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E7050 is an inhibitor of VEGFR2 with anti-tumor activity; however, its therapeutic mechanism remains incompletely understood. In the present study, we aim to evaluate the anti-angiogenic activity of E7050 in vitro and in vivo and define the underlying molecular mechanism. It was observed that treatment with E7050 markedly inhibited proliferation, migration, and capillary-like tube formation in cultured human umbilical vein endothelial cells (HUVECs). E7050 exposure in the chick embryo chorioallantoic membrane (CAM) also reduced the amount of neovessel formation in chick embryos. To understand the molecular basis, E7050 was found to suppress the phosphorylation of VEGFR2 and its downstream signaling pathway components, including PLCγ1, FAK, Src, Akt, JNK, and p38 MAPK in VEGF-stimulated HUVECs. Moreover, E7050 suppressed the phosphorylation of VEGFR2, FAK, Src, Akt, JNK, and p38 MAPK in HUVECs exposed to MES-SA/Dx5 cells-derived conditioned medium (CM). The multidrug-resistant human uterine sarcoma xenograft study revealed that E7050 significantly attenuated the growth of MES-SA/Dx5 tumor xenografts, which was associated with inhibition of tumor angiogenesis. E7050 treatment also decreased the expression of CD31 and p-VEGFR2 in MES-SA/Dx5 tumor tissue sections in comparison with the vehicle control. Collectively, E7050 may serve as a potential agent for the treatment of cancer and angiogenesis-related disorders. [ABSTRACT FROM AUTHOR]

E7050 is a potent inhibitor of c-Met receptor tyrosine kinase and has potential for cancer therapy. However, the underlying molecular mechanism involved in the anti-cancer property of E7050 has not been fully elucidated. The main objective of this study was to investigate the anti-tumor activity of E7050 in multidrug-resistant human uterine sarcoma MES-SA/Dx5 cells in vitro and in vivo, and to define its mechanisms. Our results revealed that E7050 reduced cell viability of MES-SA/Dx5 cells, which was associated with the induction of apoptosis and S phase cell cycle arrest. Additionally, E7050 treatment significantly upregulated the expression of Bax, cleaved PARP, cleaved caspase-3, p21, p53 and cyclin D1, while it downregulated the expression of survivin and cyclin A. On the other hand, the mechanistic study demonstrated that E7050 inhibited the phosphorylation of c-Met, Src, Akt and p38 in HGF-stimulated MES-SA/Dx5 cells. Further in vivo experiments showed that treatment of athymic nude mice carrying MES-SA/Dx5 xenograft tumors with E7050 remarkably suppressed tumor growth. E7050 treatment also decreased the expression of Ki-67 and p-Met, and increased the expression of cleaved caspase-3 in MES-SA/Dx5 tumor sections. Therefore, E7050 is a promising drug that can be developed for the treatment of multidrug-resistant uterine sarcoma. [ABSTRACT FROM AUTHOR]

Previous studies arguing for parental care in dinosaurs have been primarily based on fossil accumulations of adults and hatchlings, perinatal and post-hatchlings in nests and nest areas, and evidence of brooding, the majority of which date to the Late Cretaceous. Similarly, the general body proportions of preserved embryonic skeletons of the much older Early Jurassic Massospondylus have been used to suggest that hatchlings were unable to forage for themselves. Here, we approach the question of parental care in dinosaurs by using a combined morphological, chemical, and biomechanical approach to compare early embryonic and hatchling bones of the Early Jurassic sauropodomorph Lufengosaurus with those of extant avian taxa with known levels of parental care. We compare femora, the main weight-bearing limb bone, at various embryonic and post-embryonic stages in a precocious and an altricial extant avian dinosaur with those of embryonic and hatchling Lufengosaurus, and find that the rate and degree of bone development in Lufengosaurus is closer to that of the highly altricial Columba (pigeon) than the precocious Gallus (chicken), providing strong support for the hypothesis that Lufengosaurus was fully altricial. We suggest that the limb bones of Lufengosaurus hatchlings were not strong enough to forage for themselves and would likely need parental feeding. [ABSTRACT FROM AUTHOR]

Multidrug-resistant (MDR) cancer is a major clinical problem in chemotherapy of cancer patients. We have noted inappropriate PKCδ hypomethylation and overexpression of genes in the PKCδ/AP-1 pathway in the human uterus sarcoma drug-resistant cell line, MES-SA/Dx5 cells, which also overexpress p-glycoprotein (ABCB1). Recent studies have indicated that FZD1 is overexpressed in both multidrug-resistant cancer cell lines and in clinical tumor samples. These data have led us to hypothesize that the FZD1-mediated PKCδ signal-transduction pathway may play an important role in drug resistance in MES-SA/Dx5 cells. In this work, the PKCδ inhibitor Rottlerin was found to reduce ABCB1 expression and to inhibit the MDR drug pumping ability in the MES-SA/Dx5 cells when compared with the doxorubicin-sensitive parental cell line, MES-SA. PKCδ was up-regulated with concurrent up-regulation of the mRNA levels of the AP-1-related factors, c-JUN and c-FOS. Activation of AP-1 also correlated with up-regulation of the AP-1 downstream genes HGF and EGR1. Furthermore, AP-1 activities were reduced and the AP-1 downstream genes were down-regulated in Rottlerin-treated or PKCδ shRNA-transfected cells. MES-SA/Dx5 cells were resensitized to doxorubicin-induced toxicity by co-treatment with doxorubicin and Rottlerin or PKCδ shRNA. In addition, cell viability and drug pump-out ability were significantly reduced in the FZD1 inhibitor curcumin-treated and FZD1 shRNA-knockdown MES-SA/Dx5 cells, indicating involvement of PKCδ in FZD1-modulated ABCB1 expression pathway. Taken together, our data demonstrate that FZD1 regulates PKCδ, and the PKCδ/AP-1 signalling transduction pathway plays an important role in drug resistance in MES-SA/Dx5 cells. [ABSTRACT FROM AUTHOR]

The article presents a study that investigated the effect of Helicobacter pylori infection on intragastric acidity in patients with reflux esophagitis. The study found that patients with reflux esophagitis and Helicobacter pylori infection had less intragastric acidity than those without Helicobacter pylori infection. However, the extent of acid suppression was insufficient to protect the esophagus from acid injury. In addition, the degree of esophageal motility dysfunction was similar in both groups.

Background: A prospective, randomized study was conducted to evaluate the efficacy of cefuroxime-impregnated cement in the prevention of deep infection after primary total knee arthroplasties performed without so-called clean-air measures, such as laminar flow and body-exhaust suits.Methods: Three hundred and forty primary total knee arthroplasties were performed with cementless fixation of the femoral component and cement fixation of the patellar and tibial components. The knees were randomly divided into two groups. In Group 1 (178 knees), cefuroxime-impregnated cement was used for fixation, whereas in Group 2 (162 knees), the cement did not contain cefuroxime. There was no significant difference between the two groups regarding demographic variables, the preoperative or postoperative knee score, the duration of the operation or of the use of the tourniquet, or the amount of blood transfused perioperatively. The average duration of follow-up was forty-nine months (range, twenty-six to eighty months).Results: No deep infection developed in the 178 knees in Group 1, whereas a deep infection developed in five (3.1%) of the 162 knees in Group 2 (p = 0.0238). Two superficial wound infections developed in each group.Conclusions: Cefuroxime-impregnated cement was shown to be effective in the prevention of early to intermediate deep infection after primary total knee arthroplasty performed with use of perioperative systemic antibiotic prophylaxis but no so-called clean-air measures. [ABSTRACT FROM AUTHOR]

Background: This study evaluated early childhood comorbidities of cerebral palsy (CP) in low birth weight (LBW) children and assessed the impact of maternal bio-psychosocial factors on CP risk in preterm infants of varying birth weights (BWs). Methods: Data from 15,181 preterm infants (2009–2013) and 151,810 controls were analyzed using Taiwan's National Health Insurance Research Database. CP prevalence and LBW-associated comorbidities were examined, and odds ratios (ORs) were calculated. Results: This study confirmed increasing prematurity and LBW rates in Taiwan, with LBW infants showing higher CP prevalence. Significant maternal risk factors included age extremes (<20 and >40 years). LBW infants exhibited higher risks for respiratory, circulatory, nervous system, and psycho-developmental comorbidities compared with controls, with the lowest BW having even higher ORs. Maternal factors such as family income, the number of hospital admissions, and length of hospital stay were remarkably correlated with BW and subsequent complications. Each additional gestational week crucially reduced the risk of complications in premature infants. Conclusions: LBW infants are at a higher risk for CP and various comorbidities, with maternal bio-psychosocial factors playing a critical role. Addressing these factors in prenatal care and interventions is essential to improve outcomes for premature infants. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a type of brain tumor that is notorious for its aggressiveness and invasiveness, and the complete removal of GBM is still not possible, even with advanced diagnostic strategies and extensive therapeutic plans. Its dismal prognosis and short survival time after diagnosis make it a crucial public health issue. Understanding the molecular mechanisms underlying GBM may inspire novel and effective treatments against this type of cancer. At a molecular level, almost all tumor cells exhibit telomerase activity (TA), which is a major means by which they achieve immortalization. Further studies show that promoter mutations are associated with increased TA and stable telomere length. Moreover, some tumors and immortalized cells maintain their telomeres with a telomerase-independent mechanism termed the "alternative lengthening of telomeres" (ALT), which relates to the mutations of the α-thalassemia/mental retardation syndrome X-linked protein (ATRX), the death-domain associated protein (DAXX) and H3.3. By means of the mutations of the telomerase reverse transcriptase (TERT) promoter and ATRX/DAXX, cancers can immortalize and escape cell senescence and apoptosis. In this article, we review the evidence for triggering GBM cell death by targeting telomerase and the ALT pathway, with an extra focus on a plant-derived compound, butylidene phthalide (BP), which may be a promising novel anticancer compound with good potential for clinical applications. [ABSTRACT FROM AUTHOR]

Background: The development of alcohol-associated liver disease (ALD) is influenced by the amount and duration of alcohol consumption. The resulting liver damage can range from reversible stages, such as steatosis, steatohepatitis and alcoholic fibrosis, to the advanced and irreversible stage of cirrhosis. Aldo-keto reductase family 1 member A1 (AKR1A1) is a member of the aldo-keto reductase family that catalyzes the reduction of aldehyde groups to their corresponding alcohols in an NADPH-dependent manner. AKR1A1 was found to be downregulated in patients diagnosed with ALD. This study aims to interpret the protective effects of AKR1A1 on the development of ALD. Methods: A 5% alcohol-fed (AF) Akr1a1 knockout (Akr1a1−/−) mouse model and an AML12 hepatocyte model were used. The effects of AKR1A1 on liver function, inflammation, oxidative stress, lipid accumulation, and fibrosis were assessed by ELISA, western blotting, RT‒PCR, and a variety of histological staining methods in AF-induced wild-type (WT) and Akr1a1−/− mice compared to control liquid diet-fed (PF) WT and Akr1a1−/− mice. Results: The results demonstrated that AF-WT mice expressed higher levels of AKR1A1 than WT mice fed a control diet, and they did not show any noticeable liver steatosis. However, AF-Akr1a1−/− mice displayed a lower survival rate and more severe liver injury than AF-WT mice, as demonstrated by increased proinflammatory cytokines, oxidative stress, lipid accumulation, fibrosis, and reduced antioxidant enzymes in their livers. Additionally, elevated levels of 4-HNE and p53 phosphorylation were observed in AF-Akr1a1−/− mice, suggesting that the loss of AKR1A1 led to increased 4-HNE accumulation and subsequent activation of p53, which contributed to the progression of ALD. Furthermore, in AML12 hepatocytes, Akr1a1 knockdown aggravated oxidative stress and steatosis induced by palmitic acid/oleic acid (P/O) inflammation induced by lipopolysaccharide (LPS), and fibrosis induced by TGF-β1. Conclusions: This loss-of-function study suggests that AKR1A1 plays a liver-protective role during chronic alcohol consumption by reducing the accumulation of 4-HNE and inhibiting 4-HNE-mediated p53 activation. [ABSTRACT FROM AUTHOR]

Background: The development of alcohol-associated liver disease (ALD) is influenced by the amount and duration of alcohol consumption. The resulting liver damage can range from reversible stages, such as steatosis, steatohepatitis and alcoholic fibrosis, to the advanced and irreversible stage of cirrhosis. Aldo-keto reductase family 1 member A1 (AKR1A1) is a member of the aldo-keto reductase family that catalyzes the reduction of aldehyde groups to their corresponding alcohols in an NADPH-dependent manner. AKR1A1 was found to be downregulated in patients diagnosed with ALD. This study aims to interpret the protective effects of AKR1A1 on the development of ALD. Methods: A 5% alcohol-fed (AF) Akr1a1 knockout (Akr1a1−/−) mouse model and an AML12 hepatocyte model were used. The effects of AKR1A1 on liver function, inflammation, oxidative stress, lipid accumulation, and fibrosis were assessed by ELISA, western blotting, RT‒PCR, and a variety of histological staining methods in AF-induced wild-type (WT) and Akr1a1−/− mice compared to control liquid diet-fed (PF) WT and Akr1a1−/− mice. Results: The results demonstrated that AF-WT mice expressed higher levels of AKR1A1 than WT mice fed a control diet, and they did not show any noticeable liver steatosis. However, AF-Akr1a1−/− mice displayed a lower survival rate and more severe liver injury than AF-WT mice, as demonstrated by increased proinflammatory cytokines, oxidative stress, lipid accumulation, fibrosis, and reduced antioxidant enzymes in their livers. Additionally, elevated levels of 4-HNE and p53 phosphorylation were observed in AF-Akr1a1−/− mice, suggesting that the loss of AKR1A1 led to increased 4-HNE accumulation and subsequent activation of p53, which contributed to the progression of ALD. Furthermore, in AML12 hepatocytes, Akr1a1 knockdown aggravated oxidative stress and steatosis induced by palmitic acid/oleic acid (P/O) inflammation induced by lipopolysaccharide (LPS), and fibrosis induced by TGF-β1. Conclusions: This loss-of-function study suggests that AKR1A1 plays a liver-protective role during chronic alcohol consumption by reducing the accumulation of 4-HNE and inhibiting 4-HNE-mediated p53 activation. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) stands as one of the extensively investigated iron-binding glycoproteins within milk, exhibiting diverse biological functionalities. The global demand for LF has experienced consistent growth. Biotechnological strategies aimed at enhancing LF productivity through microbial expression systems offer substantial cost-effective advantages and exhibit fewer constraints compared to traditional animal bioreactor technologies. This study devised a novel recombinant plasmid, wherein the AOX1 promoter was replaced with a glucose-inducible G1 promoter (PG1) to govern the expression of recombinant porcine LF (rpLF) in Pichia pastoris GS115. High-copy-number PG1-rpLF yeast clones were meticulously selected, and subsequent induction with 0.05 g/L glucose demonstrated robust secretion of rpLF. Scaling up production transpired in a 5 L fermenter, yielding an estimated rpLF productivity of approximately 2.8 g/L by the conclusion of glycerol-fed fermentation. A three-step purification process involving tangential-flow ultrafiltration yielded approximately 6.55 g of rpLF crude (approximately 85% purity). Notably, exceptional purity of rpLF was achieved through sequential heparin and size-exclusion column purification. Comparatively, the present glucose-inducible system outperformed our previous methanol-induced system, which yielded a level of 87 mg/L of extracellular rpLF secretion. Furthermore, yeast-produced rpLF demonstrated affinity for ferric ions (Fe3+) and exhibited growth inhibition against various pathogenic microbes (E. coli, S. aureus, and C. albicans) and human cancer cells (A549, MDA-MB-231, and Hep3B), similar to commercial bovine LF (bLF). Intriguingly, the hydrolysate of rpLF (rpLFH) manifested heightened antimicrobial and anticancer effects compared to its intact form. In conclusion, this study presents an efficient glucose-inducible yeast expression system for large-scale production and purification of active rpLF protein with the potential for veterinary or medical applications. [ABSTRACT FROM AUTHOR]

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a devastating neurodegenerative disorder characterized by the accumulation of mutant Huntingtin protein (mHTT) and oxidative stress-induced neuronal damage. Based on previous reports, microRNA-196a (miR-196a) has emerged as a potential therapeutic target due to its neuroprotective effects in various neurodegenerative diseases. However, whether miR-196a functions through antioxidative effects is still unknown. In this study, we demonstrated that HD models, both in vitro and in vivo , exhibit elevated levels of reactive oxygen species (ROS) and increased neuronal death, and miR-196a mitigates ROS levels and reduces cell death in HD cells. Moreover, we elucidated that miR-196a facilitates the translocation of nuclear factor erythroid 2 (Nrf2) into the nucleus, enhancing the transcription of antioxidant genes, including heme oxygenase-1 (HO-1). We further identified ubiquitin-specific peptidase 15 (USP15), a direct target of miR-196a related to the Nrf2 pathway, and USP15 exacerbates mHTT aggregate formation while partially counteracting miR-196a-induced reductions in mHTT levels. Taken together, these findings shed light on the multifaceted role of miR-196a in HD, highlighting its potential as a therapeutic avenue for ameliorating oxidative stress and neurodegeneration in this debilitating disease. [Display omitted] • Huntington's disease displays higher level of ROS and cell death. • MiR-196a reduces ROS levels and mitigates cell death in HD models. • MiR-196a enhances Nrf2 translocation to activate antioxidant gene transcription. • MiR-196a suppresses USP15 directly to affect Nrf2 signaling. • USP15 accelerates the formation of mHTT aggregates. [ABSTRACT FROM AUTHOR]

Hemophilia is a genetic disorder linked to the sex chromosomes, resulting in impaired blood clotting due to insufficient intrinsic coagulation factors. There are approximately one million individuals worldwide with hemophilia, with hemophilia A being the most prevalent form. The current treatment for hemophilia A involves the administration of clotting factor VIII (FVIII) through regular and costly injections, which only provide temporary relief and pose inconveniences to patients. In utero transplantation (IUT) is an innovative method for addressing genetic disorders, taking advantage of the underdeveloped immune system of the fetus. This allows mesenchymal stromal cells to play a role in fetal development and potentially correct genetic abnormalities. The objective of this study was to assess the potential recovery of coagulation disorders in FVIII knockout hemophilia A mice through the administration of human amniotic fluid mesenchymal stromal cells (hAFMSCs) via IUT at the D14.5 fetal stage. The findings revealed that the transplanted human cells exhibited fusion with the recipient liver, with a ratio of approximately one human cell per 10,000 mouse cells and produced human FVIII protein in the livers of IUT-treated mice. Hemophilia A pups born to IUT recipients demonstrated substantial improvement in their coagulation issues from birth throughout the growth period of up to 12 weeks of age. Moreover, FVIII activity reached its peak at 6 weeks of age, while the levels of FVIII inhibitors remained relatively low during the 12-week testing period in mice with hemophilia. In conclusion, the results indicated that prenatal intrahepatic therapy using hAFMSCs has the potential to improve clotting issues in FVIII knockout mice, suggesting it as a potential clinical treatment for individuals with hemophilia A. [ABSTRACT FROM AUTHOR]

Comorbidities are common in children with epilepsy, with nearly half of the patients having at least one comorbidity. Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder characterized by hyperactivity and inattentiveness level disproportional to the child's developmental stage. The burden of ADHD in children with epilepsy is high and can adversely affect the patients' clinical outcomes, psychosocial aspects, and quality of life. Several hypotheses were proposed to explain the high burden of ADHD in childhood epilepsy; the well-established bidirectional connection and shared genetic/non-genetic factors between epilepsy and comorbid ADHD largely rule out the possibility of a chance in this association. Stimulants are effective in children with comorbid ADHD, and the current body of evidence supports their safety within the approved dose. Nonetheless, safety data should be further studied in randomized, double-blinded, placebo-controlled trials. Comorbid ADHD is still under-recognized in clinical practice. Early identification and management of comorbid ADHD are crucial to optimize the prognosis and reduce the risk of adverse long-term neurodevelopmental outcomes. The identification of the shared genetic background of epilepsy and ADHD can open the gate for tailoring treatment options for these patients through precision medicine. [ABSTRACT FROM AUTHOR]

Asthma is a chronic respiratory disease with symptoms such as expiratory airflow narrowing and airway hyperresponsiveness (AHR). Millions of people suffer from asthma and are at risk of life-threatening conditions. Lactoferrin (LF) is a glycoprotein with multiple physiological functions, including antioxidant, anti-inflammatory, antimicrobial, and antitumoral activities. LF has been shown to function in immunoregulatory activities in ovalbumin (OVA)-induced delayed type hypersensitivity (DTH) in mice. Hence, the purpose of this study was to investigate the roles of LF in AHR and the functions of dendritic cells (DCs) and Th2-related responses in asthma. Twenty 8-week-old male BALB/c mice were divided into normal control (NC), ovalbumin (OVA)-sensitized, and OVA-sensitized with low dose of LF (100 mg/kg) or high dose of LF (300 mg/kg) treatment groups. The mice were challenged by intranasal instillation with 5% OVA on the 21st to 27th day after the start of the sensitization period. The AHR, cytokines in bronchoalveolar lavage fluid, and pulmonary histology of each mouse were measured. Serum OVA-specific IgE and IgG1 and OVA-specific splenocyte responses were further detected. The results showed that LF exhibited protective effects in ameliorating AHR, as well as lung inflammation and damage, in reducing the expression of Th2 cytokines and the secretion of allergen-specific antibodies, in influencing the functions of DCs, and in decreasing the level of Th2 immune responses in a BALB/c mouse model of OVA-induced allergic asthma. Importantly, we demonstrated that LF has practical application in reducing DC-induced Th2 cell responses in asthma. In conclusion, LF exhibits anti-inflammation and immunoregulation activities in OVA-induced allergic asthma. These results suggest that LF may act as a supplement to prevent asthma-induced lung injury and provide an additional agent for reducing asthma severity. [ABSTRACT FROM AUTHOR]

Haploinsufficiency of genes that participate in telomere elongation and maintenance processes, such as telomerase RNA component (Terc) and telomere reverse transcriptase (Tert), often leads to premature aging-related diseases such as dyskeratosis congenita and aplastic anemia. Previously, we reported that when mouse Terc+/− tail tip fibroblasts (TTFs) were used as donor cells for somatic cell nuclear transfer (SCNT, also known as cloning), the derivative embryonic stem cells (ntESCs) had elongated telomeres. In the present work, we are interested to know if an additional round of SCNT, or recloning, could lead to further elongation of telomeres. Terc+/− TTFs were used to derive the first-generation (G1) ntESCs, followed by a second round of SCNT using G1-Terc+/− ntESCs as donor cells to derive G2-Terc+/− ntESCs. Multiple lines of G1- and G2-Terc+/− ntESCs were efficiently established, and all expressed major pluripotent markers and supported efficient chondrocyte differentiation in vitro. Compared with donor TTFs, telomere lengths of G1 ntESCs were elongated to the level comparable with that in wild-type ntESCs. Interestingly, recloning did not further elongate the telomere lengths of Terc+/− ntESCs. Together, our work demonstrates that while a single round of SCNT is a viable means to reprogram Terc haploinsufficient cells to the ESC state, and to elongate these cells' telomere lengths, a second round of SCNT does not necessarily further elongate the telomeres. [ABSTRACT FROM AUTHOR]

Aldo-keto reductase family 1 member A (AKR1A) is an NADPH-dependent aldehyde reductase widely expressed in mammalian tissues. In this study, induced differentiation of MC3T3-E1 preosteoblasts was found to increase AKR1A gene expression concomitantly increased NOx− (nitrite + nitrate), increased glucose uptake, increased [NAD(P)+]/[NAD(P)H] and lactate production but decreased reactive oxygen species (ROS) without changes in endothelial nitric oxide synthase (eNOS) expression in differentiated osteoblasts (OBs). A study using gain- and loss-of-function MC3T3-E1 cells indicated that AKR1A is essential for modulating OB differentiation and gene expression of collagen 1 A1, receptor activator of nuclear factor kappa-B ligand, and osteoprotegerin in OBs. Immunofluorescence microscopy also revealed that changes in AKR1A expression altered extracellular collagen formation in differentiated OBs. Consistently, analyses of alkaline phosphatase activity and calcium deposits of matrix mineralization by Alizarin Red S staining verified that AKR1A is involved in the regulation of OB differentiation and bone matrix formation. In addition, AKR1A gene alterations affected the levels of NOx−, eNOS expression, glucose uptake, [NAD(P)+]/[NAD(P)H] dinucleotide redox couples, lactate production, and ROS in differentiated OBs. Herein, we report that AKR1A-mediated denitrosylation may play a role in the regulation of lactate metabolism as well as redox homeostasis in cells, providing an efficient way to quickly gain energy and to significantly reduce oxidative stress for OB differentiation. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer and chemotherapy ineffectively treats PDAC, leading to the requirement for alternative tumor-targeted treatment. Human amniotic fluid mesenchymal stem cells (hAFMSCs) have been revealed to suppress tumor growth in various cancers and they are a strong candidate for treating PDAC. Methods: To evaluate the effects of hAFMSCs on human pancreatic carcinoma cells (PANC1, AsPC1 and BxPC3 cell lines) and the possible mechanism involved, an in vitro cell coculture system was used. A PANC1 orthotopic xenograft mouse model was established and hAFMSCs were injected intravenously at 4 weeks post-xenograft. Results: An in vitro coculture assay showed that hAFMSCs inhibited PANC1 cell proliferation by inducing S phase cell cycle arrest and increased cell apoptosis in a time-dependent manner. In PANC1 cells, hAFMSCs caused the downregulation of Cyclin A and Cyclin B1 as well as the upregulation of p21 (CDKN1A) at 24 h post coculture. The upregulation of pro-apoptotic factors Caspase-3/-8 and Bax at 24 h post coculture reduced the migration and invasion ability of PANC1 cells through inhibiting the epithelial-mesenchymal transition (EMT) process. In a PANC1 orthotopic xenograft mouse model, a single injection of hAFMSCs showed significant tumor growth inhibition with evidence of the modulation of cell cycle and pro-apoptotic regulatory genes and various genes involved in matrix metallopeptidase 7 (MMP7) signaling-triggered EMT process. Histopathological staining showed lower Ki67 levels in tumors from hAFMSCs-treated mice. Conclusions: Our data demonstrated that hAFMSCs strongly inhibit PDAC cell proliferation, tumor growth and invasion, possibly by altering cell cycle arrest and MMP7 signaling-triggered EMT. [ABSTRACT FROM AUTHOR]

Inverted repeat (IR) DNA sequences compose cruciform structures. Some genetic disorders are the result of genome inversion or translocation by cruciform DNA structures. The present study examined whether exogenous DNA integration into the chromosomes of transgenic animals was related to cruciform DNA structures. Large imperfect cruciform structures were frequently predicted around predestinated transgene integration sites in host genomes of microinjection-based transgenic (Tg) animals (αLA-LPH Tg goat, Akr1A1eGFP/eGFP Tg mouse, and NFκB-Luc Tg mouse) or CRISPR/Cas9 gene-editing (GE) animals (αLA-AP1 GE mouse). Transgene cassettes were imperfectly matched with their predestinated sequences. According to the analyzed data, we proposed a putative model in which the flexible cruciform DNA structures acted as a legible template for DNA integration into linear DNAs or double-strand break (DSB) alleles. To demonstrate this model, artificial inverted repeat knock-in (KI) reporter plasmids were created to analyze the KI rate using the CRISPR/Cas9 system in NIH3T3 cells. Notably, the KI rate of the 5′ homologous arm inverted repeat donor plasmid (5′IR) with the ROSA gRNA group (31.5%) was significantly higher than the knock-in reporter donor plasmid (KIR) with the ROSA gRNA group (21.3%, p < 0.05). However, the KI rate of the 3′ inverted terminal repeat/inverted repeat donor plasmid (3′ITRIR) group was not different from the KIR group (23.0% vs. 22.0%). These results demonstrated that the legibility of the sequence with the cruciform DNA existing in the transgene promoted homologous recombination (HR) with a higher KI rate. Our findings suggest that flexible cruciform DNAs folded by IR sequences improve the legibility and accelerate DNA 3′-overhang integration into the host genome via homologous recombination machinery. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a chronic liver disease caused by prolonged liver injuries. Excessive accumulation of extracellular matrix replaces the damaged hepatocytes, leading to fibrous scar formation and fibrosis induction. Lactoferrin (LF) is a glycoprotein with a conserved, monomeric signal polypeptide chain, exhibiting diverse physiological functions, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, and antitumoral activities. Previous study has shown LF's protective role against chemically-induced liver fibrosis in rats. However, the mechanisms of LF in liver fibrosis are still unclear. In this study, we investigated LF's mechanisms in thioacetamide (TAA)-induced liver fibrosis in rats and TGF-β1-treated HSC-T6 cells. Using ultrasonic imaging, H&E, Masson's, and Sirius Red staining, we demonstrated LF's ability to improve liver tissue damage and fibrosis induced by TAA. LF reduced the levels of ALT, AST, and hydroxyproline in TAA-treated liver tissues, while increasing catalase levels. Additionally, LF treatment decreased mRNA expression of inflammatory factors such as Il-1β and Icam-1 , as well as fibrogenic factors including α-Sma , Collagen I , and Ctgf in TAA-treated liver tissues. Furthermore, LF reduced TAA-induced ROS production and cell death in FL83B cells, and decreased α-SMA, Collagen I, and p-Smad2/3 productions in TGF-β1-treated HSC-T6 cells. Our study highlights LF's ability to ameliorate TAA-induced hepatocyte damage, oxidative stress, and liver fibrosis in rats, potentially through its inhibitory effect on HSC activation. These findings suggest LF's potential as a therapeutic agent for protecting against liver injuries and fibrosis. [Display omitted] • LF mitigates TAA-induced liver fibrosis via antioxidant and anti-inflammatory actions. • LF treatment reduces ALT, AST, and fibrosis markers in TAA-induced liver damage. • LF suppresses inflammatory and fibrogenic factors in TAA-treated liver tissues. • LF diminishes ROS production and cell death, offering hepatoprotective effects. • LF inhibits HSC activation, potentially serving as a therapeutic agent for liver fibrosis. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening lung disease with high mortality rates. The limited availability of effective drugs for IPF treatment, coupled with concerns regarding adverse effects and restricted responsiveness, underscores the need for alternative approaches. Kefir peptides (KPs) have demonstrated antioxidative, anti-inflammatory, and antifibrotic properties, along with the capability to modulate gut microbiota. This study aims to investigate the impact of KPs on bleomycin-induced pulmonary fibrosis. Mice were treated with KPs for four days, followed by intratracheal injection of bleomycin for 21 days. Comprehensive assessments included pulmonary functional tests, micro-computed tomography (µ-CT), in vivo image analysis using MMPsense750, evaluation of inflammation- and fibrosis-related gene expression in lung tissue, and histopathological examinations. Furthermore, a detailed investigation of the gut microbiota community was performed using full-length 16 S rRNA sequencing in control mice, bleomycin-induced fibrotic mice, and KPs-pretreated fibrotic mice. In KPs-pretreated bleomycin-induced lung fibrotic mice, notable outcomes included the absence of significant bodyweight loss, enhanced pulmonary functions, restored lung tissue architecture, and diminished thickening of inter-alveolar septa, as elucidated by morphological and histopathological analyses. Concurrently, a reduction in the expression levels of oxidative biomarkers, inflammatory factors, and fibrotic indicators was observed. Moreover, 16 S rRNA sequencing demonstrated that KPs pretreatment induced alterations in the relative abundances of gut microbiota, notably affecting Barnesiella_intestinihominis , Kineothrix_alysoides , and Clostridium_viride. Kefir peptides exerted preventive effects, protecting mice against bleomycin-induced lung oxidative stress, inflammation, and fibrosis. These effects are likely linked to modifications in the gut microbiota community. The findings highlight the therapeutic potential of KPs in mitigating pulmonary fibrosis and advocate for additional exploration in clinical settings. • Idiopathic pulmonary fibrosis (IPF), a severe lung condition with high mortality, poses a significant health threat. • A murine model effectively mimics IPF symptoms three weeks post intratracheal bleomycin administration. • Kefir peptides (KPs) alleviate bleomycin-induced lung injury, improving respiratory function and reducing fibrosis. • KPs offer multifaceted defense, combating oxidative stress, inflammation, and profibrotic factors in pulmonary fibrosis. • KPs induce structural changes in the gut microbiota of bleomycin-induced pulmonary fibrotic mice. [ABSTRACT FROM AUTHOR]

The aim of this study was designed to assess the risk factors of lag-screw cutout in the treatment of intertrochanteric fracture with a dynamic hip screw (DHS). From 2003 to 2007, 1,150 patients who had acute unilateral intertrochanteric fractures of the femur were enrolled to the study. All fractures were managed by closed reduction and internal fixation with 135° DHS devices. Patient demographics, fracture patterns, reduction and fixation and perioperative course parameters were all recorded. The follow-up period was 38 months on average (range 16-60 months). Finally, 937 patients were available for evaluation of final results in which we focused on lag-screw cutout. Excluding complications not related to screw position, 64 patients (6.8%) with screw cutout were encountered, and the remaining 873 patients had uneventful union, with the average union time of 17.5 weeks (range15-24 weeks). Upon analysis with logistic regression, the tip−apex distance (TAD) was shown to be the most important predictive factor for cutout, followed by screw position, fracture pattern, reduction and patient age. In order to decrease the risk of lag-screw cutout, it is important to ensure good fracture reduction and to place the lag screw in either the middle/middle or inferior/middle position with appropriate TAD. [ABSTRACT FROM AUTHOR]

This article reports our experience on the treatment of long-bone defects with double-strut vascular fibular graft in 11 patients. The defects were 6–12 cm in length while 10–25 cm of vascular fibular grafts were harvested. Nine patients achieved solid union in 6 months, and two patients required additional procedures to achieve solid union. No major complications were observed, except for three patients. who had knee stiffness due to long-term immobilization and one patient who had experienced a stress fracture because of strenuous exercise at 10 months after grafting procedures. Bone union in this patient was achieved 3 months after reapplying an external fixator.It is suggested that a rigid external or internal fixator is mandatory in the course of treatment for facilitating early knee mobilization to prevent exacerbation of already compromised knee-joint motion. Vigorous exercise should be avoided for at least 12 months after solid union of the graft to prevent graft fracture. We concluded that the double-strut vascular fibular graft is an effective treatment for complicated long-bone defects of lower extremity. [Copyright &y& Elsevier]

Depression is a prevalent, stress-related mental disorder that can lead to serious psychiatric diseases with morbidity and high mortality. Although some functional fermented dairy drinks have promising anxiolytic and antidepressant effects, the mechanism is still not clear. To determine the antidepressant-like effect and the potential molecule mechanism of kefir peptides (KP), various behavioral tests, including the elevated plus maze test, open field test, forced swimming test, and tail suspension test, were used. Administration of 150 mg/kg KP in mice reduced the duration of immobility in the forced swimming test and tail suspension test, elevated the time spent in the open arm and center zone in the elevated plus maze test, and increased the total distance traveled, average speed, and time spent in the center zone in the open field test compared with the mock group. These results indicated that KP dramatically ameliorated the depression-like behaviors. Kefir peptides were further isolated and identified using high-performance liquid chromatography and liquid chromatography–tandem mass spectrometry, from which 3 peptides were identified and designated KFP-1, KFP-3, and KFP-5. Among these peptides, administration of KFP-3 (15 AA residues) remarkably decreased immobility time in the forced swimming test and increased mobility time in the tail suspension test. Therefore, KFP-3 may be the major active peptide with antidepressant activity in KP. Overexpression of brain-derived neurotrophic factor, phosphorylated tropomyosin receptor kinase B, and phosphorylated ERK1/2 protein levels could be detected in the hippocampus under KP administration. Therefore, we suggest that KP improves depressive-like behaviors by activating the brain-derived neurotrophic factor–phosphorylated tropomyosin receptor kinase B signaling pathway. Kefir peptides may serve as a new type of antidepressant dairy product and may provide potent antidepressant effects for clinical use. [ABSTRACT FROM AUTHOR]

Akr1A1 is a glycolytic enzyme catalyzing the reduction of aldehyde to alcohol. This study aims to delineate the role of Akr1A1 in regulating the adipo-osteogenic lineage differentiation of mesenchymal stem cells (MSCs). MSCs derived from human bone marrow and Wharton Jelly together with gain- and loss-of-function analysis as well as supplementation with the S-Nitrosoglutathione reductase (GSNOR) inhibitor N6022 were used to study the function of Akr1A1 in controlling MSC lineage differentiation into osteoblasts and adipocytes. Akr1A1 expression, PKM2 activity, and lactate production were found to be decreased in osteoblast-committed MSCs, but PGC-1α increased to induce mitochondrial oxidative phosphorylation. Increased Akr1A1 inhibited the SIRT1-dependent pathway for decreasing the expressions of PGC-1α and TAZ but increasing PPAR γ in adipocyte-committed MSCs, hence promoting glycolysis in adipogenesis. In contrast, Akr1A1 expression, PKM2 activity and lactate production were all increased in adipocyte-differentiated cells with decreased PGC-1α for switching energy utilization to glycolytic metabolism. Reduced Akr1A1 expression in osteoblast-committed cells relieves its inhibition of SIRT1-mediated activation of PGC-1α and TAZ for facilitating osteogenesis and mitochondrial metabolism. Several metabolism-involved regulators including Akr1A1, SIRT1, PPARγ, PGC-1α and TAZ were differentially expressed in osteoblast- and adipocyte-committed MSCs. More importantly, Akr1A1 was identified as a new key regulator for controlling the MSC lineage commitment in favor of adipogenesis but detrimental to osteogenesis. Such information should be useful to develop perspective new therapeutic agents to reverse the adipo-osteogenic differentiation of BMSCs, in a way to increase in osteogenesis but decrease in adipogenesis. A graphical summary illustrates the hypothetical mechanism for Akr1A1 acting to determine MSC lineage differentiation into adipocytes (ADs) and osteoblasts (OBs). By using GSNOR inhibitor N6022, it is possible to alter the cell fate decision of BMSC toward OB differentiation. [Display omitted] • Akr1A1 is a master regulator in favor of adipogenesis but detrimental to osteogenesis. • OB-committed MSCs decreased Akr1A1, PKM2, and lactate production, but increased PGC-1α for mitochondrial metabolism. • AD-committed MSCs exhibited increases of Akr1A1, PKM2, and lactate production with decreased PGC-1α for glycolysis. • Akr1A1 inhibits the SIRT1-dependent pathway for decreasing PGC-1γ and TAZ, but increasing PPARγ in AD-committed MSCs. • Reduced Akr1A1 in OB-committed cells relieves inhibition on SIRT1-mediated activation of PGC-1γ and TAZ for osteogenesis. [ABSTRACT FROM AUTHOR]

Here, we assessed the effects of varying concentrations of gelatin coating on Receptor Activator of Nuclear Factor κ-B Ligand (RANKL)-induced RAW264.7 murine macrophage differentiation into osteoclast (OC) via osteoclastogenesis. The microstructures of coating surfaces with different concentrations of gelatin were examined by scanning electron microscopy and atomic force microscopy. Increased gelatin coating concentrations led to decreased gel rigidity but increased surface adhesion force attenuated OC differentiation and the decreased actin ring formation in RANKL-induced osteoclastogenesis. The decreased actin ring formation is associated with decreased lysosomal-associated membrane protein 1 (LAMP1) activity and bone resorption in the differentiated OCs with different gelatin coating concentrations as compared to the cells differentiated without gelatin coatings. In addition, increasing concentrations of gelatin coating attenuated the medium TGF-β1 protein levels and the expression levels of TGF-β and type-I (R1) and type-II (R2) TGF-β receptors in OCs, suggesting the gelatin-induced suppression of TGF-β signaling for the regulation of RNAKL-induced OC differentiation. Taken together, these findings showed that changes in gelatin coating concentrations, which were associated with altered gel thickness and substrate rigidity, might attenuate TGF-β signaling events to modulate OC differentiation and concomitant actin ring formation and bone matrix resorption in RANKL-induced osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Increased heart rate (HR) is a reaction to head-to-toe gravito-inertial (G) force. The anti-G straining manoeuvre (AGSM) is the crucial technique for withstanding a high-G load. Previous studies reported the main effects of HR only or AGSM only on G tolerance. We assessed the combined effect of HR and AGSM on the outcome of 9G profile exposure. A total of 530 attempts for the 9G profile were extracted to clarify the association of interest. Subjects with an AGSM effectiveness of less than 2.5G had a 2.14-fold higher likelihood of failing in the 9G profile. Trainees with HR increases of less than 20% in the first five seconds also had higher odds of 9G profile intolerance (adjusted OR 1.83, 95% CI 1.09–3.07). The adjusted OR of 9G profile disqualification was 2.93 (95% CI 1.19–7.20) for participants with smaller HR increases and lower AGSM effectiveness. The negative effect of a smaller HR increase on the outcome was likely to be affected by improved AGSM effectiveness (adjusted OR 1.26, 95% CI 0.65–2.42). We speculate that low AGSM effectiveness and a small HR increase were separately associated with failure of high-G challenge. Nonetheless, good AGSM performance seemed to reduce the negative effect of weak HR responses on the dependent variable. [ABSTRACT FROM AUTHOR]

Purpose: High levels of oxygen are usually used in ventilatory support and extracorporeal membrane oxygenation (ECMO) in the intensive care unit of hospitals. Hyperoxia may induce the production of reactive oxygen species (ROS) that can cause lung damage and even systemic injury. In this study, the NF-κB/luciferase transgenic mouse model with non-invasive real-time in vivo imaging was established to test the functions of lactoferrin (LF) in antioxidant and anti-inflammation.Procedures: The NF-κB/luciferase transgenic mice were used to assess the effects of oral administration of LF on attenuation of the systemic inflammatory response and organ damage after 72 h of hyperoxia (FiO2 > 95 %) exposure via monitoring using an in vivo imaging system (IVIS).Results: Using luciferase IVIS imaging, we found that the lungs and kidneys were the most evidently affected organs after hyperoxia treatment. The groups treated with low dose (150 mg/kg) or high dose (300 mg/kg) of LF had lower luciferase expression and less injury, with a dose-dependent effect on the lungs and kidneys. Moreover, ROS, mitogen-activated protein kinases (MAPK), and pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) expression levels were all significantly decreased (P < 0.01), and the protein level of IκB was statistically increased (P < 0.01) after LF treatment.Conclusions: Our results suggest that hyperoxia can induce systemic inflammation, and the oral administration of LF as a natural antioxidant decreases the production of ROS, attenuates inflammation, and lessens kidney and lung injuries from hyperoxia via the use of live image monitoring of the response in NF-kB/luciferase transgenic mice. [ABSTRACT FROM AUTHOR]

In the past decade, the high morbidity and mortality of atherosclerotic disease have been prevalent worldwide. High-fat food consumption has been suggested to be an overarching factor for atherosclerosis incidence. This study aims to investigate the effects of kefir peptides on high-fat diet (HFD)-induced atherosclerosis in apolipoprotein E knockout (ApoE−/−) mice. 7-week old male ApoE−/− and normal C57BL/6 mice were randomly divided into five groups (n = 8). Atherosclerotic lesion development in ApoE−/− mice was established after fed the HFD for 12 weeks compared to standard chow diet (SCD)-fed C57BL/6 and ApoE−/− control groups. Kefir peptides oral administration significantly improved atherosclerotic lesion development by protecting against endothelial dysfunction, decreasing oxidative stress, reducing aortic lipid deposition, attenuating macrophage accumulation, and suppressing the inflammatory immune response compared with the HFD/ApoE−/− mock group. Moreover, the high dose of kefir peptides substantially inhibited aortic fibrosis and restored the fibrosis in the aorta root close to that observed in the C57BL/6 normal control group. Our findings show, for the first time, anti-atherosclerotic progression via kefir peptides consumption in HFD-fed ApoE−/− mice. The profitable effects of kefir peptides provide new perspectives for its use as an anti-atherosclerotic agent in the preventive medicine. [ABSTRACT FROM AUTHOR]

We examined the effects of an Antrodia cinnamomea ethanol extract (ACEE) on lung cancer cells in vitro and tumor growth in vivo. ACEE produced dose-dependent cytotoxic effects and induced apoptosis in Lewis lung carcinoma (LLC) cells. ACEE treatment increased expression of p53 and Bax, as well as cleavage of caspase-3 and PARP, while reducing expression of survivin and Bcl-2. ACEE also reduced the levels of JAK2 and phosphorylated STAT3 in LLC cells. In a murine allograft tumor model, oral administration of ACEE significantly inhibited LLC tumor growth and metastasis without affecting serum biological parameters or body weight. ACEE increased cleavage of caspase-3 in murine tumors, while decreasing STAT3 phosphorylation. In addition, ACEE reduced the growth of human tumor xenografts in nude mice. Our findings therefore indicate that ACEE inhibits lung tumor growth and metastasis by inducing apoptosis and by inhibiting the STAT3 signaling pathway in cancer cells. [ABSTRACT FROM AUTHOR]

The porcine epidemic diarrhoea virus (PEDV) devastates the health of piglets but may not infect piglets whose CMP-N-glycolylneuraminic acid hydroxylase (CMAH) gene is mutated (knockouts, KO) by using CRISPR/Cas9 gene editing techniques. This hypothesis was tested by using KO piglets that were challenged with PEDV. Two single-guide RNAs targeting the CMAH gene and Cas9 mRNA were microinjected into the cytoplasm of newly fertilized eggs. Four live founders generated and proven to be biallelic KO, lacking detectable N-glycolylneuraminic acid (NGNA). The founders were bred, and homozygous offspring were obtained. Two-day-old (in exps. I, n = 6, and III, n = 15) and 3-day-old (in exp. II, n = 9) KO and wild-type (WT, same ages in respective exps.) piglets were inoculated with TCID50 1x103 PEDV and then fed 20 mL of infant formula (in exps. I and II) or sow’s colostrum (in exp. III) every 4 hours. In exp. III, the colostrum was offered 6 times and was then replaced with Ringer/5% glucose solution. At 72 hours post-PEDV inoculation (hpi), the animals either deceased or euthanized were necropsied and intestines were sampled. In all 3 experiments, the piglets showed apparent outward clinical manifestations suggesting that infection occurred despite the CMAH KO. In exp. I, all 6 WT piglets and only 1 of 6 KO piglets died at 72 hpi. Histopathology and immunofluorescence staining showed that the villus epithelial cells of WT piglets were severely exfoliated, but only moderate exfoliation and enterocyte vacuolization was observed in KO piglets. In exp. II, delayed clinical symptoms appeared, yet the immunofluorescence staining/histopathologic inspection (I/H) scores of the two groups differed little. In exp. III, the animals exhibited clinical and pathological signs after inoculation similar to those in exp. II. These results suggest that porcine CMAH KO with nullified NGNA expression are not immune to PEDV but that this KO may lessen the severity of the infection and delay its occurrence. [ABSTRACT FROM AUTHOR]

The mucosa is part of the first line of immune defense against pathogen exposure in humans and prevents viral and bacterial infection of the soft palate, lungs, uvula, and nasal cavity that comprise the ear-nose-throat (ENT) region. Bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1) is a secretory protein found in human upper aerodigestive tract mucosa. This innate material is secreted in mucosal fluid or found in submucosal tissue in the human soft palate, lung, uvula, and nasal cavity. BPIFA1 is a critical component of the innate immune response that prevents upper airway diseases. This review will provide a brief introduction of the roles of BPIFA1 in the upper airway (with a focus on the nasal cavity, sinus, and middle ear), specifically its history, identification, distribution in various human tissues, function, and diagnostic value in various upper airway infectious diseases. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The medicinal mushroom Antrodia cinnamomea has been used to treat cancer but its anti-angiogenic effects have not been studied in detail. Aim of the study The main objective of this study was to determine the molecular mechanism of activity underlying the anti-angiogenic effects of A. cinnamomea. Materials and methods The effects of an A. cinnamomea ethanol extract (ACEE) on cell migration and microvessel formation were investigated in endothelial cells in vitro and Matrigel plugs implanted into mice in vivo . Activation of intracellular signaling pathways was examined using Western blotting. Protein expression was assessed using immunohistochemistry in a mouse model of lung metastasis. Results We show that treatment with ACEE inhibits cell migration and tube formation in human umbilical vein endothelial cells (HUVECs). ACEE suppresses phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and expression of pro-angiogenic kinases in vascular endothelial growth factor (VEGF)-treated HUVECs, in addition to reducing expression of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3). ACEE treatment inhibits VEGF-induced microvessel formation in Matrigel plugs in vivo . In addition, ACEE significantly reduces VEGFR2 expression in Lewis lung carcinoma cells and downregulates the expression of cluster of differentiation 31 (CD31) and VEGFR2 in murine lung metastases. Conclusion These results indicate that A. cinnamomea produces anti-angiogenic effects by inhibiting the VEGFR2 signaling pathway. [ABSTRACT FROM AUTHOR]

Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control. The irradiated and non-irradiated MSCs shared similar morphology, phenotype, and hematopoiesis-supporting function. However, irradiated MSCs showed much lower proliferative and differentiative potential. Irradiation also induced clonal cytogenetic abnormalities of MSCs. Nevertheless, the carcinogenicity of irradiated MSCs is low in vitro and in vivo. In parallel with the ex vivo irradiation experiments, decreased proliferative and differentiative abilities and clonal cytogenetic abnormalities can also be found in MSCs isolated from transplant recipients who had received TBI-based conditioning previously. Thus, TBI used in HSCT drastically injury MSCs and may contribute to the development of some long-term complications associated with clonal cytogenetic abnormality and poor adipogenesis and osteogenesis after TBI. [ABSTRACT FROM AUTHOR]

The short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is an important innate material in the upper airway, and lactoferrin (LF) aids the innate functions in humans. In this study, a nasal epithelial model was used to investigate how LF modulates SPLUNC1 to reduce the inflammatory process mediated by lipopolysaccharide (LPS). The inflammation of human RPMI-2650 cells was induced with LPS to evaluate SPLUNC1 expression after treating the cells with bovine LF (bLF). The interaction pathway between LF and SPLUNC1 in LPS-induced inflammation was further investigated. Our study reveals that the addition of bLF results in the recovery of SPLUNC1 expression in nasal epithelial cells under LPS-induced inflammation. MAPK is involved in the main pathway for the SPLUNC1 and bLF interaction. Decreased SPLUNC1 function could be recovered by addition of bLF. The MEK1/2-MAPK signaling pathway is crucial for the SPLUNC1 and bLF interaction. Therefore, LF could support SPLUNC1 in the innate immunity recovery process. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features are synovial inflammation, bone erosion, and joint structural damages. Our previous studies have shown that kefir peptides (KPs) can reduce cardiovascular disease, osteoporosis and renal inflammation. In this study, we further evaluate the efficacy of KPs on adjuvant-induced arthritis (AIA) in a rat model. After the 14th day of adjuvant induction, rats were subsequently orally administered KPs (83 or 166 mg/day/kg) or tofacitinib (6.2 mg/day/kg) for 14 days. On the 28th day, the rats were anesthetized with isoflurane for ultrasonic, in vivo imaging system (IVIS), and radiographic imaging and then sacrificed for ankle tissues collection and analysis. In vitro , IL-1β-treated human synovial cells (SW982) were subjected to anti-arthritis mechanism study in the presence of KPs. The results of ultrasonography, radiograph, histology, the expression of matrix metalloproteinases (MMPs), inflammatory cytokines and RANKL/OPG ratio demonstrated decreasing severity of synovitis and bone erosion in the ankle joints after KPs treatment. Activation of the NF-κB and MAPK pathways was significantly reduced in KPs treated AIA group. Furthermore, KPs attenuated IL-1β-induced inflammatory cytokine production and the expression of MMPs in a human synovial cell line SW982. These results demonstrated that KPs alleviated adjuvant-induced arthritis in rats by inhibiting IL-1β-related inflammation and MMPs production. We concluded that KPs can exhibit anti-inflammatory effects by reducing the levels of macrophage-related inflammatory cytokines and MMPs, thus alleviating bone erosion in the ankle joint and constituting a potential therapeutic strategy for rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Purpose: Lung adenocarcinoma is characterized by a poor prognosis and high mortality worldwide. In this study, we purposed to use the live imaging techniques and a reporter gene that generates highly penetrative near-infrared (NIR) fluorescence to establish a preclinical animal model that allows in vivo monitoring of lung cancer development and provides a non-invasive tool for the research on lung cancer pathogenesis and therapeutic efficacy.Procedures: A human lung adenocarcinoma cell line (A549), which stably expressed the dual fluorescence reporting gene (pCAG-iRFP-2A-Venus), was used to generate subcutaneous or orthotopic lung cancer in nude mice. Cancer development was evaluated by live imaging via the NIR fluorescent signals from iRFP, and the signals were verified ex vivo by the green fluorescence of Venus from the gross lung. The tumor-bearing mice received miR-16 nucleic acid therapy by intranasal administration to demonstrate therapeutic efficacy in this live imaging system.Results: For the subcutaneous xenografts, the detection of iRFP fluorescent signals revealed delicate changes occurring during tumor growth that are not distinguishable by conventional methods of tumor measurement. For the orthotopic xenografts, the positive correlation between the in vivo iRFP signal from mice chests and the ex vivo green fluorescent signal from gross lung tumors and the results of the suppressed tumorigenesis by miR-16 treatment indicated that lung tumor size can be accurately quantified by the emission of NIR fluorescence. In addition, orthotopic lung tumor localization can be accurately visualized using iRFP fluorescence tomography in vivo, thus revealing the trafficking of lung tumor cells.Conclusions: We introduced a novel dual fluorescence lung cancer model that provides a non-invasive option for preclinical research via the use of NIR fluorescence in live imaging of lung. [ABSTRACT FROM AUTHOR]

Transgenic animals are important in vivo models for biological research. However, low transgenic rates are commonly reported in the literature. Lentiviral transgenesis is a promising method that has greater efficiency with regard to generating transgenic animals, although the transgenic rate of this approach is highly dependent on different transgenes and concentrated lentiviruses. In this study, we modified a method to concentrate lentiviruses using a table centrifuge, commonly available in most laboratories, and carried out analysis of the transgenic efficiency in mice. Based on 26 individual constructs and 627 live pups, we found that the overall transgenic rate was more than 30%, which is higher than obtained with pronuclear microinjection. In addition, we did not find any significant differences in transgenic efficiency when the size of inserts was less than 5000 bp. These results not only show that our modified method can successfully generate transgenic mice but also suggest that this approach could be generally applied to different constructs when the size of inserts is less than 5000 bp. It is anticipated that the results of this study can help encourage the wider laboratory use of lentiviral transgenesis in mice. [ABSTRACT FROM AUTHOR]

Fractures are the result of fragile bone structures after trauma caused by direct or indirect external impact or strong muscular contraction. Most fracture patients undergo surgical fixation to accelerate the healing process and restore the function of mutilated bone. Promoting the healing process remains an important issue for the treatment of bone fractures. Our previous studies demonstrated the remarkable bone-protective effects of kefir peptides (KPs) in ovariectomized rats and mice. In this study, we further evaluate the efficacy of KPs on fracture healing using a rat model of femoral fracture. Fifteen 8-week-old male Sprague Dawley (SD) rats were divided into the sham, mock, and KPs groups, in which the mock and the KPs groups underwent femur-fracture surgery with nail fixation, while the sham group underwent a sham operation. The next day, rats were orally administered with daily 400 mg/kg of KPs (KPs group) or distilled water (sham and mock groups) for four weeks. X-ray imaging, histochemical staining and serum osteogenic markers were applied for fracture healing evaluation. In vitro, mouse bone marrow mesenchymal stem cells (BMMSCs) and MC3T3-E1 line were subjected to osteoblast differentiation in the presence of KPs and compared with no KPs treatment. The results demonstrated that KPs treatment improved the progression of the fracture healing process (p < 0.05) and significantly increased the expressions of Col1a1, Alp, Spp1 , Vegfa and Cox2 mRNA in the femurs of the KPs-treated fractured rats compared to those of the mock-treated fracture rats. In vitro, KPs treatment promoted bone regeneration factor (Col1a1, Alp, M-csf and Phospho1) expression in MC3T3-E1-derived osteoblast cultures (on Day 3) and enhanced osteogenic differentiation and mineralization in BMMSC-derived osteoblast cultures (on Day 17 and Day 21). This is the first study to show that KPs can help with fracture healing by promoting osteogenic differentiation, and it also suggests that KPs can be used as a nutritional supplement to accelerate fracture healing. [ABSTRACT FROM AUTHOR]

The AKR1A1 protein is a member of the aldo-keto reductase superfamily that catalyzes the transformation of D -glucuronate to L -gulonate in the synthesis of L -ascorbic acid (vitamin C, Vit C). We previously demonstrated that AKR1A1 knockout mice (AKR1A1 eGFP/eGFP ) with Vit C deficiency exhibited aberrant bone formation and osteoporosis. In this study, we aimed to evaluate the osteoprotective effects of kefir peptides (KPs) in AKR1A1 eGFP/eGFP mice and uncover the underlying mechanism of KPs in the modulation of bone remodeling. Six male CD-1 mice and 24 male AKR1A1 eGFP/eGFP mice were used in this study, in which the AKR1A1 eGFP/eGFP mice were randomly divided into four groups (n = 6). KPs treatment for 12 weeks exerted several effects in AKR1A1 eGFP/eGFP mice including the reduction of serum proinflammatory cytokines (IL-1β, IL-6, TNF-α), bone resorption markers (CTX-1, RANKL), and the increase of serum bone formation markers (P1NP, OPG, OC). μ-CT analysis indicated that KPs prevented the bone loss in the femurs of AKR1A1 eGFP/eGFP mice by significantly increasing the trabecular parameters of bone mineral density, bone volume and bone number. Nanoindentation analysis demonstrated that KPs enhanced the elasticity and hardness of femoral cortical bones in AKR1A1 eGFP/eGFP mice. KPs promoted bone marrow mesenchymal stem cells (BMMSCs)-derived osteoblast differentiation and mineralization by upregulating positive regulators of osteoblastogenesis (Runx2, β-catenin, BMP-2, NFATc1). Conversely, KPs inhibited bone marrow macrophages (BMMs)-derived osteoclast differentiation and bone resorption, which was demonstrated by the facts that KPs suppressed RANKL-induced p38, NF-κB, Akt, PLCγ2 and CREB-1 phosphorylation, decreased the nuclear translocation of NFATc1 and c-Fos. Our findings demonstrate the efficacy of KPs in the prevention of osteoporosis in AKR1A1 eGFP/eGFP mice and also unveil the dual effects of KPs in osteogenic promotion and osteoclastic inhibition. This study supports the use of KPs as nutritional supplements for the prevention of osteoporosis. [Display omitted] • AKR1A1 KO mice with Vit C deficiency developed the osteoporotic phenotypes. • Kefir peptides (KPs) prevent the development of osteoporosis in AKR1A1 KO mice with Vit C deficiency. • KPs inhibit in vitro RANKL-induced osteoclastogenesis. • KPs enhance in vitro osteoblastogenesis. • KPs modulate the bone remodeling in favor of bone formation. [ABSTRACT FROM AUTHOR]

Aims. Cancer cells use the indoleamine 2,3-dioxygenase 1 (IDO1) pathway to suppress the host’s immune response in order to facilitate survival, growth, invasion, and metastasis of malignant cells. Higher IDO1 expression was shown to be involved in colorectal cancer (CRC) progression and to be correlated with impaired clinical outcome. However, the potential correlation between the expression of IDO1 in a CRC population with a low mutation rate of the APC gene remains unknown. Material and Methods. Tissues and blood samples were collected from 192 CRC patients. The expressions of IDO1, tryptophan 2,3-dioxygenase (TDO2), and beta-catenin proteins were analyzed by immunohistochemistry. Microsatellite instability (MSI) was determined by PCR amplification of microsatellite loci. Results. The results showed that high IDO1 or TDO2 protein expression was associated with characteristics of more aggressive phenotypes of CRC. For the first time, they also revealed a positive correlation between the abnormal expression of beta-catenin and IDO1 or TDO2 proteins in a CRC population with a low mutation rate of APC. Conclusion. We concluded that an IDO1-regulated molecular pathway led to abnormal expression of beta-catenin in the nucleus/cytoplasm of CRC patients with low mutation rate of APC, making IDO1 an interesting target for immunotherapy in CRC. [ABSTRACT FROM AUTHOR]

Aim Muscle atrophy is a common symptom after nerve denervation. Myostatin propeptide, a precursor of myostatin, has been documented to improve muscle growth. However, the mechanism underlying the muscle atrophy attenuation effects of myostatin propeptide in muscles and the changes in gene expression are not well established. We investigated the possible underlying mechanisms associated with myostatin propeptide gene delivery by gene gun in a rat denervation muscle atrophy model, and evaluated gene expression patterns. Main methods In a rat botulinum toxin-induced nerve denervation muscle atrophy model, we evaluated the effects of wild-type (MSPP) and mutant-type (MSPPD75A) of myostatin propeptide gene delivery, and observed changes in gene activation associated with the neuromuscular junction, muscle and nerve. Key findings Muscle mass and muscle fiber size was moderately increased in myostatin propeptide treated muscles ( p < 0.05). And enhancement of the gene expression of the muscle regulatory factors, neurite outgrowth factors (IGF-1, GAP43) and acetylcholine receptors was observed. Our results demonstrate that myostatin propeptide gene delivery, especially the mutant-type of MSPPD75A, attenuates muscle atrophy through myogenic regulatory factors and acetylcholine receptor regulation. Significance Our data concluded that myostatin propeptide gene therapy may be a promising treatment for nerve denervation induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is expressed in human nasopharyngeal and respiratory epithelium and has demonstrated antimicrobial activity. SPLUNC1 is now referred to as bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1). Reduced BPIFA1 expression is associated with bacterial colonization in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin 13 (IL-13), predominately secreted by T helper 2 (TH2) cells, has been found to contribute to airway allergies and suppress BPIFA1 expression in nasal epithelial cells. However, the molecular mechanism of IL-13 perturbation of bacterial infection and BPIFA1 expression in host airways remains unclear. In this study, we found that lipopolysaccharide (LPS)-induced BPIFA1 expression in nasal epithelial cells was mediated through the JNK/c-Jun signaling pathway and AP-1 activation. We further demonstrated that IL-13 downregulated the LPS-induced activation of phosphorylated JNK and c-Jun, followed by attenuation of BPIFA1 expression. Moreover, the immunohistochemical analysis showed that IL-13 prominently suppressed BPIFA1 expression in eosinophilic CRSwNP patients with bacterial infection. Taken together, these results suggest that IL-13 plays a critical role in attenuation of bacteria-induced BPIFA1 expression that may result in eosinophilic CRSwNP. [ABSTRACT FROM AUTHOR]

Background: Chronic adenoid infection by β-lactam-resistant Haemophilus influenzae type b (Hib) and biofilm formation contribute to adenoid hyperplasia. Middle ear disease consequently remains a critical issue in the pediatric population. The aim of this study was to investigate the correlation of Hib biofilm formation with middle ear effusion with adenoid hyperplasia (MEE-AH) and with pediatric obstructive sleep apnea (OSA).Methods: A total of 384 patients with adenoidectomy from January 2008 to December 2012 were recruited in this investigation. Thirty-two patients (14 female and 18 male; age 4-13 years) who obtained routine adenoidectomy surgery had Hib-positive cultures were enrolled in a retrospective manner. By using polysomnography, 18 patients were diagnosed as having MEE-AH with chronic adenotonsillitis, and 14 patients were diagnosed as having pediatric OSA. The results of the Hib biofilm, antibiotic resistance profiles, and scanning electron microscopy observation, which correlated with the clinical diagnosis, were analyzed by the chi-square test and Fisher exact test.Results: Biofilm formation by Hib was significantly present in the patients with MEE-AH rather than patients with OSA. β-lactam-sensitive Hib were resistant to augmentin because of the adenoid biofilm formation. However, this finding was uncommon in the pediatric OSA group.Conclusions: Properly treating β-lactam-sensitive Hib infection may be an important issue in reducing MEE-AH and adenoid vegetation in the pediatric population. Further research is warranted to elucidate the association of Hib-related biofilm formation with treatment failure and the need to consider earlier surgical intervention. [ABSTRACT FROM AUTHOR]

High throughput screening is a powerful tool to identify the potential candidate molecules involved during disease progression. However, analysis of complicated data is one of the most challenging steps on the way to obtaining useful results from this approach. Previously, we showed that a specific miRNA, miR-196a, could ameliorate the pathological phenotypes of Huntington’s disease (HD) in different models, and performed high throughput screening by using the striatum of transgenic mice. In this study, we further tried to identify the potential regulatory mechanisms using different bioinformatic tools, including Database for Annotation, Visualization and Integrated Discovery (DAVID), Molecular Signatures Database (MSigDB), TargetScan and MetaCore. The results showed that miR-196a dominantly altered “ABC transporters”, “RIG-I-like receptor signaling pathway”, immune system”, “adaptive immune system”,“tissue remodeling and wound repair” and “cytoskeleton remodeling”. In addition, miR-196a also changed the expression of several well-defined pathways of HD, such as apoptosis and cell adhesion. Since these analyses showed the regulatory pathways are highly related to the modification of the cytoskeleton, we further confirmed that miR-196a could enhance the neurite outgrowth in neuroblastoma cells, suggesting miR-196a might provide beneficial functions through the alteration of cytoskeleton structures. Since impairment of the cytoskeleton has been reported in several neuronal diseases, this study will provide not only the potential working mechanisms of miR-196a but also insights for therapeutic strategies for use with different neuronal diseases. [ABSTRACT FROM AUTHOR]

Aim Diabetic nephropathy is the leading cause of end stage renal disease in developed countries throughout the world. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system is the main problem that is responsible for the progression of diabetic kidney disease. In this study, we investigated whether human extracellular superoxide dismutase (hEC-SOD) can prevent diabetic nephropathy in the rat model. Main methods Diabetic nephropathy symptoms were induced by intraperitoneal injection with 60 mg/kg streptozotocin (STZ) in male Sprague–Dawley (SD) rats. After daily supplement of rhEC-SOD (3200 U/kg/day) for 4 weeks, the serum or urine biochemical markers (glucose, creatinine, blood urea nitrogen, triglyceride, hemoglobin A1c, and microalbuminuria), histological changes, gene expressions ( phox47 , opn , and gapdh ), and protein levels (TGF-β, AT1-R, phospho-p42/p44 MAPK, and p42/p44 MAPK) were determined. Key findings Results showed that rhEC-SOD administration could reverse SOD activity measured in kidney and diabetic-associated changes, including the fibrosis change, expression of collagen I, transforming growth factor-beta (TGF-β) and angiotensin II type I receptor (AT1-R), as well as the activation of the intracellular mitogen-activated protein kinase (MAPK) signaling pathway, associating with its inhibition of p42 MAPK /p44 MAPK (ERK1/2) phosphorylation. Additionally, diabetic nephropathy up-regulated the expression of the phox47 and opn genes, and these changes could also be suppressed. Though the proteinuria did not significantly reduce. Treatment with rhEC-SOD ameliorates STZ-induced diabetic nephropathy, leading to reduced death rates, kidney weight/body weight ratio, fibrosis change, and TGF-β1 expression through the down-regulation of ROS/ERK1/2 signaling pathway. Significance We conclude that rhEC-SOD can act as a therapeutic agent to protect the progression of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Ethnopharmacological evidence Antrodia camphorata , a highly valued polypore mushroom native only to Taiwan, has been traditionally used as a medicine for anti-inflammation. Aim of the study In this study, anti-inflammatory effects of Antrodia camphorata (AC) and its active compound, ergostatrien-3β-ol (ST1), were investigated in a mouse skin ischemia model induced by skin flap surgery on the dorsal skin. Materials and methods A U-shaped flap was elevated on the dorsal skin of the nine-week-old male mice. Mice were randomly assigned to six groups for treatment ( n =6) including normal skin/propylene glycol (PG), surgical skin flap/PG, solid-state-cultured AC (S/AC), wood-cultured AC (W/AC), high-dose ST1 (H-ST1), low-dose ST1 (L-ST1). Antrodia camphorata was dissolved in 25 μL PG and smeared on the skin flap every six hours for 24 h. At the end of the experiment, each mouse was anesthetized, and skin tissues were collected from their back for histopathological analysis, extracting RNA and protein according to our previous reports. Results Skin-flap-induced ischemia damage significantly increased the expression of the iNOS, COX2, and IL-6 proteins and decreased the expression of IκB protein. In addition, focal, moderate coagulative necrosis with inflammatory cell infiltration was found in the epidermis, and moderate inflammatory cells and necrosis with slight edema was noted in the sub-dermis at 24 h after skin flap surgery. However, treatment with solid-state-cultured or wood-cultured AC, or with its derived ST1 active compound, significantly reduced the necrosis and inflammatory cell infiltration in both the epidermis and sub-dermis of the skin flap. The treatments also reduced the inflammatory response by decreasing the expression of inflammation-related genes including iNOS, IL-6, TNF-α, and NF-κB, as shown by changes in RNA and protein expression, when compared with the surgical skin flap procedure alone. Conclusions These results demonstrated that methanolic extracts of wood-cultured fruiting bodies and solid-state-cultured mycelia from Antrodia camphorata have excellent anti-inflammatory activities and thus have great potential as an addition for hydrocolloid dressings. [ABSTRACT FROM AUTHOR]