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Aim To investigate the effect of long non- coding RNA p21 (LncRNA p21) regulating Hippo- Yes-associated protein (Hippo-YAP) signaling pathway on the formation of abdominal aortic aneurysm (AAA) in mice. Methods C57BL/6 ApoE
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ABSTRACT Objective: MCM3AP-AS1 has been characterized as an oncogenic long non-coding RNA (lncRNA) in several cancers including papillary thyroid cancer (PTC), but its role in PTC has not been fully elucidated. Considering the critical role of lncRNAs in cancer biology, further functional analysis of MCM3AP-AS1 in PTC may provide novel insights into PTC management. Subjects and methods: Paired tumor and non-tumor tissues were collected from 63 papillary thyroid carcinoma (PTC) patients. Expression levels of MCM3AP-AS1 , miR-218 and GLUT1 in tissue samples were analyzed by qRT-PCR. Cell transfection was performed to explore the interactions among MCM3AP-AS1 , miR-218 and GLUT1 . Cell proliferation assay was performed to evaluate the effects of MCM3AP-AS1 and miR-218 on cell proliferation. Results: MCM3AP-AS1 accumulated to high levels in PTC tissues and was affected by clinical stage. MCM3AP-AS1 showed a positive correlation with GLUT1 across PTC tissues. RNA interaction prediction showed that MCM3AP-AS1 could bind to miR-218 , which can directly target GLUT1 . MCM3AP-AS1 and miR-218 showed no regulatory role regulating the expression of each other, but overexpression of MCM3AP-AS1 upregulated GLUT1 and enhanced cell proliferation. In contrast, overexpression of miR-218 downregulated GLUT1 and attenuated cell proliferation. In addition, miR-218 suppressed the role of MCM3AP-AS1 in regulating the expression of GLUT1 and cell proliferation. Conclusions: MCM3AP-AS1 may serve as a competing endogenous RNA of miR-218 to upregulate GLUT1 in PTC, thereby promoting cell proliferation. The MCM3AP-AS1/miR-218/GLUT1 pathway characterized in the present study might serve as a potential target to treat PTC.
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Background Paraquat (PQ) is one of the environmental factors that can cause sporadic Parkinson's disease (PD). Microglia-mediated neuroinflammation plays an important role in the occurrence and development of PD. Our previous studies have found that low doses of PQ can activate BV-2 microglia to the M1 phenotype and exert pro-inflammatory effects, but the associated mechanism is not clear yet. Objective To explore the role of c-Jun N-terminal kinase (JNK)/activator protein 1 (AP-1) signaling pathway in PQ-induced activation of the NOD-like receptor thermal protein domain associated protoin 3 (NLRP3) inflammasome in microglia. Methods An in vitro microglia model was established. The cells were treated with 0, 0.03, 0.06,and 0.12 μmol·L−1 PQ for 24 h, the whole cell protein was extracted. The relative expression levels of JNK, AP-1 constituent proteins (c-Jun, c-Fos), NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspasse-1 precursor (pro caspase-1), interleukin-18 (IL-18), and interleukin-1β (IL-1β) were evaluated by Western blotting, to observe the effects of PQ exposure on JNK/AP-1 signaling pathway and NLRP3 inflammasome. After the treatment of 20 μmol·L−1 JNK inhibitor SP600125, the above proteins were detected again, to explore the driving effect of JNK/AP-1 signaling pathway on NLRP3 inflammasome activation. Results After PQ exposure, the relative expression levels of key proteins of JNK, c-Jun, and c-Fos, NLRP3, ASC, and pro caspase-1 in the 0.06 μmol·L−1 PQ group and the 0.12 μmol·L−1 PQ group were higher than those in the 0 μmol·L−1 PQ group (P＜0.05), and the relative expression levels of IL-18 and IL-1β increased with higher exposure (P＜0.05). After the treatment of JNK inhibitor SP600125, the relative expression levels of key proteins of JNK/AP-1 signaling pathway (JNK, c-Jun, and c-Fos), NLRP3 inflammasome (NLRP3, ASC, and Pro caspase-1), and inflammatory factors (IL-18 and IL-1β) in the control group, the 20 μmol·L−1 SP600125 group, and the 20 μmol·L−1 SP600125+0.06 μmol·L−1 PQ group were lower than those in the 0.06 μmol·L−1 PQ group (P＜0.05). Conclusion PQ exposure can activate the JNK/AP-1 signaling pathway and subsequently drive the activation of NLRP3 inflammasome in BV-2 microglia to mediate neuroinflammatory responses..
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The AP2/ERF gene family is one of the largest transcription factor families in the plant kingdom, and plays an important role in response to biological and abiotic stresses, plant hormone responses, and plant growth and development. In this study, the AP2/ERF family of Panax notoginseng was identified by bioinformatics methods, and the physicochemical properties, structure, phylogenetic relationship, expression pattern and function of PnDREB4 gene of the family were analyzed. The results showed that 140 AP2/ERF family members were identified in P. notoginseng, which were divided into DREB, ERF, AP2, RAV and Sololit subgroups. The physicochemical properties and motifs of proteins were similar among the subgroups. There were 34 differentially expressed genes in the AP2/ERF family of Fusarium oxysporum infected P. notoginseng plants, and 19 genes were up-regulated. The expression level of PnDREB84 was up-regulated with the extension of Fusarium oxysporum infection time in the range of 0-96 h. The content of ABA and SA in P. notoginseng plants overexpressing PnDREB84 gene increased after 4 ℃ stress. The results showed that PnDREB84 gene plays a dual regulatory role in the process of biological stress and abiotic stress. PnDREB84 gene can be used as a potential molecular marker for the breeding of new varieties of P. notoginseng. The identification of AP2/ERF transcription factor and function analysis of PnDREB84 gene of P. notoginseng provided data support for the analysis of stress resistance mechanism of P. notoginseng and the breeding of new varieties.
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The genomic instability may lead to an initiation of cancer in many organisms. Homologous recombination repair (HRR) is vital in maintaining cellular genomic stability. RAD51 associated protein 1 (RAD51AP1), which plays a crucial role in HRR and primarily participates in forming D-loop, was reported as an essential protein for maintaining cellular genomic stability. However, recent studies showed that RAD51AP1 was significantly overexpressed in various cancer types and correlated with poor prognosis. These results suggested that RAD51AP1 may play a significant pro-cancer effect in multiple cancers. The underlying mechanism is still unclear. Cancer stemness-maintaining effects of RAD51AP1 might be considered as the most reliable mechanism. Meanwhile, RAD51AP1 also promoted resistance to radiation therapy and chemotherapy in many cancers. Thus, researches focused on RAD51AP1, and its regulatory molecules may provide new targets for overcoming cancer progression and treatment resistance. Here, we reviewed the latest research on RAD51AP1 in cancers and summarized its differential expression and prognostic implications. In this review, we also outlined the potential mechanisms of its pro-cancer and drug resistance-promoting effects to provide several potential directions for further research. .
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Humans , DNA-Binding Proteins/metabolism , RNA-Binding Proteins/metabolism , Lung Neoplasms , DNA Repair , Genomic Instability , Rad51 Recombinase/metabolismABSTRACT
Aim To investigate the effect of nitidine chloride (NC) on the apoptosis of cervical cancer cells and its mechanism. Methods Cervical cancer cell lines HeLa and SiHa were selected as subjects. The cytotoxicity of NC and its inhibitory effect on cell growth were detected by CCK-8 assay and clone formation assay. The effect of NC on the apoptosis of cervical cancer cells was detected by TUNEL assay, and the expression of apoptosis-related proteins was detected by Western blot. The effects of NC on the interaction between p53 and E6AP protein, the level of p53 ubiquitination modification and the stability of p53 protein in cervical cancer cells were analyzed by immunoprecipi-tation assay, ubiquitination assay and Western blot assay. Results NC could significantly inhibit the proliferation and induce apoptosis of cervical cancer cells. NC could inhibit the interaction between tumor suppressor protein p53 and E6AP in cervical cancer cells, reduce the level of p53 ubiquitination modification, delay the degradation of p53 and increase the expression level of p53 protein. Conclusions NC can inhibit the ubiquitination and degradation of p53, improve the expression level of p53 protein, restore its tumor suppressor function, and thus play an anti -cervical cancer role.
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@#Objective To investigate the effect of silencing E6-associated protein(E6AP)on the level of p53 protein in human papilloma virus(HPV)negative cervical cancer cells(C33A cells).Methods The siRNA sequence silencing E6AP(siE6AP)and silencing control disordered siRNA sequence(siControl)were transfected into C33A cells with the mediation of LipofectamineTM2000 transfection reagent respectively.The silencing effect of siRNA on E6AP and the expression of p53and cleaved-caspase-3 proteins were detected by Western blot.Results The levels of E6AP protein in C33A cells of siE6AP group were significantly lower(t =-4.597,P<0.05),while the levels of p53 and cleaved-caspase-3 proteins were significantly higher than those of siControl group(t = 4.533 and 7.099 respectively,each P<0.05).Conclusion Silencing of E6AP significantly increased the expression of p53 protein in C33A cells,indicating that silencing of E6AP may restore the activity and function of p53 protein in C33A cells.
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ObjectiveTo identify the functions of the AP2/ERF family members in Pinellia ternata and promote the genetic improvement of P. ternata varieties. MethodWe identified and conducted a systematic bioinformatics analysis of the AP2/ERF family member genes in P. ternata based on the three generations of transcriptome data. Real-time polymerase Chain reaction （Real-time） PCR was employed to determine the expression pattern of AP2/ERF genes in different tissues and under different stress conditions. ResultA total of eight full-length AP2/ERF family members were identified from the transcriptome data， which were classified into three sub-gene families： AP2， ERF， and DREB. The deduced AP2/ERF proteins in P. ternata had the length of 251-512 aa， the theoretical pI of 5.29-11.72， the instability index of 45.90-82.41， subcellular localization in the nucleus， and conserved domains and motifs. AP2/ERF genes were expressed in different tissues of P. ternata， with high expression levels in the leaf. The stress response experiments showed that PtERF1 mainly responded to NaCl stress. The expression of PtERF2 and PtERF4 was significantly up-regulated under low temperature and polyethylene glycol （PEG）-simulated stress. PtERF3 responded to both low temperature and NaCl stress. The expression of PtERF5 was induced by high temperature， low temperature， NaCl and PEG stress. The expression of PtERF7 was up-regulated under high temperature， while that of PtERF8 under low temperature. ConclusionThe AP2/ERF genes in P. ternata can respond to stress and have the potential functions of regulating photosynthesis and improving root stress resistance.
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OBJECTIVE@#AP2/ERF (APETALA2/ethylene-responsive factor) superfamily is one of the largest gene families in plants and has been reported to participate in various biological processes, such as the regulation of biosynthesis of active lignan. However, few studies have investigated the genome-wide role of the AP2/ERF superfamily in Isatis indigotica. This study establishes a complete picture of the AP2/ERF superfamily in I. indigotica and contributes valuable information for further functional characterization of IiAP2/ERF genes and supports further metabolic engineering.@*METHODS@#To identify the IiAP2/ERF superfamily genes, the AP2/ERF sequences from Arabidopsis thaliana and Brassica rapa were used as query sequences in the basic local alignment search tool. Bioinformatic analyses were conducted to investigate the protein structure, motif composition, chromosome location, phylogenetic relationship, and interaction network of the IiAP2/ERF superfamily genes. The accuracy of omics data was verified by quantitative polymerase chain reaction and heatmap analyses.@*RESULTS@#One hundred and twenty-six putative IiAP2/ERF genes in total were identified from the I. indigotica genome database in this study. By sequence alignment and phylogenetic analysis, the IiAP2/ERF genes were classified into 5 groups including AP2, ERF, DREB (dehydration-responsive element-binding factor), Soloist and RAV (related to abscisic acid insensitive 3/viviparous 1) subfamilies. Among which, 122 members were unevenly distributed across seven chromosomes. Sequence alignment showed that I. indigotica and A. thaliana had 30 pairs of orthologous genes, and we constructed their interaction network. The comprehensive analysis of gene expression pattern in different tissues suggested that these genes may play a significant role in organ growth and development of I. indigotica. Members that may regulate lignan biosynthesis in roots were also preliminarily identified. Ribonucleic acid sequencing analysis revealed that the expression of 76 IiAP2/ERF genes were up- or down-regulated under salt or drought treatment, among which, 33 IiAP2/ERF genes were regulated by both stresses.@*CONCLUSION@#This study undertook a genome-wide characterization of the AP2/ERF superfamily in I. indigotica, providing valuable information for further functional characterization of IiAP2/ERF genes and discovery of genetic targets for metabolic engineering.
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Abscisic Acid , Isatis/genetics , Multigene Family , Phylogeny , Homeodomain Proteins/genetics , Genome, PlantABSTRACT
An internal opening (primary opening) in the anal canal or rectum and an exterior opening (secondary opening) in the perianal skin combine to form a ?stula-in-ano, an infiammatory track. Unhealthy fibrous tissue and granulation tissue line this tract. Intersphicteric fistulas are ones that cross the internal sphincter and then have a tract to the outside of the anus leading1. The prevalence of an anal abscess-induced fistula-in-ano ranged from 26% to 38%.In men,the prevalence is 12.3 cases per 100,000 population and in women, it is 5.6 cases per 100,000 population2. Fistula-in-ano is a complicated disease, its signs and symptoms which resembles bhagandara disease described in ?yurved?. ?c?rya su?ruta mentioned this disease under aa mah?gad?s which means difficult to cure. For the management of this painful disease many treatment modalities are enumerated in ?yurved? classics and k?ra s?tra therapy is one among them which is proved to be gold standard. Though k?ra s?tra therapy is a big revolution in the field of fistula in ano, but it has some disadvantages like it is time consuming process, severe post-procedural pain, and big scar marks. In the present case report,A 24yr old male p/t c/o pain and swelling in perianal region since three months and successfully managed with IFTAK (Interception of Fistulous tract and application of Ksharsutra) technique. which showed a greatpotential in management by minimizing the duration of treatment, mild post procedural pain and minimum scar mark
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Introduction: The management of compound trauma has always been challenging. Free ?aps are the ?rst choice when soft tissue cover cannot be provided by local ?aps. When facilities for microsurgery are not available or certain factors preclude the microsurgical anastomosis or in cases of free ?ap failure, the cross leg ?aps have a big role to play in lower limb reconstruction. We are presenting our retrospective study on 30 cases of distal leg and foot defects covered successfully by cross leg ?aps. The aim of this study is to highlight the usefulness of cross leg Aims and objectives: ?aps in lower limb reconstruction. A retrospective study was done on 30 patients from January 2015 to Material and methods: December 2021 who underwent perforator based fasciocutaneous cross leg ?ap for post traumatic soft tissue defects of distal leg and foot. The mechanism of injury, size and site of defect were recorded. All ?aps were planned in reverse and limbs were immobilised with external ?xator. Post-operative complications if any were noted. The patients were followed till the ?ap became stable. The mechanism of injury was road side accident in 26 cases, machine injury in 2 cases and fall from Results: height in 2 cases. 19 patients had soft tissue defect of distal 1/3rd of leg and 11 patients had foot defects. 26(86.67%) patients underwent distally based fasciocutaneous cross leg ?ap and 4(13.33%) patients underwent conventional anteromedially based fasciocutaneous ?ap. All ?aps survived well. 2 patients had discharge and 1 had margin necrosis but were managed conservatively. The perforators based fasciocutaneous cross leg ?aps provide an easy, simple, reliable and viable Conclusion: cover for distal leg and foot reconstruction.
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Objective:To investigate the clinical value of split domino donor auxiliary liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinco-pathological data of 3 liver transplantation recipients who were admitted to Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School and 1 liver transplantation recipient who was admitted to external hospital in September 2018 were collected. The first case was male, aged 22 years, who was diagnosed as type II citrullinemia (CTLN2). The second case undergoing liver transplantation in external hospital was male, aged 59 years, who was diagnosed as decompensated alcoholic cirrhosis. The third case was female, aged 52 years, who was diagnosed as hepatocellular carcinoma of right lobe of liver. The fourth case was female, aged 51 years, who was diagnosed as hepatocellular carcinoma of right lobe of liver. The donor liver from a brain and cardiac death donor was split in vitro into the left liver and the right liver, in which the right liver without middle hepatic vein, and the modified piggyback liver transplantation using the left liver and the classical orthotropic liver transplantation using the right liver was conducted on the first and the second case, respectively. The original liver of the first case was split in vivo into the left liver and the right liver, and the piggyback auxiliary liver transplantation using the left liver and the piggyback auxiliary liver transplantation using the right liver was conducted on the third and the fourth case who underwent extended right hemihepatectomy, respectively. Observation indicators: (1) intraoperative situations; (2) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect liver function, liver imaging, complication and survival of recipients up to October 2021.Results:(1) Intraoperative situations. Liver transplantation was conducted successfully on the first, third and fourth case, with the operation time, the volume of intraoperative blood loss, the donor liver cold ischemia time, the graft-to-recipient weight ratio were 400 minutes, 370 minutes, 390 minutes, 600 mL, 1 300 mL, 1 600 mL, 230 minutes, 152 minutes, 135 minutes, 1.2%, 0.8%, 1.1%. (2) Follow-up. B-ultrasound examination of the first, third and fourth case after liver transplantation showed that the blood flow was normal, and all the 3 cases discharged and were followed up at postoperative 1, 6 and 12 month. The liver function, the level of blood ammonia and citrulline were normal of the first, third and fourth case at postoperative 1 week. Imaging examina-tion showed normal liver morphology of the first and third case, and a transplanted liver atrophy caused by portal vein steal of the fourth case. ① The level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil) of the first case before liver transplantation, at postoperative 1 day, 2 day, 3 day, 7 day, 10 day, 6 month and 1 year were 22.8 U/L, 404.1 U/L, 355.5 U/L, 289.6 U/L, 31.0 U/L, 23.1 U/L, 42.1 U/L and 25.8 U/L, 31.5 U/L, 517.7 U/L, 327.6 U/L, 172.9 U/L, 15.9 U/L, 21.4 U/L, 47.5 U/L and 29.7 U/L, 3.8 μmol/L, 92.1 μmol/L, 87.4 μmol/L, 79.7 μmol/L, 90.1 μmol/L, 130.6 μmol/L, 33.8 μmol/L and 25.4 μmol/L, 2.3 μmol/L, 47.0 μmol/L, 44.1 μmol/L, 47.1 μmol/L, 57.4 μmol/L, 70.9 μmol/L, 24.7 μmol/L and 9.7 μmol/L, respectively. The level of citrulline and blood ammonia of the first case before and after liver transplantation were 999.0 μmol/L, 196.0 μmol/L and 14.6 μmol/L, 9.0 μmol/L, respectively. The first case was followed up for 3 years and survived without any liver transplantation related complication. ② The level of ALT, AST, TBil, DBil of the third case before liver transplantation, at postoperative 1 day, 2 day, 3 day, 7 day, 10 day, 6 month and 1 year were 21.3 U/L, 143.9 U/L, 182.0 U/L, 132.0 U/L, 17.2 U/L, 10.1 U/L, 17.6 U/L and 16.8 U/L,20.0 U/L, 291.0 U/L, 227.5 U/L, 106.4 U/L, 15.8 U/L, 10.8 U/L, 17.1 U/L and 19.4 U/L, 6.8 μmol/L, 50.9 μmol/L, 45.0 μmol/L, 34.0 μmol/L, 32.4 μmol/L, 22.3 μmol/L, 12.8 μmol/L and 14.9 μmol/L, 2.5 μmol/L, 18.4 μmol/L, 17.2 μmol/L, 14.9 μmol/L, 14.8 μmol/L, 12.1 μmol/L, 3.6 μmol/L and 4.4 μmol/L. The level of citrulline and blood ammonia of the third case after liver transplantation were 24.9 μmol/L and 16.0 μmol/L. The third case was followed up for 3 years and survived without any liver transplantation related complication. ③ The level of ALT, AST, TBil, DBil of the fourth case before liver transplantation, at postoperative 1 day, 2 day, 3 day, 7 day, 10 day, 6 month and 1 year were 35.0 U/L, 268.7 U/L, 682.0 U/L, 425.8 U/L, 57.5 U/L, 34.0 U/L, 29.4 U/L and 18.1 U/L, 37.0 U/L, 419.1 U/L, 436.2 U/L, 139.5 U/L, 35.2 U/L, 32.4 U/L, 54.7 U/L and 32.8 U/L, 7.1 μmol/L, 64.2 μmol/L, 41.4 μmol/L, 17.6 μmol/L, 34.2 μmol/L, 48.7 μmol/L, 14.1 μmol/L and 21.8 μmol/L, 2.8 μmol/L, 18.9 μmol/L, 16.1 μmol/L, 6.0 μmol/L, 14.6 μmol/L, 26.7 μmol/L, 3.9 μmol/L, 11.8 μmol/L. The level of citrulline and blood ammonia of the fourth case after liver transplantation were 8.4 μmol/L and 47.0 μmol/L. One week after surgery, the transplanted right liver of the fourth case occurred atrophy due to blood stealing from the right branch of the portal vein. B-ultrasound examination showed that the reflux of the hepatic artery and hepatic vein was unobstructed. Immunosuppressants were discontinued 3 months after operation on the fourth case and there was no complication such as rejection, bile leakage, biliary stricture, thrombosis and vascular stricture during follow-up. The fourth case died of lung metastasis 19 months after operation.Conclusion:Split domino donor auxiliary liver transplantation can be used for the treatment of metabolic liver disease and advanced hepatocellular carcinoma.
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OBJECTIVE@#To explore the transcriptional regulation mechanism and biological function of low expression of vasoactive intestinal peptide receptor 1 (VIPR1) in hepatocellular carcinoma (HCC).@*METHODS@#We constructed plasmids carrying wild-type VIPR1 promoter or two mutant VIPR1 promoter sequences for transfection of the HCC cell lines Hep3B and Huh7, and examined the effect of AP-2α expression on VIPR1 promoter activity using dual-luciferase reporter assay. Pyrosequencing was performed to detect the changes in VIPR1 promoter methylation level in HCC cells treated with a DNA methyltransferase inhibitor (DAC). Chromatin immunoprecipitation was used to evaluate the binding ability of AP-2α to VIPR1 promoter. Western blotting was used to assess the effect of AP-2α knockdown on VIPR1 expression and examine the differential expression of VIPR1 in the two cell lines. The effects of VIPR1 overexpression and knockdown on the proliferation, cell cycle and apoptosis of HCC cells were analyzed using CCK8 assay and flow cytometry. We also observed the growth of HCC xenograft with lentivirus-mediated over-expression of VIPR1 in nude mice.@*RESULTS@#Compared with the wild-type VIPR1 promoter group, co-transfection with the vector carrying two promoter mutations and the AP-2α-over-expressing plasmid obviously restored the luciferase activity in HCC cells (P < 0.05). DAC treatment of the cells significantly decreased the methylation level of VIPR1 promoter and inhibited the binding of AP-2α to VIPR1 promoter (P < 0.01). The HCC cells with AP-2α knockdown showed increased VIPR1 expression, which was lower in Huh7 cells than in Hep3B cells. VIPR1 overexpression in HCC cells caused significant cell cycle arrest in G2/M phase (P < 0.01), promoted cell apoptosis (P < 0.001), and inhibited cell proliferation (P < 0.001), while VIPR1 knockdown produced the opposite effects. In the tumor-bearing nude mice, VIPR1 overexpression in the HCC cells significantly suppressed the increase of tumor volume (P < 0.001) and weight (P < 0.05).@*CONCLUSION@#VIPR1 promoter methylation in HCC promotes the binding of AP-2α and inhibits VIPR1 expression, while VIPR1 overexpression causes cell cycle arrest, promotes cell apoptosis, and inhibits cell proliferation and tumor growth.
Subject(s)
Animals , Humans , Mice , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/pathology , Luciferases/genetics , Methylation , Mice, Nude , Receptors, Vasoactive Intestinal Polypeptide, Type I/metabolism , Transcription Factor AP-2/metabolismABSTRACT
Background:Cervical vertebraeare the most crucially located and play a dynamic role in the mobility and protection of the vital parts of the central nervous system, they are prone to undergo degenerative diseases like spinal stenosis, cervical spondylosis etc.Hence it is important to know the exact dimensions of cervical vertebralbody and spinal canal in the diagnosis, prognosis and treatment of diseasesrelated tocervical spine and spinal cord.Material And Methods:Normal plain radiographs of cervical spine of two hundred adult subjects of known sex (one hundred males and one hundred females) and of known age group (between 18 to 50 years) studied for Antero-posterior diameter of vertebral body (AP-VB), Height of vertebral body (HT-VB)and Canal body ratio (CBR) in C3 to C7 cervical vertebrae. Data tabulated and analysed by using software statistical Package for Social Sciences(SPSS).Result:Higher mean AP –VB diameter andmean Ht -VB valuesare recorded in males as compared to females.Highermean Canal body ratio (CBR) was recorded in femalesascompared to males.Conclusion:Present study showed,higher mean value of(AP-VB),(HT-VB) in males as compared to females and found to be statistically significant indicating sexual dimorphism. Canal body ratio(CBR) showed slightly higher values in females as compared to malesand found statistically significant at C6 and C7 Levels.
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Invasive fungal infections (IFIs) represent a growing public concern for clinicians to manage in many medical settings, with substantial associated morbidities and mortalities. Among many current therapeutic options for the treatment of IFIs, amphotericin B (AmB) is the most frequently used drug. AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance. In this review, we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs. We have also discussed the mechanism of actions of AmB, rationale for treating IFIs, and recent advances in formulating AmB for clinical use. Finally, this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.
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Tumor recurrence after surgery is the main cause of treatment failure. However, the initial stage of recurrence is not easy to detect, and it is difficult to cure in the late stage. In order to improve the life quality of postoperative patients, an efficient synergistic immunotherapy was developed to achieve early diagnosis and treatment of post-surgical tumor recurrence, simultaneously. In this paper, two kinds of theranostic agents based on gold nanorods (AuNRs) platform were prepared. AuNRs and quantum dots (QDs) in one agent was used for the detection of carcinoembryonic antigen (CEA), using fluorescence resonance energy transfer (FRET) technology to indicate the occurrence of
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We herein describe AncPhore, a versatile tool for drug discovery, which is characterized by pharmacophore feature analysis and anchor pharmacophore (
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Objective:To explore the effects of Xintongtai （XTT） on traditional Chinese medicine （TCM） syndrome score and collagen fibers in vascular smooth muscle cells（VSMCs） of rabbits with atherosclerosis in the regulation of p38 mitogen-activated protein kinase （p38 MAPK）/activator protien-1 （AP-1）signaling pathway. Method:A total of 120 rabbits of SPF grade were randomly divided into the sham operation group， combined phlegm and blood stasis model group， rosuvastatin group， and low-， middle-， and high-dose XTT groups. The rabbit model of atherosclerosis due to combined phlegm and blood stasis was established by exposing them to high-fat diet and balloon injury. Following modeling， the corresponding drugs were administered by gavage for eight weeks （2.3， 4.6， 9.2 g·kg<sup>-1</sup> for low-， middle-， and high-dose XTT groups and 0.55 mg·kg<sup>-1 </sup>for rosuvastatin group）. At the end of medication， the abdominal aorta was isolated and stained with htoxylin-eosin （HE） for observing the vulnerable plaque. Matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） were detected by immunohistochemistry （IHC）. The collagen fiber decomposition in VSMCs was observed after Masson staining. The protein expression levels of p38 MAPK and AP-1 in aorta was assayed by Western blotting. The combined phlegm and blood stasis syndrome was scored based on TCM syndrome scoring scale. Result:Compared with the model group， XTT at each dose and rosuvastatin significantly decreased MMP-9 content， increased TIMP-1， down-regulated p38 MAPK protein expression， and weakened the nuclear translocation of AP-1 （<italic>P</italic><0.01）. Compared with the low-dose XTT group， the middle- and high-dose XTT groups and rosuvastatin group exhibited obviously lowered MMP-9，elevated TIMP-1， down-regulated p38 MAPK protein expression， and diminished AP-1 nuclear translocation （<italic>P</italic><0.05，<italic>P</italic><0.01）. The TCM syndrome scores of the middle- and high-dose XTT groups and rosuvastatin group were significantly improved as compared with that in the model group （<italic>P</italic><0.05，<italic>P</italic><0.01）. The comparison with the low-dose XTT group revealed a remarkable improvement in TCM syndrome score of the middle- and high-dose XTT groups and rosuvastatin group （<italic>P</italic><0.01）. As demonstrated by Masson staining， the smooth muscle fibers in the model group were arranged in disorder， accompanied by enhanced collagen decomposition， thinned fibrous cap， and increased plaque vulnerability. Compared with the model group， the VSMCs in each XTT group and rosuvastatin group were orderly arranged， manifested as decreased collagen fiber decomposition and increased plaque stability. Conclusion:XTT down-regulates the expression of p38 MAPK and MMP-9， increases the level of TIMP-1， reduces the nuclear translocation of AP-1， diminishes the decomposition of collagen fibers in VSMCs， and improves the score of combined phlegm and blood stasis syndrome. XTT alleviates arteriosclerosis due to combined phlegm and blood stasis by regulating p38 MAPK/AP-1 signaling pathway and downstream cytokines and stabilizing vulnerable plaques.
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Objective:To investigate and analyze the radioactivity levels of 90Sr and 137Cs in drinking water and 137Cs in food after the installation of the first AP1000 nuclear power unit in China. Methods:From 2012 to 2019, four drinking water monitoring points around AP1000 nuclear power unit located at Sanmen nuclear power plant site were collected during the wet season and dry season, 90Sr and 137Cs and radioactivity concentrations were determined in drinking water. Local rice, cabbage, crucian and mullet were collected to determine the radioactivity concentration of 137Cs. Results:From 2012 to 2019, the radioactivity concentrations of 90Sr and 137Cs in drinking water were 1.2-9.8 mBq/L and 0.2-8.1 mBq/L, respectively. The radioactivity concentration of 137Cs in food were 1.1×10 -2-2.8×10 -1 Bq/kg, lower than the limits specified in the Limited concentrations of radioactive materials in foods (GB 14882-94). Conclusions:After the installation of the first AP1000 nuclear power unit in China, the radioactivity levels of 90Sr and 137Cs in drinking water and 137Cs in foods are stable, without environmental impact identified.
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AIM: To investigate the role of ribonucleotide reductase M2 (RRM2) in 5-fluorouracil (5-FU) resistance of HCC cells and to develop potential strategies to enhance the sensitivity of HCC cells to 5-FU. METHODS: The expression of RRM2 was examined by Western blot in BEL/5-FU cells and BEL7402 cells. The expression of RRM2 was down-regulated through RNA interference (RNAi) technology and the activity of RRM2 was inhibited by the RRM2 inhibitor 3-AP. The cell proliferation ability was detected by CCK-8 assay and colony formation assay, and the apoptosis was analyzed by Confocal high-content system. RESULTS: The expression level of RRM2 was increased by 2.5-fold in BEL/5-FU cells compared with BEL7402 cells. Compared with control siRNA, the half maximum inhibitory concentration IC