such is regulated by many factors. In this study, we aimed to indentify novel factors that regulate chondrogenesis. We investigated the possible role of isopsoralen in induction of chondrogenic differentiation in clonal mouse chondrogenic ATDC5 cells. Isopsoralen treatment stimulated the accumulation of cartilage nodules in a dose-dependent manner. Further, ATDC5 cells treated with isopsoralen were stained more intensely with Alcian blue than control cells, suggesting that isopsoralen increases the synthesis of matrix proteoglycans. Similarly, isopsoralen markedly induced the activation of alkaline phosphatase activity compared with control cells. Isopsoralen enhanced the expressions of chondrogenic marker genes such as collagen II, collagen X, OCN, Smad4 and Sox9 in a time-dependent manner. Furthermore, isopsoralen induced the activation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase, but not that of c-jun N-terminal kinase (JNK). Isopsoralen significantly enhanced the protein expression of BMP-2 in a time-dependent manner. PD98059 and SB 203580, inhibitors of ERK and p38 MAPK, respectively, decreased the number of stained cells treated with isopsoralen. Taken together, these results suggest that isopsoralen mediates a chondromodulating effect by BMP-2 or MAPK signaling pathways, and is therefore a possible therapeutic agent for bone growth disorders.

Inhibition of osteoclastogenic differentiation by Ikarisoside A in RAW 264.7 cells via JNK and NF-kappaB signaling pathways.

Osteoclasts are specialized bone-resorbing cells derived from multipotent myeloid progenitor cells. They play a crucial homeostatic role in skeletal modeling and remodeling and destroy bone in many pathologic conditions. Receptor activator of NF-kappaB ligand (RANKL) is essential to osteoclastogenesis. In this study, we investigated the effects of Ikarisoside A, isolated from Epimedium koreanum (Berberidaceae), on osteoclastogenesis in RANKL-treated murine monocyte/macrophage RAW 264.7 cells. The results indicate that Ikarisoside A is a potent inhibitor of osteoclastogenesis in RANKL-stimulated RAW 264.7 cells as well as in bone marrow-derived macrophages. The inhibitory effect of Ikarisoside A resulted in decrease of osteoclast-specific genes like matrix metalloproteinase 9 (MMP9), tartrate-resistant acid phosphatase (TRAP), receptor activator of NF-kappaB (RANK), and cathepsin K. Moreover, Ikarisoside A blocked the resorbing capacity of RAW 264.7 cells on calcium phosphate-coated plates. Ikarisoside A also has inhibitory effects on the RANKL-mediated activation of NF-kappaB, JNK, and Akt. Finally, Ikarisoside A clearly decreased the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1) as well as the transcriptional activity of NFATc1, the master regulator of osteoclast differentiation. The data indicate that Ikarisoside A has potential for use in treatment of diseases involving abnormal bone lysis such as osteoporosis, rheumatoid arthritis, and periodontal bone erosion.

Development of regenerable MgO-based sorbent promoted with K2CO3 for CO2 capture at low temperatures.

To improve their CO2 absorption capacity, alkali-based sorbents prepared by impregnation and wet mixing method of potassium carbonate on supports such as activated carbon and MgO (KACI30, KACP30, KMgI30, and KMgP30), were investigated in a fixed bed reactor (C02 absorption at 50-100 degrees C and regeneration at 150-400 degrees C). Total CO2 capture capacities of KMgI30-500 and KMgP30-500 were 178.6 and 197.6 mg CO2/g sorbent, respectively, in the presence of 11 vol % H2O even at 50 degrees C. The large amount of CO2 capture capacity of KMgP30-500 and KMgI30-500 could be explained by the fact that MgO itself, as well as K2CO3, could absorb CO2 in the presence of water vapor even at low temperatures. In particular, water vapor plays an important role in the CO2 absorption of MgO and KMgI30-500 even at low temperatures below 60 degrees C, in marked contrast to MgO and CaO which can absorb CO2 at high temperatures. The CO2 capture capacity of the KMgI30-300 sorbent, however, was less than that of KMgI30-500 due to the formation of Mg(OH)2 which did not absorb CO2. MgO based-sorbents promoted with K2CO3 after CO2 absorption formed new structures such as K2Mg(CO3)2 and K2Mg(CO3)2 x 4(H2O), unlike KACI30 which showed only the KHCO3 crystal structure. The new Mg-based sorbents promoted with K2CO3 showed excellent characteristics in that it could satisfy a large amount of CO2 absorption at low temperatures, a high CO2 absorption rate, and fast and complete regeneration.