Hyperoside protects against oxidative stress-mediated photoreceptor degeneration: therapeutic potentials for photoreceptor degenerative diseases.

BACKGROUND: Photoreceptor degeneration underpinned by oxidative stress-mediated mitochondrial dysfunction and cell death leads to progressive and irreversible vision impairment. Drug treatments that protect against photoreceptor degeneration are currently available in the clinical settings. It has been shown that hyperoside, a flavonol glycoside, protects against neuronal loss in part by suppressing oxidative stress and maintaining the functional integrity of mitochondria. However, whether hyperoside protects against photoreceptor degeneration remains unknown. METHODS: To address the pharmacological potentials of hyperoside against oxidative stress-mediated photoreceptor degeneration on molecular, cellular, structural and functional levels, multiple in vitro and in vivo methodologies were employed in the current study, including live-cell imaging, optical coherence tomography, electroretinography, histological/immunohistochemical examinations, transmission electron microscopy, RNA-sequencing and real-time qPCR. RESULTS: The in vitro results demonstrate that hyperoside suppresses oxidative stress-mediated photoreceptor cell death in part by mitigating mitochondrial dysfunction. The in vivo results reveal that hyperoside protects against photooxidative stress-induced photoreceptor morphological, functional and ultrastructural degeneration. Meanwhile, hyperoside treatment offsets the deleterious impact of photooxidative stress on multiple molecular pathways implicated in the pathogenesis of photoreceptor degeneration. Lastly, hyperoside attenuates photoreceptor degeneration-associated microglial inflammatory activation and reactive Müller cell gliosis. CONCLUSIONS: All things considered, the present study demonstrates for the first time that hyperoside attenuates oxidative stress-induced photoreceptor mitochondrial dysfunction and cell death. The photoreceptor-intrinsic protective effects of hyperoside are corroborated by hyperoside-conferred protection against photooxidative stress-mediated photoreceptor degeneration and perturbation in retinal homeostasis, warranting further evaluation of hyperoside as a photoreceptor protective agent for the treatment of related photoreceptor degenerative diseases.

Creep behavior and long-term strength characteristics of pre-peak damaged sandstone under conventional triaxial compression.

A series of creep tests were carried out on sandstone specimens with different pre-peak instantaneous damage characteristics under different confining pressures. The results revealed that the creep stress was the key factor affecting the occurrence of the three stages of creep, and the steady-state creep rate increased exponentially with increasing creep stress. Under the same confining pressure, the larger the instantaneous damage of the rock specimen was, the more quickly creep failure occurred and the lower the creep failure stress was. For the pre-peak damaged rock specimens, the strain threshold for accelerating creep was the same for a given confining pressure. The strain threshold increased with increasing confining pressure. In addition, the long-term strength was determined using the isochronous stress-strain curve and the variation in the creep contribution factor. The results revealed that the long-term strength decreased gradually with increasing pre-peak instantaneous damage under lower confining pressures. However, the instantaneous damage had little effect on the long-term strength under higher confining pressures. Finally, the macro-micro-failure modes of the sandstone were analyzed according to the fracture morphology observed via scanning electron microscopy. It was found that the macroscale creep failure patterns of the sandstone specimens could be divided into a shear-dominated failure mode under high confining pressures and a mixed shear-tensile failure mode under low confining pressures. At the microscale, as the confining pressure increased, the micro-fracture mode of the sandstone changed gradually from a single brittle fracture to a mixed brittle and ductile fracture mode.

Cuscuta chinensis Lam. Protects Against Light-Induced Retinal Degeneration: Therapeutic Implications for Photoreceptor Degenerative Disorders.

Cuscuta chinensis Lam. (CCL) is a medicinal herb widely used in traditional Chinese medicine for the treatment of ophthalmic diseases, including age-dependent vision-threatening retinal degenerative disorders that involve irreversible loss of the first-order retinal neurons, photoreceptors. However, evidence is lacking if CCL is pharmacologically active at protecting against loss of photoreceptors and photoreceptor degeneration-associated retinal structural and functional impairment. The current study thus evaluates the potential photoreceptor protective effects of CCL to better support its clinical applications in the prevention and treatment of photoreceptor degenerative diseases. Non-invasive full-retinal optical coherence tomography, electroretinography, histological examination, immunohistochemistry and real-time qPCR analysis were performed to assess the retinal protective effects of CCL in light-exposed BALB/c mice characterized by photooxidative stress-mediated photoreceptor loss and associated retinal morphological and functional impairment. The results showed that CCL treatment protected against light-induced degeneration of the photoreceptor structure and deterioration of the retinal function. Furthermore, CCL treatment increased the retinal expression of rhodopsin, S-opsin and M-opsin, supporting the protective effects of CCL in both rod and cone photoreceptors. CCL treatment suppressed photoreceptor cell death in the light-exposed retinas. The morphological integrity of the second-order retinal neurons was also preserved as a result of CCL treatment. In addition, CCL treatment attenuated light-induced reactive müller gliosis, microglial activation and inflammation in the retina. In conclusion, the current work demonstrates for the first time that CCL protects against photooxidative stress-mediated degeneration of photoreceptors and associated disturbance of structural, functional and immune homeostasis of the retina. The findings here thus provide novel experimental evidence supporting the clinical application of CCL in the prevention and treatment photoreceptor degenerative diseases.

All-Trans Retinoic Acid Prevents the Progression of Gastric Precancerous Lesions by Regulating Disordered Retinoic Acid Metabolism.

Retinoic acid (RA) is the most biologically active metabolite of vitamin A and is important for stomach physiological function. However, little is known about the metabolic status of RA in human gastric lesions. From 2015 to 2018, 1,392 local residents in Lujiang County were recruited into a cross-sectional survey program, which included a questionnaire interview and blood collection. We detected the mRNA and protein expression of RA metabolism-relevant factors in gastric tissues from 68 local patients with gastric lesions. The effects of all-trans retinoic acid (ATRA) supplementation were investigated in a gastric precancerous lesions (GPLs) rat model. In the cross-sectional survey, no significant differences in the level of RA precursor (P > 0.05) between the H. pylori seronegative and seropositive residents were observed. However, the mRNA and protein expression of RA synthesizing enzymes (RDH10 and ALDH1A1) were significantly decreased and catabolic enzyme (CYP26B1) was significantly increased in the patients (P < 0.05). Consistently, in the GPL rat model, we observed a similar disorder; however, ATRA supplementation significantly not only corrected the disorder by increasing Rdh10, Aldh1a1 and decreasing Cyp26b1, but also reduced claudin-18 (P < 0.05). Our study suggested that RA metabolism is disrupted in individuals with gastric lesions, while ATRA supplementation can prevent GPL from progressing to gastric cancer.

All-trans retinoic acid suppressed GES-1 cell proliferation induced by exosomes from patients with precancerous lesions by arresting the cell cycle in S-phase.

We aimed to detect the expression of specific LncRNAs in exosomes isolated from the serum of patients with precancerous lesions and to study the effect of these serum exosomes on the activity of GES-1 cells in patients with precancerous lesions, as well as the activity of all-trans retinoic acid on GES-1 cells with or without the exosomes. Exosomes were extracted from the serum of patients with precancerous lesions and normal controls. Based on our previous sequencing results, quantitative real time-PCR was used to detect differentially expressed LncRNAs. Exosomes from the serum of patients with precancerous lesions were cocultured with GES-1 cells, and 5 µM all-trans retinoic acid was added as an intervention. Changes in cell viability and expression of LncHOXA10 were observed. Compared with the blank group, the proliferation activity of GES-1 cells cocultured with exosomes derived from the serum of patients with precancerous lesions was increased (P < 0.01), the proportion of cells in S phase was increased (P < 0.05). After adding 5 µM all-trans retinoic acid, the viability of cells decreased significantly (P < 0.01), the proportion of cells in S phase decreased significantly (P < 0.05). The expression of LncHOXA10 was decreased (P < 0.05). All-trans retinoic acid can conduct its chemopreventive effects by inhibiting the expression of LncHOXA10, thereby reducing the activity of LncHOXA10 in GES-1 cells cocultured with serum exosomes from patients with precancerous lesions.

All-Trans Retinoic Acid Rescues the Tumor Suppressive Role of RAR-ß by Inhibiting LncHOXA10 Expression in Gastric Tumorigenesis.

Numerous long noncoding RNAs (LncRNAs) were having recently been shown to be involved in cancer development, including gastric cancer (GC). However, the precise mechanism and treatments to target these molecules have rarely been studied. Thus, we aimed to investigate the function of LncHOXA10 in gastric tumorigenesis and targeted therapy. First, we measured the differences in LncHOXA10 and retinoic acid receptor ß (RAR-ß) levels in gastric cancer tissues and cell lines compared with those in noncancerous tissues and cell lines. We observed that LncHOXA10 was significantly upregulated in gastric cancer tissues and cell lines, whereas RAR-ß showed the opposite trend. Subsequently, loss and gain of LncHOXA10 cell lines were constructed to determine whether LncHOXA10 plays a role in gastric tumorigenesis. The results showed that LncHOXA10 promoted the proliferation, migration, and invasion of cells, whereas apoptosis was markedly inhibited. Subsequently, mechanistic investigations revealed that LncHOXA10 can repress RAR-ß expression and that all-trans retinoic acid (ATRA) can rescue the expression of RAR-ß. Finally, we showed that ATRA can reverse the pro-cancerous function of LncHOXA10. We showed that LncHOXA10 may be a prognostic and therapeutic factor of gastric cancer by negatively regulating RAR-ß. Furthermore, ATRA can inhibit the role of LncHOXA10 in gastric tumorigenesis.

Dairy Consumption and Liver Cancer Risk: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

The relationship of dairy consumption and liver cancer risk is still controversial. We conducted a meta-analysis of published cohort and case-control studies to summarize the epidemiologic evidence on the relationship between dairy products consumption and the risk of liver cancer. The literatures were screened from PubMed, EMBASE, and Cochrane Library before May 2020. A total of seven cohort studies and eight case-control studies (5,121 cases) were included. The summary relative risks (RRs) were 1.17 (95% CI: 0.87‒1.57) and 1.08 (95% CI: 0.78‒1.51) for milk and total dairy, respectively. 0.50 (95% CI: 0.27-0.91) and 1.16 (95% CI: 0.83-1.52) were yogurt, cheese, and curd. Subgroup analysis revealed that study duration, alcohol, and design were associated the RRs. Dose-response analysis showed that the liver cancer risk was decreased by 5.4% (P for linear trend = 0.002) with a 40 g/day increment of yogurt intake. These results suggested that total dairy, milk, cheese, and curd were positive associations with the liver cancer risk although they were not statistically significant, however higher yogurt intake would reduce the risk. Further studies are necessary to verify the relationship of dairy foods with cancer.

The SFU Opinion and Comments Corpus: A Corpus for the Analysis of Online News Comments.

We present the SFU Opinion and Comments Corpus (SOCC ), a collection of opinion articles and the comments posted in response to the articles. The articles include all the opinion pieces published in the Canadian newspaper The Globe and Mail in the 5-year period between 2012 and 2016, a total of 10,339 articles and 663,173 comments. SOCC is part of a project that investigates the linguistic characteristics of online comments. The corpus can be used to study a host of pragmatic phenomena. Among other aspects, researchers can explore: the connections between articles and comments; the connections of comments to each other; the types of topics discussed in comments; the nice (constructive) or mean (toxic) ways in which commenters respond to each other; how language is used to convey very specific types of evaluation; and how negation affects the interpretation of evaluative meaning in discourse. Our current focus is the study of constructiveness and evaluation in the comments. To that end, we have annotated a subset of the large corpus (1043 comments) with four layers of annotations: constructiveness, toxicity, negation and Appraisal (Martin and White, The language of evaluation, Palgrave, New York, 2005). This paper details our corpus, the data collection process, the characteristics of the corpus and describes the annotations. While our focus is comments posted in response to opinion news articles, the phenomena in this corpus are likely to be present in many commenting platforms: other news comments, comments and replies in fora such as Reddit, feedback on blogs, or YouTube comments.

Shihu Yeguang Pill protects against bright light-induced photoreceptor degeneration in part through suppressing photoreceptor apoptosis.

Photoreceptor cells are first-order retinal neurons that directly contribute to the formation of vision. Photoreceptor degeneration is the primary cause of vision impairment during the course of retinopathies such as retinitis pigmentosa and age-related macular degeneration, for which photoreceptor-targeted therapies are currently unavailable. Shihu Yeguang Pill (SYP), a classic formula in traditional Chinese medicine, has a long histology of clinical application for the treatment of a wide range of retinopathies in China. However, whether SYP is pharmacological effective at protecting photoreceptor cells is unclear. The current study thus directly addressed the pharmacological implications of SYP in photoreceptor degeneration in a mouse model characterized by bright light-induced retinal degeneration. Non-invasive full-retinal assessment was carried out to evaluate the effect of SYP on the retinal structure and function through optical coherence tomography and electroretinography, respectively. In addition, photoreceptor apoptosis, second-order neuron impairment and reactive changes in retinal microglial and müller cells, hallmark pathologies associated with photoreceptor degeneration, were assessed using immunohistochemistry and real-time PCR analyses. The results showed that SYP treatment attenuated bright light-induced impairment of the retinal structure and function. Moreover, SYP treatment suppressed photoreceptor apoptosis, alleviated the impairment of bipolar and horizontal cells and mitigated the reactive changes of müller and microglial cells in the bright light-exposed retinas. Real-time PCR analyses showed that dysregulated expression of pro-apoptotic c-fos and c-jun and anti-apoptotic bcl-2 as well as proinflammatory TNF-α in the bright light-exposed retinas was partially normalized as a result of SYP treatment. In summary, the work here demonstrates for the first time that SYP treatment protects the retinas from developing bright light-induced photoreceptor degeneration and associated alterations in second-order neurons and glial cells. The findings here thus provide experimental evidence to better support the mechanism-guided clinical application of SYP in the treatment of related retinal degenerative diseases.

Epidemiological investigation of Measles in Bozhou City, China, from 2005 to 2015.

BACKGROUND: Measles is one of the most highly contagious diseases which have not been eliminated in China. This study aimed to investigate the epidemiological characteristics of measles in Bozhou city, China between 2005 and 2015 and provide scientific basis for the prevention, control and elimination of measles. METHODS: Cases of measles derived from the China Information System for Disease Prevention and Control, and demographic data were obtained from the Public Security Bureau of Bozhou city. RESULTS: Among the 2934 cases, the average annual incidence of measles was 45.934 (per 1,000,000 persons) and no death occurred. The incidence of males was higher than females (Z = 10.794, p < 0.05). Scattered children accounted for 63.2% (1854/2934) in occupation distributing. In terms of immunization history of cases, 57.5% had 0 doses, 15.0% had one dose, 7.5% had two doses and others were uncertain. CONCLUSIONS: Our study has investigated the epidemiological characteristics of measles in Bozhou City. To eventually eliminate measles in Bozhou city, improving measles vaccination coverage and quality of routine immunization services were important.