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The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Subject(s)
Humans , Membrane Proteins/genetics , Pituitary Neoplasms/genetics , BiomarkersABSTRACT
This present systematic review examines spine surgery literature supporting augmented reality (AR) technology and summarizes its current status in spinal surgery technology. Database search strategies were retrieved from PubMed, Web of Science, Cochrane Library, Embase, from the earliest records to April 1, 2021. Our review briefly examines the history of AR, and enumerates different device application workflows in a variety of spinal surgeries. We also sort out the pros and cons of current mainstream AR devices and the latest updates. A total of 45 articles are included in our review. The most prevalent surgical applications included are the augmented reality surgical navigation system and head-mounted display. The most popular application of AR is pedicle screw instrumentation in spine surgery, and the primary responsible surgical levels are thoracic and lumbar. AR guidance systems show high potential value in practical clinical applications for the spine. The overall number of cases in AR-related studies is still rare compared to traditional surgical-assisted techniques. These lack long-term clinical efficacy and robust surgical-related statistical data. Changing healthcare laws as well as the increasing prevalence of spinal surgery are generating critical data that determines the value of AR technology.
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In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.
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Objective:To explore the mechanism of miR-205-5p/E2F1 signal axis in regulating the glioma U251, U87 radiotherapy resistance.Methods:X-ray gradual ascending and intermittent induction method was used to irradiate the glioma U251 cells to establish U251/TR, U87/TR radiation-resistant cell lines. Then, the morphology, migration, invasion and proliferation abilities of cells (U251/TR, U87/TR radiation-resistant cells and U251, U87 radiation-sensitive cells) were analyzed. Luciferase gene detection system and point mutation technique were employed to analyze the mechanism of miR-205-5p and E2F1 gene activity on U251 and U87 radiation-resistant cell lines.Results:Compared with the radiation-sensitive U251 cells, the radiation-resistant cells U251/TR, U87/TR showed increased proliferation activity, enhanced migration and invasion abilities and decreased apoptosis under X-ray irradiation. miR-205-5p mimics transfection could down-regulate the expression of E2F1 factor in U251/TR cells, inhibit cell proliferation, invasion and migration and increase the radiosensitivity of U251/TR cells. miR-205-5p mimics transfection combined with with E2F1 down-regulation exerted anti-tumor effect and decreased cell tolerance by suppressing the Wnt/β-catenin signaling pathway activity.Conclusions:The glioma radiation-resistant cell line U251/TR, U87/TR can be established by X-ray gradual ascending and intermittent induction method. The miR-205-5p/E2F1 signal axis exerts tumor-suppressing effect through the classical Wnt/β-catenin signaling pathway, which can be used as an therapeutic target to increase the radiosensitivity of glioma.
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Objective To investigate the effect of anti-human immunoglobulin M (IgM) on proliferation,apoptosis,cell cycle and tumor formation in human nasopharyngeal carcinoma HNE-1 cell line in vitro and in vivo.Methods After treatment with anti-human IgM antibody,proliferation of HNE-1 cells was observed by cell proliferation inhibition assay,apoptosis and cell cycle of HNE-1 cells were detected by flow cytometry,and apoptotic cells were detected by TUNEL staining.Nude mouse models were constructed,and were injected intraperitoneally with anti-human IgM antibodies (once every 3 days).The growth of transplanted tumor was observed once every 4 days.After the fifth injection,the expression levels of IgM and gp96 protein in transplanted tumor were observed by immunohistochemical method (streptavidin-peroxidase conjugated method,SP).Results MTS assay showed that anti-human IgM antibody can significantly inhibit the proliferation of HNE-1 cells in concentration-and time-dependent manner (P＜0.05).Flow cytometry showed that the anti-human IgM antibody promoted a significant decrease in percentage of cells in G1 phase,a significant increase in percentage of cells in S phase,and a significant increase in apoptotic rate of HNE-1 cells (P＜0.05).TUNEL staining showed that the anti-human IgM antibody promoted apoptosis of HNE-1 cells (P＜0.01).Transplantation tumor experiment showed that anti-human IgM antibody can significantly inhibit the volume and weight of transplanted tumor (P＜0.05).The immunohistochemistry showed that the expression levels of IgM and gp96 proteins in mouse transplanted tumors after intraperitoneal injection with anti-human IgM antibodies were significantly lower than those of the control group (P＜0.05).Conclusion The anti-human IgM anti-body could effectively inhibit the proliferation of HNE-1 cells,promote apoptosis,and arrest cell cycle.Anti-human IgM antibody could also inhibit the growth of transplanted tumor in nude mouse,which might be related to inhibition of the expressions of IgM and gp96 proteins.
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Objective To investigate the diagnostic value of serum human epididymis protein 4 (HE4) ,carbohydrate antigen 125 (CA125) ,carbohydrate antigen antigen (CA199) ,carbohydrate antigen 153 (CA153) and alpha fetoprotein (AFP) in the early di-agnosis of ovarian cancer .Methods From February 2014 to October 2016 ,117 patients with ovarian cancers who were treated in this hospital were selected ,including 69 cases of ovarian cancer and 48 cases of benign ovarian lesions ,and 70 healthy volunteers were selected as control group .The serum levels of HE4 ,CA125 ,CA199 ,CA153 and AFP were measured in all subjects . Results The positive rates of HE4 ,CA125 ,CA199 ,CA153 and AFP in the ovarian cancer group were 59 .42% ,68 .12% ,33 .33% , 46 .38% and 39 .13% ,respectively ,which were significantly higher than those in the benign ovarian lesion group and the control group (P<0 .05) .The sensitivity of CA125 in the diagnosis of ovarian cancer was 68 .11% ,the specificity was 88 .98% ,the nega-tive predictive value was 78 .33% ,the positive predictive value was 82 .68% ,Youden index was 0 .571 .The diagnostic efficiency was better than that of other tumor markers .Pathological examination revealed 34 cases of serous adenocarcinoma ,18 cases of mucinous adenocarcinoma and 17 cases of endometrioid carcinoma in 69 cases of ovarian cancer .The positive rate of serous adenocarcinoma CA125 was 85 .29% ,significantly higher than mucinous carcinoma and endometrioid carcinoma (χ2 =9 .398 ,P<0 .05) .Conclusion CA125 has a good application value in the early diagnosis of ovarian cancer ,the positive rate is higher in serous adenocarcinoma .
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Objective To investigate the diagnostic value of serum human epididymis protein 4 (HE4) ,carbohydrate antigen 125 (CA125) ,carbohydrate antigen antigen (CA199) ,carbohydrate antigen 153 (CA153) and alpha fetoprotein (AFP) in the early di-agnosis of ovarian cancer .Methods From February 2014 to October 2016 ,117 patients with ovarian cancers who were treated in this hospital were selected ,including 69 cases of ovarian cancer and 48 cases of benign ovarian lesions ,and 70 healthy volunteers were selected as control group .The serum levels of HE4 ,CA125 ,CA199 ,CA153 and AFP were measured in all subjects . Results The positive rates of HE4 ,CA125 ,CA199 ,CA153 and AFP in the ovarian cancer group were 59 .42% ,68 .12% ,33 .33% , 46 .38% and 39 .13% ,respectively ,which were significantly higher than those in the benign ovarian lesion group and the control group (P<0 .05) .The sensitivity of CA125 in the diagnosis of ovarian cancer was 68 .11% ,the specificity was 88 .98% ,the nega-tive predictive value was 78 .33% ,the positive predictive value was 82 .68% ,Youden index was 0 .571 .The diagnostic efficiency was better than that of other tumor markers .Pathological examination revealed 34 cases of serous adenocarcinoma ,18 cases of mucinous adenocarcinoma and 17 cases of endometrioid carcinoma in 69 cases of ovarian cancer .The positive rate of serous adenocarcinoma CA125 was 85 .29% ,significantly higher than mucinous carcinoma and endometrioid carcinoma (χ2 =9 .398 ,P<0 .05) .Conclusion CA125 has a good application value in the early diagnosis of ovarian cancer ,the positive rate is higher in serous adenocarcinoma .
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Melkersson-Rosenthal syndrome (MRS) is an uncommon granulomatous disease characterized by the triad of relapsing facial paralysis, orofacial swelling, and fissured tongue. Genital swelling in MRS is rarely reported. We presented the first case of complete MRS with genital swelling in a child. Biopsy examinations of both the child's lower lip and penis showed noncaseating granuloma and intralymphatic granuloma infiltration. No symptoms or signs of other systemic disease (Crohn's disease or sarcoidosis) were observed after 2 years of follow-up. Genetic screening for CARD15/NOD2 in this patient showed negative, which further confirmed the diagnosis of MRS. Eleven other cases of suspected complete or incomplete MRS with genitalia involved were reviewed. Our case emphasizes the specific clinical feature of MRS with genitalia involved, which was genetically different from Crohn's disease and could be an independent entity. Lymphatic obstruction is responsible for localized edema in MRS.
Subject(s)
Child , Humans , Male , Biopsy , Crohn Disease , Diagnosis , Edema , Facial Paralysis , Follow-Up Studies , Genetic Testing , Genitalia , Granuloma , Lip , Lymphatic Vessels , Melkersson-Rosenthal Syndrome , Penis , Tongue, FissuredABSTRACT
Melkersson-Rosenthal syndrome (MRS) is an uncommon granulomatous disease characterized by the triad of relapsing facial paralysis, orofacial swelling, and fissured tongue. Genital swelling in MRS is rarely reported. We presented the first case of complete MRS with genital swelling in a child. Biopsy examinations of both the child's lower lip and penis showed noncaseating granuloma and intralymphatic granuloma infiltration. No symptoms or signs of other systemic disease (Crohn's disease or sarcoidosis) were observed after 2 years of follow-up. Genetic screening for CARD15/NOD2 in this patient showed negative, which further confirmed the diagnosis of MRS. Eleven other cases of suspected complete or incomplete MRS with genitalia involved were reviewed. Our case emphasizes the specific clinical feature of MRS with genitalia involved, which was genetically different from Crohn's disease and could be an independent entity. Lymphatic obstruction is responsible for localized edema in MRS.
Subject(s)
Child , Humans , Male , Biopsy , Crohn Disease , Diagnosis , Edema , Facial Paralysis , Follow-Up Studies , Genetic Testing , Genitalia , Granuloma , Lip , Lymphatic Vessels , Melkersson-Rosenthal Syndrome , Penis , Tongue, FissuredABSTRACT
BACKGROUND; Authors have proposed the hypothesis that, the mechanism change may result in the mismatch between the energy production and energy consumption during the aerobic exercise, and pyruvate can be transformed into lactic acid, which may prevent the accumulation of pyruvate in cytoplasm and in the energy production of glycolysis so as to ensure the fast energy supply in zymolysis; the mechanism of this biochemical event may be the adjustment of energizing velocity via glycomechanism zymolysis.OBJECTIVE: To observe the effect of oxygen inhalation on metabolic transition, study the mechanism of metabolic transition under the lactate threshold intensity in human body and animal, and verify the result consistency between the two.DESIGN: Randomized control observation.SETTING: Department of Physical Education, Hebei Normal University; Department of Physical Education, Langfang Teachers College.PARTICIPANTS: A total of 24 male university students majoring physical education were adopted, weight (58±4) kg,height (175±6) cm, age (21 ±2) years. They were consisted of 12 Level B national athletes and12 common students.Additionally 30 SD male rats were used.METHODS: The experiment was carried out in the Laboratory of Physical and Physiological Function, Department of Physical Education in Hebei Normal University from April to June in 2006. Twenty-four students were recruited to exercise incrementally in ergometer; in addition, thirty SD rats were assigned to swim incrementally, 15 rats in each group. First, the intensities of metabolic transition were determined, then the exercise protocol was repeated on the conditions of inhaling and not inhaling oxygen. For student group, 50 W loading was incremented every 2 minutes, while the rats were added with 1% of their weights until unacceptable. Gradually incremented loading was used to transform the aerobic mechanism to anaerobic mechanism. The vein blood oxygen partial pressure, pyruvate and lactate contents were measured before and during the exercise (lactate threshold intensity) to evidence the reliability and validity of hypothesis.MAIN OUTCOME MEASURES: The vein blood oxygen partial pressure, pyruvate and lactate contents under lactate threshold intensity and oxygen inhaling supplementary.RESULTS: All 24 testees and 30 rats were involved in the result analysis. ①During the gradually incremented exercise,the lactic acid curve obtained at the end of 2-minute loading showed the difference of metabolic transition intensity and training level in accordance with individual lactic acid threshold, which was obviously lower in the trained exercisers.②Under the lactate threshold intensity, the blood lactate was not correlated to the oxygen partial pressure whether in human body or rats and whether inhaling oxygen or not [(3.61±0.56), (5.43±0.55) mmol/L; (4.46±0.86), (7.80±0.27) kPa,r =0.31, 0.31, P ＞ 0.05]; there was significant difference between the blood lactate and pyruvate contents [(1.04±0.16),(0.91±0.37) mmol/L, P ＜ 0.001]. The human body's saturation of blood oxygen was no less than 98% during the entire protocol. ③Under the repeated exercise and lactate threshold intensity, the pyruvate average value was (0.97±0.17),(1.04±0.16) mmol/L; (0.93±0.25), (0.91 ±0.37) mmol/L, respectively. There was no significant difference between the blood pyruvate before the exercise and under the lactate threshold intensity in both human body and animals (P ＞ 0.05).CONCLUSION: There is no hypoxia at the transition from aerobic to anaerobic metabolism. Oxygen inhaling supplementary has no influence on the mechanism transition; It is not easy for the pyruvate to pass the myocyte membrane, but the lactate can. The result demonstrates that the pyruvate can transform to lactate directly, which can also prevent the accumulation of pyruvate in kytoplasm.
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<p><b>OBJECTIVE</b>In order to study the relation between polymorphisms of methylenetetrahydrofolate reductase C677T (MTHFR) and susceptibility of stomach cancer (SC).</p><p><b>METHODS</b>We conducted a case-control study with 107 cases of SC and 200 population-based controls in Huaian city of Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR genotypes were detected by PCR-RFLP method.</p><p><b>RESULTS</b>(1) The frequency of MTHFR variant genotypes (C/T + T/T) among the cases (79.4%) was significantly higher than the controls (68.5%) (P = 0.041 6); the crude OR for SC was 1.78 (95% CI: 0.99 - 3.22). After adjustment for sex and age, the OR for SC was 1.89 (95% CI: 1.08 - 3.32). (2) Subjects who had MTHFR variant genotypes and having smoking habit were at a significantly higher risk of developing SC (OR = 7.72, 95% CI: 2.23 - 26.79) compared with those who had wild-type homozygotes (C/C) genotype and no smoking habit. Individuals who had variant genotypes and who had habit of frequent alcohol drinking were at an increased risk of developing SC (OR = 3.08, 95% CI: 1.30 - 7.23) compared with those with C/C genotype and low consumption of alcohol. As compared with subjects with C/C genotype and low consumption of alcohol and no smoking habit, individuals who had variant genotypes and who had habits of frequent alcohol drinking and smoking had 12.96 (95% CI: 2.76 - 70.46) folds risk developing SC.</p><p><b>CONCLUSIONS</b>These results in the present study suggested that the polymorphisms of MTHFR C677T was associated with risk of developing SC, and there was a coordinated effect between MTHFR genotypes and habits of smoking and alcohol drinking in the development of SC.</p>