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Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer’s disease. In this paper, the combined bioassay model of acetylcholinesterase (AChE) inhibition, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, and Artemia larval lethality was used to evaluate the activity and toxicity of 35 marine fungal strains from seas around China. Their bioactive constituents were revealed by thin layer chromatography (TLC) autography, bioactivity coupled LC–MS/MS and Global Natural Products Social Molecular Networking (GNPS). The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound, ‘tacrine’, for which the ratio was 89.8% at 200 μg/ml. Six strains displayed both AChE inhibition (inhibition ratios > 20% at 200 μg/ml) and DPPH scavenging activity (scavenging ratios > 30% at 200 μg/ml) together with low Artemia larval toxicity (lethal rates Talaromyces sp. C21-1, Aspergillus terreus C23-3, Trichoderma harzianum DLEN2008005, and Penicillium corylophilum TBG1-17. From the most potent sample F-11-1-b (derived from Aspergillus terreus C23-3), five AChE inhibitors and seven antioxidants were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC–MS/MS, and LC–MS/MS coupled with DPPH incubation. Furthermore, with the aid of GNPS, the AChE inhibitors were plausibly annotated as territrem analogues including territrems A–C/D, arisugacin A and an unknown compound 4, and the seven antioxidants were assigned as butyrolactone Ι, aspernolide E, a phenolic derivative and possibly unknown compounds 8–10 and 12.

Background and aim: Adolescent suicide has become a central issue around the world, including in Malaysia, which needs attention. The current study investigated the mediating effect of coping strategy in the association between family functioning and suicidal ideation among adolescents in Kuala Lumpur, Malaysia. Method: A total of 852 school-attending adolescents aged 13-17 years were recruited by multistage cluster sampling. The relationships between all the study variables were analysed using Pearson's correlation. Moreover, the mediation model was tested using SPSS PROCESS macro, while sex differences in suicidal ideation were examined using independent samples t-test. Results: Results showed that family cohesion, family flexibility, and problem-focused coping negatively correlated with adolescents' suicidal ideation. Problem-focused coping also mediated the association between family flexibility and suicidal ideation. There was a significant difference in suicidal ideation for males and females. Conclusion: Family functioning and coping strategy are related to adolescents' suicidal ideation, while problem-focused coping plays a crucial role in the relationship between family flexibility and suicidal ideation.

Previous report has confirmed the beneficial effects of α-mangostin (α-MG), a major and representative xanthone distributed in mangosteen (Garcinia mangostana) on the cisplatin-induced rat model. However, the molecular mechanisms related to its renoprotection have not been elucidated exhaustively. The present study investigated the protective effect of α-MG against cisplatin-induced cytotoxicity in the human embryonic kidney (HEK293) cell model. In this study, α-MG prevented cisplatin-induced cell death, accompanied with the decreased levels of malondialdehyde and increased glutathione content. Particularly, α-MG significantly suppressed the overproduction of reactive oxygen species (ROS), restored the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and downregulated the c-JUN N-terminal kinase (JNK) pathways following cisplatin challenge. Subsequently, the cleavage of caspases and poly-ADP-ribose polymerase (PARP) implicating ROS-mediated apoptosis pathways induced by cisplatin was effectively inhibited by α-MG. In conclusion, our findings provided a rationale for the development of α-MG to attenuate cisplatin-induced nephrotoxicity.

A new isoflavone derivative compound 1 (psoralenone) was isolated from soybean inoculated with a marine fungus Aspergillus terreus C23-3, together with seven known compounds including isoflavones 2–6, butyrolactone I (7) and blumenol A (8). Their structures were elucidated by MS, NMR, and ECD. Psoralenone displayed moderate in vitro anti-inflammatory activity in the LPS-induced RAW264.7 cell model. Compound 2 (genistein) showed moderate acetylcholinesterase (AChE) inhibitory activity whereas compounds 2, 5 (biochanin A), 6 (psoralenol), and 7 exhibited potent larvicidal activity against brine shrimp. Compounds 3 (daidzein), 4 (4ʹ-hydroxy-6,7-dimethoxyisoflavone), and 5–7 showed broad-spectrum anti-microbial activity, and compound 7 also showed moderate 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity.

Piebaldism is a rare, autosomal dominant and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SNAI2 genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. Herein, we report a 5-month-old Chinese girl with severe piebaldism but no family history thereof. She has white forelock and large patches of depigmentation in the jaw, central anterior trunk, perineum and extremities. We performed whole-exome and Sanger sequencing and identified a de novo KIT mutation (NM_000222.2: c.2657G>A, p.Gly886Val) in exon 18 of KIT in the proband. Currently, this mutation is located in the most extreme C-terminal of the tyrosine kinase domain 2 of the KIT gene amongst all reported mutations and causes a severe clinical phenotype. We further reviewed literature on piebaldism and summarized 79 KIT gene mutations that lead to this disease. Our study may expand knowledge on the genotype-phenotype correlation in piebaldism and serve as a reference for genetic counseling and prenatal diagnosis of affected families.

To observe the therapeutic effect of low-dose amitriptyline (AMT) on epigastric pain syndrome (EPS) in patients with functional dyspepsia. Sixty patients with EPS were randomly divided into the following two groups for a four-week clinical trial: routine treatment with pantoprazole (RT group) and the AMT group. The RT group was treated with 40 mg of pantoprazole once daily. The AMT group received 25 mg of AMT once daily before bedtime. The Nepean Dyspepsia Index (NDI) checklist, Hamilton Rating Scale of Anxiety/Depression (HAMA/HAMD), and Pittsburgh Sleep Quality Index (PSQI) were employed to evaluate dyspepsia symptoms, psychological distress, and sleep, respectively. All items were similar between the two groups before treatment (0 week). After 4 weeks of treatment, the NDI–symptom checklist score as well as the severity and bothersomeness of EPS in the AMT group was significantly decreased compared with those in the RT group (p

Current antiangiogenic therapy is limited by its cytostatic property, scarce drug delivery to the tumor, and side toxicity. To address these limitations, we unveiled the role of ZEB1, a tumor endothelium–enriched zinc-finger transcription factor, during tumor progression. We discovered that the patients who had lung adenocarcinomas with high ZEB1 expression in tumor endothelium had increased prevalence of metastases and markedly reduced overall survival after the diagnosis of lung cancer. Endothelial ZEB1 deletion in tumor-bearing mice diminished tumor angiogenesis while eliciting persistent tumor vascular normalization by epigenetically repressing TGF-β signaling. This consequently led to improved blood and oxygen perfusion, enhanced chemotherapy delivery and immune effector cell infiltration, and reduced tumor growth and metastasis. Moreover, targeting vascular ZEB1 remarkably potentiated the anticancer activity of nontoxic low-dose cisplatin. Treatment with low-dose anti–programmed cell death protein 1 (anti–PD-1) antibody elicited tumor regression and markedly extended survival in ZEB1-deleted mice, conferring long-term protective anticancer immunity. Collectively, we demonstrated that inactivation of endothelial ZEB1 may offer alternative opportunities for cancer therapy with minimal side effects. Targeting endothelium-derived ZEB1 in combination with conventional chemotherapy or immune checkpoint blockade therapy may yield a potent and superior anticancer effect.

Recent interest in the control of bone metabolism has focused on a specialized subset of CD31hiendomucinhi vessels, which are reported to couple angiogenesis with osteogenesis. However, the underlying mechanisms that link these processes together remain largely undefined. Here we show that the zinc-finger transcription factor ZEB1 is predominantly expressed in CD31hiendomucinhi endothelium in human and mouse bone. Endothelial cell-specific deletion of ZEB1 in mice impairs CD31hiendomucinhi vessel formation in the bone, resulting in reduced osteogenesis. Mechanistically, ZEB1 deletion reduces histone acetylation on Dll4 and Notch1 promoters, thereby epigenetically suppressing Notch signaling, a critical pathway that controls bone angiogenesis and osteogenesis. ZEB1 expression in skeletal endothelium declines in osteoporotic mice and humans. Administration of Zeb1-packaged liposomes in osteoporotic mice restores impaired Notch activity in skeletal endothelium, thereby promoting angiogenesis-dependent osteogenesis and ameliorating bone loss. Pharmacological reversal of the low ZEB1/Notch signaling may exert therapeutic benefit in osteoporotic patients by promoting angiogenesis-dependent bone formation., An endothelial cell subtype, expressing endomucin and CD31, has been reported to couple angiogenesis with osteogenesis. Here, the authors show that loss of ZEB1 in these cells epigenetically suppresses Notch signaling, leading to impaired angiogenesis and osteogenesis, and that Zeb1 delivery via liposomes ameliorates bone loss in osteoporotic mice

Adolescence is a developmental phase marked by a high risk of depressive symptoms. The Diathesis-Stress Model of Depression proposed that different types of coping strategy can determine depression level in individuals differently. It was found that low self-esteem is linked with greater depressive symptoms among adolescents. Although past studies have discovered the effects of problem-focused coping on depression, there are limited studies examining the underlying mechanism among Malaysian adolescents. Thus, the present study investigated the intervening role of self-esteem on the association between problem-focused coping and depression among adolescents. A total of 852 secondary school students in Kuala Lumpur, Malaysia were recruited through multi-stage cluster sampling. Participants filled out self-reported questionnaires on depression, self-esteem, and problem-focused coping. SPSS macro was used to analyze the mediation model. The findings showed both self-esteem and problem-focused coping negatively correlated with adolescents’ depression. Self-esteem in turn partially mediated the association between problem-focused coping and adolescents’ depression. Thus, it is recommended that intervention on reducing depressive symptoms should focus on providing adolescents with the skills to use problem-focused coping. Workshops could be conducted to heighten adolescents’ self-esteem through the help of teachers, parents and school counselors in reducing depressive symptoms among adolescents.

In this work, a desulfurization method using natural amino acid salts (AAS), which can be green prepared by biological fermentation, is proposed to remove H

To investigate the role of NEAT1 and the microRNA (miR)-377/fibroblast growth factor receptor 1 (FGFR1) axis in cervical cancer (CC), the expression levels of NEAT1, FGFR1 and miR-377 were detected in CC tissues and cell lines. NEAT1 or FGFR1 was knocked down by transfection with short hairpin RNA (sh)-NEAT1 or sh-FGFR1, and miR-377 was overexpressed by transfection with miR-377 mimics in HeLa and C33A cells. Cell viability and migration were measured using MTT and Transwell assays, respectively. Cell apoptosis was determined by flow cytometry. A dual luciferase reporter assay was performed to confirm the presence of binding sites between miR-377 and FGFR1. The results revealed that the expression levels of NEAT1 and FGFR1 were significantly elevated, whereas miR-377 expression was markedly decreased in CC tissues and cell lines. In HeLa and C33A cells, after NEAT1 knockdown, miR-377 expression was increased, cell viability and migration were inhibited, and apoptosis was induced. Similarly, silencing FGFR1 inhibited cell viability and migration, and induced apoptosis of HeLa and C33A cells. A dual luciferase reporter gene assay verified a targeting relationship between NEAT1 and miR-377. Inhibition of miR-377 or overexpression of FGFR1 reversed the effects of NEAT1 knockdown on cell function in HeLa and C33A cells. Moreover, a dual luciferase reporter assay confirmed that FGFR1 was a direct target of miR-377. In conclusion, suppression of NEAT1 inhibited cell viability and migration, and promoted apoptosis of CC cells, and these effects were achieved through regulation of the miR-377/FGFR1 axis.

The 10-item Body Appreciation Scale-2 (BAS-2) is a measurement for individuals to self-report the extent to which they accept and respect their bodies. Although the BAS-2 has been translated into the Malay language and found to have promising qualities, the psychometric characteristics of the English version of BAS-2 remain unknown in the Malaysian context. The present study thus administered the English version BAS-2 and selfie-editing frequency scale to 797 individuals aged 18 to 56 years old in Malaysia. The dataset that was randomly divided into two halves were submitted to exploratory factor analysis and confirmatory factor analysis respectively. Both of the factor analyses consistently support a one-factor model. The Cronbach’s alpha and McDonald omega coefficients were greater than 0.90, indicating that the BAS-2 has good internal consistency. The incremental validity is also evident. A hierarchical multiple regression showed that the BAS-2 score had a positive relationship with selfie-editing frequency after controlling for age and gender. Moreover, the measurement invariance test supported scalar invariance between genders, and an analysis of covariance did not find significant gender differences. Overall, the findings replicate past findings and regularly support the usability of the BAS-2 in the Malaysian context. The implications of the BAS-2 and future directions are also discussed.

The aim of skeletal muscle tissue engineering is to replace or repair skeletal muscle functions that have been injured or lost part of their functions. Skeletal muscle tissue engineering is an important strategy for muscle injury repair. The previous review on skeletal muscle tissue engineering was limited to the discussion of seed cells, biological materials and growth factors. In recent years, research results in this field have continued to emerge. This paper first briefly introduces the anatomy of skeletal muscle, and then combines the latest domestic and foreign study, from the basic problems of tissue engineering skeletal muscle construction to its vascularization, neuralization, etc., to review the current research status of skeletal muscle tissue engineering using three-dimensional (3D) printing, and look forward to its research prospects.

Family functioning (FF) is one of the crucial family factors investigated by researchers; however, the FF studies in Malaysia are still at an early stage compared to those in Western countries. To develop studies in FF, a systematic review is done to understand the measurement of FF in Malaysia. A systematic search of literature published between 2011 and 2020 was conducted in several international and local databases. A total of 31 studies met the inclusion criteria and were included in this review. Through this review, eight FF scales, most of which were developed based on the Western culture and two newly developed scales that have not been used/validated elsewhere have been identified. This review also highlights that the most widely used FF scale in Malaysia is the Family Adaptability and Cohesion Evaluation Scale. From the Malaysian context, as the first FF scale in Malaysia, the Malaysian Family Functioning Scale stands out as the most suitable FF scale for measuring FF among Malaysians. In addition, issues surrounding the FF measurement, for example, the weaknesses found in Western FF scales when used in a non-Western context and the need for adolescent-specific FF are also discussed with recommendations for future research in this area.