Rehmannia Glutinosa Polysaccharide Regulates Bone Marrow Microenvironment via HIF-1α/NF-κB Signaling Pathway in Aplastic Anemia Mice.

Aplastic anemia (AA), a rare disorder, is associated with bone marrow microenvironment (BMM). Presently, AA treatment is of great difficulty. This study aimed to explore the mechanism of action of Rehmannia glutinosa polysaccharide (RGP) in AA. Busulfan was used to induce AA in BALB/c mice; blood cell count and Ray's Giemsa staining were used to assess the severity of hematopoietic failure; HE was performed to assess the pathological state of the marrow cavity; ELISA was performed to assess IL-4, IL-10, IL-6, IL-12, IL-1ß, TNF-α, MCP-1, VEGF, and EPO; and WB was performed to evaluate the effects of RGP on the HIF-1α/NF-κB signaling. Significant downregulation of hemocyte levels in the blood and nucleated cells in the bone marrow was reversed by RGP and Cyclosporine A (CA). Compared with the AA group, dilating blood sinusoids, inflammation, hematopoiesis, decreased bone marrow cells and megakaryocytes were alleviated by RGP and CA, and the HIF-1α/NF-κB signaling was inhibited too. Notably, RGP was more effective when used in combination with CA. In this study, we established a relationship between BMM and the HIF-1α/NF-κB signaling pathway and found that RGP regulates BMM by suppressing the activation of the HIF-1α/NF-κB signaling. Thus, RGP exerts a pharmacological effect on AA.

Relationship between HuR and tumor drug resistance.

Human resistance protein R (HuR), also known as embryonic lethal abnormal visual-like protein (ELAVL1), is an RNA-binding protein widely expressed in vivo that affects the mRNA stability of targeted and is involved in post-transcriptional regulation. Recent studies have shown that HuR is aberrantly expressed in different human cancers and is an essential factor in poor clinical prognosis. The role of HuR in numerous tumors suggests that it could be a new target for tumor therapy and as a marker for efficacy and prognostic assessment. This review focuses on the relationship between HuR and drug resistance in different tumors and briefly describes the structure, function, and inhibitors of HuR. We summarize the mechanisms by which HuR causes tumor resistance and the molecular targets affected.

[Characterization and Health Risk Assessment of Heavy Metals in PM2.5 in Xiamen Port].

PM2.5 samples at Haitian and Songyu container terminals in Xiamen Port were collected in summer and autumn/winter in 2020 and analyzed for 20 elements to investigate their temporal-spatial distribution features, sources, and health risk. The results showed that the levels of PM2.5 were relatively low and did not show significant spatial and diurnal differences. Ca and Si were the main crustal elements, and Zn and Mn were the main heavy metals in PM2.5. Compared with GB 3095-2012 guidelines, Cr(Ⅵ) was in the range of 27.4-28.6 times above the standard. Under the influence of monsoon and port throughput, the concentrations of some elements in summer were higher than those in autumn/winter. Significant diurnal variations were observed for Cu, Zn, SO2, and NO2 but not for V and Ni. Industrial sources were identified as the primary contributor (55.2%-59.4%), followed by traffic (28.7%-31.3%), ship emissions (7.1%-7.7%), and sea salt plus construction dust (4.8%-5.8%). The results of health risk assessment showed that heavy metals in PM2.5in Xiamen Port had potential carcinogenic risk (ECR>1(10-5) to people living near the port, and Cr(Ⅵ), V, and As together accounted for 97.3%-97.5% of the total risks; however, the non-carcinogenic risk was negligible (HI<1), and the major contributors were V, Mn, Ni, and As (89.6%-91.2%). The relative contributions of each contributor to ECR was in the order of traffic (47.2%-49.4%)>industrial (23.8%-24.2%)>ship emissions (16.9%-20.8%)>sea salt plus construction dust (5.7%-12.1%), and the relative contribution to HI was in the order of traffic (38.7%-42.3%)>industrial (24.5%-28.2%)>ship emissions (24.1%-27.2%)>sea salt plus construction dust (5.4%-9.6%).

Orf165 is associated with cytoplasmic male sterility in pepper.

Cytoplasmic male sterility (CMS) is a maternally inherited trait that derives from the inability to produce functional pollen in higher plants. CMS results from recombination of the mitochondrial genome. However, understanding of the molecular mechanism of CMS in pepper is limited. In this study, comparative transcriptomic analyses were performed using a near-isogenic CMS line 14A (CMS-14A) and a maintainer line 14B (ML-14B) as experimental materials. A total of 17,349 differentially expressed genes were detected between CMS-14A and ML-14B at the PMC meiosis stage. Among them, six unigenes associated with CMS and 108 unigenes involved in energy metabolism were identified. The gene orf165 was found in CMS-14A. When orf165 was introduced into ML-14B, almost 30% of transgenic plants were CMS. In addition, orf165 expression in transgenic CMS plants resulted in abnormal function of some genes involved in energy metabolism. When orf165 in transgenic CMS plant was silenced, the resulted orf165-silenced plant was male fertile and the expression patterns of some genes associated with energy metabolism were similar to ML-14B. Thus, we confirmed that orf165 influenced CMS in pepper.

Flower transcriptome dynamics during nectary development in pepper (Capsicum annuum L.).

The measurement of gene expression can provide important information about gene function and the molecular basis for developmental processes. We analyzed the transcriptomes at three different developmental stages of pepper flower [sporogenous cell division, stage (B1); pollen mother cell meiosis, stage (B2); and open flower (B3)]. In the cDNA libraries for B1, B2, and B3: 82718, 77061, and 91491 unigenes were assembled, respectively. A total of 34,445 unigene sequences and 128 pathways were annotated by KEGG pathway analysis. Several genes associated with nectar biosynthesis and nectary development were identified, and 8,955, 12,182, and 23,667 DEGs were identified in the B2 vs B1, B3 vs B1, and B3 vs. B2 comparisons. DEGs were involved in various metabolic processes, including flower development, nectar biosynthesis, and nectary development. According to the RNA-seq data, all 13 selected DEGs showed similar expression patterns after q-PCR analysis. Sucrose-phosphatase, galactinol-sucrose galactosyltransferase, and sucrose synthase played very important roles in nectar biosynthesis, and CRABS CLAW could potentially be involved in mediating nectary development. A significant number of simple sequence repeat and single nucleotide polymorphism markers were predicted in the Capsicum annuum sequences. The new results provide valuable genetic information about flower development in pepper.

Linc-OIP5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through YAP1/Notch/NRP1 signaling circuit at a tumor microenvironment.

BACKGROUND: LincRNAs have been revealed to be tightly associated with various tumorigeneses and cancer development, but the roles of specific lincRNA on tumor-related angiogenesis was hardly studied. Here, we aimed to investigate whether linc-OIP5 in breast cancer cells affects the angiogenesis of HUVECs and whether the linc-OIP5 regulations are involved in angiogenesis-related Notch and Hippo signaling pathways. METHODS: A trans-well system co-cultured HUVECs with linc-OIP5 knockdown breast cancer cell MDA-MB-231 was utilized to study the proliferation, migration and tube formation abilities of HUVECs and alterations of related signaling indicators in breast cancer cells and their conditioned medium through a series of cell and molecular experiments. RESULTS: Overexpressed linc-OIP5, YAP1, and JAG1 were found in breast cancer cell lines MCF7 and MDA-MB-231 and the expression levels of YAP1 and JAG1 were proportional to the breast cancer tissue grades. MDA-MB-231 cells with linc-OIP5 knockdown led to weakened proliferation, migration, and tube formation capacity of co-cultured HUVECs. Besides, linc-OIP5 knockdown in co-cultured MDA-MB-231 cells showed downregulated YAP1 and JAG1 expression, combined with a reduced JAG1 level in conditioned medium. Furthermore, a disrupted DLL4/Notch/NRP1 signaling in co-cultured HUVECs were also discovered under this condition. CONCLUSION: Hence, linc-OIP5 in MDA-MB-231 breast cancer cells may act on the upstream of the YAP1/Notch/NRP1 signaling circuit to affect proliferation, migration, and tube formation of co-cultured HUVECs in a non-cellular direct contact way through JAG1 in conditioned medium. These findings at least partially provide a new angiogenic signaling circuit in breast cancers and suggest linc-OIP5 could be considered as a therapeutic target in angiogenesis of breast cancers.

Linc-OIP5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through YAP1/Notch/NRP1 signaling circuit at a tumor microenvironment

BACKGROUND: LincRNAs have been revealed to be tightly associated with various tumorigeneses and cancer development, but the roles of specific lincRNA on tumor-related angiogenesis was hardly studied. Here, we aimed to investigate whether linc-OIP5 in breast cancer cells affects the angiogenesis of HUVECs and whether the linc-OIP5 regulations are involved in angiogenesis-related Notch and Hippo signaling pathways. METHODS: A trans-well system co-cultured HUVECs with linc-OIP5 knockdown breast cancer cell MDA-MB-231 was utilized to study the proliferation, migration and tube formation abilities of HUVECs and alterations of related signaling indicators in breast cancer cells and their conditioned medium through a series of cell and molecular experiments. RESULTS: Overexpressed linc-OIP5, YAP1, and JAG1 were found in breast cancer cell lines MCF7 and MDA-MB-231 and the expression levels of YAP1 and JAG1 were proportional to the breast cancer tissue grades. MDA-MB-231 cells with linc-OIP5 knockdown led to weakened proliferation, migration, and tube formation capacity of co-cultured HUVECs. Besides, linc-OIP5 knockdown in co-cultured MDA-MB-231 cells showed downregulated YAP1 and JAG1 expression, combined with a reduced JAG1 level in conditioned medium. Furthermore, a disrupted DLL4/Notch/NRP1 signaling in co-cultured HUVECs were also discovered under this condition. CONCLUSION: Hence, linc-OIP5 in MDA-MB-231 breast cancer cells may act on the upstream of the YAP1/Notch/NRP1 signaling circuit to affect proliferation, migration, and tube formation of co-cultured HUVECs in a non-cellular direct contact way through JAG1 in conditioned medium. These findings at least partially provide a new angiogenic signaling circuit in breast cancers and suggest linc-OIP5 could be considered as a therapeutic target in angiogenesis of breast cancers.

Effect of bone morphogenetic protein 6 (BMP6) on chicken granulose cells proliferation and progesterone synthesis

There is increasing evidence that bone morphogenetic protein 6 (BMP6) plays critical roles in regulating various stages of ovarian follicle development in mammals. However, the mechanisms of regulation of BMP6 in the chicken ovary remain unclear. In this study, mRNA and protein expression level of BMP6 in chicken ovarian follicles at different development stages were determined by qRT-PCR and western blot separately. Different concentrations of BMP6 protein and FSH were added to the culture medium, and the effects to proliferation of granulose cells were detected, further effect on expression pattern of progesterone synthesis associated genes were also analyzed by qRT-PCR and Western blotting and the secretion of progesterone was detected by ELISA. The results showed that mRNA and protein expression level of BMP6 increased significantly in the follicle with the development of follicle (p<0.05) and reached a peak at F1 follicle. Adding concentration of 50ng/ml and 100ng/ml of BMP6 protein promoted significantly the proliferation of granulosa cells (p<0.05), as well as up-regulated the expression of Steroid hormone synthesis acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) genes in mRNA and protein level. Meanwhile, the secretion of progesterone was significantly higher in the group that added BMP6 and FSH separately than blank control group (p<0.05) and reached a peak in the group that both added BMP6 and FSH. Collectively, these findings highlight that BMP6 is associated with proliferation of follicular cells and the synthesis of progesterone, which indicated that it took an important role in the follicular development of chicken.

Effect of bone morphogenetic protein 6 (BMP6) on chicken granulose cells proliferation and progesterone synthesis

There is increasing evidence that bone morphogenetic protein 6 (BMP6) plays critical roles in regulating various stages of ovarian follicle development in mammals. However, the mechanisms of regulation of BMP6 in the chicken ovary remain unclear. In this study, mRNA and protein expression level of BMP6 in chicken ovarian follicles at different development stages were determined by qRT-PCR and western blot separately. Different concentrations of BMP6 protein and FSH were added to the culture medium, and the effects to proliferation of granulose cells were detected, further effect on expression pattern of progesterone synthesis associated genes were also analyzed by qRT-PCR and Western blotting and the secretion of progesterone was detected by ELISA. The results showed that mRNA and protein expression level of BMP6 increased significantly in the follicle with the development of follicle (p<0.05) and reached a peak at F1 follicle. Adding concentration of 50ng/ml and 100ng/ml of BMP6 protein promoted significantly the proliferation of granulosa cells (p<0.05), as well as up-regulated the expression of Steroid hormone synthesis acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) genes in mRNA and protein level. Meanwhile, the secretion of progesterone was significantly higher in the group that added BMP6 and FSH separately than blank control group (p<0.05) and reached a peak in the group that both added BMP6 and FSH. Collectively, these findings highlight that BMP6 is associated with proliferation of follicular cells and the synthesis of progesterone, which indicated that it took an important role in the follicular development of chicken.(AU)

Mental health is the most important factor influencing quality of life in elderly left behind when families migrate out of rural China.

OBJECTIVES: to investigate the quality of life and the associated factors on left behind elderly in rural China. METHOD: the research was conducted cluster sampling to select 456 elderly left behind when family members migrated out of rural China to participate in a cross-sectional study by completing a general data questionnaire and Quality of Life questionnaire. RESULTS: 91.5% of the elderly requested psychological counseling and education. For the elderly, scores for mental health (39.56±13.73) were significantly lower compared with Chinese standard data (61.6±13.7) (P<0.001). Age, chronic disease type, gender, residence pattern and economic support from children were the main psychological factors influencing this population. CONCLUSION: mental health is the most important factor influencing quality of life of elderly left behind when family members migrated out of rural China. Our study suggested a need to widely establish a general practitioner team for psychological intervention for improving rural elderly people's Quality of Life level, especially in the psychological domain.

Mental health is the most important factor influencing quality of life in elderly left behind when families migrate out of rural China / A saúde mental é o fator mais importante que influencia a qualidade de vida de idosos deixados para trás quando as famílias emigram da China rural / La salud mental es el factor más importante que influye en la calidad de vida en los adultos mayores que se quedan cuando las familias emigran fuera de las zonas rurales de China

OBJECTIVES: to investigate the quality of life and the associated factors on left behind elderly in rural China. METHOD: the research was conducted cluster sampling to select 456 elderly left behind when family members migrated out of rural China to participate in a cross-sectional study by completing a general data questionnaire and Quality of Life questionnaire. RESULTS: 91.5% of the elderly requested psychological counseling and education. For the elderly, scores for mental health (39.56±13.73) were significantly lower compared with Chinese standard data (61.6±13.7) (P<0.001). Age, chronic disease type, gender, residence pattern and economic support from children were the main psychological factors influencing this population. CONCLUSION: mental health is the most important factor influencing quality of life of elderly left behind when family members migrated out of rural China. Our study suggested a need to widely establish a general practitioner team for psychological intervention for improving rural elderly people's Quality of Life level, especially in the psychological domain. .

OBJETIVOS: investigar a qualidade de vida e fatores associados de idosos deixados para trás na China rural. MÉTODO: foi realizada amostragem por conglomerado para selecionar 456 idosos deixados para trás quando os membros da família emigram da China rural. Este é um estudo transversal com preenchimento de um questionário de dados gerais e de qualidade de vida. RESULTADOS: 91,5% dos idosos convidados solicitaram aconselhamento e educação psicológicos. Para os idosos, os escores de saúde mental (39,56±13,73) foram significativamente menores em comparação aos dados padrões chineses (61,6±13,7) (p<0,001). A idade, tipo de doença crônica, gênero, tipo de moradia e suporte econômico dos filhos foram os principais fatores psicológicos que influenciaram essa população. CONCLUSÃO: a saúde mental é o fator mais importante que influencia a qualidade de vida de idosos deixados para trás quando os familiares emigraram da China rural. Este estudo sugere a necessidade de criação de ampla equipe de generalistas para intervenção psicológica, com o intuito de melhorar o nível de qualidade de vida de idosos de áreas rurais, especialmente no domínio psicológico. .

OBJETIVOS: investigar la calidad de vida y los factores asociados a los adultos mayores que se quedan en las zonas rurales de China. MÉTODO: la investigación se realizó por medio de muestreo por conglomerados para seleccionar 456 adultos mayores que se quedaron cuando los miembros de la familia emigraron de zonas rurales de China, para participar en un estudio de corte transversal, completando un cuestionario de datos generales y cuestionario de calidad de vida. RESULTADOS: el 91.5% de los adultos mayores solicitó asistencia psicológica y educación. Para los adultos mayores, las puntuaciones de salud mental (39.56±13.73) fueron significativamente más bajos en comparación con los datos estándar de China (61.6±13.7) (p<0.001). La edad, el tipo de enfermedad crónica, el género, el patrón de residencia y el apoyo económico de los hijos fueron los principales factores psicológicos que influencian esta población. CONCLUSIÓN: la salud mental es el factor más importante que influye la calidad de vida de los adultos mayores que se quedan cuando los miembros de la familia emigran de las zonas rurales de China. Nuestro estudio sugiere la necesidad de establecer ampliamente un equipo médico general para la intervención psicológica para mejorar el nivel de la Calidad de Vida de la población rural de edad avanzada, sobre todo en el dominio psicológico. .

The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal.

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that mediates both NADH-oxidizing and caspase-independent apoptosis. Further, the proapoptotic activity of AIF is located in the C-terminus of AIF, although the precise minimum sequence responsible for apoptosis induction remains to be investigated. In the present study, we generated two truncated AIFs, AIFDelta1-480-FLAG, which is a FLAG-tagged C-terminal peptide comprising amino acids from 481 to 613, and AIF360-480 containing amino acids from 360 to 480 of AIF. We used confocal microscopy to demonstrate that both the truncated proteins are expressed and located in the cytoplasm of transfected cells. AIFDelta1-480 but not AIF360-480 induces apoptosis in transfected cells. We also found that the expression of AIFDelta1-480 could initiate the release of cytochrome c from the mitochondria. The suppression of caspase-9 via siRNA blocked the proapoptotic activity of AIFDelta1-480. Therefore, AIFDelta1-480 is sufficient for inducing caspase-9-dependent apoptotic signaling, probably by promoting the release of cytochrome c. At last, we generated a chimeric immuno-AIFDelta1-480 protein, which comprised an HER2 antibody, a Pseudomonas exotoxin A translocation domain and AIFDelta1-480. Human Jurkat cells transfected with the immuno-AIFDeltal-480 gene could express and secrete the chimeric protein, which selectively recognize and kill HER2-overexpressing tumor cells. Our study demonstrates the feasibility of the immuno-AIFDeltal-480 gene as a novel approach to treating HER2-overexpressing cancers.

The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that mediates both NADH-oxidizing and caspase-independent apoptosis. Further, the proapoptotic activity of AIF is located in the C-terminus of AIF, although the precise minimum sequence responsible for apoptosis induction remains to be investigated. In the present study, we generated two truncated AIFs, AIFΔ1-480-FLAG, which is a FLAG-tagged C-terminal peptide comprising amino acids from 481 to 613, and AIF360-480 containing amino acids from 360 to 480 of AIF. We used confocal microscopy to demonstrate that both the truncated proteins are expressed and located in the cytoplasm of transfected cells. AIFΔ1-480 but not AIF360-480 induces apoptosis in transfected cells. We also found that the expression of AIFΔ1-480 could initiate the release of cytochrome c from the mitochondria. The suppression of caspase-9 via siRNA blocked the proapoptotic activity of AIFΔ1-480. Therefore, AIFΔ 1-480 is sufficient for inducing caspase-9-dependent apoptotic signaling, probably by promoting the release of cytochrome c. At last, we generated a chimeric immuno-AIFΔ 1-480 protein, which comprised an HER2 antibody, a Pseudomonas exotoxin A translocation domain and AIFΔ 1-480. Human Jurkat cells transfected with the immuno-AIFΔl-480 gene could express and secrete the chimeric protein, which selectively recognize and kill HER2-overexpressing tumor cells. Our study demonstrates the feasibility of the immuno-AIFΔl-480 gene as a novel approach to treating HER2-overexpressing cancers.