ABSTRACT
OBJECTIVES: To investigate the clinical and genetic features of children with 3-methylcrotonyl-coenzyme A carboxylase deficiency (MCCD). METHODS: A retrospective analysis was conducted on the clinical manifestations and genetic testing results of six children with MCCD who attended Children's Hospital Affiliated to Zhengzhou University from January 2018 to October 2023. RESULTS: Among the six children with MCCD, there were 4 boys and 2 girls, with a mean age of 7 days at the time of attending the hospital and 45 days at the time of confirmed diagnosis. Of all children, one had abnormal urine odor and five had no clinical symptoms. All six children had increases in blood 3-hydroxyisovaleryl carnitine and urinary 3-hydroxyisovaleric acid and 3-methylcrotonoylglycine, and five of them had a reduction in free carnitine. A total of six mutations were identified in the MCCC1 gene, i.e., c.1630del(p.R544Dfs*2), c.269A>G(p.D90G), c.1609T>A(p.F537I), c.639+2T>A, c.761+1G>T, and c.1331G>A(p.R444H), and three mutations were identified in the MCCC2 gene, i.e., c.838G>T(p.D280Y), c.592C>T(p.Q198*,366), and c.1342G>A(p.G448A). Among these mutations, c.269A>G(p.D90G) and c.1609T>A(p.F537I) had not been previously reported in the literature. There was one case of maternal MCCD, and the child carried a heterozygous mutation from her mother. Five children with a reduction in free carnitine were given supplementation of L-carnitine, and free carnitine was restored to the normal level at the last follow-up visit. CONCLUSIONS: This study identifies two new mutations, c.269A>G(p.D90G) and c.1609T>A(p.F537I), thereby expanding the mutation spectrum of the MCCC1 gene. A combination of blood amino acid and acylcarnitine profiles, urine organic acid analysis, and genetic testing can facilitate early diagnosis and treatment of MCCD, and provide essential data for genetic counseling.
Subject(s)
Carnitine , Mutation , Female , Humans , Infant , Infant, Newborn , Male , Carbon-Carbon Ligases/genetics , Carbon-Carbon Ligases/deficiency , Carboxy-Lyases/genetics , Carboxy-Lyases/deficiency , Carnitine/analogs & derivatives , Carnitine/blood , Retrospective Studies , Urea Cycle Disorders, Inborn/genetics , Urea Cycle Disorders, Inborn/diagnosisABSTRACT
BACKGROUND: Major depressive disorder (MDD) is treated primarily using antidepressant drugs, but clinical effects may be delayed for weeks to months. This study investigated the efficacy of brief therapeutic sleep deprivation (TSD) for inducing rapid improvements in MDD symptoms. METHODS: From November 2020 to February 2023, 54 inpatients with MDD were randomly allocated to TSD and Control groups. The TSD group (23 cases) remained awake for 36 h, while the Control group (31 cases) maintained regular sleep patterns. All participants continued regular drug therapy. Mood was assessed using the 24-item Hamilton Depression Scale (HAMD-24) at baseline and post-intervention in both groups. In the TSD group, the Visual Analogue Scale (VAS) was utilized to evaluate subjective mood during and after the intervention. Cognitive function was assessed at baseline and post-intervention using the Montreal Cognitive Assessment (MoCA). Objective sleep parameters were recorded in the TSD group by polysomnography. The follow-up period spanned one week. RESULTS: HAMD-24 scores did not differ between groups at baseline or post-intervention. However, the clinical response rate was 34.8 % higher in the TSD group on day 3 post-intervention compared to the Control group (3.2 %), but not sustained by day 7. Moreover, responders demonstrated a faster improvement in the VAS score during TSD than non-responders (p = 0.047). There were no significant differences in MoCA scores or objective sleep parameters between the groups. LIMITATIONS: Small sample size and notable attrition rate. CONCLUSIONS: Therapeutic sleep deprivation can rapidly improve MDD symptoms without influencing sleep parameters or cognitive functions. Assessment of longer-term effects and identification of factors predictive of TSD response are warranted.
Subject(s)
Depressive Disorder, Major , Sleep Deprivation , Humans , Depressive Disorder, Major/therapy , Depressive Disorder, Major/drug therapy , Female , Male , Sleep Deprivation/complications , Adult , Middle Aged , Treatment Outcome , Psychiatric Status Rating Scales , Polysomnography , Affect , Antidepressive Agents/therapeutic useABSTRACT
Acetylene (C2H2) is widely used as a raw material for producing various downstream commodities in the petrochemical and electronic industry. Therefore, the acquisition of high-purity C2H2 from a C2H2/CO2 mixture produced by partial methane combustion or thermal hydrocarbon cracking is of great significance yet highly challenging due to their similar physical and chemical properties. Herein, we report an anionic metal-organic framework (MOF) named LIFM-210, which has Li+ cations in the pores and shows a higher adsorption affinity for C2H2 than CO2. LIFM-210 is constructed by a unique tetranuclear Ni(II) cluster acting as a 10-connected node and an organic ligand acting as a 5-connected node. Single-component adsorption and transient breakthrough experiments demonstrate the good C2H2 selective separation performance of LIFM-210. Theoretical calculations revealed that Li+ ions strongly prefer C2H2 to CO2 and are primary adsorption sites, playing vital roles in the selective separation of C2H2/CO2.
ABSTRACT
OBJECTIVE: Charcot-Marie-Tooth disease (CMT) severely affects patient activity, and may cause disability. However, no clinical treatment is available to reverse the disease course. The combination of CRISPR/Cas9 and iPSCs may have therapeutic potential against nervous diseases, such as CMT. METHODS: In the present study, the skin fibroblasts of CMT type 2D (CMT2D) patients with the c.880G>A heterozygous nucleotide mutation in the GARS gene were reprogrammed into iPSCs using three plasmids (pCXLE-hSK, pCXLE-hUL and pCXLE-hOCT3/4-shp5-F). Then, CRISPR/Cas9 technology was used to repair the mutated gene sites at the iPSC level. RESULTS: An iPSC line derived from the GARS (G294R) family with fibular atrophy was successfully induced, and the mutated gene loci were repaired at the iPSC level using CRISPR/Cas9 technology. These findings lay the foundation for future research on drug screening and cell therapy. CONCLUSION: iPSCs can differentiate into different cell types, and originate from autologous cells. Therefore, they are promising for the development of autologous cell therapies for degenerative diseases. The combination of CRISPR/Cas9 and iPSCs may open a new avenue for the treatment of nervous diseases, such as CMT.
Subject(s)
Charcot-Marie-Tooth Disease , Induced Pluripotent Stem Cells , Targeted Gene Repair , Humans , Charcot-Marie-Tooth Disease/genetics , Charcot-Marie-Tooth Disease/therapy , Charcot-Marie-Tooth Disease/metabolism , CRISPR-Cas Systems/genetics , Induced Pluripotent Stem Cells/metabolism , Mutation , Targeted Gene Repair/methodsABSTRACT
Accurate and integral cellular DNA replication is modulated by multiple replication-associated proteins, which is fundamental to preserve genome stability. Furthermore, replication proteins cooperate with multiple DNA damage factors to deal with replication stress through mechanisms beyond their role in replication. Cancer cells with chronic replication stress exhibit aberrant DNA replication and DNA damage response, providing an exploitable therapeutic target in tumors. Numerous evidence has indicated that posttranslational modifications (PTMs) of replication proteins present distinct functions in DNA replication and respond to replication stress. In addition, abundant replication proteins are involved in tumorigenesis and development, which act as diagnostic and prognostic biomarkers in some tumors, implying these proteins act as therapeutic targets in clinical. Replication-target cancer therapy emerges as the times require. In this context, we outline the current investigation of the DNA replication mechanism, and simultaneously enumerate the aberrant expression of replication proteins as hallmark for various diseases, revealing their therapeutic potential for target therapy. Meanwhile, we also discuss current observations that the novel PTM of replication proteins in response to replication stress, which seems to be a promising strategy to eliminate diseases.
ABSTRACT
Background: Currently, the optimum surgical approach for treating adherent otitis media is debatable. The traditional treatment is usually performed by microscopic tympanoplasty combined with temporal myofascial tympanic tube placement. In recent years, the application of whole ear endoscopic surgery in the treatment of middle ear diseases has gradually increased, otoendoscopy has been used in the operation of adhesive otitis media, but its safety and effectiveness are still controversial. Methods: This study retrospectively analyzed 17 patients with adhesive otitis media treated by endoscopic ear surgery (EES) in our hospital from January 2018 to July 2021 over a 6-month period post-surgery. Of the 17 patients, 8 were males and 9 were females (mean age, 53 years; age range, 24-70 years). There were 12 and 5 cases of adhesive otitis media involving the left and right ear, respectively. The patients had follow-up evaluations 1 week, 2 weeks, 1 month, 3 months, and 6 months after surgery. Results: A total of 17 patients with adhesive otitis were enrolled, including 1 patient with Dornhoffer stage II; 6 patients with stage III; and 10 patients with stage IV. Adhesive otitis media was combined with middle ear cholesteatoma in 4 patients (24%). Fourteen patients (82%) had disruption or interruption of the ossicular chain (8 malleus, 14 incus, and 4 stapes lesions), 11 of whom had artificial ossicular chain reconstruction [8 with partial ossicular reconstruction prosthesis (PORP) and 3 with total ossicular reconstruction prosthesis (TORP) implantation]. All patients had good tympanic membrane and graft morphology, no invaginations, and no perforations. The mean postoperative air-conduction hearing threshold [49.06±22.15 dB hearing level (dB HL)] and mean air-bone gap (19.94±10.00 dB HL) were significantly improved compared with the preoperative values (65.29±21.53 and 32.53±8.21 dB HL, respectively; P<0.05). No recurrences, secondary cholesteatomas, or secondary surgeries were reported. Conclusions: EES seems to be a safe and effective surgical method for the management of adhesive otitis media. The study has limitations due to its small sample size and lack of controlled studies. It still needs to be proven in clinical randomized controlled trials.
ABSTRACT
BACKGROUND: Improved patient satisfaction in endoscopy is worthy of study as it is an invasive and potentially uncomfortable procedure. There is growing literature on patient satisfaction assessment in endoscopy as part of improving quality assurance. This study aimed to determine whether virtual reality (VR) technology can decrease patients' pain and nervousness during colonoscopies. METHODS: Patients enrolled without sedation were randomly categorised into groups that watched VR (VR group; n=58) and those that did not watch VR (control group; n=59). The primary outcomes were pain score and skin conductance. Secondary endpoints included heart rate, systolic and diastolic arterial pressures, overall patient satisfaction, willingness to repeat the procedure, the difficulty of the procedure, the procedure duration, and bowel preparation. RESULTS: The median (interquartile range (IQR)) pain scores were 7 (6-8) and 5 (4-6) in the control and VR groups, respectively (p<0.001). The median (IQR) skin conductance values after colonoscope insertion were 0.660 (0.490-0.840) and 0.390 (0.280-0.600) in the control and VR groups, respectively (p<0.001). Overall, patient satisfaction was significantly improved with the use of VR, along with a significant reduction in the difficulty perceived by the endoscopist. CONCLUSION: VR technology helped to reduce patients' pain and nervousness and to improve patients' satisfaction during colonoscopies.
Subject(s)
Virtual Reality , Anxiety , Colonoscopy , Humans , Pain , Prospective Studies , TechnologyABSTRACT
Human ribosomes have long been thought to be uniform factories with little regulatory function. Accumulating evidence emphasizes the heterogeneity of ribosomal protein (RP) expression in specific cellular functions and development. However, a systematic understanding of functional relevance of RPs is lacking. Here, we surveyed translational and transcriptional changes after individual knockdown of 75 RPs, 44 from the large subunit (60S) and 31 from the small subunit (40S), by Ribo-seq and RNA-seq analyses. Deficiency of individual RPs altered specific subsets of genes transcriptionally and translationally. RP genes were under cotranslational regulation upon ribosomal stress, and deficiency of the 60S RPs and the 40S RPs had opposite effects. RP deficiency altered the expression of genes related to eight major functional classes, including the cell cycle, cellular metabolism, signal transduction and development. 60S RP deficiency led to greater inhibitory effects on cell growth than did 40S RP deficiency, through P53 signaling. Particularly, we showed that eS8/RPS8 deficiency stimulated apoptosis while eL13/RPL13 or eL18/RPL18 deficiency promoted senescence. We also validated the phenotypic impacts of uL5/RPL11 and eL15/RPL15 deficiency on retina development and angiogenesis, respectively. Overall, our study provides a valuable resource for and novel insights into ribosome regulation in cellular activities, development and diseases.
Ribosomes are the main effector of the translational machinery to synthesize proteins. In this study, the authors characterized genome-wide transcriptional and translational changes after knocking-down 75 individual human ribosomal proteins (RPs). They revealed that deficiency of individual RPs perturbed expression of specific subsets of genes, enriched in eight major functional classes, such as cell cycle and development. RPs were subjected to co-translational regulation under ribosomal stress where deficiency of the 60S RPs and the 40S RPs had opposite effects on the two subunits. They also showed that RPS8 deficiency stimulated cellular apoptosis while RPL13 and RPL18 deficiency promoted cellular senescence. They further showed functional and regulatory roles of RPL11 and RPL15 in retina development and angiogenesis, respectively.
Subject(s)
Ribosomal Proteins , Ribosome Subunits, Large, Eukaryotic/metabolism , Ribosome Subunits, Small, Eukaryotic/metabolism , Gene Knockdown Techniques , Humans , Protein Biosynthesis , Ribosomal Proteins/genetics , Ribosomal Proteins/metabolism , Transcription, GeneticABSTRACT
Through theoretical computation, it was demonstrated that perfluorobenzene can form π-holeâ â â π bonds with polycyclic aromatic hydrocarbons (PAHs). Then, the π-hole bond was firstly introduced in solid phase extraction in which perfluorobenzene-bonded silica sorbent was synthesized and used for the solid phase extraction of sixteen PAHs in water. Compared with the traditional octadecyl silica sorbent, the perfluorobenzene-bonded silica sorbent showed higher adsorbabilities for the PAHs with 4-6 benzene rings, for which the recoveries increased by approximately 20%. Under the optimized conditions, the proposed SPE-HPLC-FLD/UV method was successfully applied for the analysis of 16 PAHs in river water and waste water samples with the limits of detection ranged from 0.002 to 0.08 µgâ L-1. In addition, when the perfluorobenzene-bonded silica sorbent compared with the phenyl-bonded silica sorbent, the results indicated that π-holeâ â â π bonds between perfluorobenzene and PAHs were stronger than the π-π interactions between the PAHs and benzene in hexane solution, which highlights the remarkable potential for the application of the π-hole bond in the SPE field.
Subject(s)
Polycyclic Aromatic Hydrocarbons/analysis , Polycyclic Aromatic Hydrocarbons/isolation & purification , Solid Phase Extraction/methods , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/isolation & purification , Adsorption , Chromatography, High Pressure Liquid , Limit of Detection , Polycyclic Aromatic Hydrocarbons/chemistry , Silicon Dioxide/chemistry , Water Pollutants, Chemical/chemistryABSTRACT
AIM: To study the quality of life of adult patients with intermittent exotropia (IXT) in China and analyze the factors affecting the quality of life in IXT patients. METHODS: Totally 109 cases of normal eye (control group), 77 cases of IXT (IXT group) and 115 cases of strabismus control group (except IXT) were collected. The quality of life of the patients was assessed by Chinese version of adult strabismus patient's quality of life scale (CAS-20). The differences of general characteristics, visual function and quality of life were analyzed, and the effects of individual factors and visual function on quality of life of patients with IXT were analyzed. RESULTS: The IXT group had a high proportion of patients with family history, low proportion of patients with amblyopia compared with strabismus control group. The proportion with normal near and far stereopsis of IXT group were lower than that of normal control group. The best corrected visual acuity of IXT group was higher than that of strabismus control group, but lower than the control group. In addition, the median strabismus degree in IXT group was higher than that in other strabismus control group. The median psychosocial scores and median visual function scores of the IXT group was lower than that of the normal control group, but not different from strabismus control group. Occupation status, course of disease, far stereopsis and near stereopsis significantly affected the quality of life in IXT patients. CONCLUSION: Adult IXT patients in China have a certain proportion of family history and lower quality of life, The main factors affecting the quality of life of IXT patients is stereopsis, course of disease and occupation status.
ABSTRACT
Salmonella spp. is among the main foodborne pathogens which cause serious foodborne diseases. An isothermal real-time recombinase polymerase amplification (RPA) and lateral flow strip detection (LFS RPA) were used to detect Salmonella spp. targeting the conserved sequence of invasion protein A (invA). The Real-time RPA was performed in a portable florescence scanner at 39°C for 20 min. The LFS RPA was performed in an incubator block at 39°C for 15 min, under the same condition that the amplifications could be inspected by the naked eyes on the LFS within 5 min. The detection limit of Salmonella spp. DNA using real-time RPA was 1.1 × 101 fg, which was the same with real-time PCR but 10 times higher than that of LFS RPA assay. Moreover, the practicality of discovering Salmonella spp. was validated with artificially contaminated lamb, chicken, and broccoli samples. The analyzing time dropped from 60 min to proximately 5-12 min on the basis of the real-time and LFS RPA assays compared with the real-time PCR assay. Real-time and LFS RPA assays' results were equally reliable. There was no cross-reactivity with other pathogens in both assays. In addition, the assays had good stability. All of these helped to show that the developed RPA assays were simple, rapid, sensitive, credible, and could be a potential point-of-need (PON) test required mere resources.
Subject(s)
Nucleic Acid Amplification Techniques , Recombinases , Animals , Nucleotidyltransferases , Salmonella , Sensitivity and Specificity , SheepABSTRACT
Glomerulosclerosis and renal interstitial fibrosis occur with the aging kidney. In this study, we examined the expression of miR-21, peroxisome proliferator-activated receptor(PPARα), hypoxia-inducible factor(HIF-1α) in the kidney of 3-month-old rats fed ad libitum (YAL), 24-month-old rats fed ad libitum (OAL) and 24-month-old rats subjected to a 70% calorie-restricted diet for 8 months (OCR). We found long-term caloric restriction (CR) ameliorated aging and aging-related fibrosis. CR ameliorated the increment of miR-21 and HIF-1α, as well as the decrement of PPARα in old ad libitum group. Human proximal tubular cells (HPTCs) presented phenotypes of senescence and epithelial to mesenchymal transition (EMT) under high-glucose conditions, in which senescence occurred earlier than EMT. Senescent cells secreted extracellular vesicles (EVs) which contained miR-21 into the recipient cells. Inhibiting miR-21 of donor cells prevented the occurrence of EMT in recipient cells. In addition, miR-21 induced EMT through targeting PPARα protein and consequently enhancing HIF-1α expression, although other pathways cannot be ruled out. These findings demonstrated that miR-21-containing EVs derived from the senescent cells could facilitate EMT of HPTCs via PPARα-HIF-1α signaling pathway. Long-term caloric restriction and caloric restriction mimetics alleviated aging-related-fibrosis of kidney through downregulation of miR-21.
ABSTRACT
INTRODUCTION: This study aimed to present the case of a patient in whom a chopstick, which had been in the duodenum for 10 years, was finally removed by endoscopy. This case was reported because of the long-time retention and noninvasive removal by endoscopy without sedation or complication. PATIENT CONCERNS: A 30-year-old male patient with intermittent upper abdominal pain. DIAGNOSES: During upper-gastrointestinal (GI) endoscopy, a long-strip foreign body (Fb) was seen in the descending part of the duodenum. An upper-GI barium examination was performed, which revealed a linear Fb in the duodenum cavity. The Fb was >10-cm long. Combined with his history (the patient admitted swallowing a chopstick 10 years ago in a bet), the diagnosis of Fb in the duodenum was confirmed. INTERVENTIONS: The Fb was removed from the duodenum cavity by upper-GI endoscopy successfully. OUTCOMES: The patient was discharged after the removal of the Fb. CONCLUSION: Endoscopic removal and nonoperative management might be feasible in carefully selected patients with a long and old Fb in the duodenum without the need for anesthesia or surgery as well as no occurrence of complications and laceration.
Subject(s)
Duodenoscopy/methods , Duodenum/surgery , Foreign Bodies/surgery , Adult , Humans , Male , Time FactorsABSTRACT
Because of its notable electrical and mechanical properties, the highly conductive graphene paper has great potential applications in future flexible electronics. In this study, we report a simple and effective method to prepare vertically aligned graphene oxide papers from graphene oxide suspensions by an improved electrospray deposition technique with a moving stage, which is controlled by computer. Then, the flexible reduced graphene oxide papers are successfully synthesized after reduction by using hydroiodic acid. The obtained reduced graphene oxide paper has an electrical conductivity as high as 6180 S/m, which is more than one and a half times of the reduced graphene oxide paper film, which was fabricated by using the electrospray deposition technique without the moving stage. The experimental results approved for the first time that the degree of alignment of reduced graphene oxide sheets can affect the conductivity of the reduced graphene oxide papers. Further electrochemical measurements for a symmetrical supercapacitor device based on the prepared reduced graphene oxide paper indicate that it has great capacitive performance and electrochemical stability. It exhibited relatively high specific capacitance (174 F·g-1) at a current density of 1 A·g-1 in 6 M KOH aqueous solution, and its capacitance can retain approximately 86% after 1000 cycles. In addition, patterned freestanding reduced graphene oxide papers, which have potential applications in many fields such as stretchable electronics and wearable devices, also can be fabricated by using this method.
ABSTRACT
Stretchable sensors, as the important components of flexible electronic devices, have achieved progress in a variety of applications for monitoring physical or environmental conditions, such as sound, temperature, vibration, and pressure. However, it still remains a challenge to fabricate high performance stretchable humidity sensors. Herein, we present a novel stretchable humidity sensor, which was fabricated based on an ultrastretchable polyaniline composite fiber. Because of the composite fiber with a "twining spring" configuration (cotton fibers twining spirally around a polyurethane fiber) it maintains a stable electrical conductivity up to a strain of 200%. In addition, the conductivity of the composite fiber remains perfectly stable after 5000 cyclic stretching events of 200% strain. Incorporating the humidity sensitive properties of nanostructured polyaniline, the stretchable humidity sensor based on the composite fiber effectively maintains its humidity sensitivity at different elongations.
ABSTRACT
Kaschin-Beck disease (KBD) is an endemic osteoarthritis, and the etiology is closely related with levels of trace elements in the human body. Currently, it is clear that the selenium (Se) status of children in KBD areas is lower than that in non-KBD areas in the Tibetan Plateau, whereas role of other elements are yet unknown. This study aimed to assess some essential trace elements (Se, Mo, Mn, Zn, Fe, Cu, Co, and Sr) in children using scalp hair as a biomarker, and 157 samples from school children aged 8-14 years old were collected from both KBD and non-KBD areas in Shigatse, Tibet. Se and Mo were measured by inductive coupled plasma mass spectrometry, and the other elements were determined by inductive coupled plasma optical emission spectrometry. Compared with the non-KBD areas, Se, Mo, Mn, Fe, Zn, Co, and Sr levels of children in KBD areas were found to be significantly different (P < 0.05); while in linear discriminant analysis, only Se and Zn were found to contribute to the KBD prevalence in the study area. The hair Se level of children in KBD areas ranged from 0.115 to 0.299 mg/kg, while in non-KBD areas it ranged from 0.135 to 0.519 mg/kg. The Zn content of children's hair was between 83 and 207 mg/kg in KBD areas, while it was 37 and 219 mg/kg in non-KBD areas. Lower Se and higher Zn levels in children in KBD areas was found when compared with non-KBD groups. In addition, Mo levels were found to be different between KBD areas and non-KBD areas on the opposite side of the Yarlung Zangbo River, but no close relationship was shown because there was no difference compared with the non-KBD area on the same side of the river. Our observations suggest that Se deficiency is still an important factor for the occurrence and prevalence of KBD, while the relationship between Zn and KBD needs to be further explored in the Tibetan Plateau.
Subject(s)
Hair/chemistry , Kashin-Beck Disease/epidemiology , Selenium/deficiency , Trace Elements/analysis , Adolescent , Child , Female , Humans , Male , Scalp , Selenium/analysis , Tibet/epidemiology , Zinc/analysisABSTRACT
Renal fibrosis contributes to declining renal function in the elderly. What is unclear however, is whether epithelial-mesenchymal transition (EMT) contributes to this age-related renal fibrosis. Here, we analyzed indicators of EMT during kidney aging and investigated the protective effects and mechanisms of short-term regimens of caloric restriction (CR) or caloric restriction mimetics (CRMs), including resveratrol and metformin. High glucose was used to induce premature senescence and EMT in human primary proximal tubular cells (PTCs) in vitro. To test the role of AMPK-mTOR signaling, siRNA was used to deplete AMPK. Cellular senescence and AMPK-mTOR signaling markers associated with EMT were detected. CR or CRMs treatment alleviated age-related EMT in aging kidneys, which was accompanied by activation of AMPK-mTOR signaling. High glucose induced premature senescence and EMT in PTCs in vitro, which was accompanied by down-regulation of AMPK/mTOR signaling. CRMs alleviated high glucose-induced senescence and EMT via stimulation of AMPK/mTOR signaling. Activation of AMPK/mTOR signaling protected PTCs from high glucose-induced EMT and cellular senescence. Short-term regimens of CR and CRMs alleviated age-related EMT via AMPK-mTOR signaling, suggesting a potential approach to reducing renal fibrosis during aging.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Aging/drug effects , Caloric Restriction , Epithelial-Mesenchymal Transition/drug effects , Metformin/pharmacology , Stilbenes/pharmacology , TOR Serine-Threonine Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Adult , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Blotting, Western , Cells, Cultured , Cellular Senescence/drug effects , Glucose/pharmacology , Humans , Hypoglycemic Agents/pharmacology , Kidney Tubules, Proximal/cytology , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/metabolism , Male , Microscopy, Fluorescence , Rats, Sprague-Dawley , Resveratrol , Signal Transduction/drug effectsABSTRACT
OBJECTIVE: To study the levels of Pb, Se, As and Hg in brick-teas from main producing areas in China and evaluate the safety. METHODS: A total of 31 samples of brick tea from seven provinces where minority nationalities were accustomed to drinking a large quantity of brick tea were collected, Pb concentrations were determined by inductively coupled plasma-mass spectrometry, and concentrations of As, Se, Hg were detected by hydride generation atomic fluorescence spectrometry. The data were analyzed by SPSS 22. 0 software. RESULTS: The average lead levels in brick tea was 6. 232 mg/kg, which exceeded the limit standard of GB 2762-2012. There was a great difference of Pbconcentrations among the various kinds of brick tea producing in different provinces, and the lower Pb concentrations detected in Tuo tea and Puerh tea producing in Yunnan Province, was 1. 337 mg/kg, and the highest determined in Kang brick producing in Sichuan Province, was 9. 998 mg/kg. In addition, the concentrations of As and Hg were all below the limit standard of NY 659-2003. For people accustomed to drinking brick tea for a long term, the average intake amounts of Pb, As, Hg through brick tea contributed 13. 63%, 1. 71% and 0. 29% to dietary Pb, As, Hg of the provisional tolerable weekly intake( PTWI) recommended by Joint FAO/WHO Expert Committee of Food Additives( JECFA) which was in safe range. Otherwise, the daily selenium intake through brick tea was 0. 188 µg, which contributed 0. 38% to the selenium recommended nutrient intake( RNI) by Chinese Nutrition Society. CONCLUSION: Excessive levels of lead in the brick tea is prominent. As, Hg and Se in brick tea are in low exposure level.