Effect of holographic Guasha on sleep quality of older adults with hypertension in the community: A prospective study.

To explore the effect of holographic Guasha therapy on the Pittsburg Sleep Quality Index (PSQI) and Hamilton Anxiety Rating Scale (HAMA) in older adults with hypertension living in the community. This prospective study was conducted from July 2019 to December 2020. Older adults with hypertension (systolic pressure ≥ 140 mm Hg, diastolic pressure ≥ 90 mm Hg) were divided into the control and Guasha groups. The PSQI and HAMA were assessed before and after 4 weeks of intervention. 62 patients were enrolled, with 31/group (Guasha: 72.4 ±â€…6.9 years, 23.0 ±â€…3.1 kg/m2; control: 71.4 ±â€…6.3 years; 22.9 ±â€…2.9 kg/m2). The total PSQI score did not decrease in the control group after 4 weeks (from 14.8 ±â€…1.2 to 14.8 ±â€…1.8, P = .498) but decreased in the Guasha group (from 14.9 ±â€…1.1 to 6.8 ±â€…3.5, P < .001). All PSQI subscores decreased in the Guasha group after 4 weeks of Guasha intervention (all P < .05), except for the use of sleep medication, since the use of such drugs was an exclusion criterion. The HAMA index scores did not change in the control or Guasha group (both P > .05). Holographic Guasha appears to achieve better sleep outcomes than conventional treatment in improving the sleep quality of older adults with hypertension living in the community. The participants were not randomly assigned to the treatments, and the results should be confirmed in a formal trial.

Endothelial-derived small extracellular vesicles support B-cell acute lymphoblastic leukemia development.

PURPOSE: The bone marrow niche plays an important role in leukemia development. However, the contributions of different niche components to leukemia development and their underlying mechanisms remain largely unclear. METHOD: Cre/LoxP-based conditional knockout technology was used to delete VPS33B or ANGPTL2 gene in niche cells. Murine B-ALL model was established by overexpressing the N-Myc oncogene in hematopoietic stem progenitor cells. The frequency of leukemia cells and immunophenotypic B220+ CD43+ LICs was detected by flow cytometry. SEVs was isolated by sequential centrifugation and mass spectrometry was performed to analyze the different components of SEVs. Immunoprecipitation and western blot were used to measure the interaction of VPS33B and ANGPTL2. RESULTS: Here, we showed that specific knockout of vascular protein sorting 33b (Vps33b) in endothelial cells (ECs), but not megakaryocytes or mesenchymal stem cells, resulted in a significant decrease in the secretion of small extracellular vesicles (SEVs) and a delay in the development of B-cell lymphoblastic leukemia (B-ALL). Vps33b knockdown endothelial cells contained much lower levels of SEVs that contained angiopoietin-like protein 2 (ANGPTL2) than the control cells. Importantly, conditional knockout of Angptl2 in ECs significantly delayed B-ALL progression. Moreover, C-terminal region of ANGPTL2 (aa247-471) could directly interact with Sec1-like domain 1 of VPS33B (aa1-aa146). We further demonstrated that the point mutations R399H and G402S in ANGPTL2 led to a dramatic decrease in the secretion of ANGPTL2-SEVs. We also showed that wild-type ANGPTL2-containing SEVs, but not mutant ANGPTL2-containing SEVs, significantly enhanced B-ALL development. CONCLUSION: In summary, our findings indicate that the secretion of ANGPTL2-containing SEVs in ECs sustains the leukemogenic activities of B-ALL cells, which is fine-tuned by the direct interaction of VPS33B and ANGPTL2. These findings reveal that niche-specific SEVs play an important role in B-ALL development.

ANGPTL3 negatively regulates IL-1ß-induced NF-κB activation by inhibiting the IL1R1-associated signaling complex assembly.

Interleukin-1ß (IL-1ß)-induced signaling is one of the most important pathways in regulating inflammation and immunity. The assembly of the receptor complex, consisting of the ligand IL-1ß, the IL-1 receptor (IL-1R) type 1 (IL1R1), and the IL-1R accessory protein (IL1RAP), initiates this signaling. However, how the IL1R1-associated complex is regulated remains elusive. Angiopoietin like 3 (ANGPTL3), a key inhibitor of plasma triglyceride clearance, is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms. Presently, ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases. However, most studies have focused on the secreted form of ANGPTL3, while its intracellular role is still largely unknown. Here, we report that intracellular ANGPTL3 acts as a negative regulator of IL-1ß-triggered signaling. Overexpression of ANGPTL3 inhibited IL-1ß-induced NF-κB activation and the transcription of inflammatory genes in HepG2, THP1, and HEK293T cells, while knockdown or knockout of ANGPTL3 resulted in opposite effects. Mechanistically, ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain (FLD) and disrupted the assembly of the IL1R1-associated complex. Taken together, our study reveals a novel role for ANGPTL3 in inflammation, whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.

Catheter-related superior vena cava obstruction: A rare cause of chylothorax in maintenance hemodialysis patients.

With the extensive use of dialysis catheters in patients undergoing hemodialysis, superior vena cava (SVC) syndrome has gradually attracted attention in recent years. Chylothorax caused by SVC syndrome is rarely reported. In this paper, we report a case of chylothorax secondary to superior vena cava obstruction (SVCO) in a maintenance hemodialysis patient after multiple dialysis catheter placements. Relieving the SVCO through intravascular intervention could effectively treat chylothorax. In the past fourteen months, no recurrence of symptoms has been observed.

Multigenerational maternal obesity increases the incidence of HCC in offspring via miR-27a-3p.

BACKGROUND & AIMS: Obesity is an independent risk factor for malignancies, including hepatocellular carcinoma (HCC). However, it remains unknown whether maternal obesity affects the incidence of HCC in offspring. Thus, we aimed to investigate this association and its underlying mechanisms. METHODS: Diethylnitrosamine (DEN) was used to induce HCC in a high-fat diet (HFD)-induced multigenerational obesity model. RNA-sequencing was performed to identify the genes and microRNAs (miRNAs) that were altered over generations. The role of the miR-27a-3p-Acsl1/Aldh2 axis in HCC was evaluated in cell lines and HCC-bearing nude mice, and its intergenerational impact was studied in pregnant mice and their offspring. RESULTS: Under HFD stress, maternal obesity caused susceptibility of offspring to DEN-induced HCC, and such susceptibility was cumulative over generations. We identified that Acsl1 and Aldh2, direct targets of miR-27a-3p, were gradually changed over generations. Under hyperlipidemic conditions, downregulation of Acsl1 and Aldh2 increased cell proliferation (in vitro) or tumor growth (in vivo) in synergy. Intratumor injection of an miR-27a-3p agomir exacerbated tumor growth by downregulating Acsl1 and Aldh2; while intratumor injection of an miR-27a-3p antagomir had the opposite effect. Moreover, serum miR-27a-3p levels gradually increased in the HFD-fed maternal lineage over generations. Injecting pregnant mice with an miR-27a-3p agomir not only upregulated hepatic miR-27a-3p and downregulated Acsl1/Aldh2 in offspring (fetus, young and adult stages), but also exacerbated HCC development in DEN-treated offspring. In human HCC, upregulated miR-27a-3p and downregulated Acsl1/Aldh2 were negatively correlated with survival on TCGA analysis; while, hepatic miR-27a-3p was negatively correlated with Acsl1/Aldh2 expression in tumor/non-tumor tissues from fatty/non-fatty livers. CONCLUSIONS: Maternal obesity plays a role in regulating cumulative susceptibility to HCC development in offspring over multiple generations through the miR-27a-3p-Acsl1/Aldh2 axis. LAY SUMMARY: It is not currently known how maternal obesity affects the incidence of liver cancer in offspring. In this study, we identified a microRNA (miR-27a-3p) that was upregulated in obese mothers and could be passed on to their offspring. This microRNA enhanced the risk of liver cancer in offspring by regulating 2 genes (Acsl1 and Aldh2). This mechanism could be a future therapeutic target.

USP15 potentiates NF-κB activation by differentially stabilizing TAB2 and TAB3.

Tumor necrosis factor α (TNFα)- and interleukin 1ß (IL-1ß)-induced nuclear factor-κB (NF-κB) activation play key roles in inflammation, immunity, and cancer development. Here, we identified one of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 15 (USP15), as a positive regulator in both TNFα- and IL-1ß-induced NF-κB activation. Overexpression of USP15 potentiated TNFα- or IL-1ß-triggered NF-κB activation and downstream gene transcription, whereas knockdown of USP15 had opposite effects. Mechanistically, upon TNFα stimulation, USP15 showed an enhanced interaction with transforming growth factor-ß activated kinase-1 (TAK1)-TAK1 binding protein (TAB) complex to inhibit the proteolysis of TAB2/3 by different pathways. Apart from deubiquitination dependently inducing cleavage of lysine 48-linked TAB2 ubiquitination, USP15 also DUB independently inhibited lysosome-associated TAB2 degradation, thus enhanced TAB2 stabilization. For TAB3, USP15 inhibited NBR1-mediated selective autophagic TAB3 degradation independent of its deubiquitinating activity. Together, our results reveal a novel USP15-mediated mechanism through which efficient NF-κB activation is achieved by differentially maintaining the TAB2/3 stability.

Histone methyltransferase G9a protects against acute liver injury through GSTP1.

Acute liver injury is commonly caused by bacterial endotoxin/lipopolysaccharide (LPS), and by drug overdose such as acetaminophen (APAP). The exact role of epigenetic modification in acute liver injury remains elusive. Here, we investigated the role of histone methyltransferase G9a in LPS- or APAP overdose-induced acute liver injury. Under D-galactosamine sensitization, liver-specific G9a-deficient mice (L-G9a-/-) exhibited 100% mortality after LPS injection, while the control and L-G9a+/- littermates showed very mild mortality. Moreover, abrogation of hepatic G9a or inhibiting the methyltransferase activity of G9a aggravated LPS-induced liver damage. Similarly, under sublethal APAP overdose, L-G9a-/- mice displayed more severe liver injury. Mechanistically, ablation of G9a inhibited H3K9me1 levels at the promoters of Gstp1/2, two liver detoxifying enzymes, and consequently suppressed their transcription. Notably, treating L-G9a-/- mice with recombinant mouse GSTP1 reversed the LPS- or APAP overdose-induced liver damage. Taken together, we identify a novel beneficial role of G9a-GSTP1 axis in protecting against acute liver injury.

Fat-Specific Knockout of Mecp2 Upregulates Slpi to Reduce Obesity by Enhancing Browning.

Abnormalities of methyl-CpG binding protein 2 (Mecp2) cause neurological disorders with metabolic dysfunction; however, its role in adipose tissues remains unclear. Here, we report upregulated Mecp2 in white adipose tissues (WAT) of obese humans, as well as in obese mice and during in vitro adipogenesis. Normal chow-fed adipocyte-specific Mecp2 knockout mice (Mecp2 Adi KO mice) showed a lean phenotype, with downregulated lipogenic genes and upregulated thermogenic genes that were identified using RNA sequencing. Consistently, the deficiency of Mecp2 in adipocytes protected mice from high-fat diet (HFD)-induced obesity and inhibited in vitro adipogenesis. Furthermore, Mecp2 Adi KO mice showed increased browning under different stimuli, including cold treatment. Mechanistically, Mecp2 bound to the promoter of secretory leukocyte protease inhibitor (Slpi) and negatively regulated its expression. Knockdown of Slpi in inguinal WAT of Mecp2 Adi KO mice prevented cold-induced browning. Moreover, recombinant SLPI treatment reduced the HFD-induced obesity via enhancing browning. Together, our results suggest a novel non-central nervous system function of Mecp2 in obesity by suppressing browning, at least partially, through regulating adipokine Slpi.

RETRACTED: Biosynthesis of Clinacanthus nutans Lindau leaf extract mediated ag NPs, au NPs and their comparative strong muscle relaxant, analgesic activities for pain management in nursing care for using in intensive nursing care unit.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor. After a thorough investigation, the Editor has concluded that the acceptance of this article was partly based upon the positive advice of one illegitimate reviewer report. The report was submitted from an email account which was provided by the corresponding author as a suggested reviewer during the submission of the article. Although purportedly a real reviewer account, the Editor has concluded that this was not of an appropriate, independent reviewer. This manipulation of the peer-review process represents a clear violation of the fundamentals of peer review, our publishing policies, and publishing ethics standards. Apologies are offered to the reviewer whose identity was assumed and to the readers of the journal that this deception was not detected during the submission process.

Preparation of Ag Doped Keratin/PA6 Nanofiber Membrane with Enhanced Air Filtration and Antimicrobial Properties.

Coarse wool is a kind of goat wool that is difficult to further process in the textile industry due to its large diameter, dispersion, better strength, and less bending. Therefore, coarse wool is often discarded as waste or made into low-cost products. In this work, keratin was extracted from coarse wool by a high-efficiency method, and then, an Ag-doped keratin/PA6 composite nanofiber membrane with enhanced filtration and antibacterial performance was prepared using HCOOH as solvent and reductant. HAADF-STEM (high-angle annular dark field-scanning transmission electron microscopy) shows that AgNPs are uniformly distributed in keratin/PA6 (30/70) nanofibers. TGA (Thermogravimetric Analysis) and DSC (Differential Scanning Calorimetry) were employed to investigate the thermal stability of composite membranes with different keratin and AgNP contents. The present keratin as a dopant with polyamide-6 (PA6) was found not only to improve air filtration efficiency but also to enhance water-vapour transmission (WVT). The addition of the Ag nanoparticles (AgNPs) gave a strong antibacterial activity to the composite membrane against Staphylococcus aureus (99.62%) and Escherichia coli (99.10%). Bacterial filtration efficiency (BFE) of the composite membrane against S. aureus and E. coli were up to 96.8% and 95.6%, respectively. All of the results suggested a great potential for coarse wool extraction and application in the air filtration field.

Effects of lactic acid on drug-metabolizing enzymes in Chinese mitten crab (Eriocheir sisnensis) after oral enrofloxacin.

Enrofloxacin (ENR) is the most commonly used antibiotic in crustacean farming in China. Diet supplementation with lactic acid (LA) may, however, affect the efficacy and safety of ENR-based drugs. The aims of this study were to investigate the effects of LA on drug residues and elimination of oral ENR in Chinese mitten crab (Eriocheir sinensis) and to determine ENR and gene expression levels of drug-metabolizing enzymes in the hepatopancreas. To this end, ENR was orally administered to the crabs at a dose of 10.0 mg kg-1 body weight on the eighth day after feeding diets supplemented with 0.3%LA. The results showed that ENR levels in the hepatopancreas were significantly different at 1 and 12 h between the ENR and ENR + 0.3% LA groups (P < 0.05). Lactic acid did not significantly affect the expression of CYP2A (phase I). However, the expressions of CYP3 (phase I) and GST (phase II) were significantly up-regulated by LA during the elimination process of ENR (6-24 h). At Tmax (1 h), the expression of phosphoenolpyruvate carboxykinase (PEPCK) was induced and expression of succinate dehydrogenase (SDH) was inhibited by LA. Both of these enzymes were significantly inhibited during the elimination process of ENR. The results suggest that LA contributes to the elimination of ENR, and thus, enhances hepatopancreas biotransformation and anti-injury capacity in E. sinensis.

Association between brain metastasis from lung cancer and the serum level of myelin basic protein.

The aim of the present study was to determine the association between the expression of myelin basic protein in the serum and the metastasis of lung cancer to the brain. A total of 68 lung cancer patients, treated in the Department of Respiratory Medicine of the People's Hospital of Rizhao (Rizhao, China), were divided into two groups, those with brain metastasis (32 cases) and those without brain metastasis (36 cases). The expression levels of myelin basic protein were measured for all the patients. The results indicated that the expression levels of myelin basic protein in the brain metastasis group were significantly higher when compared with those in the group without metastasis (P<0.05). However, there was no statistically significant correlation between the size of the brain metastasis and the expression levels of myelin basic protein (P>0.05). Furthermore, no statistically significant difference was found in the average level of myelin basic protein between the two subgroups of patients with brain tumor diameters of >1.5 cm and <1.5 cm (P>0.05). Therefore, the results demonstrated a statistically significant correlation between the expression of myelin basic protein in the serum and the metastasis of lung cancer to the brain. Myelin basic protein may thus prove useful in the early diagnosis of brain metastases in lung cancer patients.