Experiences from youth advisors in chronic disease prevention research.

Engaging young people in research is a promising approach to tackling issues like chronic disease prevention. Our involvement as youth advisors provided valuable experiences, including being at the forefront of change and learning to work within a research team. Furthermore, our experience provides greater insight and learnings for future youth engagement in research.

We are a group of 16 diverse young people from New South Wales, Australia, who are passionate about youth health. In 2021 and 2022, we formed the Health Advisory Panel for Youth at the University of Sydney (HAPYUS, pronounced 'Happy Us') working with researchers on projects to prevent chronic diseases in young people. We brainstormed health issues from our own experiences and other research and summarised them into the top three youth health concerns. From these, we helped develop and test programs to support healthy behaviours in young people. We used scientific and public events to present our findings. Finally, we presented our results in a research paper and through traditional and social media. One of the most rewarding experiences was the opportunity to be part of all stages of the research process of improving youth health especially because COVID-19 and social media changed the way we need to think about youth mental and physical health. We also learned how to work together amongst ourselves as young people and within a research team. We hope that other young people can learn from our experiences and feel inspired to become active contributors in projects for meaningful change in the lives of young people.

mTOR signaling promotes rapid m6A mRNA methylation to regulate NK-cell activation and effector functions.

Natural killer (NK) cells can be rapidly activated in response to cytokines during host defense against malignant cells or viral infection. However, it remains unclear what mechanisms precisely and rapidly regulate the expression of the numerous genes involved in activating NK cells. In this study, we discovered that NK-cell N6-methyladenosine (m6A) methylation levels were rapidly upregulated upon short-term NK-cell activation and were repressed in the tumor microenvironment. Deficiency of methyltransferase-like 3 (METTL3) or METTL14 moderately influenced NK-cell homeostasis, while double knockout of METTL3/14 significantly impacted NK-cell homeostasis, maturation, and antitumor immunity. This suggests a cooperative role of METTL3 and METTL14 in regulating NK-cell development and effector functions. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq), we demonstrated that genes involved in NK-cell effector functions, such as Prf1 and Gzmb, were directly modified by m6A methylation. Furthermore, inhibiting mTOR complex 1 (mTORC1) activation prevented m6A methylation levels from increasing when NK cells were activated, and this could be restored by S-adenosylmethionine (SAM) supplementation. Collectively, we have unraveled crucial roles for rapid m6A mRNA methylation downstream of the mTORC1-SAM signal axis in regulating NK-cell activation and effector functions.

Mental health and wellbeing outcomes of youth participation: A scoping review protocol.

There is growing recognition that young people should be given opportunities to participate in the decisions that affect their lives, such as advisory groups, representative councils, advocacy or activism. Positive youth development theory and sociopolitical development theory propose pathways through which youth participation can influence mental health and wellbeing outcomes. However, there is limited empirical research synthesising the impact of participation on youth mental health and/or wellbeing, or the characteristics of activities that are associated with better or worse mental health and/or wellbeing outcomes. This scoping review seeks to address this gap by investigating the scope and nature of evidence detailing how youth participation initiatives can influence mental health and/or wellbeing outcomes for participants. To be eligible, literature must describe youth (aged 15-24) in participation activities and the impact of this engagement on participant mental health and/or wellbeing outcomes. A systematic scoping review of peer-reviewed and grey literature will be conducted using Scopus, PsycINFO, Embase, Medline and grey literature databases. The scoping review will apply established methodology by Arksey and O'Malley, Levac and colleagues and the Joanna Briggs Institute. Title, abstract, and full text screening will be completed by two reviewers, data will be extracted by one reviewer. Findings will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), including a qualitative summary of the characteristics of youth participation and their influence on youth mental health outcomes. Youth advisory group members will be invited to deliver governance on the project from the outset; participate in, and contribute to, all stages of the review process; reflect on their own experiences of participation; and co-author the resulting publication. This scoping review will provide essential knowledge on how participation activities can be better designed to maximise beneficial psychosocial outcomes for involved youth.

Use of Microscopic Characteristics and Multielemental Fingerprinting Analysis to Trace Three Different Cultivation Modes of Medicinal and Edible Dendrobium officinale in China.

The traceability of different cultivation modes is critical for ensuring the commercial viability of high-value Dendrobium officinale. In this study, by means of polarizing microscopy, SEM-EDX, ICP-MS and ICP-AES, the possibility of combining microscopic characteristics, multielemental analysis and multivariate statistical authenticity analysis was realized to determine the origins of the fresh stem and dried stem powder of D. officinale derived from three different cultivation modes from six provinces of China. The microscopic structure, chemical elements on the surface of the main microstructures and concentrations of Ca, K, Ba, Cs, As and Cu varied among specimens derived from different cultivation modes. The fresh stems of D. officinale derived from different cultivation modes can be effectively and quickly identified by various microscopic characteristics and different contents of Ca on the surface of the parenchyma, phloem and xylem. Meanwhile, linear discriminant analysis showed that 98.1% of the dried stem powder samples were correctly classified, and the accuracy of cross-validation was 95.3%. This study facilitated an effective integrated method for determining the traceability of the fresh stem and dried stem powder of D. officinale derived from three different cultivation modes. This approach offers a potential method for identifying the origins of medicinal plants derived from different cultivation modes.

Synthesis and evaluation of antitumor activity of dibenzodiazepine derivatives.

A series of dibenzodiazepine 2-position derivatives, bearing N-methylpiperazine at the C-11 position, were prepared by using a concise approach. Their inhibitory activities of tumor cell proliferation in vitro were tested in five cell lines, including breast cancer cell BCAP37, gastric cancer cell SGC7901, liver cancer cell HepG2, cervical cancer cell HeLa and acute promyelocytic leukemia cell HL-60. Several compounds showed efficient tumor activity with IC50 values down to 0.30 µM. These compounds are expected to be a new class of potential anticancer lead compounds.

Complete chloroplast genome of a medicinal species Polygonatum kingianum in China (Asparagaceae, Asparagales).

Polygonatum kingianum is a medicinal and food plant distributed in most of countries throughout the temperate Northern Hemisphere. Here we report on the complete chloroplast (cp) genome sequence of P. kingianum. The cp genome is 155,399 bp in size and includes two inverted repeat regions of 52,7411 bp, which is separated by a large single-copy region of 84,234 bp and a small single copy region of 18,424 bp. A total of 130 genes were predicted, including 38 tRNA, 8 rRNA, and 84 protein-coding genes. Phylogenetic analysis placed P. kingianum under the subfamily Nolinoideae of the family Asparagaceae.

Up-regulation of GhPAP1A results in moderate anthocyanin accumulation and pigmentation in sub-red cotton.

Anthocyanins are a group of important secondary metabolites, functioning as colorant in plant organs as well as protective agents against several stresses. Sub-red plant (Rs) cottons, accumulating moderate level of anthocyanins in shoots, had increased photosynthesis efficiency compared to green- (GL) and red-plant (R1) cottons. The present work aimed to clarify the molecular base of anthocyanin regulation in Rs cotton. It was found that GhPAP1A was significantly up-regulated in Rs plants compared to GL cottons, but its expression level is lower than that of GhPAP1D in R1 plants. Virus induced gene silencing of GhPAP1s inhibited the red pigmentation in Rs plants. Comparative cloning revealed a 50-bp tandem repeat in the promoter of GhPAP1A in Rs cotton, which showed stronger activity to drive the expression of downstream genes in petals. Considered that the coding sequence of GhPAP1As from Rs and GL cottons had similar functions to promote anthocyanin biosynthesis in transgenic tobaccos, we attributed moderate anthocyanin accumulation in Rs cotton to increased transcription of GhPAP1A, resulted from varied promoter structure. Our works suggested GhPAP1s as useful tool to manipulate anthocyanin level and several breeding targets, including herbivore- and pathogen- resistance, high photosynthesis efficiency and colored fibers.

Network pharmacology study on the active components of Pterocypsela elata and the mechanism of their effect against cerebral ischemia.

OBJECTIVE: The aim of this study was to identify the active anti-ischemic components of Pterocypsela elata (P. elata) using a network pharmacology approach to construct an effective component anti-cerebral ischemic target network and systematically analyze this medicinal material. METHODS: Pharmacological studies have shown that P. elata has an obvious effect against cerebral ischemia. To identify the potential targets, 14 components of P. elata were docked to each structural element of the targets in the DRAR-CPI database by reverse docking technology. We then compared the identified potential targets with FDA-approved targets for stroke/cerebral infarction treatment in the DrugBank database and identified the active components of P. elata and their potential targets for stroke/cerebral infarction treatment. The active component-target networks were constructed using Cytoscape 3.5.1 software. The target protein-protein interactions were analyzed using the STRING database. KEGG pathway analysis and gene ontology (GO) enrichment analysis were performed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: There were 14 active components identified from P. elata and 21 potential targets identified for cerebral ischemia treatment, including carbonic anhydrase 2, ribosyldihydronicotinamide dehydrogenase, cholinesterase, and glutathione S-transferase P. The main involved pathways include metabolic pathways, complement and coagulation cascades and steroid hormone biosynthesis. CONCLUSION: Through a network pharmacology approach, we predicted the active components of P. elata and their potential targets for cerebral ischemia treatment. Our results provide new perspectives and clues for further studies on the anti-cerebral ischemia mechanism of P. elata.

Enriched environment combined with fluoxetine ameliorates depression-like behaviors and hippocampal SYP expression in a rat CUS model.

Effects of enriched environment (EE) combined with fluoxetine in a chronic unpredictable stress (CUS) rat model were examined in our study. Thirty male Sprague-Dawley rats were randomly divided into control group, CUS group, CUS+EE group, CUS+fluoxetine group, and CUS+EE+fluoxetine group (n=six per group). Rats in the CUS group were bred under conditions of CUS and separation for 6 weeks; Control group animals were bred in group cages (three rats per cage) under standard laboratory conditions for 6 weeks; Rats in CUS+EE group, CUS+fluoxetine group, and CUS+EE+fluoxetine groups were bred under the conditions of CUS and separation for 6 weeks and had an intervention of EE, an oral gavage of fluoxetine, and an intervention of EE+oral gavage of fluoxetine, respectively, every day for the final 3 weeks. Every rat underwent a behavioral assessment at the beginning of the 1st week, at the end of the 3rd week and at the end of the 6th week. Behavioral assessments included sucrose water consumption, weight measurement, and an open field test (measuring horizontal moving distance, rearing behavior, and defecation). Finally, the level of synaptophysin expressed in the hippocampus was measured with immunohistochemistry. We found that EE, fluoxetine, and EE+fluoxetine all reversed the depression-like behaviors of CUS rats. The effect of EE+fluoxetine appeared to be superior to EE or fluoxetine alone; the expression level of synaptophysin in CA1, CA3, and DG of the hippocampus was decreased in CUS rats, however, exposure to EE, fluoxetine, and EE+fluoxetine all reversed this decrease.

Alterations in splenic function and gene expression in mice with depressive-like behavior induced by exposure to corticosterone.

Depressed patients present with increased cortisol levels and attenuated immune responses. However, little is known about the association between depression and the spleen, as this is the largest peripheral immune organ. In this study, we examined alterations in splenic function and gene expression in mice with depressive-like behavior, well as the expression of certain proteins in related pathways. A mouse model of depression was established with the use of corticosterone. Splenic function and histopathology were assessed using Wright and H&E staining. The Agilent Whole Mouse Genome Oligo Microarray containing >41,174 transcript probes was used to measure the levels of gene-expression in the spleens from control and model mice, and the levels of certain proteins associated with depression were measured by western blot analysis in the brain and spleen separately. We found that splenic function and immunity in the mice with depressive-like behavior were markedly impaired. A total of 53 genes exhibited a differential response in the mice with depressive-like behavior, 11 of which were more notable, including collagen, type VI, α5 (Col6a5), immunoglobulin superfamily, member 11 (Igsf11), D site albumin promoter binding protein (Dbp), tachykinin 2 (Tac2) and γ-aminobutyric acid B receptor 2 (Gabbr2). Pathway analysis revealed that the amino acid biosynthesis and the clock gene pathways were more meaningful among these genes. The levels of GABBR2, DBP and substance P (SP; encoded by the Tac2 gene) related proteins in the brain were markedly downregulated, and similar results were observed in the spleen. The anti-depressant, fluoxetine, reversed the changes in the levels of these proteins. The findings of our study regarding changes occurring in the spleen during depression may indirectly elucidate and shed light into the pathogenesis of depression and depressive-like behavior.

Epigallocatechin gallate based magnetic gold nanoshells nanoplatform for cancer theranostic applications.

Recently, gold nanomaterials and iron oxide nanoparticles (NPs) have attracted much attention due to their unique physical, chemical and biological properties. In this study, polyethyleneimine (PEI)-modified Fe3O4 NPs (inner cores) were first prepared, and then gold shells (AuNSs) were innovatively formed on the cores using epigallocatechin gallate (EGCG) as the reducing agent to obtain Fe3O4-PEI@AuNSs-EGCG core-shell NPs. After PEG modification, the Fe3O4-PEI@AuNSs-EGCG/PEG nanoplatform was completed. This highly integrated nanoplatform has shown remarkable biostability, rapid cellular uptake, and excellent in vitro and in vivo anti-tumour activity. Moreover, this nanoplatform can also be used as a magnetic resonance (MR)/X-ray dual-mode imaging agent. In all, the results of this study showed that Fe3O4-PEI@AuNSs-EGCG/PEG is a promising, potentially effective, theranostic nanoplatform for tumour treatment.

Synthesis and antitumor activity evaluation of lamiridosin A derivatives.

A series of lamiridosin A derivatives were synthesized through simple procedures. Their antitumor activities were evaluated against EC9706, MGC803, and B16 cell lines in vitro. Several compounds showed potent antitumor activity, especially compound 10, with IC50 value of 2.36 µmol/L against MGC803 cell lines, is more potent than marketed positive drug 5-fluorouridine (5-FU).

[Chemical Constituents from Melissa officinalis Leaves].

OBJECTIVE: To investigate the chemical constituents of Melissa officinalis leaves. METHODS: The chemical constituents were separated by silica gel column chromatography and their structures were determined by spectroscopic experiments. RESULTS: 13 compounds were isolated and identified as protocatechuyl aldehyde(1), serratagenic acid(2), vanillin(3), 2α,3ß-dihydroxy-urs-12-en-28-oic acid(4), ursolic acid(5), oleanolic acid(6), daucosterol(7),2α,3ß,23,29-tetrahydroxyolean-12-en-28-oic acid-29-O-ß-D-gluco- pyranoside(8), luteolin(9) rosmarinic acid(10), luteolin-7-O-ß-D-glucoside (11), ß-stitosterol(12) and palmitic acid(13). CONCLUSION: Compounds 1 ~ 8 are separated from this plant for the first time and compounds 1-4 and 8 are isolated from this genus for the first time.

[Chemical constituents from Punica granatum flowers].

OBJECTIVE: To investigate the chemical constituents in the flowers of Punica granatum. METHODS: The chemical constituents were separated by silica gel column chromatography and their structures were determined by spectroscopic experiments. RESULTS: As a result, twelve compounds were isolated and identified as oleanolic acid (1), ursolic acid (2), palmitic acid (3), tricin (4), catechin (5), rutin (6), apigenin (7), apigenin-7-O-glucoside (8), 2S, 3S, 4S-trihydroxypentanoic acid (9), gallic acid (10), beta-stitosterol (11), and daucosterol (12). CONCLUSION: Compounds 3, 4, 7, 8 and 9 are separated from this plant for the first time, and compounds 3, 4 and 9 are isolated from this genus for the first time.

A new sesquiterpenoid from the rhizomes of Homalomena occulta.

Chemical constituents of EtOAc extract from the rhizomes of traditional Chinese medicine Qian-nian-jian (Homalomena occulta) have been studied, a new sesquiterpenoid, named euadesma-4-ene-1ß,15-diol (1), and four related known compounds, polydactin B (2), oplodiol (3), 1ß,4ß,7α-trihydroxyeudesmane (4), and (-)1ß,4ß,6α-trihydroxy-eudesmane (5), were isolated. Their structures were elucidated using spectroscopic methods including 1D and 2D NMR techniques and mass spectrometry. All the isolates were tested against the human lung adenocarcinoma A549 using MTT assay method. Oplodiol (3) and (-)1ß,4ß,6α-trihydroxy-eudesmane (5) were found to show moderate cytotoxic effects on A549 with IC50 values at 25.5 and 15.0 µg/mL, respectively.

Lettuce glycoside B ameliorates cerebral ischemia reperfusion injury by increasing nerve growth factor and neurotrophin-3 expression of cerebral cortex in rats.

AIMS: The aim of the study was to investigate the effects of LGB on cerebral ischemia-reperfusion (I/R) injury in rats and the mechanisms of action of LGB. MATERIALS AND METHODS: The study involved extracting LGB from P. laciniata, exploring affects of LGB on brain ischemia and action mechanism at the molecular level. The cerebral ischemia reperfusion injury of middle cerebral artery occlusion was established. We measured brain histopathology and brain infarct rate to evaluate the effects of LGB on brain ischemia injury. The expressions of nerve growth factor (NGF) and neurotrophin-3 (NT-3) were also measured to investigate the mechanisms of action by the real-time polymerase chain reaction and immunohistochemistry. STATISTICAL ANALYSIS: All results were mentioned as mean ± standard deviation. One-way analysis of variance was used to determine statistically significant differences among the groups. Values of P < 0.05 were considered to be statistically significant. RESULTS: Intraperitoneal injection of LGB at the dose of 12, 24, and 48 mg/kg after brain ischemia injury remarkably ameliorated the morphology of neurons and brain infarct rate (P < 0.05, P < 0.01). LGB significantly increased NGF and NT-3 mRNA (messenger RNA) and both protein expression in cerebral cortex at the 24 and 72 h after drug administration (P < 0.05, P < 0.01). CONCLUSIONS: LGB has a neuroprotective effect in cerebral I/R injury and this effect might be attributed to its upregulation of NGF and NT-3 expression ability in the brain cortex during the latter phase of brain ischemia.

Lactuside B decreases aquaporin-4 and caspase-3 mRNA expression in the hippocampus and striatum following cerebral ischaemia-reperfusion injury in rats.

This study aimed to investigate the effects of lactuside B (LB) on aquaporin-4 (AQP4) and caspase-3 mRNA expression in the hippocampus and the striatum following cerebral ischaemia-reperfusion (I/R) injury in rats. Cerebral I/R injury was established in Sprague-Dawley rats by occluding the middle cerebral artery for 2 h and then inducing reperfusion. Rats in the I/R + LB groups were treated with various doses of LB following reperfusion. Neurological deficit scores and brain water content were obtained to determine the pharmacodynamics of LB. Reverse transcription polymerase chain reaction was performed to determine the expression levels of AQP4 and caspase-3 mRNA in the hippocampus and the striatum. The results of the present study indicate that LB decreased the neurological deficit scores and the brain water content. In the hippocampus, AQP4 and caspase-3 mRNA expression levels were significantly downregulated in the I/R + LB groups at 24 and 72 h following drug administration, compared with those in the I/R group (P<0.05). In the striatum, LB was also shown to significantly reduce AQP4 and caspase-3 mRNA expression levels at 24 and 72 h following drug administration, compared with those in the I/R group (P<0.05). The effects became stronger as the LB dose was increased. The most significant reductions in AQP4 and caspase-3 mRNA expression were noted in the I/R + LB 25 mg/kg and I/R + LB 50 mg/kg groups at 72 h following drug administration. The results of the present study show that LB is capable of significantly downregulating AQP4 and caspase-3 mRNA expression in the hippocampus and striatum following cerebral I/R injury in rats. The mechanism by which LB improved ischaemic brain injury may be associated with changes in AQP4 and caspase-3 mRNA expression in the hippocampus and the striatum.

Two new dammarane-type glycosides from Phlomis umbrosa.

Two new dammarane-type glycosides, phlomisumbroside A (1) and phlomisumbroside B (2), together with 15 known compounds (3-17) were isolated from the leaves of Phlomis umbrosa Turcz. Their structures were established by the spectroscopic methods including 2D NMR techniques.

Oxytocin in the periaqueductal grey regulates nociception in the rat.

Studies have demonstrated that oxytocin (OXT) plays important roles in pain modulation in the central nervous system, and there are OXT receptors in the periaqueductal grey (PAG). The experiment was designed to investigate the effect of OXT in the PAG on antinociception. The results showed that (1) intra-PAG injection of OXT increased the pain threshold, whereas the local administration of the high specific OXT receptor antagonist, desGly-NH(2), d(CH(2))(5)[D-Tyr(2), Thr-sup-4]OVT decreased the pain threshold in a dose-dependent manner; (2) Pain stimulation could elevate OXT concentration in the PAG perfusion liquid. The data suggested that OXT in the PAG was involved in the antinociceptive process through the OXT receptor.

Two new diterpenoids and other constituents from Isodon rubescens.

Two new ent-kaurene diterpenoids, 15α-acetoxyl-6,11α-epoxy-6α-hydroxy-20-oxo-6,7-seco-ent-kaur-16-en-1,7-olide (1), 15α-hydroxy-20-oxo-6,7-seco-ent-kaur-16-en-1,7α(6,11α)-diolide (2), together with ten known compounds (5-14) were isolated from the leaves of Isodon rubescens. Their structures were elucidated mainly by various spectroscopic techniques and finally confirmed by single-crystal X-ray diffraction. Compounds 1, 2, 8 and 12 were evaluated for their cytotoxicities against EC-1, U87, A549, MCF-7 and Hela cell lines.