Müller Cell Regulated Microglial Activation and Migration in Rats With N-Methyl-N-Nitrosourea-Induced Retinal Degeneration

During the pathogenesis of retinitis pigmentosa (RP), the roles of retinal microglial cells after activation have not been fully elucidated. Herein, experimental RP was induced in Sprague Dawley rats by intraperitoneal injection of N-methyl-N-nitrosourea (MNU) at 50 mg/kg, and the effects of MNU on the retinas were evaluated, respectively, by retinal histology and electroretinography recordings at serial time points. Time-dependent and gradual loss of photoreceptor cells, disrupted arrangement of the outer nuclear layer (ONL), and significant reductions in both a-wave and b-wave amplitudes were observed. Morphology changes were observed in retinal microglial cells; meanwhile, with time, the number of Iba1-positive microglia and their infiltration into the ONL gradually increased. Furthermore, physical interaction of microglial-Müller cell processes following microglial activation was observed after MNU injection. In addition, Müller cells increased CX3CL1 secretion, enhanced microglial cell migration, and upregulated the CX3CR1 expression of the latter. Our observations implied that, during the pathogenesis of RP by MNU, microglial cells exhibit a prominent morphology change and Müller cells can induce activated microglia infiltration by increasing secretion of the chemotaxis factor, CX3CL1, and promoting the migration of retinal microglial cells. This novel finding highlights a potential therapeutic target aimed at regulating the microglial response

Effects of yeast culture and oxalic acid supplementation on in vitro nutrient disappearance, rumen fermentation, and bacterial community composition

Hemicellulose is an important polysaccharide in ruminant nutrition, but it has not been studied as thoroughly as cellulose. Further research is needed to explore supplements that can improve its digestibility and ruminal buffering effects. Our previous research demonstrated the efficacy of oxalic acid (OA) as an essential nutrient in yeast culture (YC) for improving rumen fermentation performance. Consequently, we conducted in vitro rumen digestion experiments to examine the effects of YC and OA on rumen fermentation and bacterial composition. Two diets containing different levels of hemicellulose were formulated: diet 1 with 10.3% and diet 2 with 17% hemicellulose. Three levels of YC (0.00, 0.625, and 1.25 g/kg) and three doses of OA (0.0, 0.4, and 0.8 g/kg, DM) were added into each diet with a 3 × 3 factorial design. A comprehensive assessment was conducted on a total of 18 experimental treatments at fermentation periods of 0, 6, 12, 24, and 48 h. In the first experiment (diet 1), the supplementation of YC, OA, and their interaction significantly increased in vitro DM disappearance (IVDMD) and NDF disappearance (IVNDFD; p < 0.001). In the second experiment (diet 2), the supplementation of OA and the interaction between YC and OA (p < 0.001) increased IVDMD and IVCPD, but had no significant effects on IVNDFD. The interactions of YC and OA significantly increased ammonia nitrogen (p < 0.001). The production of acetic acid, propionic acid, and total volatile fatty acids (TVFA), and pH levels were significantly higher in treatments supplemented with YC and OA (p < 0.001). YC and OA in both diets significantly altered the rumen bacterial community leading to increased Shannon and Simpson diversity indices (p < 0.001). In both diets, OA supplementation significantly increased the relative abundance of the phylum Bacteroidetes and Prevotella genus. The result also showed a positive correlation between the Prevotella and Selenomonas genera with IVDMD, IVNDFD, propionic acid, and TVFA production, suggesting that these dominant bacteria enhanced nutrient disappearance in the rumen. In conclusion, adding YC and OA resulted in modifications to the bacterial community’s composition and diversity, and improved nutrient disappearance. These changes indicate improved rumen fermentation efficiency, which is promising for future in vivo studies

Mechanistic insights into inositol-mediated rumen function promotion and metabolic alteration using in vitro and in vivo models

Inositol is a bioactive factor that is widely found in nature; however, there are few studies on its use in ruminant nutrition. This study investigated the effects of different inositol doses and fermentation times on rumen fermentation and microbial diversity, as well as the levels of rumen and blood metabolites in sheep. Rumen fermentation parameters, microbial diversity, and metabolites after different inositol doses were determined in vitro. According to the in vitro results, six small-tailed Han sheep fitted with permanent rumen fistulas were used in a 3 × 3 Latin square feeding experiment where inositol was injected into the rumen twice a day and rumen fluid and blood samples were collected. The in vitro results showed that inositol could increase in vitro dry matter digestibility, in vitro crude protein digestibility, NH3-N, acetic acid, propionic acid, and rumen microbial diversity and affect rumen metabolic pathways (p < 0.05). The feeding experiment results showed that inositol increased the blood concentration of high-density lipoprotein and IgG, IgM, and IL-4 levels. The rumen microbial composition was significantly affected (p < 0.05). Differential metabolites in the rumen were mainly involved in ABC transporters, biotin metabolism, and phenylalanine metabolism, whereas those in the blood were mainly involved in arginine biosynthesis and glutathione and tyrosine metabolism. In conclusion, inositol improves rumen function, affects rumen microorganisms and rumen and blood metabolites and may reduce inflammation, improving animal health

Mouthwash use and cancer of the head and neck: a pooled analysis from the International Head and Neck Cancer Epidemiology Consortium

Most mouthwashes contain alcohol, a known cause of head and neck cancer (oral cavity, pharynx, larynx), likely through the carcinogenic activity of acetaldehyde, formed in the oral cavity from alcohol

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 case-control studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, and 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium, and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, and pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR=0.76, 95% CI=0.59-0.96) and with ever use of calcium supplement (OR=0.64, 95% CI=0.42-0.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR=0.72, 95% CI=0.54-0.97) and more than 365 tablets of cumulative calcium intake (OR=0.36, 95% CI=0.16-0.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of head and neck cancer

Stability analysis and H∞ control of discrete T–S fuzzy hyperbolic systems

This paper focuses on the problem of constraint control for a class of discrete-time nonlinear systems. Firstly, a new discrete T–S fuzzy hyperbolic model is proposed to represent a class of discrete-time nonlinear systems. By means of the parallel distributed compensation (PDC) method, a novel asymptotic stabilizing control law with the “soft” constraint property is designed. The main advantage is that the proposed control method may achieve a small control amplitude. Secondly, for an uncertain discrete T–S fuzzy hyperbolic system with external disturbances, by the proposed control method, the robust stability and H∞ performance are developed by using a Lyapunov function, and some sufficient conditions are established through seeking feasible solutions of some linear matrix inequalities (LMIs) to obtain several positive diagonally dominant (PDD) matrices. Finally, the validity and feasibility of the proposed schemes are demonstrated by a numerical example and a Van de Vusse one, and some comparisons of the discrete T–S fuzzy hyperbolic model with the discrete T–S fuzzy linear one are also given to illustrate the advantage of our approach

Bisphenol A and Di(2-Ethylhexyl) Phthalate promote pulmonary carcinoma in female rats via estrogen receptor beta: In vivo and in silico analysis

The prevalence of lung cancer in women currently merits our attentions. However, cigarette exposure alone does not tell the whole story that lung cancer is more prevalent among non-smoking women. Since female lung cancer is closely linked to estrogen levels, many of endocrine disrupting chemicals (EDCs), as the substances similar to estrogen, affect hormone levels and become a potential risk of female lung cancer. Additionally, the combined toxicity of EDCs in daily environment has only been discussed on a limited scale. Consequently, this study explored the cancer-promoting effect of two representative substances of EDCs namely Bisphenol A (BPA) and Di(2-Ethylhexyl) Phthalate (DEHP) after their exposure alone or in combination, using a rat pulmonary tumor model published previously, combining bioinformatics analysis based on The Comparative Toxicogenomics Database (CTD) and The Cancer Genome Atlas (TCGA) databases. It demonstrated that BPA and DEHP enhanced the promotion of pulmonary tumor in female rats, either alone or in combination. Mechanistically, BPA and DEHP mainly directly bound and activated ESR2 protein, phosphorylated CREB protein, activated HDAC6 transcriptionally, induced the production of the proto-oncogene c-MYC, and accelerated the formation of pulmonary tumor in female rats. Remarkably, BPA, rather than DEHP, exhibited a much more critical effect in female lung cancer. Additionally, the transcription factor ESR2 was most affected in carcinogenesis, causing genetic disruption. Furthermore, the TCGA database revealed that ESR2 could enhance the promotion and progression of non-small cell lung cancer in females via activating the WNT/β-catenin pathway. Finally, our findings demonstrated that BPA and DEHP could enhance the promotion of pulmonary carcinoma via ESR2 in female rats and provide a potential and valuable insight into the causes and prevention of lung cancer in non-smoking women due to EDCs exposure