PKM2/Hif-1α signal suppression involved in therapeutics of pulmonary fibrosis with microcystin-RR but not with pirfenidone.

To date there are only pirfenidone (PFD) and nintedanib to be given conditional recommendation in idiopathic pulmonary fibrosis (IPF) therapies with slowing disease progression, but neither has prospectively shown a reduced mortality. It is one of the urgent topics to find effective drugs for pulmonary fibrosis in medicine. Previous studies have demonstrated that microcystin-RR (MC-RR) effectively alleviates bleomycin-induced pulmonary fibrosis, but the mechanism has not been fully elucidated yet. We further conducted a comparison of therapeutic effect on the model animals of pulmonary fibrosis between MC-RR and PFD with histopathology and the expression of the molecular markers involved in differentiation, proliferation and metabolism of myofibroblasts, a major effector cell of tissue fibrosis. The levels of the enzyme molecules for maintaining the stability of interstitial structure were also evaluated. Our results showed that MC-RR and PFD effectively alleviated pulmonary fibrosis in model mice with a decreased signaling and marker molecules associated with myofibroblast differentiation and lung fibrotic lesion. In the meantime, both MC-RR and PFD treatment are beneficial to restore molecular dynamics of interstitial tissue and maintain the stability of interstitial architecture. Unexpectedly, MC-RR, rather than PFD, showed a significant effect on inhibiting PKM2-HIF-1α signaling and reducing the level of p-STAT3. Additionally, MC-RR showed a better inhibition effect on FGFR1 expression. Given that PKM2-HIF-1α and activated STAT3 molecular present a critical role in promoting the proliferation of myofibroblasts, MC-RR as a new strategy for IPF treatment has potential advantage over PFD.

Clinical application of repetitive transcranial magnetic stimulation for post-traumatic stress disorder: A literature review.

The efficacy of traditional treatment for post-traumatic stress disorder (PTSD) is still unsatisfactory. Repetitive transcranial magnetic stimulation (rTMS) has been widely used in the treatment of various types of mental disorders, including PTSD. Although rTMS has been demonstrated to be effective in many cases, there are still arguments regarding its mechanism and protocol. This review aims to summarize the origin, development, principle, and future direction of rTMS and introduce this neuro-stimulation therapy to relevant clinicians.

Apigenin Inhibits Proliferation, Migration, and Invasion of Human Tongue Carcinoma Tca8113 Cells Through Regulating the MAPK Signaling Pathways.

OBJECTIVE: This study aimed to examine the effects of apigenin (API) on the proliferation, migration, and invasion of human tongue squamous cell carcinoma Tca8113 cells and explore its probable mechanisms. METHODS: After treating Tca8113 cells with API, the cell proliferation, migration, and invasive capacities were identified by tetrazolium salt colorimetry (MTT) assay, cell scratch test, and Transwell chamber test. Cellular immunofluorescence staining was used to localize mitogen-activated protein kinase 1 (MAPK1) and extracellular regulated protein kinase (ERK) 1/2 proteins. Western blot was used to detect the variations of the related protein expression levels. RESULTS: 1)Through the MTT assay, API significantly inhibited cell proliferation (P<0.01). 2) In the cell scratch test, the distance of lateral migration after the API treatment was significantly shorter compared to the control group (P<0.01). 3) The invasion rate in the lower chamber of the Transwell chamber was lower in the API group (P<0.01). 4) Cellular immunofluorescence staining presented that the total-MEKK1 was localized in the cytoplasm, p-MEKK1 was localized in the nuclear membrane and cytoplasm, and p-ERK1/2 was localized in the cytoplasm and nucleus. ⑤ After API was applied to cells, the expressions of p-MEKK1 and p-ERK1/2 proteins significantly reduced (P<0.01). CONCLUSION: Apigenin (API) significantly inhibits the proliferation, migration, and invasion of Tca8113 cells and its mechanism may be associated with the MAPK signaling pathway.

Psychometric property study of the posttraumatic stress disorder checklist for DSM-5 (PCL-5) in Chinese healthcare workers during the outbreak of corona virus disease 2019.

BACKGROUND: Previous studies about the reliability and validity of the updated PCL version for the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders (PCL-5) have only been evaluated in certain samples of the population, which lacks in the sample of Healthcare Workers. Our study focused on the factor structure, reliability and validity of the PCL-5 among Chinese Healthcare Workers during the Outbreak of Corona Virus Disease 2019. METHODS: We conducted an online survey of frontline healthcare workers using the PCL-5 for PTSD. Total of 212 frontline healthcare providers were included in this study. RESULTS: The findings showed that PCL-5 is a reliable instrument in our sample. The total and subscale scores showed good internal consistency. The convergent and discriminant validity of the PCL-5 were also well demonstrated. Our result showed a better fit with the seven-factor hybrid model compared with other models and supported that the PCL-5 Chinese version can be used as a reliable screening tool to conduct psychological screening for Chinese healthcare workers. LIMITATION: We could not examine other aspects of reliability and validity like test-retest reliability or criterion validity. We didn't use the gold-standard structured interview for PTSD in our study. Besides, most of our samples were young people who had access to the internet. Not all professional levels and seniorities were presented because our sample had a lower mean income and educational level. CONCLUSION: Our study shows that the Chinese PCL-5 has good validity and reliability in frontline healthcare workers during the outbreak.

Dual-modal aptasensor for the detection of isocarbophos in vegetables.

An aptamer-based colorimetric-phosphorescent assay was developed for the detection of isocarbophos. The colorimetric assay relied on the aggregation of gold nanoparticles (AuNPs) caused by the competitive binding of aptamer between isocarbophos and AuNPs in the presence of a high salt concentration. The further addition of persistent luminescence nanorods (PLNRs) into the system showed the phosphorescence sensitively proportional to the concentration of isocarbophos, due to the inner filter effect between PLNRs and AuNPs. The assay showed good linearity within 50-500 µg/L and 5-160 µg/L, and limit of detection of 7.1 µg/L and 0.54 µg/L in colorimetry and phosphorescence mode, respectively. The feasibility of this approach for food analysis was demonstrated with the sensitive and selective determination of isocarbophos residues in vegetables.

Complete Genome Sequence of Wohlfahrtiimonas chitiniclastica Strain SH04, Isolated from Chrysomya megacephala Collected from Pudong International Airport in China.

Wohlfahrtiimonas chitiniclastica bacilli that live in the larvae of a parasitic fly were recently isolated and are speculated to be the cause of fulminant sepsis. Here we report and analyze the complete genome sequence of Wohlfahrtiimonas chitiniclastica strain SH04. No complete genome sequence of a Wohlfahrtiimonas chitiniclastica isolate has been documented previously.

Salvianolic acid B reverses the epithelial-to-mesenchymal transition of HK-2 cells that is induced by transforming growth factor-ß.

Salvianolic acid B (Sal B) is the most abundant bioactive molecule from Radix Salviae Miltiorrhizae, and has recently been used for treating renal fibrosis in traditional Chinese medicine. Here we investigated the ability reversal of Sal B to reverse the transdifferentiation of human kidney proximal tubular epithelial cells that was induced by transforming growth factor-beta 1 (TGF-ß1). The effects of Sal B on HK-2 cell morphology were observed by phase contrast microscopy, while alpha smooth muscle actin and E-cadherin were studied by immunocytochemistry and real-time reverse transcription polymerase chain reaction, respectively. Exposure of HK-2 cells to TGF-ß1 for 72 h induced a complete conversion of the epithelial cells to myofibroblasts. When HK-2 cells were co-incubated with Sal B and TGF-ß1 for a further 72 h, the morphology of myofibroblasts returned to that of proximal tubular epithelial cells, whereas the myofibroblast phenotype was maintained after exposure of cells to TGF-ß1 for 144 h. Sal B reduced alpha smooth muscle actin levels and increased E-cadherin levels compared with their epithelial-to-mesenchymal transition controls. The reversal effect of Sal B was dose-dependent. That Sal B reverses the epithelial-to-mesenchymal transition in vitro suggests that it could possibly facilitate the repair of tubular epithelial structures and the regression of renal fibrosis in injured kidneys.

Ideal strengths, structure transitions, and bonding properties of a ZnO single crystal under tension.

We perform a first-principles computational tensile test (FPCTT) on a ZnO single crystal based on density functional theory to systematically investigate structural transitions, mechanical, and intrinsic bonding properties in the three representative directions, [Formula: see text], [0001], and [Formula: see text]. Stress as a function of tensile strain shows that the ideal tensile strengths in the three directions are 16.2 GPa, 22.4 GPa, and 19.0 GPa, corresponding to strains of 0.20, 0.16, and 0.16, respectively. The [0001] is the strongest direction due to the strongest bonding between the most closely packed Zn and O(0001) layers. We demonstrate that different structures in these three directions lead to different structural transitions, i.e. from a wurtzite (WZ) to a body-centered tetragonal (BCT) structure for [Formula: see text], to a graphite-like (GP-like) structure for [0001], and to a quasi-hexagonal (quasi-HX) structure for [Formula: see text], respectively. Bond length and charge density evolution under tension indicate the occurrence of bond formation and disassociation during these structure transitions. New O-Zn bonds form in the WZ [Formula: see text] BCT and WZ [Formula: see text] quasi-HX transitions, and the original O-Zn bonds break in the WZ [Formula: see text] GP-like transition.

Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients.

AIM: To evaluate the diagnostic role of serum RASSF1A promoter hypermethylation in gastric and colorectal adenocarcinoma. METHODS: Methylation-specific polymerase chain reaction (MSPCR) was used to examine the promoter methylation status of the serum RASSF1A gene in 47 gastric adenocarcinoma patients, 45 colorectal adenocarcinoma patients, 60 patients with benign gastrointestinal disease (30 with benign gastric disease and 30 with benign colorectal disease), and 30 healthy donor controls. A paired study of RASSF1A promoter methylation status in primary tumor, adjacent normal tissue, and postoperative serum were conducted in 25 gastric and colorectal adenocarcinoma patients who later were underwent surgical therapy. RESULTS: The frequencies of detection of serum RASSF1A promoter hypermethylation in gastric (34.0%) and colorectal (28.9%) adenocarcinoma patients were significantly higher than those in patients with benign gastric (3.3%) or colorectal (6.7%) disease or in healthy donors (0%) (P < 0.01). The methylation status of RASSF1A promoter in serum samples was consistent with that in paired primary tumors, and the MSPCR results for RASSF1A promoter methylation status in paired preoperative samples were consistent with those in postoperative serum samples. The serum RASSF1A promoter hypermethylation did not correlate with patient sex, age, tumor differentiation grade, surgical therapy, or serum carcinoembryonic antigen level. Although the serum RASSF1A promoter hypermethylation frequency tended to be higher in patients with distant metastases, there was no correlation between methylation status and metastasis. CONCLUSION: Aberrant CpG island methylation within the promoter region of RASSF1A is a promising biomarker for gastric and colorectal cancer.

Effective protection of Terminalia catappa L. leaves from damage induced by carbon tetrachloride in liver mitochondria.

The protective effects of chloroform extracts of Terminalia catappa L. leaves (TCCE) on carbon tetrachloride (CCl4)-induced liver damage and the possible mechanisms involved in the protection were investigated in mice. We found that increases in the activity of serum aspartate aminotransferase and alanine aminotransferase and the level of liver lipid peroxidation (2.0-fold, 5.7-fold and 2.8-fold) induced by CCl4 were significantly inhibited by oral pretreatment with 20, 50 or 100 mg/kg of TCCE. Morphological observation further confirmed the hepatoprotective effects of TCCE. In addition, the disruption of mitochondrial membrane potential (14.8%), intramitochondrial Ca2+ overload (2.1-fold) and suppression of mitochondrial Ca2+-ATPase activity (42.0%) in the liver of CCl4-insulted mice were effectively prevented by pretreatment with TCCE. It can be concluded that TCCE have protective activities against liver mitochondrial damage induced by CCl4, which suggests a new mechanism of the hepatoprotective effects of TCCE.

Hepatoprotection of oleanolic acid is related to its inhibition on mitochondrial permeability transition.

The protective effects of oleanolic acid (OA) on carbon tetrachloride (CCl4)-induced liver mitochondrial damage and the possible mechanisms were investigated. Pretreatment with OA prior to the administration of CCl4 significantly suppressed the increases of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (4.2- and 19.9-fold, respectively) in a dose-dependent manner in mice. The dissipation of mitochondrial membrane potential (14.8%) and intra-mitochondrial Ca2+ overload (2.1-fold) in livers of CCl4-insulted mice were also dose-dependently prevented by pretreatment with 20, 50 or 100 mg/kg OA. In addition, the effects of OA on liver mitochondria permeability transition (MPT) induced by Ca2+ were assessed by measuring the change in mitochondrial membrane potential, release of matrix Ca2+ and mitochondrial swelling in vitro. The results showed that preincubation with 50 or 100 microg/ml OA obviously inhibited the Ca2+-induced mitochondrial swelling, mitochondrial membrane depolarization and intra-mitochondrial Ca2+ release. It could be concluded that OA has protective effects on liver mitochondria and the mechanisms underlying its protection may be related to its inhibitory action on MPT.

Inhibitory effect of TCCE on CCl4-induced overexpression of IL-6 in acute liver injury.

Terminalia catappa L. leaves have been shown to protect against acute liver injury produced by some hepatotoxicants, but the active components and mechanisms are not clear. This study was designed to characterize the protective effects of the chloroform fraction of the ethanol extract of T. catappa leaves (TCCE) against carbon tetrachloride (CCl4)-induced hepatotoxicity in mice, and analyze the changes in expression level of interleukin-6 (IL-6) in the process. It was found that TCCE pretreatment (10 or 30 mg/kg, ig) protected mice from CCl4 toxicity, as evidenced by the reversed alterations in serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST) activities. Additionally liver tissues were subjected to RT-PCR, Western blot and immunohistochemistry to analyze changes in IL-6 expression. It was found that TCCE markedly suppressed the CCl4-induced over-transcription of IL-6 gene. Consistent with the result, the expression of IL-6 protein was also blocked by TCCE in CCl4-stimulated mice, especially in the area around central vein on liver tissue section. In conclusion, TCCE is effective in protecting mice from the hepatotoxicity produced by CCl4, and the mechanisms underlying its protective effects may be related to the inhibition on the overexpression of IL-6 mainly around terminal hepatic vein.

Mechanisms of hepatoprotection of Terminalia catappa L. extract on D-Galactosamine-induced liver damage.

The hepatoprotective effects of the extract of Terminalia catappa L. leaves (TCE) against D-Galactosamine (D-GalN)-induced liver injury and the mechanisms underlying its protection were studied. In acute hepatic injury test, it was found that serum ALT activity was remarkably increased (3.35-fold) after injection of D-GalN in mice. But with oral pretreatment of TCE (20, 50 and 100 mg/kg/d) for 7days, change in serum ALT was notably reversed. In primary cultured hepatocytes from fetal mice, it was found that cell viability was decreased by 45.0% after addition of D-GalN, while incubation with TCE (0.1, 0.5 and 1.0 mg/ml) for 36 hours could prevent the decrease in a dose-dependent manner. Meanwhile, D-GalN-induced both the increase of AST level (1.9-fold) and the decrease of SOD activity (48.0%) in supernatant of primary cultured hepatocytes could also be inhibited by pretreatment with TCE. In order to study the possible mechanisms underlying its hepatoprotective effects, one effective component separated from TCE, 2alpha, 3beta, 23-trihydroxyursane-12-en-28-oic acid (DHUA), was used to determine anti-mitochondrial swelling activity and superoxide radicals scavenging activity in vitro. It was found that at the concentration range of 50-500 micromol/L DHUA, Ca2+ -induced mitochondrial swelling was dose-dependently inhibited, and superoxide radicals scavenging activity was also shown in a dose-dependent manner. It was concluded that TCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the direct mitochondrion protection and strong scavenging activity on reactive oxygen species (ROS).

[Protective effect of the extract of Terminalia catappa leaves on acute liver injury induced by D-GalN in mice].

OBJECTIVE: To study the hepatoprotective effect of the extract of Terminala catappa leaves (TCE) and the possible mechanisms underlying its protection on acute liver injury induced by D-Galactosamine (D-GalN). METHOD: In vivo: D-GalN-induced liver injury model was used to evaluate the effect of TCE on the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice. Structure of liver was observed and liver mitochondrial swelling was measured following D-GalN injection without or with TCE. In vitro: D-GalN-induced primary cultured hepatocytes injury model was used to value the effect of TCE on cultured hepatocytes. Cell viability was measured by means of MTT assay, and the AST and superoxide dismutase (SOD) activities in supernatant of cultured cells were investigated also. RESULT: In acute hepatic injury test, with oral pretreatment of TCE, remarkable rises in serum AST and ALT activities (2.95 fold and 3.35 fold) induced by D-GalN were obviously reversed and significant morphological changes were remarkably lessened. In addition, the decrease in sensitivity of mitochondrial swelling to the exotic Ca2+ stimulation induced by D-GalN was also prevented by TCE. In primary cultured hepatocytes of mice, it was found that incubation with TCE could prevent the decrease in cell viability in a dose-dependent manner. It was also found that both the increase in AST level (1.9 fold) and the decrease in SOD activity (48.0%) in supernatant of primary cultured hepatocytes induced by D-GalN could be inhibited by pretreatment of TCE. CONCLUSION: TCE has hepatoprotective activity and the mechanisms underlying its protective effect may be related to its antioxidant activity and protection on both hepatocytes and liver mitochondria.

[Hepatoprotective effects of chloroform extract from leaf of Terminalia catappa in relation to the inhibition of liver IL-6 expression].

OBJECTIVE: To study the hepatoprotective effects of Terminalia catappa chloroform extract (TCCE) and its effects on IL-6 gene over expression in liver of CCl4-treated mice. METHOD: Mice were orally pretreated with TCCE (20, 50, 100 mg x kg(-1) x d(-1)) for 5 days, and the sALT activity of mice was detected 24 hours after the intraperitoneal injection of CCl4 on the 5 th day. Meanwhile, IL-6 mRNA level was determined by using the method of RT-PCR. And the liver morphological changes were also observed. RESULT: sALT activity was remarkably increased (5.6 fold) after the injection of CCl4. However, with oral pretreatment of TCCE, changes in sALT were dose-dependently reversed. On the other hand, significant increase in IL-6 mRNA level induced by CCl4 was remarkably decreased. The level of IL-6 mRNA in 100 mg x kg(-1) TCCE treated mice was reversed to that of control. In addition, histological changes such as the infiltration of numerous inflammatory cells and hepatocyte swelling in injured mice were effectively lessened by the pretreatment of TCCE. CONCLUSION: TCCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the inhibition on the over expression of IL-6 gene in liver.