Open Life Sciences最新文献

Fibrosis is the primary cause of retinal detachment and visual decline. Here, we investigated the role of Prohibitin 2 (PHB2) in modulating fibrosis in ARPE-19 cells stimulated by transforming growth factor (TGF)-β2. The proliferation, migration, and apoptosis of ARPE-19 cells were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, and flow cytometry assays, and levels of fibrosis-associated and pathway-related proteins were determined by performing western blotting. To examine the mechanisms underlying ARPE-19 cell fibrosis, we performed RNA sequencing, protein-protein interaction network, and enrichment analyses. We detected increases in the expression of the fibrosis-related proteins fibronectin and collagen I in response to TGF-β2 treatment, whereas the expression of PHB2 was downregulated. PHB2 overexpression suppressed the proliferation and migration of TGF-β2-stimulated ARPE-19 cells, promoted apoptosis, and inhibited fibrosis and Smad and non-Smad pathways. PHB2 overexpression inhibited the advanced glycation end-product (AGE)-receptor of advanced glycation end-product (RAGE) pathway activated by TGF-β2 treatment, which contributed to enhancing the effects of PHB2 on cellular processes, fibrosis, and Smad and non-Smad pathways. Conversely, exogenous application of AGE counteracted the effects of PHB2 overexpression. We conclude that by suppressing the AGE-RAGE pathway, PHB2 exerts an inhibitory effect on TGF-β2-induced fibrosis in ARPE-19 cells.

The resistance of tumor cells to chemotherapy drugs is a critical determinant in the recurrence and metastasis of nasopharyngeal carcinoma (NPC). Therefore, it is crucial to identify effective biotargets that can enhance the sensitivity of NPC cells to chemotherapy drugs. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) plays a central role in regulating chemotherapy resistance across various tumor types. However, its specific function in NPC cells remains unclear. This study reveals that hnRNPK is overexpressed in NPC tissues while weakly expressed in normal nasopharyngeal tissues. The expression level of hnRNPK is negatively associated with NPC patient survival. Importantly, hnRNPK is a key inducer of chemotherapy resistance in NPC, as evidenced by the significant increase in NPC cell sensitivity to cisplatin following hnRNPK knockdown. Mechanistically, hnRNPK induces chemotherapy resistance in NPC cells by suppressing the activation of the Akt/caspase 3 pathway. In NPC tumor-bearing mice, hnRNPK knockdown enhances the efficacy of cisplatin chemotherapy. Consequently, this work identifies a potential target for enhancing the sensitivity of NPC cells to chemotherapy.

Milk microbiome contributes substantially to the formation of specific organoleptic and physicochemical characteristics of dairy products. The assessment of the composition and abundance of milk microbiota is a challenging task strongly influenced by many environmental factors. Specific dairy products may be designated by the Protected Designation of Origin (PDO) and Protected Geographical Indication (PGI) labeling, which however, occasionally fail to differentiate them according to specific quality characteristics, which are defined by different microbiota-driven reactions. Combining the above limitations, the scope of the present study, was to summarize the existing information toward three main issues. First, to assess the influence level of the diet type and grazing to rumen-GI tract, mammary gland, and udder microbiome formation in ruminants. Second, to discuss the factors affecting milk microbiota, as well as the effect of the endo-mammary route on milk microbial taxa. Lastly, to evaluate "milk microbiome" as a tool for product differentiation, according to origin, which will contribute to a more robust PDO and PGI labeling. Although the limitations are still a matter of fact (especially considering the sample collection, process, evaluation, and avoidance of its contamination), significant progress has been made, regarding the identification of the factors affecting dairy products' microbiota and its core composition. In conclusion, although so far not totally efficient in dairy products molecular identification, with the progress in soil, water, plant, and animal host's microbiota assembly's characterization, microbiomics could provide a powerful tool for authentication and traceability of dairy products.

In our prior research, it was noted that slit guidance ligand 3 (SLIT3), a member of the SLIT-secreted protein family, may play a potential role in tumorigenesis. In addition, our prior work has found that the SLIT3 gene is highly methylated, especially in advanced-stage lung cancer tissues. Herein, we propose the hypothesis that abnormal SLIT3 expression may be linked to lung cancer development. In this study, decreased SLIT3 at the transcriptome and proteome levels was observed in lung cancer tissues. Furthermore, the downregulation of SLIT3 was related to a higher tumor stage and poorer prognosis. Silencing SLIT3 expression enhanced cell proliferation and migration, indicating potential characteristics of a tumor suppressor gene of SLIT3 in non-small-cell lung cancer (NSCLC). Furthermore, SLIT3 deficiency stimulates UBE2C upregulation and regulates NSCLC progression through Wnt3A/β-catenin signaling. The activation of the WNT signaling pathway was highly correlated with chemoresistance development in lung cancer. In conclusion, SLIT3 deficiency promotes lung cancer onset and progression by modulating UBE2C/WNT signaling. SLIT3/UBE2C/WNT may serve as novel biomarkers and therapeutic targets in NSCLC.

To explore the impact of score in patients with diabetes peripheral neuropathy (DPN) treated with traditional Chinese medicine package (TCMP) plus red light therapy and lipoic acid on malondialdehyde (MDA), erythrocyte superoxide dismutase (SOD), total antioxidant capacity (TAOC), motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), and Toronto Clinical Scoring System (TSS). A total of 108 patients with DPN hospitalized in the hospital were chosen and divided into groups with the random number table. In the control group (CG) 54 patients were treated with conventional lipoic acid, and 54 patients in the experimental group (EG) accepted TCMP plus red light on the basis of the CG. The MDA, SOD, TAOC, MNCV, SNCV, and TSS scores before treatment and after treatment were compared between the two groups. Before treatment, there was no statistically significant difference in the levels of oxidation indicators, nerve conduction velocity, and symptom scores between the two groups (P > 0.05). After treatment, the MDA in the EG was lower than that in the CG, with a statistical significance difference (P < 0.05). The SOD and TAOC in the EG were higher than those in the CG, and the difference was statistically significant (P < 0.05). The MNCV and SNCV of median nerve, common peroneal nerve, and tibial nerve in the EG were significantly higher than those in the CG (P < 0.05). The TSS score of the EG was lower than that of the CG, and the difference was statistically significant (P < 0.05). The treatment of patients with DPN with lipoic acid plus TCMP and red light therapy can improve the symptoms and signs of disease, promote the recovery of motor and sensory conduction velocity, and optimize the body oxidation indicators.

Calcium homeostasis is correlated closely with the occurrence and development of various cancers. The role of calcium homeostasis in prostate cancer has remained unclear. The present study aimed to investigate the relationship between transmembrane and crimp-crimp domain 1 (TMCO1) and calreticulin (CALR) in the pathological characteristics of prostate cancer and the mechanism of action on prostate cancer metastasis. Effects of CALR recombinant protein and TMCO1 knockdown on prostate cancer cells were investigated using following methods: cell cloning, Transwell, wound scratch assay, JC-1 assay, Fluo-4 Assay, endoplasmic reticulum (ER) fluorescent probe, mitochondrial fluorescence probe, Western blot and Immunofluorescence. TMCO1 and CALR are overexpressed in prostate cancer and knockdown of TMCO1 significantly inhibited the invasion, migration and cell proliferation. Furthermore, knocking down TMCO1 modulated the intensity of ER probes and mitochondrial fluorescence probes, and affected the levels of intracellular calcium ion and mitochondrial membrane potential. In addition, CALR recombinant protein upregulated the expression of epithelial-mesenchymal transition marker, Vimentin, Conversely, knockout of TMCO1 significantly reduced the expression of CALR and Vimentin. Knockout of TMCO1 can reverse the effect of CALR recombinant protein, elucidating the pivotal roles of TMCO1 and CALR in the regulation of prostate cancer metastasis through modulation of calcium homeostasis.

The heterogeneity of ovarian cancer (OC) has made developing effective treatments difficult. Nowadays, hormone therapy plays a growing role in the treatment of OC; however, hormone modulators have had only limited success so far. To provide a more rigorous foundation for hormonal therapy for different OC subtypes, the current study used a series of bioinformatics approaches to analyse the expression profiles of genes encoding membrane progesterone (PGRMC1, progestins and the adipoQ receptor [PAQR] family), and androgen (zinc transporter member 9 [ZIP9], OXER1) receptors. Our work investigated also their prognostic value in the context of OC. We found differences in expression of ZIP9 and OXER1 between different OC subtypes, as well as between patient tumour and normal tissues. Expression of mRNA encoding PAQR7 and PAQR8 in a panel of OC cell lines was below the qPCR detection limit and was downregulated in tumour tissue samples, whereas high expression of PGRMC1 and PAQR4 mRNA was observed in rare subtypes of OC cell lines. In addition, chemical inhibition of PGRMC1 reduced the viability of rare OCs represented by COV434 cells. In conclusion, PGRMC1 and PAQR4 are promising targets for anticancer therapy, particularly for rare subtypes of OC. These findings may reflect differences in the observed responses of various OC subtypes to hormone therapy.

Environmental pollution and overfishing of wild spiny loach have led to the increased demand for breeding the fish. However, the nutritional value between the wild and cultivated spiny loaches was unknown. Therefore, this study aimed to evaluate the nutritional components among the wild and cultivated spiny loaches at different growth stages by analyzing and comparing the proximate compositions, fatty acids, amino acids and volatile compounds. Results showed that the cultivated ones had significantly higher energy and fat contents than the wild. Particularly, the cultivated second-age spiny loach contained the highest contents of polyunsaturated fatty acids (4.83 ± 0.01%) and EPA + DHA (0.85 ± 0.02%). Besides, the total essential amino acid content of cultivated second-age spiny loach was 2201.28, exceeding that recommended in the FAO/WTO scoring pattern (2,190). And it had the highest flavor amino acid (6.24 ± 0.04 g/100 g), essential amino acid index value (71.82) and higher contents of volatile compounds. Overall, the cultivated spiny loach, especially that at the second growth stage, displayed the highest nutritional value. The findings of this study would help farmers to harvest the suitable breeding stage of spiny loaches from the perspective of nutritional value, which is beneficial to the sustainable fish farming.

This study examined the effects of exogenous 2,4-epibrassinolide (EBR) on photosynthetic traits of 53 cowpea varieties under NaCl stress. The results of different analysis and correlation analysis showed that these 53 germplasm resources had rich genetic diversity, and significant correlations existed among various photosynthetic traits. Under NaCl stress, Pn was highly significantly positively correlated with Gs and Tr and extremely significantly negatively correlated with Ci. Under EBR treatment, Pn was extremely significantly positively correlated with Gs, Ci, Tr and it was significantly negatively correlated with Chla, Chlb, Chl(a + b), and Y(II). Under EBR treatment and NaCl stress, Pn was extremely significantly positively correlated with Tr, and significantly positively correlated with Gs and carotenoid reflectance index. Principal component analysis shows that in CK group and EBR treatment group, cowpea photosynthesis traits can be summarized as six principal components, contributing 82.298 and 83.046%, respectively, can replace 19 photosynthetic traits to evaluate 53 cowpea varieties; under NaCl stress group and EBR + NaCl stress group, photosynthesis traits can be summarized as seven principal components, with cumulative contribution rate of 84.564 and 85.742%, respectively. In the untreated case, the cluster analysis was used to screen 32 cowpea varieties exhibiting the strongest photosynthetic capacity. Under salt stress, six of these varieties were classified as salt-tolerant. Under EBR spraying + salt stress, all four varieties showed strong photosynthetic capacity, and EBR showed the best relief of salt stress. The results of this study will provide a theoretical basis for the application of exogenous EBR to alleviate cowpea salt stress damage.

The study aimed to verify the pathogenic malarial kidney infections and histopathological pictures in mice infected with Plasmodium chabaudi using Indigofera oblongifolia leaf extract silver nanoparticles (IOLEAgNPs). Fifty healthy adult female mice C57BL/6 were used. Animals were divided into five groups, with each group of ten mice. The first control non-infected group was given distilled water for 7 days. The second group was orally given 50 mg/kg of IOLEAgNPs. The third, fourth, and fifth groups were injected intraperitoneally with 10⁵ parasitized erythrocytes of P. chabaudi. After 1 h, the fourth group received 50 mg/kg of IOLEAgNPs, while the fifth group orally received 10 mg/kg chloroquine phosphate. The histopathology of the kidney was studied by routine histology method with hematoxylin-eosin staining. The kidney revealed cerebral microvessel congestion, hemorrhages, and necrosis. Cast formation, glomerulonephritis, tubular necrosis, and congestion were observed in the kidney cortex. Consequently, the targeted medical IOLEAgNPs reduced this degeneration impact on renal tissue. Proven that plant-source synthesized IOLEAgNPs play a preventive role as antimalarial agents in female mice infected with P. chabaudi.