ABSTRACT
This study aimed to perform a meta-analysis to determine the efficacy and safety of emricasan. Nine databases were searched for clinical trials investigating the efficacy of emricasan treatment in patients with liver cirrhosis or fibrosis. A manual search was conducted to identify the missing trials. The quality of the included studies was assessed using the revised Cochrane risk of bias tool. Efficacy of emricasan treatment was defined as a positive change in apoptosis-related parameters from baseline to the last follow-up visit. Overall, emricasan treatment is more effective in patients with liver cirrhosis or fibrosis than placebo (standardized mean difference [SMD] [95% confidence intervals (CI)]=0.28 [0.14; 0.41]). No significant change in model for end-stage liver disease (MELD) score between the emricasan and placebo groups was noted (SMD [95% CI]=0.18 [-0.01; 0.36]; p=0.058). A 50 mg dose of emricasan had the highest efficacy rate compared to placebo (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012), followed by the 5 mg dosing regimen (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012). Treatment with emricasan resulted in significant reductions in ALT (mean difference (MD) [95% CI]=-5.89 [-10.59; -1.20]; p=0.014) and caspase3/7 levels (MD [95%CI]=-1215.93 [-1238.53; -1193.33]; p<0.001), respectively. No significant increase in the rate of overall adverse events was noted (OR [95% CI]=1.52 [0.97; 2.37]; p=0.069). Treatment with emricasan is more effective in improving liver function and apoptosis parameters compared to placebo, with a well-tolerated safety profile. However, due to the poor quality of the analyzed studies, the small number of trials and patients, and the short follow-up periods, more robust trials are still warranted.
Subject(s)
End Stage Liver Disease , Fibrosis , Humans , Liver Cirrhosis/drug therapy , Pentanoic Acids , Severity of Illness IndexABSTRACT
Background: Long non-coding RNAs (lncRNAs) can remarkably regulate human malignancies in terms of the development and the progression. Previously, lncRNA LINC00847 (LINC00847) has been reported to present dysregulation in several tumors. However, the expression and function of LINC00847 in non-small cell lung cancer (NSCLC) have not been investigated. Methods: RT-qPCR was performed to determine the expressions of LINC00847 in collected tissue samples and cell lines. The clinical significance of LINC00847 was statistically analyzed. CCK-8 test, cell scratch test and trans-well test were used to evaluate the proliferation, invasion and migration abilities of NSCLC cells, respectively. The xenograft tumor model was constructed to confirm the effects of LINC00847 knockdown on NSCLC in vivo. Further, luciferase reporter assays and Western blot were performed to explore molecular mechanisms underlying the functions of LINC00847. Results: Increased expressions of LINC00847 were observed in NSCLC samples as well as cell lines. Additionally, E2F1 could be capable of directly binding to the LINC00847 promoter region, followed by promoting its expression. Clinically, LINC00847 high-expression could lead to poor prognosis of NSCLC patients. Functionally, LINC00847 knockdown noticeably repressed NSCLC cell growth and metastasis. Mechanically, miR-147a/IFITM1 axis was a downstream target of LINC00847, and silencing of miR-147a could rescue the anti-cancer effects of LINC00847 knockdown on NSCLC cell behaviors. Conclusion: Overall, up regulation of LINC00847 induced by E2F1 promoted the progression of NSCLC by modulating miR-147a/IFITM1 axis, representing a novel regulatory mechanism for NSCLC progression.
ABSTRACT
This study aimed to perform a meta-analysis to determine the efficacy and safety of emricasan. Nine databases were searched for clinical trials investigating the efficacy of emricasan treatment in patients with liver cirrhosis or fibrosis. A manual search was conducted to identify the missing trials. The quality of the included studies was assessed using the revised Cochrane risk of bias tool. Efficacy of emricasan treatment was defined as a positive change in apoptosis-related parameters from baseline to the last follow-up visit. Overall, emricasan treatment is more effective in patients with liver cirrhosis or fibrosis than placebo (standardized mean difference [SMD] [95% confidence intervals (CI)]=0.28 [0.14; 0.41]). No significant change in model for end-stage liver disease (MELD) score between the emricasan and placebo groups was noted (SMD [95% CI]=0.18 [-0.01; 0.36]; p=0.058). A 50 mg dose of emricasan had the highest efficacy rate compared to placebo (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012), followed by the 5 mg dosing regimen (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012). Treatment with emricasan resulted in significant reductions in ALT (mean difference (MD) [95% CI]=-5.89 [-10.59; -1.20]; p=0.014) and caspase3/7 levels (MD [95%CI]=-1215.93 [-1238.53; -1193.33]; p<0.001), respectively. No significant increase in the rate of overall adverse events was noted (OR [95% CI]=1.52 [0.97; 2.37]; p=0.069). Treatment with emricasan is more effective in improving liver function and apoptosis parameters compared to placebo, with a well-tolerated safety profile. However, due to the poor quality of the analyzed studies, the small number of trials and patients, and the short follow-up periods, more robust trials are still warranted.
Subject(s)
Humans , End Stage Liver Disease , Pentanoic Acids , Severity of Illness Index , Fibrosis , Liver Cirrhosis/drug therapyABSTRACT
Long noncoding RNA (OGFRP1) has been reported to be involved in the progression of non-small cell lung cancer (NSCLC). However, the expression pattern, functions and molecular mechanisms of OGFRP1 in NSCLC remains unclear. In the present study, we found that OGFRP1 expression was significantly up-regulated in both NSCLC tissues and cell lines, and the upregulation of OGFRP1 expression is a powerful predictor of advanced clinical stage, lymph nodes metastasis and poor prognosis for NSCLC patients. Loss-of-function assay indicated that knockdown of OGFRP1 inhibited proliferation, migration and invasion, and induced apoptosis in vitro. Mechanistically, OGFRP1 could directly bind to miR-124-3p and effectively act as a competing endogenous RNA (ceRNA) for miR-124-3p to promote the expression of the target gene LYPD3. Taken together, OGFRP1 contributed to progression of NSCLC at least partly through upregulating LYPD3 expression by sponging miR-124-3p, indicating that OGFRP1 may be a novel prognostic biomarker and therapeutic target in NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cell Adhesion Molecules/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , RNA, Long Noncoding/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Cell Adhesion Molecules/metabolism , Cell Line, Tumor , Disease Progression , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Lung Neoplasms/pathology , MicroRNAs/metabolism , PrognosisABSTRACT
Varicocele is commonly associated with male infertility because it impairs normal sperm morphology and activity. Polyunsaturated fatty acids (PUFA) are important determinants of sperm cell structure and function, but their relationship with varicocele remains unclear. The aim of the present study was to investigate the PUFA composition in spermatozoa of infertile men with varicocele and to evaluate the potential relationship between PUFA and varicocele. This case control study recruited 92 infertile men with varicocele, 99 infertile men without varicocele and 95 fertile male control subjects. Semen morphology and activity parameters were assessed and seminal plasma 8-hydroxy-2-deoxyguanosine (8-OHdG) content was determined by ELISA. Sperm concentrations of omega-3 and omega-6 fatty acids were measured by gas chromatography. Infertile men with varicocele had lower concentrations of omega-3 PUFA, higher omega-6:omega-3 PUFA ratios and greater oxidative DNA damage in spermatozoa compared with infertile men without varicocele and normal subjects. The degree of varicocele and DNA damage was associated with decreased omega-3 PUFA concentrations and semen quality in infertile men with varicocele. The findings suggest that omega-3 PUFA deficiency could be implicated in varicocele-associated infertility, and highlight the need for intervention trials to test the usefulness of omega-3 supplementation in reducing sperm abnormalities in infertile men with varicocele.
Subject(s)
DNA Damage , Fatty Acids, Omega-3/analysis , Fertility , Infertility, Male/metabolism , Oxidative Stress , Spermatozoa/chemistry , Varicocele/metabolism , 8-Hydroxy-2'-Deoxyguanosine , Adult , Case-Control Studies , Chromatography, Gas , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/analysis , Down-Regulation , Enzyme-Linked Immunosorbent Assay , Fatty Acids, Omega-6/analysis , Humans , Infertility, Male/diagnosis , Infertility, Male/pathology , Infertility, Male/physiopathology , Male , Semen/chemistry , Sperm Count , Sperm Motility , Spermatozoa/pathology , Varicocele/diagnosis , Varicocele/pathology , Varicocele/physiopathologyABSTRACT
Semen samples were collected from 1213 fertile men whose partners had a time-to-pregnancy (TTP) ≤12 months in Guangdong Province in Southern China, and semen parameters including semen volume, sperm concentration, total counts, motility, and morphology were evaluated according to the World Health Organization (WHO) 2010 guideline. All semen parameters analyzed were normal in ~62.2% of the total samples, whereas ~37.8% showed at least one of the semen parameters below normal threshold values. The fifth centiles (with 95% confidence intervals) were 1.3 (1.2-1.5) ml for semen volume, 20 × 10 6 (18×10 6 -20×10 6 ) ml-1 for sperm concentration, 40 × 10 6 (38×10 6 -44×10 6 ) per ejaculate for total sperm counts, 48% (47%-53%) for vitality, 39% (36%-43%) for total motility, 25% (23%-27%) for sperm progressive motility, 5.0% (4%-5%) for normal morphology. The pH values ranged from 7.2 to 8.0 with the mean ± standard deviation at 7.32 ± 0.17. No effects of age and body mass index were found on semen parameters. Occupation, smoking and alcohol abuse, varicocele appeared to decrease semen quality. Sperm concentration, but not sperm morphology, is positively correlated with TTP, whereas vitality is negatively correlated with TTP. Our study provides the latest reference values for the semen parameters of Chinese fertile men in Guangdong Province, which are close to those described in the new WHO guidelines (5 th Edition).
Subject(s)
Fertility/physiology , Semen Analysis/methods , Semen/physiology , Spermatozoa/physiology , Adult , China , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Reference Values , Retrospective Studies , Sperm Count , Sperm Motility/physiologyABSTRACT
OBJECTIVE: To study the semen quality of confirmed fertile men with the time to pregnancy (TTP) of 12 months or less, and analyze the correlation of semen parameters with TTP. METHODS: We recruited 1 152 men aged 18 -50 years and with TTP of 12 months. We used questionnaire investigation, physical examination and semen analysis, calculated the normal reference ranges of semen parameters, and analyzed the effects of TTP and other biological characteristics on semen quality. RESULTS: Seminal examinations showed that the semen volume was 1.5 ml, sperm concentration 17 million per ml, total sperm number 39 million per ejaculate, total sperm motility 41%, progressive sperm motility 33%, normal sperm morphology 5.0%, sperm vitality 53%, and total number of progressively motile sperm 17 million per ejaculate in the 1 152 subjects. In comparison, the total number of progressively motile sperm was significantly smaller in those aged > or = 35 years (P < 0.01), morphologically normal sperm were markedly less in those with BMI > 25.0 (P < 0.01), and sperm concentration, total number of sperm, morphologically normal sperm rate and total number of progressively motile sperm were remarkably lower in those with BMI < 18. 5 (P < 0.05). Cigarette smoking significantly reduced the sperm volume (P < 0.01), and drinking (> 10 g per week) decreased the sperm volume and the total numbers of sperm, morphologically normal sperm and progressively motile perm (P < 0.05). TTP was negatively correlated with sperm concentration, total number of sperm and total number of progressively motile sperm (P < 0.01). The subjects with sexual abstinence of 5 -7 days showed markedly higher sperm concentration, total number of sperm and total number of progressively motile sperm than others (P < 0.01). CONCLUSION: In normal fertile men, the fifth centile of semen parameters is close to the WHO normal reference range, TTP is negatively correlated with semen quality, and age, BMI and lifestyle may affect some of the semen parameters.
Subject(s)
Semen Analysis , Sperm Count , Adolescent , Adult , Female , Humans , Male , Middle Aged , Pregnancy , Reference Values , Young AdultABSTRACT
OBJECTIVE: To study the incidence of the chromosome abnormalities and Y chromosome microdeletions in Chinese patients with azoospermia and cryptozoospermia. METHODS: Conventional chromosomal karyotyping was used to analyze the chromosome abnormalities. Genomic DNA was extracted from peripheral blood samples and multiplex polymerase chain reactions (PCR) analyses were performed using specific primers to confirm the presence or absence of Y chromosome microdeletions. A total of 997 patients with azoospermia and cryptozoospermia were enrolled in the study. RESULTS: The incidence of chromosome abnormalities in the patient with azoospermia and cryptozoospermia was 28.4%. The major abnormal karyotypes included 47,XXY, 46,XY (Y>G), 46,XX, chimera and translocations. The incidence of the Y chromosome microdeletions was 17.4%. They were mainly found in the karyotypes of 46,XY and 46,XY (Y>G). CONCLUSION: Chromosome abnormalities were the most common hereditary causes of the patients with azoospermia and cryptozoospermia. The incidence of Y chromosome microdeletion was higher in the patients with karyotype of 46,XY and 46,XY (Y>G). Therefore, detection of the AZF microdeletion in these patients is helpful to determine the etiology and avoid the unnecessary treatment and vertical transmission of the genetic defects.
Subject(s)
Azoospermia/genetics , Chromosome Deletion , Chromosomes, Human, Y/genetics , Infertility, Male/genetics , Oligospermia/genetics , Female , Genetic Testing , Humans , Male , Middle Aged , Seminal Plasma Proteins/geneticsABSTRACT
OBJECTIVE: To study the relationship between the testis volume and types of spermatogenic cells derived from testicular biopsy in patients with azoospermia or cryptozoospermia. METHODS: We collected testicular pathological biopsies from 492 infertile patients with azoospermia or cryptozoospermia reported in our hospital, classified them according to the testicular histological classification methods in WHO Manual for Standardized Investigation, Diagnosis and Management of the Infertile Male, and analyzed the relationship of the testis volume with the results of semen analyses and testicular histology. RESULTS: Of the 492 cases, 90.5% (445/492) were azoospermia and 9.5% (47/492) cryptozoospermia; mature spermatozoa were present in the seminiferous tubules in 17.9% (88/492) but absent in 42.9% (211/492), and Sertoli cell-only syndrome indicated in 39.2% (193/492); the testis volume was < or = 10 ml in 38.6% (190/492) and < or = 5 ml in 7.9% (39/492). Cryptozoospermia was detected in 14.8% (13/88) of those with mature spermatozoa in the seminiferous tubules, in 11.4% (24/211) of those without, and in 5.2% (10/193) of those with Sertoli cell-only syndrome, with a significantly lower rate in the latter group than in the former two (P < 0.05). CONCLUSION: Spermatogenesis of the testis may be focal and difficult to be completely reflected by a single testicular biopsy, and it may exist even if the testis volume is significantly below the reference value. The indications for testicular biopsy should not be improperly expanded. The WHO testicular histological classification methods have provided a convenient and effective guidance for further clinical examinations and establishment of a protocol.
Subject(s)
Azoospermia/pathology , Spermatozoa/pathology , Testis/pathology , Adult , Biopsy , Humans , Male , Middle Aged , Semen Analysis , SpermatogenesisABSTRACT
OBJECTIVE: To assess the role of Zhongji (CV 3) in treatment of benign hyperplasia of prostate. METHODS: Multi-central, randomized, controlled, single bland clinical method was adopted, and 276 cases were divided into an electroacupuncture (EA) group and a medication group, 138 cases in each group. The EA group were treated with EA at Zhongji (CV 3) and the medication group with oral administration of Qianliekang tablets. After treatment of 1 course, their therapeutic effects and changes of international prostate symptom (I-PSS) cumulative score, life quality index (L) cumulative score, nocturia times, urine stream state, lower abdominal symptom, maximal volume of urine flow, residual urine volume, prostatic volume, etc. Were assessed in the two groups. RESULTS: The total effective rate was 96.4% in the EA group and 86.2% in the medication group, the former being better than the latter (P<0. 01); the two groups were effective in improvement of international prostate symptom (I-PSS) cumulative score, life quality index (L) cumulative score, nocturia times, urine stream state, hypogastrium symptom, maximal volume of urine flow, residual urine volume, prostatic volume, etc. with the former better than the latter. CONCLUSION: Acupuncture at Zhongji (CV 3) has a significant therapeutic effect for treatment of benign hyperplasia of prostate.
Subject(s)
Acupuncture Points , Electroacupuncture/methods , Prostatic Hyperplasia/therapy , Aged , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: To explore the correlation between the biological characteristics of volunteer donors and sperm parameters. METHODS: Sperm parameters were analyzed for 778 primary volunteer donors by CASA system with standard methods recommended by WHO including sperm concentration, motility rate, VCL, VSL, ALH, LIN, STR and BCF, and their biological characteristics were recorded. RESULTS: Of all the volunteer donors, students accounted for more than a third, 89.2 percent were under the age of 35 years, 71.6 percent between 166 and 175 cm in height, 91.7 percent of normal weight and 77.1 percent with college education. The median sperm concentration and motility rate were 107.00 x 10(6)/ml and 75 percent respectively. Age was weakly correlated with such semen indexes as concentration (r = 0.210, P = 0.000) , motility rate (r = 0.213, P = 0.000), volume (r = 0.165, P = 0.002), VAP (r = 0.259, P = 0.000), VSL (r = 0.281, P = 0.000), VCL (r = 0.190, P = 0.000), BCF (r = 0.243, P = 0.000) and LIN (r = 0.192, P = 0.000). The semen indexes of the 26-35 age group were a little better than those of the 20-25. Height showed no correlation to semen indexes. Education and occupation were somewhat related with other sperm parameters (P < 0.01) than ALH (P = 0.695/0.886). CONCLUSION: Age, occupation and education bear some correlation with sperm parameters except ALH, while height has none with any of them.
Subject(s)
Semen , Spermatozoa/physiology , Tissue Donors/statistics & numerical data , Adult , Age Factors , Humans , Image Processing, Computer-Assisted/methods , Male , Occupations , Semen/cytology , Sperm Count , Sperm Motility/physiology , StudentsABSTRACT
OBJECTIVE: To explore the role of Ca(2+) in the damage to myocardial mitochondrial respiratory function in the early stage after severe burns. METHODS: An experimental model of 30%TBSA full-thickness skin scalding was reproduced in rats. Myocardial mitochondria were isolated from control and burned rats in the 1st, 3rd, 6th, 12th and 24th hour post-burn. The mitochondrial respiratory function, contents of mitochondrial calcium ([Ca(2+)](m)), activities of mtPLA(2), mtNOS, F(0)F(1)-ATPase and cytochrome c oxidase were determined. RESULTS: (1) At the 1st hour post-burn, [Ca(2+)](m) was increased significantly and the myocardial mitochondrial respiratory function was significantly reinforced. At the same time, mitochondrial respiratory control rate (RCR) was elevated and positively correlated with [Ca(2+)](m) (r=0.8415, P<0.01). At the 3rd, 6th, 12th and 24th hour post-burn, [Ca(2+)](m) increased further to a higher level, however, the mitochondrial respiratory function was decreased from the peak value at 6h, and RCR was negatively correlated with [Ca(2+)](m). (2) The activities of mtNOS and mtPLA(2) were higher significantly at the 3rd, 6th, 12th and 24th hour post-burn than that of the control. After severe burns, mtNOS and mtPLA(2) activities were both positively correlated with [Ca(2+)](m) (r=0.8945, P<0.05; r=0.9271, P<0.01, respectively). (3) The F(0)F(1)-ATPase synthetic activity increased at the 1st hour post-burn, but it decreased to 51.4, 44.9, 77.6 and 87.4% of that of the control at the 3rd, 6th, 12th and 24th hour post-burn respectively. The F(0)F(1)-ATPase hydrolytic activity decreased at the 1st hour post-burn and increased at the 3rd, however, it decreased again at the 6th, 12th and 24th hour post-burn. The activity of cytochrome c oxidase at the 3rd, 6th, 12th and 24th hour was low compared to the control. CONCLUSIONS: The changes of [Ca(2+)](m) were involved in damage to or regulation of mitochondrial respiratory function after severe burns. Appropriate increase of [Ca(2+)](m) reinforced the mitochondrial respiration at 1st hour after of burn injury, but Ca(2+) severe overload impairing F(0)F(1)-ATPase and cytochrome c oxidase directly, or, indirectly by activation of mtPLA(2) and mtNOS, might play an important role in damage to myocardial mitochondrial respiratory function at later stages after severe burns.