Music Therapy in Pediatric Asthma: A Short Review.

Music therapy (MT) is a common modality that performs a complementary and integrative role along with standard treatments for many pediatric diseases. This article briefly reviewed the effects of MT on children aged 5-11 years old and adolescents with asthma from previous studies, specified its functional target towards asthma symptoms, and sorted out the design and investigation of selected research. Medline/PubMed, Embase, SportDis-cus, Cochrane Library, Teacher Reference Centre, Web of Science, Academic Search Complete, PsycARTICLES, and Scopus were queried for experimental and observational studies published between 1990 and 2021. Then, researchers showed that MT lessened patients' asthma symptoms, improved medication compliance, pulmonary function, and quality of life, and helped children and their parents manage anxiety and depression. This article may serve as a reference for clinical research for pediatric asthma therapies and lay the foundation for future research on MT and its clinical practice.

Association of maternal pre-pregnancy dietary intake with adverse maternal and neonatal outcomes: A systematic review and meta-analysis of prospective studies.

This study aimed to summarize the evidence regarding the effects of dietary intake before conception on pregnancy outcomes by performing a systematic review and meta-analysis of prospective studies. Electronic databases were searched from inception up to August 2021. Overall, 65 studies involving 831 798 participants were included and 38 studies were quantitatively pooled. With regard to maternal outcomes, pre-pregnancy intake of fried food, fast food, red and processed meat, heme iron and a low-carbohydrate dietary pattern was positively associated with the risk of gestational diabetes mellitus (GDM) (all P < 0.05). However, a high dietary fiber intake and folic acid supplementation were negatively associated with GDM risk (both P < 0.05). With regard to neonatal outcomes, maternal caffeine intake before pregnancy significantly increased the risk of spontaneous abortion, while folic acid supplementation had protective effects on total adverse neonatal outcomes, preterm birth, and small-for-gestational age (SGA, all P < 0.05). However, no significant associations were found between adverse pregnancy outcomes (i.e., GDM and SGA) and the pre-pregnancy dietary intake of sugar-sweetened beverages, potato, fish, and carbohydrates and the Healthy Eating Index. Our study suggests that maintaining a healthy diet before conception has significant beneficial effects on pregnancy outcomes.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1989658.

One-Two Punch Therapy for the Treatment of T-Cell Malignancies Involving p53-Dependent Cellular Senescence.

T-cell malignancies are still difficult to treat due to a paucity of plans that target critical dependencies. Drug-induced cellular senescence provides a permanent cell cycle arrest during tumorigenesis and cancer development, particularly when combined with senolytics to promote apoptosis of senescent cells, which is an innovation for cancer therapy. Here, our research found that wogonin, a well-known natural flavonoid compound, not only had a potential to inhibit cell growth and proliferation but also induced cellular senescence in T-cell malignancies with nonlethal concentration. Transcription activity of senescence-suppression human telomerase reverse transcriptase (hTERT) and oncogenic C-MYC was suppressed in wogonin-induced senescent cells, resulting in the inhibition of telomerase activity. We also substantiated the occurrence of DNA damage during the wogonin-induced aging process. Results showed that wogonin increased the activity of senescence-associated ß-galactosidase (SA-ß-Gal) and activated the DNA damage response pathway mediated by p53. In addition, we found the upregulated expression of BCL-2 in senescent T-cell malignancies because of the antiapoptotic properties of senescent cells. Following up this result, we identified a BCL-2 inhibitor Navitoclax (ABT-263), which was highly effective in decreasing cell viability and inducing apoptotic cell death in wogonin-induced senescent cells. Thus, the "one-two punch" approach increased the sensibility of T-cell malignancies with low expression of BCL-2 to Navitoclax. In conclusion, our research revealed that wogonin possesses potential antitumor effects based on senescence induction, offering a better insight into the development of novel therapeutic methods for T-cell malignancies.

Ginsenoside Prolongs the Lifespan of C. elegans via Lipid Metabolism and Activating the Stress Response Signaling Pathway.

Panax ginseng is a valuable traditional Chinese medicine in Northeast China. Ginsenoside, the active component of ginseng, has not been investigated much for its effects on aging and its underlying mechanism(s) of action. Here, we investigated the effects of total ginsenoside (TG), a mixture of the primary active ginsenosides from Panax ginseng, on the lifespan of Caenorhabditis elegans (C. elegans). We found that TG extended the lifespan of C. elegans and reduced lipofuscin accumulation. Moreover, TG increased the survival of C. elegans in response to heat and oxidative stress via the reduction of ROS. Next, we used RNA-seq to fully define the antiaging mechanism(s) of TG. The KEGG pathway analysis showed that TG can prolong the lifespan and is involved in the longevity regulating pathway. qPCR showed that TG upregulated the expression of nrh-80, daf-12, daf-16, hsf-1 and their downstream genes. TG also reduced the fat accumulation and promoted lipid metabolism. Moreover, TG failed to extend the lifespan of daf-16 and hsf-1 mutants, highlighting their role in the antiaging effects of TG in C. elegans. The four main constitution of TG were then confirmed by HPLC and included ginsenoside Re, Rg1, Rg2 and Rd. Of the ginsenosides, only ginsenoside Rd prolonged the lifespan of C. elegans to levels comparable to TG. These findings provided mechanistic insight into the antiaging effects of ginsenoside in C. elegans.

Pharmacologic targeting of the P-TEFb complex as a therapeutic strategy for chronic myeloid leukemia.

BACKGROUND: The positive transcription elongation factor b (P-TEFb) kinase activity is involved in the process of transcription. Cyclin-dependent kinase 9 (CDK9), a core component of P-TEFb, regulates the process of transcription elongation, which is associated with differentiation and apoptosis in many cancer types. Wogonin, a natural CDK9 inhibitor isolated from Scutellaria baicalensis. This study aimed to investigate the involved molecular mechanisms of wogonin on anti- chronic myeloid leukemia (CML) cells. MATERIALS AND METHODS: mRNA and protein levels were analysed by RT-qPCR and western blot. Flow cytometry was used to assess cell differentiation and apoptosis. Cell transfection, immunofluorescence analysis and co-immunoprecipitation (co-IP) assays were applied to address the potential regulatory mechanism of wogonin. KU-812 cells xenograft NOD/SCID mice model was used to assess and verify the mechanism in vivo. RESULTS: We reported that the anti-CML effects in K562, KU-812 and primary CML cells induced by wogonin were regulated by P-TEFb complex. We also confirmed the relationship between CDK9 and erythroid differentiation via knockdown the expression of CDK9. For further study the mechanism of erythroid differentiation induced by wogonin, co-IP experiments were used to demonstrate that wogonin increased the binding between GATA-1 and FOG-1 but decreased the binding between GATA-1 and RUNX1, which were depended on P-TEFb. Also, wogonin induced apoptosis and decreased the mRNA and protein levels of MCL-1 in KU-812 cells, which is the downstream of P-TEFb. In vivo studies showed wogonin had good anti-tumor effects in KU-812 xenografts NOD/ SCID mice model and decreased the proportion of human CD45+ cells in spleens of mice. We also verified that wogonin exhibited anti-CML effects through modulating P-TEFb activity in vivo. CONCLUSIONS: Our study indicated a special mechanism involving the regulation of P-TEFb kinase activity in CML cells, providing evidences for further application of wogonin in CML clinical treatment. Video Abstract.

Ferulic Acid Supplementation Increases Lifespan and Stress Resistance via Insulin/IGF-1 Signaling Pathway in C. elegans.

Ferulic acid (FA) is a naturally-occurring well-known potent antioxidant and free radical scavenger. FA supplementation is an effective strategy to delay aging, but the underlying mechanism remains unknown. In the present study, we examined the effects of FA on lifespan extension and its mechanism of FA in Caenorhabditis elegans (C. elegans). Results suggested that FA increased the lifespan of C. elegans, rather than altering the growth of E. coli OP50. Meanwhile, FA promoted the healthspan of C. elegans by improving locomotion and reducing fat accumulation and polyQ aggregation. FA increased the resistance to heat and oxidative stress through reducing ROS. The upregulating of the expression of the hlh-30, skn-1, and hsf-1 were involved in the FA-mediated lifespan extension. Furthermore, FA treatment had no impact on the lifespan of daf-2, hlh-30, skn-1, and hsf-1 mutants, confirming that insulin/IGF-1 signaling pathway and multiple longevity mechanisms were associated with the longevity mechanism of FA. We further found that mitochondrial signaling pathway was modulation involved in FA-mediated lifespan extension. With the results from RNA-seq results and mutants lifespan assay. These findings contribute to our knowledge of the lifespan extension and underlying mechanism of action of FA in C. elegans.

Diselenium-containing ultrathin polymer nanocapsules for highly efficient targeted drug delivery and combined anticancer effect.

The combination of selenium and pillararenes to prepare selenium-containing pillararene-based biomaterials is of great significance for the development of biomedicine. Herein, using a covalent self-assembly strategy, we successfully developed new diselenium-containing ultrathin polymer nanocapsules based on lateral cross-linked pillararenes. The new system exhibited a very potent anticancer effect; additionally, the incorporation of the cleavable redox diselenium bond into the polymer nanocapsules provided a smart nanocarrier for drug delivery. Moreover, the polymer nanocapsules were developed for anticancer drug targeting delivery by loading an anticancer drug and introducing the tumor-penetrating peptide RGD through the host-guest interaction strategy. The targeting DOX-loaded diselenium-containing polymer nanocapsules exhibited enhanced stability, self-anticancer effect, targeted delivery and controlled drug release, resulting in effective combined inhibition of tumor progression.

Indigenous microorganisms residing in oil sands tailings biodegrade residual bitumen.

The purpose of this study was to determine the capacity of indigenous microbes in tailings to degrade bitumen aerobically, and if acetate biostimulation further improved degradation. Fluid fine tailings, from Base Mine Lake (BML), were used as microbial inocula, and bitumen in the tailings served as a potential carbon source during the experiment. The tailings were capped with 0.22 µm-filtered BML surface water with or without BML bitumen and acetate addition and incubated for 100 days at 20 °C. CO2 production and petroleum hydrocarbon reductions (50-70% for the biostimulation treatment) in the tailings were observed. DNA was extracted directly from the tailings, and increased bacterial density was observed by qPCR targeting the rpoB gene in the biostimulated group. 16 S rRNA sequencing was used to determine microbial composition profiles in each treatment group. The microbial communities indigenous to the tailings shifted after the bitumen was added. Acidovorax, Rhodoferax, Pseudomonas and Pseudoxanthomonas spp. significantly increased compared to the original microbial community and demonstrated tolerance to bitumen-based toxicity. The first three genera showed more potential for biostimulation treatment with acetate and may be important bitumen/hydrocarbon-degraders in an oil sands end pit lake environment.

Oroxylin A, a natural compound, mitigates the negative effects of TNFα-treated acute myelogenous leukemia cells.

Tumor necrosis factor alpha (TNFα) is a complicated cytokine which is involved in proliferation and differentiation of acute myelogenous leukemia (AML) cells through a poorly understood mechanism. Mechanistic studies indicate that TNFα induced binding of PI3K subunit p85α to N-terminal truncated nuclear receptor RXRα (tRXRα) proteins, and activated AKT. The activated PI3K/AKT pathway negatively regulated differentiation of AML cells through the upregulation of c-Myc. In addition, TNFα also induced activation of nuclear factor κB (NF-κB), a nuclear transcription factor which was shown to promote cell proliferation. The present study demonstrates that oroxylin A, a natural compound isolated from Scutellariae radix, sensitizes leukemia cells to TNFα and markedly enhances TNFα-induced growth inhibition and differentiation of AML cell including human leukemia cell lines and primary AML cells. Activation of PI3K/AKT pathway could be inhibited by oroxylin A through inhibiting expression of tRXRα in NB4 and HL-60-resistant cells. Furthermore, we found that oroxylin A inhibited the activation of NF-κB and the DNA binding activity by TNFα proved by EMSA in these two AML cell lines. Moreover, in vivo studies showed that treatment with oroxylin A in combination with TNFα decreased AML cell population and prolonged survival in NOD/SCID mice with xenografts of primary AML cells. Overall, our results indicate that oroxylin A is able to inhibit the negative effects of TNFα for AML therapy, suggesting that combination of oroxylin A and TNFα have the potential to delay growth or eliminate the abnormal leukemic cells, thus representing a promising strategy for AML treatment.