Colorectal cancer(CRC)is a pervasive health concern worldwide,ranking third in malignancy prevalence and second in cancer-related mortality.The primary chemotherapeutic agent for CRC is 5-fluorouracil(5-Fu).Unfortunat...Colorectal cancer(CRC)is a pervasive health concern worldwide,ranking third in malignancy prevalence and second in cancer-related mortality.The primary chemotherapeutic agent for CRC is 5-fluorouracil(5-Fu).Unfortunately,drug resistance is almost inevitable in patients,significantly reducing its efficacy.Therefore,underlying the mechanisms of 5-Fu resistance and exploring reversal strategies are crucial.展开更多
The process and regulation of cellular metabolism are extremely complex and accomplished through multiple signalling pathways that operate in parallel,and often experience significant overlap in upstream and downstrea...The process and regulation of cellular metabolism are extremely complex and accomplished through multiple signalling pathways that operate in parallel,and often experience significant overlap in upstream and downstream a signal transduction.Despite this complexity,single pathway or even single protein activations are commonly used to extrapolate broad characterizations of cellular metabolism.Furthermore,multiple routes for peptide-chain translation initiation exist,some of which may be either exclusive or overlapping depending on the state and environment of the cell.While it may be highly impractical to account for every aspect of metabolic regulation and permutation of mRNA translation,it is important to acknowledge that investigations relating to these pathways are often incomplete and not necessarily indicative of the overall metabolic status.This becomes urgent when considering the role that cellular anabolism plays in both healthy cellular functions and the aetiology of several disease's altered metabolisms.This review describes recent advances in the understanding of cellular metabolic regulation,with specific focus given to the complexity of‘downstream’mRNA translation initiation through both mTOR-dependent and mTOR-independent signallings.展开更多
This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to110 of gestation with either rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)on placental amino acid(...This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to110 of gestation with either rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)on placental amino acid(AA)transport,angiogenic gene expression,and steroid anabolism.On d 35 of gestation,32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups,each consisting of eight ewes,and were fed the following diets:A diet providing 100%of NRC’s nutrient requirements for pregnant ewes(CON);A diet providing 50%of NRC’s nutrient requirements for pregnant ewes(RES);RES diet plus 5 g/d NCG(RES+NCG);or RES diet plus 20 g/d RP-Arg(RES+ARG).On the d 110 of pregnancy,blood samples were taken from the mother,and samples were collected from type A cotyledons(COT;the fetal portions of the placenta).The levels of 17β-estradiol and progesterone in the maternal serum and both the capillary area density(CAD)and capillary surface density(CSD)in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group.The concentrations of arginine,leucine,putrescine and spermidine in type A COT were higher(P<0.05)in the RES+ARG or RES+NCG group than in the RES group.The mRNA expression levels of inducible nitric oxide synthase(iNOS)and solute carrier family 15,member 1(SLC15A1)were increased(P<0.05)while those of progesterone receptor(PGR)and fibroblast growth factor 2(FGF2)were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group.The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport,and reduces the expression of angiogenic growth factor genes and steroid anabolism,leading to better fetal development.展开更多
Improving the efficiency of athletic performance and reducing the likelihood of overtraining are primarily determined goals that can be achieved by the correct organization of the training process.The nature of adapta...Improving the efficiency of athletic performance and reducing the likelihood of overtraining are primarily determined goals that can be achieved by the correct organization of the training process.The nature of adaptation to physical stress is associated with the specificity,focus,and degree of biochemical and functional changes that occur during muscular work.In this study,we aimed to develop a diagnostic model for predicting metabolic processes in athletes based on standard biochemical blood analysis indicators.The study involved athletes from the track and field athletics team(men,n=42,average age was[22.55±3.68]years).Blood samples were collected in the morning at the beginning and end of the training week during the annual cycle.During the entire period,3625 laboratory parameter tests were conducted.Capillary blood sampling in athletes was conducted from the distal phalanx of the finger after overnight fasting,according to standard diagnostic procedures.To determine the predominance of anabolic or catabolic processes,equations were derived from a linear discriminant function.The discriminant function of predicting metabolic processes in athletes has a high information capacity(92.1%),as confirmed by the biochemical results of neuroendocrine system activity,which characterized the body's stage of adaptive regulatory mechanisms in response to stress factors.The classification matrix used to predict the metabolic processes based on the results of the discriminant function calculation demonstrates the statistical significance of the model(p<0.01).Consequently,an informative mathematical model was developed,which enabled the reliable and timely prediction of the prevalence of one of the metabolic activity phases in the athlete's body.The use of the developed model will also allow us to assess the nature of adaptation to specific muscular work,identify an athlete's weaknesses,forecast the success of their performance,and timely adjust both the training process and the recovery program.展开更多
Prolonged hyperglycemia conditions are a risk factor for chronic degenerative diseases such as diabetes and obesity.Testosterone is known to cause muscle hypertrophy,reduced fat mass,and increased body strength.The st...Prolonged hyperglycemia conditions are a risk factor for chronic degenerative diseases such as diabetes and obesity.Testosterone is known to cause muscle hypertrophy,reduced fat mass,and increased body strength.The study aimed to verify possible alterations and differences in the influence of testosterone on the physical performance in post-exercise conditions of young and old animals with alloxan-induced hyperglycemia.We randomly assigned 32 young Wistar rats to groups of untreated non-diabetic young,treated non-diabetic young,untreated diabetic young,and treated diabetic young rats,and 32 aged Wistar rats to groups of untreated non-diabetic elderly,treated non-diabetic elderly,untreated diabetic elderly,and treated diabetic elderly rats,with eight animals each group.The treated non-diabetic and treated diabetic groups received injections of 15 mg/kg weight Durateston^(TM).All the trained groups performed aquatic training with an overload of 5% of the body mass.Following the experiment,we anesthetized and euthanized the animals after exercise(exhaustion).Hemoglobin,erythrocytes,and hematocrit values were higher in the treated groups.The treated diabetic elderly group had the highest leukocyte and neutrophil counts compared to the untreated young groups(p<0.05).As for the lipid profile,untreated rats had the highest values.Glucose concentration was higher at rest and after exercise in the untreated diabetic groups(p<0.05).Lactate was more elevated in the untreated diabetic groups,and the testosterone-treated groups performed the longest swimming time after the maximal test(p<0.05).The use of testosterone in conjunction with physical exercise improved physical performance in water,blood glucose,and lipid profiles.展开更多
Background:There are many forms of anabolic steroids,including stanozolol(Winstrol),which are popular for their muscle-building effects but dangerous to the heart.This pre-sent work is aimed at evaluating the pharmaco...Background:There are many forms of anabolic steroids,including stanozolol(Winstrol),which are popular for their muscle-building effects but dangerous to the heart.This pre-sent work is aimed at evaluating the pharmacologica impact of allicin,a natural attribute obtained from garlic,on obstructing cardiac injury in rabbits that received stanozolol.Methods:Thirty rabbits were divided into three groups:control,stanozolol-treated,and stanozolol plus allicin.Cardiac function was assessed by measuring troponin,creatine kinase(CK),Galectin-3,and GDF-15.Oxidative stress and antioxidant markers,includ-ing malondialdehyde(MDA),glutathione,and catalase,were analyzed.Inflammatory mediators such as C-reactive protein(CRP),interleukin-6(IL-6),NF-κB,iNOS,nitric oxide(NO),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were evaluated.Lipid profile parameters,including total cholesterol,low-density lipoprotein(LDL),and high-density lipoprotein(HDL),were measured.Histopathological examina-tion assessed myocardial damage,fibrosis,and collagen deposition.Results:Stanozolol administration significantly increased cardiac damage markers,oxidative stress,and inflammatory mediators while causing dyslipidemia,characterized by elevated LDL and total cholesterol and reduced HDL.Allicin co-administration effectively countered these effects by reducing oxidative stress and inflammation,restoring antioxidant balance,and improving lipid profiles.Histopathological analysis revealed severe myocardial disor-ganization,necrosis,and fibrosis in the stanozolol group,whereas the allicin-treated group exhibited preserved myocardial structure with reduced collagen deposition.Conclusion:Allicin significantly mitigates stanozolol-induced cardiotoxicity by reduc-ing oxidative stress,inflammation,lipid dysregulation,and myocardial damage,as evidenced by biochemical and histopathological findings.These results suggest that allicin may serve as a potential therapeutic agent to counteract the cardiovascular risks associated with anabolic steroid use.展开更多
Cancer stem cells(CSCs)comprise a subpopulation of cancer cells with stem cell properties,which exhibit the characteristics of high tumorigenicity,self-renewal,and tumor initiation and are associated with the occurren...Cancer stem cells(CSCs)comprise a subpopulation of cancer cells with stem cell properties,which exhibit the characteristics of high tumorigenicity,self-renewal,and tumor initiation and are associated with the occurrence,metastasis,therapy resistance,and relapse of cancer.Compared with differentiated cells,CSCs have unique metabolic characteristics,and metabolic reprogramming contributes to the self-renewal and maintenance of stem cells.It has been reported that CSCs are highly dependent on lipid metabolism to maintain stemness and satisfy the requirements of biosynthesis and energy metabolism.In this review,we demonstrate that lipid anabolism alterations promote the survival of CSCs,including de novo lipogenesis,lipid desaturation,and cholesterol synthesis.In addition,we also emphasize the molecular mechanism underlying the relationship between lipid synthesis and stem cell survival,the signal transduction pathways involved,and the application prospect of lipid synthesis reprogramming in CSC therapy.It is demonstrated that the dependence on lipid synthesis makes targeting of lipid synthesis metabolism a promising therapeutic strategy for eliminating CSCs.Targeting key molecules in lipid synthesis will play an important role in anti-CSC therapy.展开更多
Bovine urine was centrifuged.Added the internal standard(ZER-d4 and DES-d8) into the supernate.The extract was cleaned up by two immunoaffinity columns respectively.A C8 analytical column was used and the analytes wer...Bovine urine was centrifuged.Added the internal standard(ZER-d4 and DES-d8) into the supernate.The extract was cleaned up by two immunoaffinity columns respectively.A C8 analytical column was used and the analytes were chromatographed by acetonitrile-water(70:30,v/v).With HPLC-MS/MS,data acquisition was achieved by using atmospheric pressure chemical ionization (APCI) in negative scan mode and multiple reaction monitoring (MRM) determination mode.Quantification was made by internal standarad method.The limits of determination of DES and DEN are 0.05 ng·g-1,the recovery level was 80 %-106% between 0.5 and 10 ng·g-1.The limits of determination of HEX and ZER are 0.025 ng·g-1,the recovery level was 83%-104% between 0.25 and 5 ng·g-1.展开更多
Vertebral and nonvertebral fractures prevention is the main goal for osteoporosis therapy by inhibiting bone resorption and/or stimulating bone formation.Antiresorptive drugs decrease the activation frequency,thereby ...Vertebral and nonvertebral fractures prevention is the main goal for osteoporosis therapy by inhibiting bone resorption and/or stimulating bone formation.Antiresorptive drugs decrease the activation frequency,thereby determining a secondary decrease in bone formation rate and a low bone turnover.Bisphosphonates are today’s mainstay among antiresorptive treatment of osteoporosis.Also,oral selective estrogen receptor modulators and recently denosumab have a negative effect on bone turnover.Agents active on bone formation are considered a better perspective in the treatment of severe osteoporosis.Recombinant-human parathyroid hormone(PTH)has showed to increase bone formation and significantly decrease vertebral fractures in severe patients,but with a modest effect on nonvertebral fractures.The study of Wnt signaling pathway,that induces prevalently an osteoblastic activity,opens large possibilities to antagonists of Wnt-inhibitors,such as sclerostin antibodies and dickkopf-1 antagonists,with potential effects not only on trabecular bone but also on cortical bone.展开更多
A gas chromatography-mass spectrometry(GC-MS)method to determine eight anabolic steroids(diethylstilbestrol,methyltestosterone,norethindrone,17α-ethynylestradiol,estradiol,6α-methyl-17α-hydroxy-progesterone,estradi...A gas chromatography-mass spectrometry(GC-MS)method to determine eight anabolic steroids(diethylstilbestrol,methyltestosterone,norethindrone,17α-ethynylestradiol,estradiol,6α-methyl-17α-hydroxy-progesterone,estradiol benzoate,and chlormadinone acetate)was developed.Muscle samples were extracted with liquid-liquid extraction and clean-up was performed in two steps,the extracts obtained were derivatized with heptafluorbutyric(HBF)anhydride and analyzed by GC-MS.In the above method,the linear scope was 2.5-50μg kg^-1.The range of the recoveries was 78.5-148%for diethylstilbestrol,70.8-109%for methyltestosterone,69.8-87.2%for norethindrone,67.7-120%for 17α-ethynylestradiol,82.8-103%for estradiol,70.3-99.2%for 6α-methyl-17α-hydroxy-progesterone,73.0-104%for estradiol benzoate,and 72.9-91.8%for chlormadinone acetate.The range of the coefficients of variation within batches was 0.4-12%;the range of the coefficients of variation between batches was 6.4-11%.The limit of detections and the detection capability were 0.99 and 3.30μg kg^-1 for diethylstilbestrol,1.05 and 3.50μg kg^-1 for methyltestosterone,1.19 and 3.97μg kg^-1 for norethindrone,0.94 and 3.13μg kg^-1 for 17α-ethynylestradiol,1.45 and 4.83μg kg^-1 for estradiol,1.56 and 5.20μg kg^-1 for 6α-methyl-17α-hydroxy-progesterone,1.92 and 6.40μg kg^-1 for estradiol benzoate,and 2.41 and 8.03μg kg^-1 for chlormadinone acetate,respectively.These results showed that the method was widely available,accurate,and sensitive.展开更多
The use of testosterone replacement therapy （TRT） for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgeni...The use of testosterone replacement therapy （TRT） for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids （AAS） within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal （HPG） axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.展开更多
We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor （AR）-regulated genes in in vitro and in vivo models. The expression of the my...We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor （AR）-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity （AR△ZF2） versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR△ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7, p57Kip2, IEf2 and calcineurin Aa, was increased in AR△ZF2 muscle, and the expression of all but p57kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.展开更多
Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroid...Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re- growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.展开更多
A highly sensitive method was developed for the simultaneous determination of 8 steroid hormones in high-fat fish tissues using ultra high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The 8 s...A highly sensitive method was developed for the simultaneous determination of 8 steroid hormones in high-fat fish tissues using ultra high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The 8 steroid hormones were extracted from the tissues with diethyl ether.Differing from other common purification methods,the extract solutions were cleaned by gel permeation chromatography(GPC) using ethyl acetate-cyclohexane solution(1:1,v/v) as the mobile phase.The separation of target compounds was carried out by a BEH C18 column and a gradient elution consisting of acetonitrile and 0.2% aqueous formic acid(v/v).The compounds were detected under the multiple reaction monitoring(MRM) mode and quantified with external standard method.This method was validated with respect to linearity,specificity,accuracy and precision.A linearity with correlation coefficient larger than 0.995 was achieved in the range of 0.5 to 50 ng m L^(-1).The average recoveries at the spiked levels of 1.0,5.0,and 10.0 μg kg^(–1) varied between 81.7% and 90.8%,with the relative standard deviations(n=5) ranged from 3.50% to 10.0%.The limit of quantification(LOQ) for 8 steroid hormones ranged from 0.2 to 1.5 μg kg^(-1).It was concluded that this method can be successfully applied for the determination of 8 steroid hormones in complicated matrices including high-fat fish tissues.展开更多
Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human ...Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombi- nant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH＇ s rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span （24-36 hours） from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial. However, work with different approaches to develop an alternative, reliable test is ongoing.展开更多
The hypoxia inducible factors （Hifs） are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary f...The hypoxia inducible factors （Hifs） are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone （PTH）. Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of β-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.展开更多
In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The p...In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate(DMMIC)was used to label the amino group of metabolites,and a reductant of dithiothreitol(DTT)was employed to stabilize the thiol group.By combining DMMIC derivatization with LC-MS,it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples,which had good linearity(R^(2)=0.99810.9999),precision(interday precision of 1.6%e19.0%and intraday precision of 1.4%e19.8%)and accuracy(83.4%-115.7%).Moreover,the recovery assessments in tissues(82.5%e107.3%)and in cells(98.1%e118.9%)with GSH-^(13)C2,^(15)N,and Cys-^(15)N demonstrated the reliability of the method in detecting tissues and cells.Following a methodological evaluation,the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma(ESCC)and the effect of p-hydroxycinnamaldehyde(CMSP)on the GAP in KYSE150 esophageal cancer cells.The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes,which can contribute to research on drugs and diseases.展开更多
Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type Ⅱ fractures are the most common fracture pattern in elderly patients. Treatment(rigid and non-rigid im...Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type Ⅱ fractures are the most common fracture pattern in elderly patients. Treatment(rigid and non-rigid immobilization, anterior screw fixation of the odontoid and posterior C1-C2 fusion) remains controversial and represents a unique challenge for the treating surgeon. The aims of treatment in the elderly is to quickly restore pre-injury function while decreasing morbidity and mortality associated with inactivity, immobilization with rigid collar and prolonged hospitalization. Conservative treatment of type Ⅱ odontoid fractures is associated with relatively high rates of non-union and in a few cases delayed instability. Options for treatment of symptomatic non-unions include surgical fixation or prolonged rigid immobilization. In this report we present the case of a 73-year-old woman with post-traumatic odontoid nonunion successfully treated with Teriparatide systemic anabolic therapy. Complete fusion and resolution of the symptoms was achieved 12 wk after the onset of the treatment. Several animal and clinical studies have confirmed the potential role of Teriparatide in enhancing fracture healing. Our case suggests that Teriparatide may have a role in improving fusion rates of C2 fractures in elderly patients.展开更多
Purpose： To evaluate the efficacy and safety of the glycoside fraction of fenugreek （Trigonellafoenum-graecum） seeds （Fenu-FG） on physiologi- cal parameters related to muscle anabolism, androgenic hormones, and b...Purpose： To evaluate the efficacy and safety of the glycoside fraction of fenugreek （Trigonellafoenum-graecum） seeds （Fenu-FG） on physiologi- cal parameters related to muscle anabolism, androgenic hormones, and body fat in healthy male subjects during an 8-week resistance training program using a prospective, randomized, double-blind, placebo controlled design. Methods： Sixty healthy male subjects were randomized to ingest capsules of Fenu-FG （1 capsule of 300 rag, twice per day） or the matching placebo at a 1：1 ratio. The subjects participated in a supervised 4-day per week resistance-training program for 8 weeks. The outcome measurements were recorded at recruitment （baseline） and at the end of the treatment （8 weeks）. The efficacy outcome included serum testosterone （total and free） levels, muscle strength and repetitions to failure, metabolic markers for anabolic activity （serum creatinine and blood urea nitrogen）, and % body fat. The standard safety measurements such as adverse events monitoring, vital signs, hematology, biochemistry, and urinalysis were performed. Results： Fenu-FG supplementation demonstrated significant anabolic and androgenic activity as compared with the placebo. Fenu-FG treated subjects showed significant improvements in body fat without a reduction in muscle strength or repetitions to failure. The Fenu-FG supplemen- tation was found to be safe and well-tolerated. Conclusion： Fenu-FG supplementation showed beneficial effects in male subjects during resistance training without any clinical side effects.展开更多
Aim： To investigate the reversibility of the effect of nandrolone decanoate （ND） on sperm parameters after discontinuing the drug. Methods： Three groups of rats received peanut oil （control）, low and high doses ...Aim： To investigate the reversibility of the effect of nandrolone decanoate （ND） on sperm parameters after discontinuing the drug. Methods： Three groups of rats received peanut oil （control）, low and high doses of ND for 14 weeks, respectively. Each group was divided into subgroups A and B, in which rats were killed 14 and 28 weeks after initiating the injection, respectively. Results： Sperm count and motile sperm fraction were decreased in the subgroups A and B that received low and high doses of ND in comparison with the controls A and B, respectively. The sperm count and motile sperm fraction increased in the subgroups B that received low and high doses of ND in comparison with their corresponding subgroups A. The number of normal morphology sperm was decreased significantly in subgroups A receiving low and high doses of ND in comparison with the control subgroup A. However, this parameter was not decreased in subgroups B receiving low and high doses in comparison with the control subgroup B. The normal sperm morphology did not show any significant differences in the subgroups B in comparison with their corresponding subgroups A. Conclusion： The 14-week injection of low and high doses of ND decreases sperm quality and quantity in rats. These parameters were improved after discontinuing ND, but not recovered completely even when they are left untreated for 14 weeks.展开更多
基金National Natural Science Foundation of China(Grant No.:82274115)Top Talent Support Program for Young and Middle-aged People of Wuxi Health Committee,China(Grant Nos.:BJ2023042,HB2023060)+1 种基金Wuxi Medical Key Discipline,China(Grant No.:ZDXK2021002)Associate Professor Kaisa Cui(Affiliated Hospital of Jiangnan University,China)for his kind assistance in data processing.
文摘Colorectal cancer(CRC)is a pervasive health concern worldwide,ranking third in malignancy prevalence and second in cancer-related mortality.The primary chemotherapeutic agent for CRC is 5-fluorouracil(5-Fu).Unfortunately,drug resistance is almost inevitable in patients,significantly reducing its efficacy.Therefore,underlying the mechanisms of 5-Fu resistance and exploring reversal strategies are crucial.
文摘The process and regulation of cellular metabolism are extremely complex and accomplished through multiple signalling pathways that operate in parallel,and often experience significant overlap in upstream and downstream a signal transduction.Despite this complexity,single pathway or even single protein activations are commonly used to extrapolate broad characterizations of cellular metabolism.Furthermore,multiple routes for peptide-chain translation initiation exist,some of which may be either exclusive or overlapping depending on the state and environment of the cell.While it may be highly impractical to account for every aspect of metabolic regulation and permutation of mRNA translation,it is important to acknowledge that investigations relating to these pathways are often incomplete and not necessarily indicative of the overall metabolic status.This becomes urgent when considering the role that cellular anabolism plays in both healthy cellular functions and the aetiology of several disease's altered metabolisms.This review describes recent advances in the understanding of cellular metabolic regulation,with specific focus given to the complexity of‘downstream’mRNA translation initiation through both mTOR-dependent and mTOR-independent signallings.
基金The research was supported by the fund for the Top Talents Award Plan of Yangzhou University(2020)the Cyanine Project of Yangzhou University(2020).
文摘This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to110 of gestation with either rumen-protected L-arginine(RP-Arg)or N-carbamylglutamate(NCG)on placental amino acid(AA)transport,angiogenic gene expression,and steroid anabolism.On d 35 of gestation,32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups,each consisting of eight ewes,and were fed the following diets:A diet providing 100%of NRC’s nutrient requirements for pregnant ewes(CON);A diet providing 50%of NRC’s nutrient requirements for pregnant ewes(RES);RES diet plus 5 g/d NCG(RES+NCG);or RES diet plus 20 g/d RP-Arg(RES+ARG).On the d 110 of pregnancy,blood samples were taken from the mother,and samples were collected from type A cotyledons(COT;the fetal portions of the placenta).The levels of 17β-estradiol and progesterone in the maternal serum and both the capillary area density(CAD)and capillary surface density(CSD)in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group.The concentrations of arginine,leucine,putrescine and spermidine in type A COT were higher(P<0.05)in the RES+ARG or RES+NCG group than in the RES group.The mRNA expression levels of inducible nitric oxide synthase(iNOS)and solute carrier family 15,member 1(SLC15A1)were increased(P<0.05)while those of progesterone receptor(PGR)and fibroblast growth factor 2(FGF2)were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group.The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport,and reduces the expression of angiogenic growth factor genes and steroid anabolism,leading to better fetal development.
基金financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers‘Digital Biodesign and Personalized Healthcare’No 75-15-2022-305.
文摘Improving the efficiency of athletic performance and reducing the likelihood of overtraining are primarily determined goals that can be achieved by the correct organization of the training process.The nature of adaptation to physical stress is associated with the specificity,focus,and degree of biochemical and functional changes that occur during muscular work.In this study,we aimed to develop a diagnostic model for predicting metabolic processes in athletes based on standard biochemical blood analysis indicators.The study involved athletes from the track and field athletics team(men,n=42,average age was[22.55±3.68]years).Blood samples were collected in the morning at the beginning and end of the training week during the annual cycle.During the entire period,3625 laboratory parameter tests were conducted.Capillary blood sampling in athletes was conducted from the distal phalanx of the finger after overnight fasting,according to standard diagnostic procedures.To determine the predominance of anabolic or catabolic processes,equations were derived from a linear discriminant function.The discriminant function of predicting metabolic processes in athletes has a high information capacity(92.1%),as confirmed by the biochemical results of neuroendocrine system activity,which characterized the body's stage of adaptive regulatory mechanisms in response to stress factors.The classification matrix used to predict the metabolic processes based on the results of the discriminant function calculation demonstrates the statistical significance of the model(p<0.01).Consequently,an informative mathematical model was developed,which enabled the reliable and timely prediction of the prevalence of one of the metabolic activity phases in the athlete's body.The use of the developed model will also allow us to assess the nature of adaptation to specific muscular work,identify an athlete's weaknesses,forecast the success of their performance,and timely adjust both the training process and the recovery program.
文摘Prolonged hyperglycemia conditions are a risk factor for chronic degenerative diseases such as diabetes and obesity.Testosterone is known to cause muscle hypertrophy,reduced fat mass,and increased body strength.The study aimed to verify possible alterations and differences in the influence of testosterone on the physical performance in post-exercise conditions of young and old animals with alloxan-induced hyperglycemia.We randomly assigned 32 young Wistar rats to groups of untreated non-diabetic young,treated non-diabetic young,untreated diabetic young,and treated diabetic young rats,and 32 aged Wistar rats to groups of untreated non-diabetic elderly,treated non-diabetic elderly,untreated diabetic elderly,and treated diabetic elderly rats,with eight animals each group.The treated non-diabetic and treated diabetic groups received injections of 15 mg/kg weight Durateston^(TM).All the trained groups performed aquatic training with an overload of 5% of the body mass.Following the experiment,we anesthetized and euthanized the animals after exercise(exhaustion).Hemoglobin,erythrocytes,and hematocrit values were higher in the treated groups.The treated diabetic elderly group had the highest leukocyte and neutrophil counts compared to the untreated young groups(p<0.05).As for the lipid profile,untreated rats had the highest values.Glucose concentration was higher at rest and after exercise in the untreated diabetic groups(p<0.05).Lactate was more elevated in the untreated diabetic groups,and the testosterone-treated groups performed the longest swimming time after the maximal test(p<0.05).The use of testosterone in conjunction with physical exercise improved physical performance in water,blood glucose,and lipid profiles.
基金the College of Pharmacy, Mustansiriyah University, for providing the necessary facilities and support to carry out this research.
文摘Background:There are many forms of anabolic steroids,including stanozolol(Winstrol),which are popular for their muscle-building effects but dangerous to the heart.This pre-sent work is aimed at evaluating the pharmacologica impact of allicin,a natural attribute obtained from garlic,on obstructing cardiac injury in rabbits that received stanozolol.Methods:Thirty rabbits were divided into three groups:control,stanozolol-treated,and stanozolol plus allicin.Cardiac function was assessed by measuring troponin,creatine kinase(CK),Galectin-3,and GDF-15.Oxidative stress and antioxidant markers,includ-ing malondialdehyde(MDA),glutathione,and catalase,were analyzed.Inflammatory mediators such as C-reactive protein(CRP),interleukin-6(IL-6),NF-κB,iNOS,nitric oxide(NO),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were evaluated.Lipid profile parameters,including total cholesterol,low-density lipoprotein(LDL),and high-density lipoprotein(HDL),were measured.Histopathological examina-tion assessed myocardial damage,fibrosis,and collagen deposition.Results:Stanozolol administration significantly increased cardiac damage markers,oxidative stress,and inflammatory mediators while causing dyslipidemia,characterized by elevated LDL and total cholesterol and reduced HDL.Allicin co-administration effectively countered these effects by reducing oxidative stress and inflammation,restoring antioxidant balance,and improving lipid profiles.Histopathological analysis revealed severe myocardial disor-ganization,necrosis,and fibrosis in the stanozolol group,whereas the allicin-treated group exhibited preserved myocardial structure with reduced collagen deposition.Conclusion:Allicin significantly mitigates stanozolol-induced cardiotoxicity by reduc-ing oxidative stress,inflammation,lipid dysregulation,and myocardial damage,as evidenced by biochemical and histopathological findings.These results suggest that allicin may serve as a potential therapeutic agent to counteract the cardiovascular risks associated with anabolic steroid use.
基金Supported by the National Natural Science Foundation of China,No.82001044 and No.81630025the China Postdoctoral Science Foundation,No.2020M673019+1 种基金the Guangdong Basic and Applied Basic Research Foundation,No.2019A1515110071the Natural Science Foundation of Guangdong Province,No.2017A030311033.
文摘Cancer stem cells(CSCs)comprise a subpopulation of cancer cells with stem cell properties,which exhibit the characteristics of high tumorigenicity,self-renewal,and tumor initiation and are associated with the occurrence,metastasis,therapy resistance,and relapse of cancer.Compared with differentiated cells,CSCs have unique metabolic characteristics,and metabolic reprogramming contributes to the self-renewal and maintenance of stem cells.It has been reported that CSCs are highly dependent on lipid metabolism to maintain stemness and satisfy the requirements of biosynthesis and energy metabolism.In this review,we demonstrate that lipid anabolism alterations promote the survival of CSCs,including de novo lipogenesis,lipid desaturation,and cholesterol synthesis.In addition,we also emphasize the molecular mechanism underlying the relationship between lipid synthesis and stem cell survival,the signal transduction pathways involved,and the application prospect of lipid synthesis reprogramming in CSC therapy.It is demonstrated that the dependence on lipid synthesis makes targeting of lipid synthesis metabolism a promising therapeutic strategy for eliminating CSCs.Targeting key molecules in lipid synthesis will play an important role in anti-CSC therapy.
文摘Bovine urine was centrifuged.Added the internal standard(ZER-d4 and DES-d8) into the supernate.The extract was cleaned up by two immunoaffinity columns respectively.A C8 analytical column was used and the analytes were chromatographed by acetonitrile-water(70:30,v/v).With HPLC-MS/MS,data acquisition was achieved by using atmospheric pressure chemical ionization (APCI) in negative scan mode and multiple reaction monitoring (MRM) determination mode.Quantification was made by internal standarad method.The limits of determination of DES and DEN are 0.05 ng·g-1,the recovery level was 80 %-106% between 0.5 and 10 ng·g-1.The limits of determination of HEX and ZER are 0.025 ng·g-1,the recovery level was 83%-104% between 0.25 and 5 ng·g-1.
文摘Vertebral and nonvertebral fractures prevention is the main goal for osteoporosis therapy by inhibiting bone resorption and/or stimulating bone formation.Antiresorptive drugs decrease the activation frequency,thereby determining a secondary decrease in bone formation rate and a low bone turnover.Bisphosphonates are today’s mainstay among antiresorptive treatment of osteoporosis.Also,oral selective estrogen receptor modulators and recently denosumab have a negative effect on bone turnover.Agents active on bone formation are considered a better perspective in the treatment of severe osteoporosis.Recombinant-human parathyroid hormone(PTH)has showed to increase bone formation and significantly decrease vertebral fractures in severe patients,but with a modest effect on nonvertebral fractures.The study of Wnt signaling pathway,that induces prevalently an osteoblastic activity,opens large possibilities to antagonists of Wnt-inhibitors,such as sclerostin antibodies and dickkopf-1 antagonists,with potential effects not only on trabecular bone but also on cortical bone.
基金supposed by the Projects of Agricultural Standards for Veterinary Drug Residues,China
文摘A gas chromatography-mass spectrometry(GC-MS)method to determine eight anabolic steroids(diethylstilbestrol,methyltestosterone,norethindrone,17α-ethynylestradiol,estradiol,6α-methyl-17α-hydroxy-progesterone,estradiol benzoate,and chlormadinone acetate)was developed.Muscle samples were extracted with liquid-liquid extraction and clean-up was performed in two steps,the extracts obtained were derivatized with heptafluorbutyric(HBF)anhydride and analyzed by GC-MS.In the above method,the linear scope was 2.5-50μg kg^-1.The range of the recoveries was 78.5-148%for diethylstilbestrol,70.8-109%for methyltestosterone,69.8-87.2%for norethindrone,67.7-120%for 17α-ethynylestradiol,82.8-103%for estradiol,70.3-99.2%for 6α-methyl-17α-hydroxy-progesterone,73.0-104%for estradiol benzoate,and 72.9-91.8%for chlormadinone acetate.The range of the coefficients of variation within batches was 0.4-12%;the range of the coefficients of variation between batches was 6.4-11%.The limit of detections and the detection capability were 0.99 and 3.30μg kg^-1 for diethylstilbestrol,1.05 and 3.50μg kg^-1 for methyltestosterone,1.19 and 3.97μg kg^-1 for norethindrone,0.94 and 3.13μg kg^-1 for 17α-ethynylestradiol,1.45 and 4.83μg kg^-1 for estradiol,1.56 and 5.20μg kg^-1 for 6α-methyl-17α-hydroxy-progesterone,1.92 and 6.40μg kg^-1 for estradiol benzoate,and 2.41 and 8.03μg kg^-1 for chlormadinone acetate,respectively.These results showed that the method was widely available,accurate,and sensitive.
文摘The use of testosterone replacement therapy （TRT） for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids （AAS） within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal （HPG） axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.
文摘We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor （AR）-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity （AR△ZF2） versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR△ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7, p57Kip2, IEf2 and calcineurin Aa, was increased in AR△ZF2 muscle, and the expression of all but p57kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.
文摘Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re- growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.
基金supported by the Natural Science Foundation of Zhejiang Province,China(No.LY17C200009)the Foundation of Zhejiang Educational Committee(No.Y201328477)
文摘A highly sensitive method was developed for the simultaneous determination of 8 steroid hormones in high-fat fish tissues using ultra high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The 8 steroid hormones were extracted from the tissues with diethyl ether.Differing from other common purification methods,the extract solutions were cleaned by gel permeation chromatography(GPC) using ethyl acetate-cyclohexane solution(1:1,v/v) as the mobile phase.The separation of target compounds was carried out by a BEH C18 column and a gradient elution consisting of acetonitrile and 0.2% aqueous formic acid(v/v).The compounds were detected under the multiple reaction monitoring(MRM) mode and quantified with external standard method.This method was validated with respect to linearity,specificity,accuracy and precision.A linearity with correlation coefficient larger than 0.995 was achieved in the range of 0.5 to 50 ng m L^(-1).The average recoveries at the spiked levels of 1.0,5.0,and 10.0 μg kg^(–1) varied between 81.7% and 90.8%,with the relative standard deviations(n=5) ranged from 3.50% to 10.0%.The limit of quantification(LOQ) for 8 steroid hormones ranged from 0.2 to 1.5 μg kg^(-1).It was concluded that this method can be successfully applied for the determination of 8 steroid hormones in complicated matrices including high-fat fish tissues.
文摘Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombi- nant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH＇ s rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span （24-36 hours） from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial. However, work with different approaches to develop an alternative, reliable test is ongoing.
基金Support was provided by a Career Development Award (RCR, BX001284) from the Veterans Administration
文摘The hypoxia inducible factors （Hifs） are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone （PTH）. Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of β-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.
基金We thank the Shanghai Municipal Committee of Science and Technology(Grant Nos.:20XD1423400,23ZR1460900 and 20DZ2201100)Shanghai Municipal Health Commission/Shanghai Municipal Administration of Traditional Chinese Medicine(Grant No.:ZY(2021e2023)-0501)+2 种基金Shanghai Science and Technology Development Fund from Central Leading Local Government(Grant No.:YDZX20223100001004)National Natural Science Foundation of China(Grant No.:21672249)Expenditure Budget Program of Shanghai University of Traditional Chinese Medicine(Grant Nos.:2020LK051,and 2021LK001).
文摘In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate(DMMIC)was used to label the amino group of metabolites,and a reductant of dithiothreitol(DTT)was employed to stabilize the thiol group.By combining DMMIC derivatization with LC-MS,it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples,which had good linearity(R^(2)=0.99810.9999),precision(interday precision of 1.6%e19.0%and intraday precision of 1.4%e19.8%)and accuracy(83.4%-115.7%).Moreover,the recovery assessments in tissues(82.5%e107.3%)and in cells(98.1%e118.9%)with GSH-^(13)C2,^(15)N,and Cys-^(15)N demonstrated the reliability of the method in detecting tissues and cells.Following a methodological evaluation,the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma(ESCC)and the effect of p-hydroxycinnamaldehyde(CMSP)on the GAP in KYSE150 esophageal cancer cells.The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes,which can contribute to research on drugs and diseases.
文摘Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type Ⅱ fractures are the most common fracture pattern in elderly patients. Treatment(rigid and non-rigid immobilization, anterior screw fixation of the odontoid and posterior C1-C2 fusion) remains controversial and represents a unique challenge for the treating surgeon. The aims of treatment in the elderly is to quickly restore pre-injury function while decreasing morbidity and mortality associated with inactivity, immobilization with rigid collar and prolonged hospitalization. Conservative treatment of type Ⅱ odontoid fractures is associated with relatively high rates of non-union and in a few cases delayed instability. Options for treatment of symptomatic non-unions include surgical fixation or prolonged rigid immobilization. In this report we present the case of a 73-year-old woman with post-traumatic odontoid nonunion successfully treated with Teriparatide systemic anabolic therapy. Complete fusion and resolution of the symptoms was achieved 12 wk after the onset of the treatment. Several animal and clinical studies have confirmed the potential role of Teriparatide in enhancing fracture healing. Our case suggests that Teriparatide may have a role in improving fusion rates of C2 fractures in elderly patients.
基金supported by the Indus Biotech Private Ltd.,Pune with no role in the collection,analysis,and interpretation of data and the writing of the report
文摘Purpose： To evaluate the efficacy and safety of the glycoside fraction of fenugreek （Trigonellafoenum-graecum） seeds （Fenu-FG） on physiologi- cal parameters related to muscle anabolism, androgenic hormones, and body fat in healthy male subjects during an 8-week resistance training program using a prospective, randomized, double-blind, placebo controlled design. Methods： Sixty healthy male subjects were randomized to ingest capsules of Fenu-FG （1 capsule of 300 rag, twice per day） or the matching placebo at a 1：1 ratio. The subjects participated in a supervised 4-day per week resistance-training program for 8 weeks. The outcome measurements were recorded at recruitment （baseline） and at the end of the treatment （8 weeks）. The efficacy outcome included serum testosterone （total and free） levels, muscle strength and repetitions to failure, metabolic markers for anabolic activity （serum creatinine and blood urea nitrogen）, and % body fat. The standard safety measurements such as adverse events monitoring, vital signs, hematology, biochemistry, and urinalysis were performed. Results： Fenu-FG supplementation demonstrated significant anabolic and androgenic activity as compared with the placebo. Fenu-FG treated subjects showed significant improvements in body fat without a reduction in muscle strength or repetitions to failure. The Fenu-FG supplemen- tation was found to be safe and well-tolerated. Conclusion： Fenu-FG supplementation showed beneficial effects in male subjects during resistance training without any clinical side effects.
文摘Aim： To investigate the reversibility of the effect of nandrolone decanoate （ND） on sperm parameters after discontinuing the drug. Methods： Three groups of rats received peanut oil （control）, low and high doses of ND for 14 weeks, respectively. Each group was divided into subgroups A and B, in which rats were killed 14 and 28 weeks after initiating the injection, respectively. Results： Sperm count and motile sperm fraction were decreased in the subgroups A and B that received low and high doses of ND in comparison with the controls A and B, respectively. The sperm count and motile sperm fraction increased in the subgroups B that received low and high doses of ND in comparison with their corresponding subgroups A. The number of normal morphology sperm was decreased significantly in subgroups A receiving low and high doses of ND in comparison with the control subgroup A. However, this parameter was not decreased in subgroups B receiving low and high doses in comparison with the control subgroup B. The normal sperm morphology did not show any significant differences in the subgroups B in comparison with their corresponding subgroups A. Conclusion： The 14-week injection of low and high doses of ND decreases sperm quality and quantity in rats. These parameters were improved after discontinuing ND, but not recovered completely even when they are left untreated for 14 weeks.
