Hypoxia-induced autophagy promotes human prostate stromal cells survival and ER-stress.

Benign prostatic hyperplasia (BPH) is emerging as one of the most common diseases seriously threatening the health of elderly men. Accumulating evidences indicate that hypoxia could induce BPH. However, the underlying mechanism of BPH induced by hypoxia is not clear. In the study, hypoxia-induced autophagy could promote cell survival and endoplasmic reticula stress (ER stress) in WPMY-1 cells. Cell viability induced by hypoxia could been decreased by autophagy inhibitors (3-methyladenine, bafilomycin A1) or siRNA interference in two autophagy genes (Beclin1, ATG5) in WPMY-1 cells. Furthermore, ER stress was present in hypoxia-treated WPMY-1 cells, while autophagy and cell survival could been inhibited by C/EBP-homologous protein siRNA (CHOP), which is an important protein of ER stress pathway. Taken together, our data support a novel model that autophagy as a cytoprotective response promotes cell survival via ER stress under hypoxia in human prostate stromal cells.

Resistance training combined with ß-hydroxy ß-methylbutyrate for patients with critical illness: A four-arm, mixed-methods, feasibility randomised controlled trial.

OBJECTIVES: This study aimed to assess the feasibility, safety, acceptability, and potential effectiveness of resistance training (RT) with or without ß-Hydroxy ß-Methylbutyrate (HMB) intervention program for ICU patients. DESIGN: Open-label, parallel group, mixed method, randomized controlled trial. SETTINGS: A tertiary general hospital in Fuzhou, China. METHODS: Participants were randomly allocated to one of four groups. The RT group received supervised multilevel resistance training (RT) using elastic bands, administered by trained ICU nurses. The HMB group received an additional daily dose of 3.0 g HMB. The combination group underwent both interventions concurrently, while the control group received standard care. These interventions were implemented throughout the entire hospitalization period. Primary outcomes included feasibility indicators such as recruitment rate, enrollment rate, retention rate, and compliance rate. Secondary outcomes covered adverse events, acceptability (evaluated through questionnaires and qualitative interviews), and physical function. Quantitative analysis utilized a generalized estimation equation model, while qualitative analysis employed directed content analysis. RESULTS: All feasibility indicators met predetermined criteria. Forty-eight patients were randomly assigned across four arms, achieving a 96% enrollment rate. Most patients adhered to the intervention until discharge, resulting in a 97.9% retention rate. Compliance rates for both RT and HMB interventions approached or exceeded 85%. No adverse events were reported. The intervention achieved 100% acceptability, with a prevailing expression of positive experiences and perception of appropriateness. The RT intervention shows potential improvement in physical function, while HMB does not. CONCLUSIONS: Implementing nurse-led resistance training with elastic bands with or without HMB proved to be feasible and safe for ICU patients. IMPLICATIONS FOR CLINICAL PRACTICE: A large-scale, multicenter clinical trials are imperative to definitively assess the impact of this intervention on functional outcomes in this population.

CENPE and LDHA were potential prognostic biomarkers of chromophobe renal cell carcinoma.

BACKGROUND: Most sarcomatoid differentiated renal cell carcinoma was differentiated from Chromophobe renal cell carcinoma (KICH) and related to a bad prognosis. Thus, finding biomarkers is important for the therapy of KICH. METHODS: The UCSC was used for determining the expression of mRNA and miRNA and clinical data in KICH and normal samples. KEGG and GO were used for predicting potential function of differently expressed genes (DEGs). Optimal prognostic markers were determined by Lasso regression. Kaplan-Meier survival, ROC, and cox regression were used for assessing prognosis value. GSEA was used for predicting potential function of markers. The relations between markers and immune cell infiltration were determined by Pearson method. The upstream miRNA of markers was predicted in TargetScan and DIANA. RESULTS: The 6162 upregulated and 13,903 downregulated DEGs were identified in KICH. Further CENPE and LDHA were screened out as optimal prognostic risk signatures. CENPE was highly expressed while LDHA was lowly expressed in KICH samples, and the high expressions of 2 genes contributed to bad prognosis. The functions of CENPE and LDHA were mainly enriched in proliferation related pathways such as cell cycle and DNA replication. In addition, the correlation of 2 genes with immune infiltrates in KICH was also observed. Finally, we found that has-miR-577 was the common upstream of 2 genes and the binding sites can be predicted. CONCLUSION: CENPE and LDHA were identified as the important prognostic biomarkers in KICH, and they might be involved in the proliferation of cancer cell.

Secondary reversion to sexual monomorphism associated with tissue-specific loss of doublesex expression.

Animal evolution is characterized by frequent turnover of sexually dimorphic traits-new sex-specific characters are gained, and some ancestral sex-specific characters are lost, in many lineages. In insects, sexual differentiation is predominantly cell autonomous and depends on the expression of the doublesex (dsx) transcription factor. In most cases, cells that transcribe dsx have the potential to undergo sex-specific differentiation, while those that lack dsx expression do not. Consistent with this mode of development, comparative research has shown that the origin of new sex-specific traits can be associated with the origin of new spatial domains of dsx expression. In this report, we examine the opposite situation-a secondary loss of the sex comb, a male-specific grasping structure that develops on the front legs of some drosophilid species. We show that while the origin of the sex comb is linked to an evolutionary gain of dsx expression in the leg, sex comb loss in a newly identified species of Lordiphosa (Drosophilidae) is associated with a secondary loss of dsx expression. We discuss how the developmental control of sexual dimorphism affects the mechanisms by which sex-specific traits can evolve.

[Study on ingredients of essential oils of Curcuma wenyujin extracted by supercritical-CO2 fluid extraction and steam distillation].

OBJECTIVE: To compare the ingredients of essential oils of Curcuma wenyujin extracted by supercritical-CO2 fluid extraction and by steam distillation. METHOD: GC-MS was applied in this experiment. RESULT: The ingredients and physical and chemical properties of essential oils of C. wenyujin extracted by supercritical-CO2 fluid extraction and by steam distillation are similar. CONCLUSION: Supercritical-CO2 fluid extraction is better than steam distillation in extraction time, power consumption, recovery and purity.

Caffeine Suppresses Apoptosis of Bladder Cancer RT4 Cells in Response to Ionizing Radiation by Inhibiting Ataxia Telangiectasia Mutated-Chk2-p53 Axis.

BACKGROUND: Caffeine suppresses ataxia telangiectasia and Rad3 related and ataxia telangiectasia mutated (ATM) activities; ATM is the major kinase for DNA damage detection. This study aimed to investigate the effects of caffeine on DNA damage responses in cells from the bladder cancer cell line RT4 those were exposed to ionizing radiation (IR). METHODS: Immunofluorescent staining was performed to investigate changes in the proteins involved in DNA damage responses with or without caffeine. A mouse xenograft model was used to study the effects of caffeine on the DNA damage responses. Western blotting was used to investigate the effects of caffeine pretreatment on the ATM-Chk2-p53-Puma axis, while real-time polymerase chain reaction (RT-PCR) assessed changes in messenger RNA levels of p53 and downstream targets responding to IR. Finally, terminal deoxynucleotidyl transferase-dUTP nick end labeling assay. Western blotting and colony formation assay were used to measure the effects of caffeine on radiation-related apoptosis. All of the data were analyzed with a two-tailed Student's t-test. RESULTS: Immunofluorescent staining showed that caffeine pretreatment profoundly suppressed the formation of γH2AXand p53-binding protein 1 foci in RT4 cells in response to irradiation. Cellular and animal experiments suggested that this suppression was mediated by suppression of the ATM-Chk2-p53-Puma DNA damage-signaling axis. RT-PCR indicated caffeine also attenuated transactivation of p53 and p53-inducible genes. The colony formation assay revealed that caffeine displayed radioprotective effects on RT4 cells in response to low-dose radiation compared to the radiosensitization effects on T24 cells. CONCLUSION: Caffeine may inhibit IR-related apoptosis of bladder cancer RT4 cells by suppressing activation of the ATM-Chk2-p53-Puma axis.

[Effects of epimedium total flavonoids phytosomes on preventing and treating bone-loss of ovariectomized rats].

OBJECTIVE: To observe the effects of Epimedium total Flavonoids Phytosomes on preventing and treating bone-loss of the castrate osteoporosis rat model. METHOD: The osteoporosis model was established with 4-month-odl panther's rats, their ovaries on both sides castrated. Dual energy X-ray scanning was used to determine the bone density, and immunity and ELASA were used to assay concentration of estradiol and IL-6 in serum respectively, then determine their effect. RESULT: The BMP and E2 of high dosage group nilestriol group and normal group are higher than those of model group (P < 0.01), while their content of IL-6 is apparently lower than that of model group(P < 0.01). CONCLUSION: The osteoporosis model was established successfully and the using of EFP can improve the bone density, enhance E2 level and decrease the IL-6 concentration in serum.

Taxonomy of the Colocasiomyia gigantea species group (Diptera, Drosophilidae), with descriptions of four new species from Yunnan, China.

Species of the genus Colocasiomyia de Meijere feed/breed on inflorescences/infructescences of the plants from the families Araceae, Arecaceae and Magnoliaceae. Although most of them utilize plants from the subfamily Aroideae of Araceae, three species of the recently established C. gigantea species group make use of plants of the subfamily Monsteroideae. We describe four new species of the gigantea group found from Yunnan, China: Colocasiomyia longifilamentata Li & Gao, sp. n., C. longivalva Li & Gao, sp. n., C. hailini Li & Gao, sp. n., and C. yini Li & Gao, sp. n. The species delimitation is proved in virtue of not only morphology but also DNA barcodes, i.e., sequences of the partial mitochondrial COI (cytochrome c oxidase subunit I) gene. Some nucleotide sites with fixed status in the alignment of the COI sequences (658 sites in length) are used as "pure" molecular diagnostic characters to delineate species in the gigantea group.

Interactions between quinolone antibiotics and phospholipid membrane for prediction of alveolar macrophage uptake in vitro.

AIM: To compare the effectiveness of the different parameters for predicting alveolar macrophage (AM) uptake, interactions between quinolones, including two amphipathic bases, and phospholipid membrane were evaluated by three different membrane-like systems. METHODS: AM cells were isolated, cultured as confluent monolayers, then incubated with drug solution at 37 degrees C. At designated time points, uptake was terminated by aspirating solution, followed by rinsing, cell lysis, a nd analysis of drug and protein concentrations. Immobilized artificial membrane (IAM) chromatography and liposome/buffer system were used to determine interactions with phospholipid membrane, expressed as lipophilicity indices, lg k(IAM) and lg D(L/B,7.4), respectively. An n-octano l/buffer system was also employed as the reference hydrophobicity, lg D(O/B,7.4)4. RESULTS: For the tested set, lg k(IAM) correlated more significantly with lg D(L/B,7.4) (r2 = 0.93) than with lgD(O/B,7.4) (r2 = 0.65). There were better correlations between either lg k(IAM) or lg D(L/B,7.4) and the extent of accumulation in AM than did lg DO/B,7.4 (r2 = 0.89, 0.92, and 0.67, respectively). Correlations obtained using lg k(IAM), lg D(L/B,7.4), and lg D(O/B,7.4) were comparable when regressed against the logarithm of influx rate into AM f or a set consisting of five amphoteric quinolones and quinidine. CONCLUSION: Liposome/buffer system and IAM chromatography could provide nearly similar scale of lipophilicity measurement, both distinct from n-octanol/buffer system. Accumulation by AM was better described by lg k(IAM) or lg D(L/B,7.4) than lg D(O/B,7.4), and the passive diffusion was principal form during drugs transported across AM membrane.