Hyperhomocysteinemia and abnormal blood lipids are independent risk factors for stroke. However, whether both factors exert a synergistic effect in the onset of stroke remains unclear. The present study is a retrospec...Hyperhomocysteinemia and abnormal blood lipids are independent risk factors for stroke. However, whether both factors exert a synergistic effect in the onset of stroke remains unclear. The present study is a retrospective analysJs of 2 089 cases of stroke and 2 089 control cases of simple in- tervertebral disk protrusion using a paired multivariate logistic regression method. Adjusting for known confounding variables including the patients' age, gender, smoking status, alcohol con- sumption status, patient and family medical history, and clinical biochemical indices, elevated ho- mocysteine level was related to the onset of stroke. Patients with elevated homocysteJne levels and abnormal blood lipids showed a 40.9 % increase in the risk for stroke compared to patients with normal homocysteine levels and blood lipids (odds ratio 1.409; 95% confidence interval 1.127-1.761). These results indicate that elevated homocysteine and abnormal blood lipids exert synergistic effects in the onset of stroke. Patients with elevated homocysteine levels and abnormal blood lipids are predisposed to stroke.展开更多
Objective:This study aims to explore the expression patterns of cysteine string protein alpha(CSPα)and cysteine string protein beta(CSPβ)in the mammalian inner ear,with an emphasis on their temporal dynamics during ...Objective:This study aims to explore the expression patterns of cysteine string protein alpha(CSPα)and cysteine string protein beta(CSPβ)in the mammalian inner ear,with an emphasis on their temporal dynamics during the developmental stages of C57BL/6 mice.Methods:We utilized immunofluorescence staining to assess the localization and distribution of CSPαand CSPβwithin the inner ears of C57BL/6 mice and miniature pigs.Additionally,this method facilitated the investigation of their temporal expression profiles.Results:In adult C57BL/6 mice and miniature pigs,CSPαand CSPβwere identified in the cytoplasm of inner hair cells and spiral ganglion cells,yet were absent in outer hair cells.Both proteins were found to colocalize with Ctbp2 on the basal side of the cytoplasm in inner hair cells’basilar membrane.Expression of CSPαwas observed at the nerve fiber termini at the basilar membrane’s base of inner and outer hair cells 10 days postnatally in C57BL/6 mice.Notably,expression of both CSPαand CSPβin the cytoplasm of inner hair cells emerged on the 12th day post-birth,aligning with the timeline for registering cochlear potentials.The expression levels of both proteins increased with age,but were consistently absent in outer hair cells.Contrastingly,expression of CSPαand CSPβwas present in the cytoplasm of inner hair cells in miniature pigs as early as one day post-birth,yet remained absent in the three rows of outer hair cells.Conclusion:CSPαand CSPβexhibit predominant and specific expression in inner hair cells and spiral ganglion cells.A unique expression pattern was observed for CSPα,which was also present at the nerve fiber endings of both inner and outer hair cells.The developmental expression trajectory of CSPαand CSPβin mouse inner hair cells is characterized by an initial absence,followed by a gradual increase.Moreover,the timing of expression onset between mice and miniature pigs indicates distinct temporal dynamics,suggesting a potential role in auditory development.展开更多
Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD...Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD.The evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic accuracy.As the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for patients.However,the expensive and invasive nature of these tests limits their scalability.展开更多
Premature neonates have immature antioxidant enzyme systems rendering them more susceptible to oxidative injury. One key antioxidant is glutathione (GSH). The rate limiting amino acid (AA) in GSH production is thought...Premature neonates have immature antioxidant enzyme systems rendering them more susceptible to oxidative injury. One key antioxidant is glutathione (GSH). The rate limiting amino acid (AA) in GSH production is thought to be cysteine. Critically ill premature neonates who are parenterally fed are often supplemented with additional cysteine, yet the need for cysteine and optimal dose is unknown. This was a prospective, un-blinded, three-group, randomized crossover study aimed to evaluate three doses of cysteine by analyzing red blood cell (RBC) GSH, plasma AA, weight, and nitrogen balance. Neonates were randomized to receive 72 hours of each of the following cysteine doses: 10 mg/g AA, 20 mg/g AA, and 40 mg/g AA. GSH, plasma AAs, weight, and nitrogen balance were evaluated at baseline (after 72 hours of 0 mg/g AA), day three, day six, and day nine. Sixteen patients completed all doses of cysteine, which resulted in significantly increased RBC GSH concentrations over baseline. Plasma concentrations of cystine, total and free cysteine/cystine, glycine and serine increased with cysteine dose. All cysteine doses were associated with adequate weight gain, and positive nitrogen balance. These results are contrary to more recent studies of cysteine effect on RBC GSH concentrations in preterm neonates and infants, but may reflect the severity of illness in our study subjects, where cysteine requirements may be increased.展开更多
The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting...The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.展开更多
BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resol...BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO2 laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.展开更多
Objective: To investigate the correlation between morning blood pressure surge, homocysteine (Hcy) and left ventricular hypertrophy (LVH) in elderly patients with primary hypertension. Method: 215 cases of patients wi...Objective: To investigate the correlation between morning blood pressure surge, homocysteine (Hcy) and left ventricular hypertrophy (LVH) in elderly patients with primary hypertension. Method: 215 cases of patients with hypertension from January 2015 to June 2016 were randomly selected from TianYou Hospital attached to WUST.Blood pressure was monitored 24 hours;according to the results, patients were divided into 81 cases of morning blood pressure surge group (study group) and 134 cases of non-morning blood pressure surge group (control group). Biochemical indicators of the two groups were measured, such as Hcy, Glu, blood lipid (TC, TG, LDL-C, HDL-C). The ventricular structure index (IVST, LVDD, LVPWT, LVMI) were measured by color doppler ultrasound.Result: 1) The IVST, LVDD, LVPWT and LVMI were significantly higher in study group than in control group (P 0.05), and the incidence of left ventricular hypertrophy (LVH) (74.1%) was significantly higher in study group than in control group (22.4%) (P 0.05). 2) There was no statistical difference in TC, TG, LDL-C and HDL-C between the two groups (P > 0.05). The serum levels of Hcy [(16.89 ± 5.84) mmol/L] in study group were significantly higher than those in control group [(10.88 ± 4.07) mmol/L] (P 0.05). 3) Multivariate logistic regression analysis showed that morning blood pressure surge and Hcy were the risk factors of left ventricular hypertrophy. Conclusion: In elderly patients with?hypertension, the higher the morning blood pressure surge and Hcy level, the more probability of left ventricular hypertrophy and the more obvious degree.展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological bi...Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.展开更多
Hyperhomocysteinemia and oxidative stress may be strongly linked to hypertension, atherosclerosis and other cardiovascular diseases. The present study was performed to investigate possible relationships among plasma t...Hyperhomocysteinemia and oxidative stress may be strongly linked to hypertension, atherosclerosis and other cardiovascular diseases. The present study was performed to investigate possible relationships among plasma total homocysteine, plasma 8-iso-prostaglandin F2α (8-isoPG F2α: an index of oxidative stress), and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertension. We measured the membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive men using an electron spin resonance (ESR) and spin-labeling method. Membrane fluidity of RBCs was significantly decreased in hypertensive men compared with normotensive men. Plasma total homocysteine levels were significantly higher in hypertensive men than in normotensive men, and correlated with plasma 8-isoPG F2α. In contrast, plasma nitric oxide (NO)-metabolites (an index of endothelial function) were lower in hypertensive men than in normotensive men. The reduced membrane fluidity of RBCs was associated with increased total homocysteine and plasma 8-isoPG F2α levels and decreased plasma NO-metabolite levels. Multivariate regression analysis showed that, after adjusting for general risk factors, plasma total homocysteine and 8-isoPG F2α were significant determinants of membrane fluidity of RBCs, respectively. These results suggest that hyperhomocysteinemia and oxidative stress with endothelial dysfunction might have a close correlation with impaired rheologic behavior of RBCs and circulatory disorders in hypertensive men.展开更多
Objective:To investigate clinical significance of the effects of smoking on blood lipids, C-reactive protein,and homocysteine in young ischemic stroke patients.Methods:The clinical data of 423 young stroke patients in...Objective:To investigate clinical significance of the effects of smoking on blood lipids, C-reactive protein,and homocysteine in young ischemic stroke patients.Methods:The clinical data of 423 young stroke patients in the department of neurology at Taihe Hospital in Shiyan City, China were retrospectively analyzed, including age,gender,drinking history,family history,and atrial fibrillation history. Patients were divided into two groups according to whether they smoked,and the blood lipids, C-reactive protein, and homocysteine were compared between groups.Results:The proportion of smokers was 41.83%.The levels of total cholesterol,triglycerides (TG), low density lipoprotein (LDL), and homocysteine were higher in patients who smoked than in those who did not(P < 0.05). High density lipoprotein (HDL) was lower in the smoking group (P < 0.05). C-reactive protein test results were divided into groups according to whether the levels exceeded the normal range or not, and no correlation was found between C-reactive protein levels and smoking(P>0.05). Conclusion:Total cholesterol, TG, LDL, HDL, and homocysteine were significantly different between stroke patients who smoked and those who did not. We therefore suggest that smoking cessation take place as soon as possible and that it be avoided entirely in order to reduce the incidence of atherosclerosis and stroke.展开更多
Aim Cysteine proteases are closely associated with many human and non-human pathological processes and are potential targets for metal ions especially Hg^2+ and the related species. In the present work, on the basis ...Aim Cysteine proteases are closely associated with many human and non-human pathological processes and are potential targets for metal ions especially Hg^2+ and the related species. In the present work, on the basis of to the general study on the effects of some metal ions on the activity of papain, a well-known representative of cysteine protease family, the inhibitory effects of Hg^2+ and polysulfide complexes were studied. Results All the metal ions tested (Hg^2+, Cu^2+, Ag^+, Au^3+, Zn^2+, Cd^2+, Fe^3+, Mn^2+, Pb^2+, Yb^3+) inhibit the activity of papain anda good correlation between the inhibitory potency and softness-and-hardness was observed. Among the metals, Hg^2+ was shown to be a potent inhibitor of papain with a Kiof 2 × 10^-7 mol·L^-1 among. Excessive amounts of glutathione and cysteine could reactivate the enzyme activity of papain deactivated by Hg^2+. These evidences supported that Hg^2+ might bind to the catalytic site of papain. Interestingly, Hg (Ⅱ) polysulfide complexes were for the first time found to inhibit papain with a Ki of 7 × 10^-6 mol·L^-1, whose potency is close to a well known mercury compound, thimerosal (Ki=2.7 × 10^-6). In addition, Hg (Ⅱ) polysulfide complexes exhibit good permeability ( 1.9 × 10-5 cm· s^-1) to caco-2 monolayer. Conclusion These results suggested that mercury polysulfide complexes might be potential bioactive species in the interaction with cysteine proteases and other- SH-content proteins, providing a new clue to understand the mechanism of the toxicological and pharmacological actions of cinnabar and other insoluble mercury compounds.展开更多
With the progress of plant genome research, more than 50 plant metallothionein_like (MT_L) genes have been found, but only several MT_L proteins have been detected and no experimental structural information for MT_L p...With the progress of plant genome research, more than 50 plant metallothionein_like (MT_L) genes have been found, but only several MT_L proteins have been detected and no experimental structural information for MT_L proteins has been reported so far. Since detailed knowledge of the protein tertiary structure is required to understand its biological function, a method is needed to determine the structure of these proteins. In this study, the structural data of known mammal MT was used to determine the interatomic distance constraints of the CXC and CXXC motifs and the metal_sulfur chelating cluster. Then several possible MT conformations were predicted using a distance geometry algorithm. The statistical analysis was used to select those with much lower target function values and lower conformation energies as the predicted tertiary structural models of the cysteine_rich (CR) domains of these proteins. A suitable prediction method for modeling the CR domain of the plant MT_L protein was constructed. The accurately predicted result for the known structure of an MT protein from blue crab suggests that this method is practicable. The tertiary structures of CR domains of rape MT_L protein LSC54 was then modeled with this method.展开更多
AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.
Triangular silver nanoprisms were prepared and applied to make colorimetric detection of cysteine based on our findings that cysteine could lead to the blue shift of the dipole plasmon resonance absorption, but other ...Triangular silver nanoprisms were prepared and applied to make colorimetric detection of cysteine based on our findings that cysteine could lead to the blue shift of the dipole plasmon resonance absorption, but other 19 kinds of natural amino acids could not. Cysteine with a concentration 160 nmol/L can result in a color change that can be discerned with naked eyes.展开更多
BACKGROUND Aberrant methylation in DNA regulatory regions could downregulate tumor suppressor genes without changing the sequences.However,our knowledge of secreted protein acidic and rich in cysteine(SPARC)and its ab...BACKGROUND Aberrant methylation in DNA regulatory regions could downregulate tumor suppressor genes without changing the sequences.However,our knowledge of secreted protein acidic and rich in cysteine(SPARC)and its aberrant methylation in gastric cancer(GC)is still inadequate.In the present research,we performed fundamental research to clarify the precise function of methylation on SPARC and its significance in GC.AIM To investigate promoter methylation and the effects of the SPARC gene in GC cells and tissues and to evaluate its clinical significance.METHODS Plasmids that overexpressed the SPARC gene were transfected into human GC BGC-823 cells;non-transfected cells were used as a control group(NC group).Quantitative real-time polymerase chain reaction and western blotting(WB)were then used to detect the expression of SPARC.Methylation-specific polymerase chain reaction was executed to analyze the gene promoter methylation status.Cell viability was measured by the cell counting kit-8 assay.The migration and invasion ability of cells were detected by scratch assays and transwell chamber assays,respectively.Cell cycle events and apoptosis were observed with a flow cytometer.RESULTS The expression of SPARC mRNA in GC tissues and cells was significantly lower and showed differing degrees of hypermethylation,respectively,than that in normal adjacent tissues and control cells.Treatment with 5-Aza-2’-deoxycytidine(5-Aza-Cdr)was able to restore the expression of SPARC and reverse promoter hypermethylation.Overexpression of the SPARC gene significantly inhibited proliferation,migration,and invasion of GC cells,while also causing cell cycle arrest and apoptosis;the NC group exhibited the opposite effects.CONCLUSION This study demonstrated that SPARC could function as a tumor suppressor and might be silenced by promoter hypermethylation.Furthermore,in GC cells,SPARC inhibited migration,invasion,and proliferation,caused cell cycle arrest at the G0/G1 phase,and promoted apoptosis.展开更多
Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical...Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.展开更多
In this work,a kind of stabilized ferrofluid based on magnetite nanoparticles(mean core and its coating size about 21.9 and 1.6 nm,respectively)was synthesized via coprecipitation method.Cysteine was used as surfactan...In this work,a kind of stabilized ferrofluid based on magnetite nanoparticles(mean core and its coating size about 21.9 and 1.6 nm,respectively)was synthesized via coprecipitation method.Cysteine was used as surfactant due to its proper conjunction to the surface of magnetite nanoparticles.Coating density and synthesized ferrofluids were characterized by using transmission electron microscope,thermogravimetry analysis,dynamic light scattering and fourier transform infrared spectroscopy techniques.Magnetic resonance imaging studies show that the synthesized ferrofluid can be used as a potential contrast enhancement agent especially for imaging lymphatic system.展开更多
基金supported by a grant from Medical Science DataSharing Network,Ministry of Science and Technology,China,No.2005DKA32403Military Medical Scientific Research grants,No.11BJZ32,No.12BJZ271 and No.10BJZ202
文摘Hyperhomocysteinemia and abnormal blood lipids are independent risk factors for stroke. However, whether both factors exert a synergistic effect in the onset of stroke remains unclear. The present study is a retrospective analysJs of 2 089 cases of stroke and 2 089 control cases of simple in- tervertebral disk protrusion using a paired multivariate logistic regression method. Adjusting for known confounding variables including the patients' age, gender, smoking status, alcohol con- sumption status, patient and family medical history, and clinical biochemical indices, elevated ho- mocysteine level was related to the onset of stroke. Patients with elevated homocysteJne levels and abnormal blood lipids showed a 40.9 % increase in the risk for stroke compared to patients with normal homocysteine levels and blood lipids (odds ratio 1.409; 95% confidence interval 1.127-1.761). These results indicate that elevated homocysteine and abnormal blood lipids exert synergistic effects in the onset of stroke. Patients with elevated homocysteine levels and abnormal blood lipids are predisposed to stroke.
基金supported by the Science and Technology Development aid Project of Xuzhou Science and Technology Bureau(KC21249)supported by Hainan Provincial Natural Science Foundation of China(824MS052)Scientific Research Startup Foundation of Hainan University.
文摘Objective:This study aims to explore the expression patterns of cysteine string protein alpha(CSPα)and cysteine string protein beta(CSPβ)in the mammalian inner ear,with an emphasis on their temporal dynamics during the developmental stages of C57BL/6 mice.Methods:We utilized immunofluorescence staining to assess the localization and distribution of CSPαand CSPβwithin the inner ears of C57BL/6 mice and miniature pigs.Additionally,this method facilitated the investigation of their temporal expression profiles.Results:In adult C57BL/6 mice and miniature pigs,CSPαand CSPβwere identified in the cytoplasm of inner hair cells and spiral ganglion cells,yet were absent in outer hair cells.Both proteins were found to colocalize with Ctbp2 on the basal side of the cytoplasm in inner hair cells’basilar membrane.Expression of CSPαwas observed at the nerve fiber termini at the basilar membrane’s base of inner and outer hair cells 10 days postnatally in C57BL/6 mice.Notably,expression of both CSPαand CSPβin the cytoplasm of inner hair cells emerged on the 12th day post-birth,aligning with the timeline for registering cochlear potentials.The expression levels of both proteins increased with age,but were consistently absent in outer hair cells.Contrastingly,expression of CSPαand CSPβwas present in the cytoplasm of inner hair cells in miniature pigs as early as one day post-birth,yet remained absent in the three rows of outer hair cells.Conclusion:CSPαand CSPβexhibit predominant and specific expression in inner hair cells and spiral ganglion cells.A unique expression pattern was observed for CSPα,which was also present at the nerve fiber endings of both inner and outer hair cells.The developmental expression trajectory of CSPαand CSPβin mouse inner hair cells is characterized by an initial absence,followed by a gradual increase.Moreover,the timing of expression onset between mice and miniature pigs indicates distinct temporal dynamics,suggesting a potential role in auditory development.
文摘Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD.The evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic accuracy.As the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for patients.However,the expensive and invasive nature of these tests limits their scalability.
文摘Premature neonates have immature antioxidant enzyme systems rendering them more susceptible to oxidative injury. One key antioxidant is glutathione (GSH). The rate limiting amino acid (AA) in GSH production is thought to be cysteine. Critically ill premature neonates who are parenterally fed are often supplemented with additional cysteine, yet the need for cysteine and optimal dose is unknown. This was a prospective, un-blinded, three-group, randomized crossover study aimed to evaluate three doses of cysteine by analyzing red blood cell (RBC) GSH, plasma AA, weight, and nitrogen balance. Neonates were randomized to receive 72 hours of each of the following cysteine doses: 10 mg/g AA, 20 mg/g AA, and 40 mg/g AA. GSH, plasma AAs, weight, and nitrogen balance were evaluated at baseline (after 72 hours of 0 mg/g AA), day three, day six, and day nine. Sixteen patients completed all doses of cysteine, which resulted in significantly increased RBC GSH concentrations over baseline. Plasma concentrations of cystine, total and free cysteine/cystine, glycine and serine increased with cysteine dose. All cysteine doses were associated with adequate weight gain, and positive nitrogen balance. These results are contrary to more recent studies of cysteine effect on RBC GSH concentrations in preterm neonates and infants, but may reflect the severity of illness in our study subjects, where cysteine requirements may be increased.
基金supported by the grants from the Spanish Ministry of Economy and Competitiveness(SAF2017-85602-R)the Spanish Ministry of Science and Innovation(PID2020-119638RB-I00 to EGR)FPU-program(FPU17/02616 to JCG)。
文摘The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.
基金Supported by The New Faculty Research Grant of Pusan National University,2023The Research Grant of the Chungbuk National University in 2023.
文摘BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO2 laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.
文摘Objective: To investigate the correlation between morning blood pressure surge, homocysteine (Hcy) and left ventricular hypertrophy (LVH) in elderly patients with primary hypertension. Method: 215 cases of patients with hypertension from January 2015 to June 2016 were randomly selected from TianYou Hospital attached to WUST.Blood pressure was monitored 24 hours;according to the results, patients were divided into 81 cases of morning blood pressure surge group (study group) and 134 cases of non-morning blood pressure surge group (control group). Biochemical indicators of the two groups were measured, such as Hcy, Glu, blood lipid (TC, TG, LDL-C, HDL-C). The ventricular structure index (IVST, LVDD, LVPWT, LVMI) were measured by color doppler ultrasound.Result: 1) The IVST, LVDD, LVPWT and LVMI were significantly higher in study group than in control group (P 0.05), and the incidence of left ventricular hypertrophy (LVH) (74.1%) was significantly higher in study group than in control group (22.4%) (P 0.05). 2) There was no statistical difference in TC, TG, LDL-C and HDL-C between the two groups (P > 0.05). The serum levels of Hcy [(16.89 ± 5.84) mmol/L] in study group were significantly higher than those in control group [(10.88 ± 4.07) mmol/L] (P 0.05). 3) Multivariate logistic regression analysis showed that morning blood pressure surge and Hcy were the risk factors of left ventricular hypertrophy. Conclusion: In elderly patients with?hypertension, the higher the morning blood pressure surge and Hcy level, the more probability of left ventricular hypertrophy and the more obvious degree.
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
基金supported by Hunan Provincial Key Research and Development Program,No.2021SK2002(to BW)the Natural Science Foundation of Hunan Province of China(General Program),No.2021JJ30938(to YL)。
文摘Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.
文摘Hyperhomocysteinemia and oxidative stress may be strongly linked to hypertension, atherosclerosis and other cardiovascular diseases. The present study was performed to investigate possible relationships among plasma total homocysteine, plasma 8-iso-prostaglandin F2α (8-isoPG F2α: an index of oxidative stress), and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertension. We measured the membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive men using an electron spin resonance (ESR) and spin-labeling method. Membrane fluidity of RBCs was significantly decreased in hypertensive men compared with normotensive men. Plasma total homocysteine levels were significantly higher in hypertensive men than in normotensive men, and correlated with plasma 8-isoPG F2α. In contrast, plasma nitric oxide (NO)-metabolites (an index of endothelial function) were lower in hypertensive men than in normotensive men. The reduced membrane fluidity of RBCs was associated with increased total homocysteine and plasma 8-isoPG F2α levels and decreased plasma NO-metabolite levels. Multivariate regression analysis showed that, after adjusting for general risk factors, plasma total homocysteine and 8-isoPG F2α were significant determinants of membrane fluidity of RBCs, respectively. These results suggest that hyperhomocysteinemia and oxidative stress with endothelial dysfunction might have a close correlation with impaired rheologic behavior of RBCs and circulatory disorders in hypertensive men.
文摘Objective:To investigate clinical significance of the effects of smoking on blood lipids, C-reactive protein,and homocysteine in young ischemic stroke patients.Methods:The clinical data of 423 young stroke patients in the department of neurology at Taihe Hospital in Shiyan City, China were retrospectively analyzed, including age,gender,drinking history,family history,and atrial fibrillation history. Patients were divided into two groups according to whether they smoked,and the blood lipids, C-reactive protein, and homocysteine were compared between groups.Results:The proportion of smokers was 41.83%.The levels of total cholesterol,triglycerides (TG), low density lipoprotein (LDL), and homocysteine were higher in patients who smoked than in those who did not(P < 0.05). High density lipoprotein (HDL) was lower in the smoking group (P < 0.05). C-reactive protein test results were divided into groups according to whether the levels exceeded the normal range or not, and no correlation was found between C-reactive protein levels and smoking(P>0.05). Conclusion:Total cholesterol, TG, LDL, HDL, and homocysteine were significantly different between stroke patients who smoked and those who did not. We therefore suggest that smoking cessation take place as soon as possible and that it be avoided entirely in order to reduce the incidence of atherosclerosis and stroke.
文摘Aim Cysteine proteases are closely associated with many human and non-human pathological processes and are potential targets for metal ions especially Hg^2+ and the related species. In the present work, on the basis of to the general study on the effects of some metal ions on the activity of papain, a well-known representative of cysteine protease family, the inhibitory effects of Hg^2+ and polysulfide complexes were studied. Results All the metal ions tested (Hg^2+, Cu^2+, Ag^+, Au^3+, Zn^2+, Cd^2+, Fe^3+, Mn^2+, Pb^2+, Yb^3+) inhibit the activity of papain anda good correlation between the inhibitory potency and softness-and-hardness was observed. Among the metals, Hg^2+ was shown to be a potent inhibitor of papain with a Kiof 2 × 10^-7 mol·L^-1 among. Excessive amounts of glutathione and cysteine could reactivate the enzyme activity of papain deactivated by Hg^2+. These evidences supported that Hg^2+ might bind to the catalytic site of papain. Interestingly, Hg (Ⅱ) polysulfide complexes were for the first time found to inhibit papain with a Ki of 7 × 10^-6 mol·L^-1, whose potency is close to a well known mercury compound, thimerosal (Ki=2.7 × 10^-6). In addition, Hg (Ⅱ) polysulfide complexes exhibit good permeability ( 1.9 × 10-5 cm· s^-1) to caco-2 monolayer. Conclusion These results suggested that mercury polysulfide complexes might be potential bioactive species in the interaction with cysteine proteases and other- SH-content proteins, providing a new clue to understand the mechanism of the toxicological and pharmacological actions of cinnabar and other insoluble mercury compounds.
文摘With the progress of plant genome research, more than 50 plant metallothionein_like (MT_L) genes have been found, but only several MT_L proteins have been detected and no experimental structural information for MT_L proteins has been reported so far. Since detailed knowledge of the protein tertiary structure is required to understand its biological function, a method is needed to determine the structure of these proteins. In this study, the structural data of known mammal MT was used to determine the interatomic distance constraints of the CXC and CXXC motifs and the metal_sulfur chelating cluster. Then several possible MT conformations were predicted using a distance geometry algorithm. The statistical analysis was used to select those with much lower target function values and lower conformation energies as the predicted tertiary structural models of the cysteine_rich (CR) domains of these proteins. A suitable prediction method for modeling the CR domain of the plant MT_L protein was constructed. The accurately predicted result for the known structure of an MT protein from blue crab suggests that this method is practicable. The tertiary structures of CR domains of rape MT_L protein LSC54 was then modeled with this method.
文摘AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.
基金the financial support of the Ministry of Science and Technology of the People's Republic of China(No.2006CB 933100).
文摘Triangular silver nanoprisms were prepared and applied to make colorimetric detection of cysteine based on our findings that cysteine could lead to the blue shift of the dipole plasmon resonance absorption, but other 19 kinds of natural amino acids could not. Cysteine with a concentration 160 nmol/L can result in a color change that can be discerned with naked eyes.
基金Supported by the Natural Science Foundation of Liaoning Province,No.201602817
文摘BACKGROUND Aberrant methylation in DNA regulatory regions could downregulate tumor suppressor genes without changing the sequences.However,our knowledge of secreted protein acidic and rich in cysteine(SPARC)and its aberrant methylation in gastric cancer(GC)is still inadequate.In the present research,we performed fundamental research to clarify the precise function of methylation on SPARC and its significance in GC.AIM To investigate promoter methylation and the effects of the SPARC gene in GC cells and tissues and to evaluate its clinical significance.METHODS Plasmids that overexpressed the SPARC gene were transfected into human GC BGC-823 cells;non-transfected cells were used as a control group(NC group).Quantitative real-time polymerase chain reaction and western blotting(WB)were then used to detect the expression of SPARC.Methylation-specific polymerase chain reaction was executed to analyze the gene promoter methylation status.Cell viability was measured by the cell counting kit-8 assay.The migration and invasion ability of cells were detected by scratch assays and transwell chamber assays,respectively.Cell cycle events and apoptosis were observed with a flow cytometer.RESULTS The expression of SPARC mRNA in GC tissues and cells was significantly lower and showed differing degrees of hypermethylation,respectively,than that in normal adjacent tissues and control cells.Treatment with 5-Aza-2’-deoxycytidine(5-Aza-Cdr)was able to restore the expression of SPARC and reverse promoter hypermethylation.Overexpression of the SPARC gene significantly inhibited proliferation,migration,and invasion of GC cells,while also causing cell cycle arrest and apoptosis;the NC group exhibited the opposite effects.CONCLUSION This study demonstrated that SPARC could function as a tumor suppressor and might be silenced by promoter hypermethylation.Furthermore,in GC cells,SPARC inhibited migration,invasion,and proliferation,caused cell cycle arrest at the G0/G1 phase,and promoted apoptosis.
基金supported by the Beijing Natural Science Foundation Program(Grant number:5102040)the Open Foundation of the Beijing Key Laboratory of Hypertension Research(Grant number:2015GXYB01)
文摘Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.
文摘In this work,a kind of stabilized ferrofluid based on magnetite nanoparticles(mean core and its coating size about 21.9 and 1.6 nm,respectively)was synthesized via coprecipitation method.Cysteine was used as surfactant due to its proper conjunction to the surface of magnetite nanoparticles.Coating density and synthesized ferrofluids were characterized by using transmission electron microscope,thermogravimetry analysis,dynamic light scattering and fourier transform infrared spectroscopy techniques.Magnetic resonance imaging studies show that the synthesized ferrofluid can be used as a potential contrast enhancement agent especially for imaging lymphatic system.