Oncogenic roles of GPR176 in breast cancer: a potential marker of aggressiveness and a potential target of gene therapy.

BACKGROUND: Belonging to the G-protein coupled receptor 1 family, G protein-coupled receptor 176 (GPR176) is associated with the Gz/Gx G-protein subclass and is capable of decreasing cAMP production. METHODS: GPR176 expression was detected by qRT-PCR, bioinformatics analysis, Western blot and immunohistochemistry, and compared with clinicopathological characteristics of breast cancer. GPR176-related genes and pathways were subjected to bioinformatic analysis. We also explored the effects of GPR176 on the phenotypes of breast cancer cells. RESULTS: Lower expression of GPR176 mRNA was seen in breast cancer than in normal tissues, but the opposite pattern was found for its protein (p < 0.05). GPR176 mRNA was associated with female sex, low T staging, non-Her-2+ subtypes, non-mutant p53 status in breast cancer (p < 0.05). GPR176 methylation was negatively correlated with its mRNA level and T staging in breast cancer, and was higher in breast cancer than normal tissues (p < 0.05). GPR176 protein expression was positively correlated with older age, small tumor size, and non-luminal-B subtype of breast cancers (p < 0.05). The differential genes of GPR176 were involved in receptor-ligand interaction, RNA maturation, and so forth (p < 0.05). GPR176-related genes were categorized into cell mobility, membrane structure, and so on (p < 0.05). GPR176 knockdown weakened the proliferation, glucose catabolism, anti-apoptosis, anti-pyroptosis, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. CONCLUSION: These results indicate that GPR176 might be involved in the tumorigenesis and subsequent progression of breast cancer by deteriorating aggressive phenotypes. It might be utilized as a potential biomarker to indicate the aggressive behaviors and poor prognosis of breast cancer and a potential target of genetic therapy.

Phenolic compounds and antioxidant properties of wheat fermented with Agaricus brasiliensis and Agaricus bisporus.

Solid-state fermentation with Agaricus brasiliensis and Agaricus bisporus on whole grain wheat was carried out. Phenolic compounds and antioxidant properties of fermented wheat were determined. The results showed that the maximum values of polyphenols contents in wheat fermented with A. brasiliensis and A. bisporus reached, respectively (3.16 ± 0.21) and (3.93 ± 0.23) mg GAE/g, which were 2.90 and 3.61 times of unfermented control. By employing ultra performance liquid chromatography coupled to mass spectrometry (UPLC-MS), 18 kinds of phenolic compounds were identified from fermented wheat. Compared with control, only 4-hydroxy-benzaldehyde was the same compound. It indicated that fermentation with the two fungi changed polyphenols contents and phenolic compounds composition in wheat to a great extent. Among these phenolic compounds, except for 4-hydroxy-benzaldehyde, 4-hydroxy-benzoic acid and ß-N-(γ-glutamyl)-4-formylphenylhydrazine, other 15 kinds of phenolic compounds were first identified from mushroom samples (including fruit bodies, mycelia and fermentation products). DPPH radical scavenging capacity, reducing power, ferrous ion chelating ability and inhibition of lipid peroxidation of fermented wheat were significantly stronger than control (P < 0.05).

Examination of Ureaplasma urealyticum and Mycoplasma hominis in 4082 Chinese patients

The objective of this study was to analyze the infection rate and drug resistance of Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) in the genitourinary tract of Chinese patients. From December 2018 to June 2019, vaginal secretion or urinary secretion of outpatients in our hospital were selected for culture and drug sensitivity analysis of Ureaplasma urealyticum and Mycoplasma hominis. In 4082 Chinese samples, 1567 Mycoplasma were detected, a detection rate of 38.39%, among which 1366 cases were UU single positive, accounting for 33.47%, 15 cases were MH single positive, accounting for 0.36%, 186 cases were UU and MH mixed positive, accounting for 4.56%. The most affected age groups were 21-30 years and 31-40 years, accounting for 19.09 and 15.05%, respectively. The results of drug sensitivity showed that doxycycline, minocycline, josamycin, clarithromycin, and roxithromycin were more sensitive to mycoplasma infection. The distribution of Ureaplasma urealyticum and Mycoplasma hominis in the human genitourinary system and their sensitivity to antibiotics is different for sex and age groups.

Examination of Ureaplasma urealyticum and Mycoplasma hominis in 4082 Chinese patients.

The objective of this study was to analyze the infection rate and drug resistance of Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) in the genitourinary tract of Chinese patients. From December 2018 to June 2019, vaginal secretion or urinary secretion of outpatients in our hospital were selected for culture and drug sensitivity analysis of Ureaplasma urealyticum and Mycoplasma hominis. In 4082 Chinese samples, 1567 Mycoplasma were detected, a detection rate of 38.39%, among which 1366 cases were UU single positive, accounting for 33.47%, 15 cases were MH single positive, accounting for 0.36%, 186 cases were UU and MH mixed positive, accounting for 4.56%. The most affected age groups were 21-30 years and 31-40 years, accounting for 19.09 and 15.05%, respectively. The results of drug sensitivity showed that doxycycline, minocycline, josamycin, clarithromycin, and roxithromycin were more sensitive to mycoplasma infection. The distribution of Ureaplasma urealyticum and Mycoplasma hominis in the human genitourinary system and their sensitivity to antibiotics is different for sex and age groups.

Purinergic Receptors in Basal Ganglia Diseases: Shared Molecular Mechanisms between Huntington's and Parkinson's Disease.

Huntington's (HD) and Parkinson's diseases (PD) are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms, respectively. We review here the participation of purinergic receptors through intracellular Ca2+ signaling in these neurodegenerative diseases. The adenosine A2A receptor stimulates striatopallidal GABAergic neurons, resulting in inhibitory actions on GABAergic neurons of the globus pallidus. A2A and dopamine D2 receptors form functional heteromeric complexes inducing allosteric inhibition, and A2A receptor activation results in motor inhibition. Furthermore, the A2A receptor physically and functionally interacts with glutamate receptors, mainly with the mGlu5 receptor subtype. This interaction facilitates glutamate release, resulting in NMDA glutamate receptor activation and an increase of Ca2+ influx. P2X7 receptor activation also promotes glutamate release and neuronal damage. Thus, modulation of purinergic receptor activity, such as A2A and P2X7 receptors, and subsequent aberrant Ca2+ signaling, might present interesting therapeutic potential for HD and PD.

Correction to: The H741D mutation in Tac1p contributes to the upregulation of CDR1 and CDR2 expression in Candida albicans.

Unfortunately, an error occurred in the author affiliations.

New features on the genomic organization of a novel dicistrovirus identified from the sweet potato whitefly Bemisia tabaci.

The whitefly Bemisia tabaci is an agricultural pest causing large economic losses worldwide. We analysed the genomic sequence of a new viral member of the family Dicistroviridae identified by high-throughput sequencing of total RNA extracted from whiteflies. The virus, tentatively named Bemisia-associated dicistrovirus 2 (BaDV-2), has a genome of 8012 nucleotides with a polyadenylated 3' end. In contrast to typical dicistroviruses, BaDV-2 has a genome containing three open reading frames (ORFs) encoding predicted proteins of 1078 (ORF1a), 481 (ORF1b) and 834 (ORF2) amino acids, which correspond to replicase A (containing helicase and cysteine protease domains), replicase B (a domain of an RNA-dependent RNA polymerase - RdRP) and capsid proteins, respectively. The 3' end of ORF1a contains a potential frameshift signal, suggesting that ORF1a and ORF1b may be expressed as a single polyprotein (replicaseFS), corresponding to other dicistroviruses. The BaDV-2 genomic sequence shares the highest nucleotide identity (61.1 %) with Bemisia-associated dicistrovirus 1 (BaDV-1), another dicistrovirus identified from whiteflies. The full BaDV-2 replicaseFS polyprotein clustered with aparaviruses, whereas the capsid polyprotein clustered with cripaviruses in phylogenetic analyses, as with BaDV-1. The intergenic region (IGR) between ORF1b and ORF2 is predicted to adopt a secondary structure with atypical features that resembles the dicistrovirus IGR IRES structure. Our analyses indicate that BaDV-2 is a novel dicistrovirus and that BaDV-2 together with BaDV-1 may not be appropriately grouped in any of the three currently accepted dicistrovirus genera.

The H741D mutation in Tac1p contributes to the upregulation of CDR1 and CDR2 expression in Candida albicans.

The wide use of antifungal agents has led to the development of resistance in the pathogenic yeast strain Candida albicans. Gain-of-function mutations in transcription factors such as Tac1p demonstrated their ability to control expression of the ABC transporter genes CDR1 and CDR2, and mediation of azole resistance. Previously, we obtained a series of azole-resistant isolates with high-level expression of CDR1 or/and CDR2, and identified the novel H741D mutation in Tac1p. In the present study, the TAC1 alleles from isolate C13 were introduced into tac1Δ/Δ mutant. The H741D change was seen in TAC1C13 in addition to several other amino acid differences. Hyperactive alleles TAC1C13 exhibited higher minimum inhibitory concentrations (MICs) of fluconazole and itraconazole than that observed in SN152 containing the wild-type TAC1 allele. And alleles TAC1C13 conferred constitutively high levels of Cdr1p and Cdr2p. Moreover, the importance of H741D in conferring hyperactivity to TAC1 was also confirmed by site-directed mutagenesis. Compared with SN152, the presence of H741D resulted in > 2-fold increase in CDR1 and CDR2 gene and protein expression, > 4-fold increase in fluconazole and itraconazole MICs and higher rates of Rhodamine 6G efflux by 43.24%.

Clinical assessment of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for endometrial cancer.

OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.

Clinical assessment of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for endometrial cancer

OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.

Natural killer cells in hepatitis B virus infection

Natural killer cells are a unique type of lymphocytes with cytotoxic capacity, and play important roles against tumors and infections. Recently, natural killer cells have been increasingly valued in their effects in hepatitis B virus infection. Since hepatitis B virus is not cytopathic, the subsequent antiviral immune responses of the host are responsible for sustaining the liver injury, which may result in cirrhosis and even hepatocellular carcinoma. Many studies have confirmed that natural killer cells participate in anti-hepatitis B virus responses both in the early phase after infection and in the chronic phase viacytolysis, degranulation, and cytokine secretion. However, natural killer cells play dichotomic roles: they exert antiviral and immunoregulatory functions whilst contribute to the pathogenesis of liver injury. Here, we review the roles of natural killer cells in hepatitis B virus infection, introducing novel therapeutic strategies for controlling hepatitis B virus infection viathe modulation of natural killer cells.

Natural killer cells in hepatitis B virus infection.

Natural killer cells are a unique type of lymphocytes with cytotoxic capacity, and play important roles against tumors and infections. Recently, natural killer cells have been increasingly valued in their effects in hepatitis B virus infection. Since hepatitis B virus is not cytopathic, the subsequent antiviral immune responses of the host are responsible for sustaining the liver injury, which may result in cirrhosis and even hepatocellular carcinoma. Many studies have confirmed that natural killer cells participate in anti-hepatitis B virus responses both in the early phase after infection and in the chronic phase via cytolysis, degranulation, and cytokine secretion. However, natural killer cells play dichotomic roles: they exert antiviral and immunoregulatory functions whilst contribute to the pathogenesis of liver injury. Here, we review the roles of natural killer cells in hepatitis B virus infection, introducing novel therapeutic strategies for controlling hepatitis B virus infection via the modulation of natural killer cells.