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"Wang, Yu-Meng"
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Diplomacy of quasi-alliances in the Middle East
Quasi-alliance refers to the ideation, mechanism and behavior of policy-makers to carry out security cooperation through informal political and security arrangements. As a \"gray zone\" between alliance and neutrality, quasi-alliance is a hidden national security statecraft. Based on declassified archives and secondary sources, this book probes the theory and practice of quasi-alliances in the Middle East. Four cases are chosen to test the hypotheses of quasi-alliance, one of which is the Anglo-French-Israeli quasi-alliance during the Suez Canal War of 1956.
Book
Combining the oncolytic peptide LTX-315 with doxorubicin demonstrates therapeutic potential in a triple-negative breast cancer model
Background
Immunochemotherapy, the combined use of immunotherapy and chemotherapy, has demonstrated great promise in several cancers. LTX-315 is an oncolytic peptide with potent immunomodulatory properties designed for the local treatment of solid tumors. By inducing rapid immunogenic cell death through the release of danger-associated molecular pattern molecules (DAMPs), LTX-315 is capable of reshaping the tumor microenvironment, turning “cold” tumors “hot” through a significant increase in tumor-infiltrating lymphocytes.
Methods
We investigated the potential of LTX-315 to be used in combination with standard-of-care chemotherapy (doxorubicin, brand name CAELYX®) against triple-negative breast cancer in an orthotopic 4 T1 mammary fat pad model. Tumor growth curves were compared using one-way ANOVA analysis of variance and Tukey’s multiple comparisons test, and animal survival curves were compared using the log-rank (Mantel-Cox) test. We considered
p
values ≤0.05 to indicate statistical significance.
Results
We found that LTX-315 displayed a strong additive antitumoral effect when used in combination with CAELYX®, and induced immune-mediated changes in the tumor microenvironment, followed by complete regression in the majority of animals treated. Furthermore, imaging techniques and histological examination showed that the combination induced strong local necrosis, followed by an increase in the infiltration of CD4+ and CD8+ immune cells into the tumor parenchymal tissue.
Conclusions
Our data demonstrate that LTX-315 is a promising combination partner with CAELYX® for the treatment of triple-negative breast cancer.
Journal Article
Vitamin D and Ocular Diseases: A Systematic Review
The contributory roles of vitamin D in ocular and visual health have long been discussed, with numerous studies pointing to the adverse effects of vitamin D deficiency. In this paper, we provide a systematic review of recent findings on the association between vitamin D and different ocular diseases, including myopia, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), dry eye syndrome (DES), thyroid eye disease (TED), uveitis, retinoblastoma (RB), cataract, and others, from epidemiological, clinical and basic studies, and briefly discuss vitamin D metabolism in the eye. We searched two research databases for articles examining the association between vitamin D deficiency and different ocular diseases. One hundred and sixty-two studies were found. There is evidence on the association between vitamin D and myopia, AMD, DR, and DES. Overall, 17 out of 27 studies reported an association between vitamin D and AMD, while 48 out of 54 studies reported that vitamin D was associated with DR, and 25 out of 27 studies reported an association between vitamin D and DES. However, the available evidence for the association with other ocular diseases, such as glaucoma, TED, and RB, remains limited.
Journal Article
Comparison of Corneal Tomography and a New Combined Tomographic Biomechanical Index in Subclinical Keratoconus
To investigate and compare the diagnostic ability of corneal tomography and biomechanical and combined parameters for detection of corneal ectasia.
Consecutive patients with subclinical keratoconus (SCKC) and age-matched controls were included. Only one eye from each patient was selected for analysis. The final D value from the Belin/Ambrósio Enhanced Ectasia Display (BAD) was obtained from the Pentacam (Oculus Optikgeräte, Wetzlar, Germany). The tomographic biomechanical index (TBI) was derived from the Pentacam and Corvis ST (Oculus Optikgeräte). Classification analysis between normal and subclinical keratoconus (SCKC) was evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) and partial AUC (pAUC) with specificity of 80% or greater were compared.
Twenty-three eyes with SCKC and 37 normal eyes were included. All Pentacam-derived parameters (P < .001) and all but two Corvis ST-derived parameters (P < .020) were significantly different between normal and SCKC eyes. A significant difference was found in the final D value (P ≤ .020) and TBI (P ≤ .040) between normal and SCKC eyes. For differentiating normal and SCKC eyes, TBI and BAD final D value demonstrated the highest AUC (0.925 and 0.786, respectively) and pAUC (0.150 and 0.088, respectively). TBI demonstrated 84.4% sensitivity and 82.4% specificity using a cut-off of 0.16. Comparative analysis between these parameters showed that AUC and pAUC of TBI were significantly higher than all parameters from Pentacam (P ≤ .032).
In the current study, combined use of tomographic and biomechanical parameters demonstrated a higher capability in differentiating normal and SCKC eyes when compared to tomographic analysis alone. [J Refract Surg. 2018;34(9):616-621.].
Journal Article
Myopia Genetics and Heredity
Myopia is the most common eye condition leading to visual impairment and is greatly influenced by genetics. Over the last two decades, more than 400 associated gene loci have been mapped for myopia and refractive errors via family linkage analyses, candidate gene studies, genome-wide association studies (GWAS), and next-generation sequencing (NGS). Lifestyle factors, such as excessive near work and short outdoor time, are the primary external factors affecting myopia onset and progression. Notably, besides becoming a global health issue, myopia is more prevalent and severe among East Asians than among Caucasians, especially individuals of Chinese, Japanese, and Korean ancestry. Myopia, especially high myopia, can be serious in consequences. The etiology of high myopia is complex. Prediction for progression of myopia to high myopia can help with prevention and early interventions. Prediction models are thus warranted for risk stratification. There have been vigorous investigations on molecular genetics and lifestyle factors to establish polygenic risk estimations for myopia. However, genes causing myopia have to be identified in order to shed light on pathogenesis and pathway mechanisms. This report aims to examine current evidence regarding (1) the genetic architecture of myopia; (2) currently associated myopia loci identified from the OMIM database, genetic association studies, and NGS studies; (3) gene-environment interactions; and (4) the prediction of myopia via polygenic risk scores (PRSs). The report also discusses various perspectives on myopia genetics and heredity.
Journal Article
MeCP2 duplication causes hyperandrogenism by upregulating LHCGR and downregulating RORα
Duplication of
MECP2
(methyl-CpG-binding protein 2) gene causes a serious neurological and developmental disorder called
MECP2
duplication syndrome (MDS), which is usually found in males. A previous clinical study reported that MDS patient has precocious puberty with hyperandrogenism, suggesting increased MeCP2 may cause male hyperandrogenism. Here we use an MDS mouse model and confirm that
MECP2
duplication significantly upregulates androgen levels. We show for the first time that MeCP2 is highly expressed in the Leydig cells of testis, where androgen is synthesized. Mechanistically,
MECP2
duplication increases androgen synthesis and decreases androgen to estrogen conversion through either the upregulation of luteinizing hormone receptor (LHCGR) in testis, as a result of MeCP2 binds to G-quadruplex structure of
Lhcgr
promoter and recruits the transcription activator CREB1 or the downregulation of the expression of aromatase in testis by binding the CpG island of
Rorα
, an upstream regulator of aromatase. Taken together, we demonstrate that MeCP2 plays an important role in androgen synthesis, supporting a novel non-CNS function of MeCP2 in the process of sex hormone synthesis.
Journal Article
Chemical Constituents of Stems and Leaves of Tagetespatula L. and Its Fingerprint
Tagetespatula L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (1, 2) and fourteen known metabolites (3–16) were isolated from the stems and leaves of T. patula (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds 1 and 2 were determined by ECD calculations. Compounds 1 and 2 exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC50 values of 41.20 μmol/L and 30.43 μmol/L, respectively. The fingerprint profiles of stems and leaves of T. patula with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright.
Journal Article
Prevalence of strabismus and its risk factors among school aged children: The Hong Kong Children Eye Study
The study aims to determine the prevalence of strabismus and its risk factors among school children in Hong Kong. This is a cross-sectional study involving 6–8 year old children from different districts in Hong Kong. 4273 children received comprehensive ophthalmological examination, cycloplegic auto-refraction, best corrected visual acuity (BCVA), anterior segment examination, cover/uncover test, ocular motility, and fundus examination. Demographic information, pre- and post- natal background, parental smoking status, and family history of strabismus were obtained through questionnaires. Strabismus was found among 133 children (3.11%, 95% CI 2.59–3.63%), including 117 (2.74%) exotropia and 12 (0.28%) esotropia cases (exotropia-esotropia ratio: 9.75:1). There was no significant difference in prevalence across age (6–8 years) and gender. Multivariate analysis revealed associations of strabismus with myopia (≤ − 1.00D; OR 1.61; 95% CI 1.03–2.52;
P
= 0.037) hyperopia (≥ + 2.00D; OR 2.49; 95% CI 1.42–4.39;
P
= 0.002), astigmatism (≥ + 2.00D; OR 2.32; 95% CI 1.36–3.94;
P
= 0.002), and anisometropia (≥ 2.00D; OR 3.21; 95% CI 1.36–7.55;
P
= 0.008). Other risk factors for strabismus included maternal smoking during pregnancy (OR 4.21; 95% CI 1.80–9.81;
P
= 0.001), family history of strabismus (OR 6.36; 95% CI 2.78–14.50,
P
< 0.0001) and advanced maternal age at childbirth (> 35 years; OR 1.65; CI 1.09–2.49,
P
= 0.018). The prevalence of strabismus among children aged 6—8 years in Hong Kong is 3.11%. Refractive errors, family history of strabismus and maternal smoking history during pregnancy are risk factors. Early correction of refractive errors and avoidance of maternal smoking during pregnancy are potentially helpful in preventing strabismus.
Journal Article
MicroRNA-197 controls ADAM10 expression to mediate MeCP2’s role in the differentiation of neuronal progenitors
Duplication of MECP2 (Methyl-CpG-binding protein 2) causes severe mental illness called MECP2 duplication syndrome (MDS), yet the underlying mechanism remains elusive. Here we show, in Tg(MECP2) transgenic mouse brain or cultured neural progenitor cells (NPCs), that elevated MeCP2 expression promotes NPC differentiation into neurons. Ectopic expression of MeCP2 inhibits ADAM10 and thus the NOTCH pathway during NPC differentiation. In human cells, this downregulation on ADAM10 was mediated by miRNA-197, which is upregulated by MeCP2. Surprisingly, miR-197 binds to the ADAM10 3′-UTR via its 3′ side, not the canonical seed sequence on the 5′ side. In mouse cells, a noncoding RNA Gm28836 is used to replace the function of miR-197 between MeCP2 and ADAM10. Similar to MeCP2, overexpressing miR-197 also promotes NPCs differentiation into neurons. Interestingly, three rare missense mutations (H371R, E394K, and G428S) in MECP2, which we identified in a Han Chinese autism spectrum disorders (ASD) cohort showed loss-of-function effects in NPC differentiation assay. These mutations cannot upregulate miR-197. Overexpressing miR-197 together with these MeCP2 mutations could rescue the downregulation on ADAM10. Not only the inhibitor of miR-197 could reverse the effect of overexpressed MeCP2 on NPCs differentiation, but also overexpression of miR-197 could reverse the NPCs differentiation defects caused by MECP2 mutations. Our results revealed that a regulatory axis involving MeCP2, miR-197, ADAM10, and NOTCH signaling is critical for NPC differentiation, which is affected by both MeCP2 duplication and mutation.
Journal Article
Comparison of optical coherence tomography angiography metrics in primary angle-closure glaucoma and normal-tension glaucoma
To investigate the peripapillary vascular metrics in early normal tension glaucoma (NTG) and early primary angle closure glaucoma (PACG) eyes using optical coherence tomography angiography (OCT-A). One or both eyes of each subject were imaged for a 3 × 3 mm peripapillary region by swept-source OCT-A (DRI-OCT Triton, Topcon, Japan) and assessed by an automated MATLAB program. OCT-A metrics including circumpapillary vessel density (cpVD) and fractal dimension (cpFD) were compared. Their association with visual field (VF) parameters and retinal nerve fiber layer (RNFL) thickness were determined. Sixty-eight eyes of 51 PACG, 68 eyes of 48 NTG, and 68 eyes of 49 control subjects were cross-sectionally analyzed. NTG eyes had significantly lower global cpVD (52.369 ± 0.781%) compared with PACG eyes (55.389 ± 0.721%,
P
= 0.004) that had comparable disease severity and average RNFL thickness. Multivariable analysis revealed that, for PACG and NTG eyes, decreased cpVD ([PACG] β = −4.242; CI: −8.120, −0.363 vs [NTG] β = −5.531; CI: −9.472, −1.590) and cpFD ([PACG] β = −8.894;CI: −11.925, −5.864 vs [NTG] β = −12.064; CI: −17.095, −6.932) were associated with decreased RNFL thickness (all
P
≤ 0.032); with a stronger association between decrease cpFD and decreased RNFL thickness in NTG eyes (
P
= 0.028). Decreased cpVD was associated with decrease mean deviation (MD) in NTG eyes (β = −0.707; CI: −1.090, −0.324;
P
≤ 0.001) and not associated with the visual field parameters in PACG eyes. Early NTG had lower global cpVD compared with early PACG, despite similar disease severity and average RNFL thickness.
Journal Article