The efficacy of natural products for the treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating in the nasopharyngeal epithelium with a high incidence in southern China and parts of Southeast Asia. The current treatment methods are mainly radiotherapy and chemotherapy. However, they often have side effects and are not suitable for long-term exposure. Natural products have received more and more attention in cancer prevention and treatment because of their its high efficiency, low toxic side effects, and low toxicity. Natural products can serve as a viable alternative, and this study aimed to review the efficacy and mechanisms of natural products in the treatment of NPC by examining previous literature. Most natural products act by inhibiting cell proliferation, metastasis, inducing cell cycle arrest, and apoptosis. Although further research is needed to verify their effectiveness and safety, natural products can significantly improve the treatment of NPC.

Relationship between allergic diseases and mental disorders in women: A systematic review and meta-analysis.

Background: The relationship between allergic diseases (AD) and mental disorders (MD) in women has not been fully systematically evaluated. We aimed at validating this correlation. Methods: The relevant cohort and case-control studies from the establishment of the database to February 18, 2022 in PubMed, Embase, and Cochrane library were searched by computer. The researchers conducted the quality evaluation of the included articles by reviewing and discussing with reference to relevant standards, and conducted the analysis of the correlation between female patients with AD and MD by using Review Manager 5.4. Results: Six observational studies from 2631 studies (n = 1160858 women) were assessed as medium and high-quality studies. The meta-analysis demonstrated that AD was correlated with MD in female patients (OR = 1.21, 95%CI: 1.14-1.29), including asthma (OR = 1.16, 95%CI: 1.11-1.22), allergic rhinitis (OR = 1.31, 95%CI: 1.06-1.63), and atopic dermatitis in women (OR = 1.37, 95%CI: 1.24-1.50) were associated with MD. At the same time, subgroup analysis was performed according to region, study design, criteria of AD and MD, and the results demonstrated that both AD and MD were correlated in these different conditions. Conclusion: Allergic diseases in female patients do have an association with mental disorders. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022311146].

The Efficacy and Safety of Probiotics for Allergic Rhinitis: A Systematic Review and Meta-Analysis.

Background: Probiotics have proven beneficial in a number of immune-mediated and allergic diseases. Several human studies have evaluated the efficacy and safety of probiotics in allergic rhinitis; however, evidence for their use has yet to be firmly established. Objective: We undertook a systematic review and meta-analysis aiming to address the effect and safety of probiotics on allergic rhinitis. Methods: We systematically searched databases [MEDLINE (PubMed), Embase, and the Cochrane Central Register of Controlled Trials] from inception until June 1, 2021. Qualified literature was selected according to inclusion and exclusion criteria, the data were extracted, and a systematic review and meta-analysis was conducted. Results: Twenty-eight studies were included. The results showed that probiotics significantly relieved allergic rhinitis symptoms (standardized mean difference [SMD], -0.29, 95% confidence interval (CI) [-0.44, -0.13]; p = 0.0003, I2 = 89%), decreased Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores compared with the control group (SMD, -0.64, 95% CI [-0.79, -0.49], p < 0.00001, I2 = 97%), and increased T helper cell 1(Th1)/Th2 ratio (mean difference [MD], -2.47, 95% CI [-3.27, -1.68], p < 0.00001, I2 = 72%). There was no significant change in overall or specific IgE levels between probiotic-treated and placebo-treated subjects (SMD, 0.09, 95% CI [-0.16, 0.34], I2 = 0%, and SMD, -0.03, 95% CI [-0.18, 0.13], p = 0.72, I2 = 0%, respectively). Conclusions: To sum up, probiotic supplement seems to be effective in ameliorating allergic rhinitis symptoms and improving the quality of life, but there is high heterogeneity in some results after subgroup analysis and clinicians should be cautious when recommending probiotics in treating allergic rhinitis. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO (CRD42021242645).

TMEM98 mRNA promotes proliferation and invasion of gastric cells by directly interacting with NF90 protein.

Transmembrane protein 98 (TMEM98) is a recently discovered gene, the inhibition of which has preliminarily been demonstrated to inhibit progression of several solid cancers in vitro. However, its involvement in tumorigenesis of gastric cancer (GC) has not been reported. Here, we aimed to explore the expression of TMEM98 in GC tissues and cell lines and to determine the role of TMEM98 in GC cell proliferation and invasion. TMEM98 was significantly upregulated in GC tissues, which was associated with low survival rate of GC patients. Interestingly, GC cell proliferation and invasion were promoted by TMEM98 messenger RNA (mRNA) upregulation and inhibited by TMEM98 mRNA downregulation, but not affected by TMEM98 protein. Using RNA-binding protein immunoprecipitation assay and RNA pull-down assay, we demonstrated that TMEM98 mRNA could directly bind with and upregulate nuclear factor 90 (NF90). Similarly, NF90 protein could not only enhance the stability of TMEM98 mRNA but antagonize the suppressive effect of TMEM98-small interfering RNA on proliferation and invasion in MKN-45 cells. Moreover, RNA pull-down assay, with wild-type (WT) and binding-site-mutated biotinylated TMEM98 mRNA transcripts, demonstrated that WT TMEM98 mRNA bound with NF90 protein through an 8-nt motif at the last exon, but the motif mutation abolished the capacity of TMEM98 mRNA binding to NF90 protein. Furthermore, overexpression of the WT last exon of TMEM98 increased NF90 expression and cell proliferation/invasion expectedly, but overexpression of the mutated last exon had no obvious effect. In conclusion, TMEM98 mRNA enhanced the proliferation and invasion of GC cells by interacting with the NF90 protein.

VPA selectively regulates pluripotency gene expression on donor cell and improve SCNT embryo development.

SCNT technology has been successfully used to clone a variety of mammals, but the cloning efficiency is very low. This low efficiency is likely due to the incomplete reprogramming of SCNT embryos. Histone modification and DNA methylation may participate in these events. Thus, it would be interesting to attempt to improve the efficiency of SCNT by using a HDACi VPA. In order to guarantee the effect of VPA and reduce its cytotoxicity, a comprehensive analysis of the cell proliferation and histone modification was performed. The results showed that 0.5 and 1 mM VPA treatment for 24 h were the optimal condition. According to the results, H3K4me3 was increased in 0.5 and 1 mM VPA groups, whereas H3K9me2 was significantly decreased. These are the signals of gene-activation. In addition, VPA treatment led to the overexpression of Oct4 and Nanog. These indicated that VPA-treated cells had similar patterns of histone to zygotic embryos, and may be more favorable for reprograming. A total of 833 cloned embryos were produced from the experimental replicates of VPA-treated donor cells. In 1 mM treatment group, the blastocyst rates were significantly increased compared with control. At the same time, our findings demonstrated the interrelation between DNA methylation and histone modifications.

Activation-induced cytidine deaminase selectively catalyzed active DNA demethylation in pluripotency gene and improved cell reprogramming in bovine SCNT embryo.

DNA methylation in mammals is an epigenetic marker and necessary for normal embryogenesis. The global genomic demethylation of 5-methylcytosine occurs during the first cell cycle following fertilization. Activation-induced cytidine deaminase (AID), which is well-known for the function in antibody diversification, has been implicated to play a role in active demethylation, but its role in cell reprogramming and its crosstalk with other DNA demethylation mechanism need to be clarified. In this study, the dynamic epigenetic regulation of cell pluripotency and embryo development by AID in bovine preimplantation embryos was investigated. The analysis of an AID overexpressing transgenic cell line showed that AID overexpression did not change the global genomic methylation but did change the methylation status of the promoters of the OCT4, NANOG and SOX2 genes, thereby causing changes in their expression. The siRNA-mediated AID knockdown in early embryonic development indicated that AID interference did not affect oocyte maturation or the following embryo development after in vitro fertilization but influenced the DNA methylation status of OCT4 and NANOG. To clarify the role of AID in preimplantation embryos, SCNT embryos were obtained using AID-overexpressing cells as nuclear donors. Compared to the control group, the cleavage and blastocyst rates were both significantly improved in the AID-overexpression group. The expression of OCT4 and NANOG was increased in the SCNT embryos, whereas the methylation levels of their promoters were reduced. In conclusion, this study demonstrated that AID selectively catalyzes DNA demethylation of pluripotency genes to play a role in regulation their expression, improves bovine SCNT embryo development by increased expression levels.

The effect of valproic acid on bovine oocyte maturation and early embryonic development in vitro.

Our objective is to investigate the effect of valproic acid (VPA), a histone deacetylase inhibitor, on early embryonic development. We studied the effect of VPA on the in vitro maturation of bovine oocytes, and on the development of bovine embryos derived from in vitro fertilization (IVF) or parthenogenesis. Germinal vesicle stage bovine oocytes were cultured with different concentrations of VPA for 24 h; low dose VPA treatment (0.03 and 0.3 mM) had no effect on oocyte maturation, but 3 and 6 mM VPA significantly decreased maturation rate; when used for IVF or parthenogenesis, VPA-treated oocytes generated significantly lowered blastocyst rate. Oocytes matured in vitro were fertilized or underwent parthenogenetic activation; 6 h later, they were exposed to VPA for 48 h, and then the cleavage rate, blastocyst rate and mRNA expression levels of transcription factors (Oct4, Nanog, and Cdx2) were assessed. For embryos cultured in 0.3 mM VPA, there was no remarkable change in cleavage rate or blastocyst rate, but the expression of Oct4 and Nanog in blastocysts was significantly increased. For embryos treated with 3.0 mM VPA, the cleavage rate and blastocyst rate were significantly decreased. In conclusion, low dose VPA has no effect on oocyte maturation but affects subsequent embryonic development. Low dose VPA administration to IVF embryos had no effect on embryonic development, but the expression of several important transcription factors was increased. Treatment of IVF embryos with low dose VPA may improve their development potential.

Production of transgenic cashmere goat embryos expressing red fluorescent protein and containing IGF1 hair-follicle-cell specific expression cassette by somatic cell nuclear transfer.

In the present study, cashmere goat fetal fibroblasts were transfected with pCDsR-KI, a hair-follicle-cell specific expression vector for insulin-like growth factor 1 (IGF1) that contains two markers for selection (red fluorescent protein gene and neomycin resistant gene). The transgenic fibroblasts cell lines were obtained after G418 selection. Prior to the somatic cell nuclear transfer (SCNT), the maturation rate of caprine cumulus oocytes complexes (COCs) was optimized to an in vitro maturation time of 18 h. Parthenogenetic ooctyes were used as a model to investigate the effect of two activation methods, one with calcium ionophore IA23187 plus 6-DMAP and the other with ethanol plus 6-DMAP. The cleavage rates after 48 h were respectively 88.7% and 86.4%, with no significant difference (P>0.05). There was no significant difference between the cleavage rate and the blastocyst rate in two different media (SO-Faa and CR1aa; 86.3% vs 83.9%, P>0.05 and 23.1% vs 17.2%, P>0.05). The fusion rate of a 190 V/mm group (62.4%) was significantly higher than 130 V/mm (32.8%) and 200 V/mm (42.9%), groups (P>0.05). After transgenic somatic cell nuclear transfer (TSCNT) manipulation, 203 reconstructed embryos were obtained in which the cleavage rate after in vitro development (IVD) for 48 h was 79.3% (161/203). The blastocyst rate after IVD for 7 to 9 d was 15.3% (31/203). There were 17 embryos out of 31 strongly expressing red fluorescence. Two of the red fluorescent blastocysts were randomly selected to identify transgene by polymerase chain reaction. Both were positive. These results showed that: (i) RFP and Neo ( r ) genes were correctly expressed indicating that transgenic somatic cell lines and positive transgenic embryos were obtained; (ii) one more selection at the blastocyst stage was necessary although the donor cells were transgenic positive, because only partially transgenic embryos expressing red fluorescence were obtained; and (iii) through TSCNT manipulation and optimization, transgenic cashmere goat embryos expressing red fluorescence and containing an IGF1 expression cassette were obtained, which was sufficient for production of transgenic cashmere goats.