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"Ching, Jacqueline"
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Understanding women's rights
Discusses the history of women's rights in the United States, from the colonial era to the modern day, including the women's suffrage movement, twentieth-century feminism, and modern post-feminist America.
Book
Gene expression of stearoyl-ACP desaturase and Δ12 fatty acid desaturase 2 is modulated during seed development of flax (Linum usitatissimum)
Flax's recent popularity in human and animal foods is mostly due to its desirable FA composition. Flax is an excellent source of omega-3 FA, which have been shown to have many health benefits. To date, little is known about the genetic and environmental factors that control the FA composition of flax seeds. To elucidate some of the important genetic components, reverse transcriptase (RT)-PCR and real-time PCR were used to determine the expression profiles of two key FA biosynthetic genes during seed development. Plants of flax cultivar AC McDuff were grown under field conditions, and RNA was extracted from ovaries and developing bolls collected from 2 d after anthesis (DAA) to maturity. Desaturation enzymes stearoyl-ACP desaturase (SAD) and Δ12 FA desaturase 2 (FAD2) were both expressed in ovaries, and their expression was differentially modulated throughout seed development. SAD was most highly expressed in ovaries. Its expression quickly decreased until 4 DAA; this was followed by a slight peak at 8 DAA, only to return to relatively low levels of expression in maturing bolls, ranging from 2.1% to 4.5% relative to the level observed in ovaries. FAD2 expression displayed a different temporal pattern. While expression of FAD2 did decrease in the early stages of seed development, expression increased starting at 8 DAA, peaking at 16 DAA, when it was 158% relative to the level observed in ovaries. FAD2, which desaturates oleic acid (18:1 cisΔ9) into linoleic acid (18:2 cisΔ9, 12), is therefore controlled at the transcription level. To relate enzyme expression with FA profile, GC was performed on the same subsamples used for RT-PCR and real-time PCR, and proportions of palmitic, stearic, oleic, linoleic, and linolenic acids were determined for the same developmental stages. Although FAD2 expression increased from 8 to 16 DAA, relative changes in linoleic acid (18:2 cis Δ9, 12) were not observed. However, linolenic acid (ALA; α-18:3; 18:3 cisΔ9, 12, 15) levels increased steadily, meaning that linoleic acid (18:2 cisΔ9, 12) is a transient substrate converted by FAD3 as quickly as it is produced by FAD2. Phenotypes are the result of genotypes, environment, and the interaction of the two. To evaluate the environmental impact on the production of FA in flax, FA profiles were assessed in a total of four environments (two locations, two years). Warm and dry environmental conditions resulted in lower levels of PUFA 18:2 cisΔ9, 12 and 18:3 cisΔ9, 12, 15, and higher levels of 18:1 cisΔ9. FAD2 expression and/or activity may therefore be affected by the environment.
Journal Article
Surgical outcomes of orbital evisceration with primary orbital implant placement in patients with endophthalmitis
Objectives
This study reports the surgical outcomes of evisceration with primary orbital implant placement in patients with endophthalmitis and analyses the association with implant exposure and extrusion.
Methods
A retrospective, multicentre, Chinese cohort study. Review of medical records and orbital images of patients who underwent evisceration with primary orbital implant placement between January 2005 and January 2021.
Results
Out of 79 patients who underwent orbital evisceration with primary orbital implant placement, 26 (26 eyes) of them (male = 13) suffered from endophthalmitis. The duration from endophthalmitis diagnosis (19 = exogenous, 7 = endogenous) to evisceration was 9 standard deviation ± 5 (range: 1–15) days. The follow-up was 70 ± 46 (24–180) months after operation. The orbital implant size was 17 ± 3 (14–20) mm, and silicone was the most used material (69%, 18/26 of patients). The most frequent post-operative complication was orbital implant exposure (42%, 11/26), followed by orbital implant extrusion (12% 3/26) and ptosis (8%, 2/26). Implant exposure or extrusion was more commonly associated with endophthalmitis in comparison to non-endophthalmitis patients that required evisceration and primary orbital implant placement (54% versus 17%,
P
< 0.05). Univariate analysis showed single scleral closure technique (100% versus 58%,
P
< 0.05) and endogenous endophthalmitis (50% versus 0%,
P
< 0.05) were associated with implant exposure or extrusion, and only endogenous endophthalmitis was significant with multivariate analysis (
P
< 0.05).
Conclusions
Primary implant placement during evisceration should be avoided in eyes with endophthalmitis especially in those with an endogenous source, and double scleral closure technique may be a better alternative for primary orbital implant placement in infected eyes.
Journal Article
Gene Expression of Stearoyl-ACP Desaturase and Delta12 Fatty Acid Desaturase 2 Is Modulated During Seed Development of Flax (Linum usitatissimum)
Flax's recent popularity in human and animal foods is mostly due to its desirable FA composition. Flax is an excellent source of omega-3 FA, which have been shown to have many health benefits. To date, little is known about the genetic and environmental factors that control the FA composition of flax seeds. To elucidate some of the important genetic components, reverse transcriptase (RT)-PCR and real-time PCR were used to determine the expression profiles of two key FA biosynthetic genes during seed development. Plants of flax cultivar AC McDuff were grown under field conditions, and RNA was extracted from ovaries and developing bolls collected from 2 d after anthesis (DAA) to maturity. Desaturation enzymes stearoyl-ACP desaturase (SAD) and delta12 FA desaturase 2 (FAD2) were both expressed in ovaries, and their expression was differentially modulated throughout seed development. SAD was most highly expressed in ovaries. Its expression quickly decreased until 4 DAA; this was followed by a slight peak at 8 DAA, only to return to relatively low levels of expression in maturing bolls, ranging from 2.1% to 4.5% relative to the level observed in ovaries. FAD2 expression displayed a different temporal pattern. While expression of FAD2 did decrease in the early stages of seed development, expression increased starting at 8 DAA, peaking at 16 DAA, when it was 158% relative to the level observed in ovaries. FAD2, which desaturates oleic acid (18:1cisdelta9) into linoleic acid (18:2cisdelta9,12), is therefore controlled at the transcription level. To relate enzyme expression with FA profile, GC was performed on the same subsamples used for RT-PCR and real-time PCR, and proportions of palmitic, stearic, oleic, linoleic, and linolenic acids were determined for the same developmental stages. Although FAD2 expression increased from 8 to 16 DAA, relative changes in linoleic acid (18:2cis delta9,12) were not observed. However, linolenic acid (ALA; alpha-18:3; 18:3cisdelta9,12,15) levels increased steadily, meaning that linoleic acid (18:2cisdelta9,12) is a transient substrate converted by FAD3 as quickly as it is produced by FAD2. Phenotypes are the result of genotypes, environment, and the interaction of the two. To evaluate the environmental impact on the production of FA in flax, FA profiles were assessed in a total of four environments (two locations, two years). Warm and dry environmental conditions resulted in lower levels of PUFA 18:2cisdelta9,12 and 18:3cisdelta9,12,15, and higher levels of 18:1 cisdelta9. FAD2 expression and/or activity may therefore be affected by the environment.
Journal Article
Gene expression of stearoyl-ACP desaturase and delta12 fatty acid desaturase 2 is modulated during seed development of flax (Linum usitatissimum)
Flax's recent popularity in human and animal foods is mostly due to its desirable FA composition. Flax is an excellent source of omega-3 FA, which have been shown to have many health benefits. To date, little is known about the genetic and environmental factors that control the FA composition of flax seeds. To elucidate some of the important genetic components, reverse transcriptase (RT)-PCR and real-time PCR were used to determine the expression profiles of two key FA biosynthetic genes during seed development. Plants of flax cultivar AC McDuff were grown under field conditions, and RNA was extracted from ovaries and developing bolls collected from 2 d after anthesis (DAA) to maturity. Desaturation enzymes stearoyl-ACP desaturase (SAD) and delta12 FA desaturase 2 (FAD2) were both expressed in ovaries, and their expression was differentially modulated throughout seed development. SAD was most highly expressed in ovaries. Its expression quickly decreased until 4 DAA; this was followed by a slight peak at 8 DAA, only to return to relatively low levels of expression in maturing bolls, ranging from 2.1% to 4.5% relative to the level observed in ovaries. FAD2 expression displayed a different temporal pattern. While expression of FAD2 did decrease in the early stages of seed development, expression increased starting at 8 DAA, peaking at 16 DAA, when it was 158% relative to the level observed in ovaries. FAD2, which desaturates oleic acid (18:1cisdelta9) into linoleic acid (18:2cisdelta9,12), is therefore controlled at the transcription level. To relate enzyme expression with FA profile, GC was performed on the same subsamples used for RT-PCR and real-time PCR, and proportions of palmitic, stearic, oleic, linoleic, and linolenic acids were determined for the same developmental stages. Although FAD2 expression increased from 8 to 16 DAA, relative changes in linoleic acid (18:2cis delta9,12) were not observed. However, linolenic acid (ALA; alpha-18:3; 18:3cisdelta9,12,15) levels increased steadily, meaning that linoleic acid (18:2cisdelta9,12) is a transient substrate converted by FAD3 as quickly as it is produced by FAD2. Phenotypes are the result of genotypes, environment, and the interaction of the two. To evaluate the environmental impact on the production of FA in flax, FA profiles were assessed in a total of four environments (two locations, two years). Warm and dry environmental conditions resulted in lower levels of PUFA 18:2cisdelta9,12 and 18:3cisdelta9,12,15, and higher levels of 18:1 cisdelta9. FAD2 expression and/or activity may therefore be affected by the environment.
Journal Article
Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder
Relapse of neuromyelitis optica spectrum disorder occurred in 20% of patients who received satralizumab, a subcutaneous anti–interleukin-6 antibody, as compared with 43% of those in the placebo group. The drug may have been more effective in patients with anti–aquaporin-4 IgG antibody than in those without the antibody.
Journal Article
Ovatodiolide suppresses colon tumorigenesis and prevents polarization of M2 tumor-associated macrophages through YAP oncogenic pathways
Background
An increased expression of Yes-associated protein (YAP1) has been shown to promote tumorigenesis in many cancer types including colon. However, the role of YAP1 in promoting colon tumorigenesis remains unclear. Here, we demonstrate that YAP1 expression is associated with M2 tumor-associated macrophage polarization and the generation of colon cancer stem-like cells. YAP1 downregulation by gene silencing or a phytochemical, ovatodiolide, not only suppresses colon cancer tumorigenesis but also prevents M2 TAM polarization.
Methods
Human monocytic cells, THP-1, and colon cancer cell lines, HCT116 and DLD-1, were co-cultured to mimic the interactions between tumor and its microenvironment. M2 polarization of the THP-1 cells were examined using both flow cytometry and q-PCR technique. The inhibition of YAP1 signaling was achieved by gene-silencing technique or ovatodiolide. The molecular consequences of YAP1 inhibition was demonstrated via colony formation, migration, and colon-sphere formation assays. 5-FU and ovatodiolide were used in drug combination studies. Xenograft and syngeneic mouse models were used to investigate the role of YAP1 in colon tumorigenesis and TAM generation.
Results
An increased YAP1 expression was found to be associated with a poor prognosis in patients with colon cancer using bioinformatics approach. We showed an increased YAP1 expression in the colon spheres, and colon cancer cells co-cultured with M2 TAMs. YAP1-silencing led to the concomitant decreased expression of major oncogenic pathways including Kras, mTOR, β-catenin, and M2-promoting IL-4 and tumor-promoting IL-6 cytokines. TAM co-cultured colon spheres showed a significantly higher tumor-initiating ability in vivo. Ovatodiolide treatment alone and in combination with 5-FU significantly suppressed in vivo tumorigenesis and less TAM infiltration in CT26 syngeneic mouse model.
Conclusions
We have identified the dual function of YAP1 where its suppression not only inhibited tumorigenesis but also prevented the generation of cancer stem-like cells and M2 TAM polarization. Ovatodiolide treatment suppressed YAP1 oncogenic pathways to inhibit colon tumorigenesis and M2 TAM generation both in vitro and in vivo. Ovatodiolide should be considered for its potential for adjuvant therapeutic development.
Journal Article
Protective role of VEGF/VEGFR2 signaling against high fatality associated with hepatic encephalopathy via sustaining mitochondrial bioenergetics functions
Background
The lack of better understanding of the pathophysiology and cellular mechanisms associated with high mortality seen in hepatic encephalopathy (HE), a neurological complication arising from acute hepatic failure, remains a challenging medical issue. Clinical reports showed that the degree of baroreflex dysregulation is related to the severity of HE. Furthermore, mitochondrial dysfunction in the rostral ventrolateral medulla (RVLM), a key component of the baroreflex loop that maintains blood pressure and sympathetic vasomotor tone, is known to underpin impairment of baroreflex. Realizing that in addition to angiogenic and vasculogenic effects, by acting on its key receptor (VEGFR2), vascular endothelial growth factor (VEGF) elicits neuroprotection via maintenance of mitochondrial function, the guiding hypothesis of the present study is that the VEGF/VEGFR2 signaling plays a protective role against mitochondrial dysfunction in the RVLM to ameliorate baroreflex dysregulation that underpins the high fatality associated with HE.
Methods
Physiological, pharmacological and biochemical investigations were carried out in proof-of-concept experiments using an in vitro model of HE that involved incubation of cultured mouse hippocampal neurons with ammonium chloride. This was followed by corroboratory experiments employing a mouse model of HE, in which adult male C57BL/6 mice and VEGFR2 wild-type and heterozygous mice received an intraperitoneal injection of azoxymethane, a toxin used to induce acute hepatic failure.
Results
We demonstrated that VEGFR2 is present in cultured neurons, and observed that whereas recombinant VEGF protein maintained cell viability, gene-knockdown of
vegfr2
enhanced the reduction of cell viability in our in vitro model of HE. In our in vivo model of HE, we found that VEGFR2 heterozygous mice exhibited shorter survival rate and time when compared to wild-type mice. In C57BL/6 mice, there was a progressive reduction in VEGFR2 mRNA and protein expression, mitochondrial membrane potential and ATP levels, alongside augmentation of apoptotic cell death in the RVLM, accompanied by a decrease in baroreflex-mediated sympathetic vasomotor tone and hypotension. Immunoneutralization of VEGF exacerbated all those biochemical and physiological events.
Conclusions
Our results suggest that, acting via VEGFR2, the endogenous VEGF plays a protective role against high fatality associated with HE by amelioration of the dysregulated baroreflex-mediated sympathetic vasomotor tone through sustaining mitochondrial bioenergetics functions and eliciting antiapoptotic action in the RVLM.
Journal Article
A study protocol for a pragmatic pre-post trial to determine the feasibility and effectiveness of a novel co-designed service to support health and wellbeing of older carers of older people
Older carers (≥50 years) of older people (≥65 years) are an important sub-group of carers performing valuable roles in providing informal care but often do not have the time or give priority to supporting their own health and wellbeing. Current services supporting older carers’ health and wellbeing are fragmented and inadequate. Through previous research and co-design activity by our team, an innovative multidisciplinary Carer Health and Wellbeing Service (CHWS) has been developed. The purpose of this protocol paper is to describe the rationale for the CHWS and the methods proposed to evaluate its effectiveness and implementation outcomes. The CHWS commenced in March 2024 at Peninsula Health, Melbourne, Australia. Older carers of older people can be referred from multiple sources, including self-referral. A pre-post mixed methods study design is being utilised. Initial assessments include the Carer Support Assessment Needs Tool (CSNAT) and carer prioritisation of their needs, which guides further assessment and interventions. Assessments will occur at Service intake and 6 months later. The primary effectiveness outcome is the Preparedness for Caregiving Scale, and primary implementation outcomes are reach and adoption. Interviews of carers, referrers and staff, and a cost-utility analysis will be undertaken. The target sample size is 137 carers undertaking assessment and intervention over the 15 months data collection. Generalised linear regression will be used to compare pre- and post-continuous outcome measures. Qualitative data will be thematically analysed. Results will inform future scaling up of this innovative approach to optimising health and wellbeing of older carers of older people. Trial registration number: Australian New Zealand Clinical Trials Registry (ANZCTR) – ACTRN: 12625000245493.
Journal Article
Anti–PD-L1 and anti-CD73 combination therapy promotes T cell response to EGFR-mutated NSCLC
Treatment with anti-PD-1 and anti-PD-L1 therapies has shown durable clinical benefit in non-small cell lung cancer (NSCLC). However, patients with NSCLC with epidermal growth factor receptor (EGFR) mutations do not respond as well to treatment as patients without an EGFR mutation. We show that EGFR-mutated NSCLC expressed higher levels of CD73 compared with EGFR WT tumors and that CD73 expression was regulated by EGFR signaling. EGFR-mutated cell lines were significantly more resistant to T cell killing compared with WT cell lines through suppression of T cell proliferation and function. In a xenograft mouse model of EGFR-mutated NSCLC, neither anti-PD-L1 nor anti-CD73 antibody alone inhibited tumor growth compared with the isotype control. In contrast, the combination of both antibodies significantly inhibited tumor growth, increased the number of tumor-infiltrating CD8+ T cells, and enhanced IFN-γ and TNF-α production of these T cells. Consistently, there were increases in gene expression that corresponded to inflammation and T cell function in tumors treated with the combination of anti-PD-L1 and anti-CD73. Together, these results further support the combination of anti-CD73 and anti-PD-L1 therapies in treating EGFR-mutated NSCLC, while suggesting that increased T cell activity may play a role in response to therapy.
Journal Article