ABSTRACT
Prunin of desirable bioactivity and bioavailability can be transformed from plant-derived naringin by the key enzyme α-L-rhamnosidase. However, the production was limited by unsatisfactory properties of α-L-rhamnosidase such as thermostability and organic solvent tolerance. In this study, biochemical characteristics, and hydrolysis capacity of a novel α-L-rhamnosidase from Spirochaeta thermophila (St-Rha) were investigated, which was the first characterized α-L-rhamnosidase for Spirochaeta genus. St-Rha showed a higher substrate specificity towards naringin and exhibited excellent thermostability and methanol tolerance. The Km of St-Rha in the methanol cosolvent system was decreased 7.2-fold comparing that in the aqueous phase system, while kcat/Km value of St-Rha was enhanced 9.3-fold. Meanwhile, a preliminary conformational study was implemented through comparative molecular dynamics simulation analysis to explore the mechanism underlying the methanol tolerance of St-Rha for the first time. Furthermore, the catalytic ability of St-Rha for prunin preparation in the 20% methanol cosolvent system was explored, and 200 g/L naringin was transformed into 125.5 g/L prunin for 24 h reaction with a corresponding space-time yield of 5.2 g/L/h. These results indicated that St-Rha was a novel α-L-rhamnosidase suitable for hydrolyzing naringin in the methanol cosolvent system and provided a better alternative for improving the efficient production yield of prunin.
Subject(s)
Phlorhizin/analogs & derivatives , Spirochaeta , Methanol , Glycoside Hydrolases/chemistry , SolventsABSTRACT
Individual omega-6 polyunsaturated fatty acids (PUFAs), principally linoleic acid (LA) and arachidonic acid (AA), may have differential impacts on cardiovascular risk. We aimed to summarize the up-to-date epidemiology evidence on the relationship between blood levels of omega-6 PUFAs and the risk of coronary heart disease (CHD). Population-based studies determining PUFA levels in blood were identified until May 2021 in PubMed, Embase, Web of Science, and Cochrane Library. Random-effects meta-analyses of cohorts comparing the highest versus lowest category were conducted to combine study-specific risk ratios (RRs) with 95% confidence intervals (CIs). Blood levels of omega-6 PUFAs were compared between the CHD case and non-case, presented as a weight mean difference (WMD). Twenty-one cohorts and eleven case-control studies were included. The WMD was -0.71 (95% CI: -1.20, -0.21) for LA and 0.08 (95% CI: -0.28, 0.43) for AA. LA levels were inversely associated with total CHD risk (RR: 0.85, 95% CI: 0.71, 1.00), but not AA. Each one-SD increase in LA levels resulted in 10% reductions in the risk of fatal CHD (RR: 0.90, 95% CI: 0.86, 0.95), but not in non-fatal CHD. Such findings highlight that the current recommendation for optimal intakes of omega-6 PUFAs (most LA) may offer a coronary benefit in primary prevention.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2056867 .
Subject(s)
Coronary Disease , Fatty Acids, Omega-3 , Humans , Coronary Disease/epidemiology , Coronary Disease/prevention & control , Fatty Acids, Omega-6 , Fatty Acids, Unsaturated , Case-Control StudiesABSTRACT
Objective To design and validate a novel surgical guide for retrieval of foreign body in jaw. Methods Firstly, a surgical guide based on cone beam computed tomography and trephine technique was designed to remove broken dental instrument fragments. Its feasibility and accuracy were assessed by removing broken dental instrument in goat mandible, and then it was successfully applied in clinical cases. The linear and angular discrepancies between actual and planned columnar bone with imaginary fragment was analyzed. The euclidean distance was measured at the hex and apex of the columnar bone and the angle of axis deviation was also calculated. We obtained seven parameters (cdh, cda, hdh, hda, vdh, vda, and ad) to describe deviations. Results Mean central deviation at the hex and apex was (0.51 ± 0.14) mm and (0.62 ± 0.19) mm, respectively. Accompanying mean values were as follow: horizontal deviation at the hex was (0.48 ± 0.16) mm, horizontal deviation at the apex was (0.52 ± 0.22) mm, vertical deviation at the hex was (0.17 ± 0.09) mm, vertical deviation at the apex was (0.29 ± 0.13) mm, and angular deviation of (5.38 ± 3.43) degrees. In a clinical case, the guide successfully located and removed the fracture file. Conclusion This study reveals that this kind novel surgical guide could aid to locate and remove the foreign body in jaw.
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:Aim To study the effects of continuous dai¬ly administration of ramelteon starting at the subacute period of cryogenic traumatic brain injury (cTBI) on neurological function and brain tissue repair in mice. Methods Thirty male C57BL/6 mice were randomly divided into sham group, vehicle group and ramelteon treatment groups. The right sensory-motor cortex was damaged by pressing a copper probe precooled by liq¬uid nitrogen onto the skull. Ramelteon ( 10 nig 'kg-1 • d"1) was administered by gavage every day starting at different time points after cTBI (1 h, 1 d,3 d) until sacrifice on day 14. Beam walking test and open field test were used to evaluate the motor function. Toluidine blue staining was used to measure the infarct volume. Immunofluorescence was used to detect the expression of GAP-43 and synaptophysin in peri-infarct area. Mi¬croglia activation was detected using Iba-1. The area and thickness of glial scars were analyzed by detecting GFAP positive areas. Results All three treatment ( 1 h - 14 d, 1 - 14 d, and 3 - 14 d) significantly im¬proved cTBI induced motor dysfunction, reduced the infarct volume, elevated the expression of GAP -43 and synaptophysin, and decreased the area and thick¬ness of glial scar and microglia activation. In addition, all ramelteon treatment groups had similar effects on the above indexes. Conclusions Delayed ramelteon treatment can improve neurological dysfunction after cTBI,and the therapeutic time window can be delayed for up to three days after cTBI. Inhibiting glial scar formation and microglia activation, and promoting ax- onal regeneration and synaptogenesis may contribute to the beneficial effects of ramelteon.
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The traditional life concept of "body-mind holism" in Chinese medicine has drawn a special attention with the development of modern psychosomatic medicine. The "body-mind holism" is valuable in the guidance for clinical acupuncture practice, but, it is only remained on the theoretical significance by the medical masters in the past dynasties. In the paper, based on the understanding of Huangdi Neijing (Yellow Emperor's Internal Classic), the similarities and differences are compared between the body-mind theory and psychosomatic medicine. In association with clinical observation, from three aspects, i.e. body-mind pathogenesis, acupoint detection and observing the mind, and body-mind treatment, the guidance of "body-mind holism" is explored for the clinical diagnosis and treatment of acupuncture and moxibustion; the referents of "body" and "mind" are clarified in views of disease, diagnosis and treatment; and the treatment strategies of acupuncture and moxibustion are discussed in the perspective of "body-mind holism".
Subject(s)
Moxibustion , Psychosomatic Medicine , Acupuncture Therapy , Acupuncture , Acupuncture Points , Medicine, Chinese Traditional , MeridiansABSTRACT
Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure to establish a portosystemic shunt between the hepatic vein and the portal vein via the jugular approach, so as to reduce portal venous pressure and control acute esophagogastric variceal bleeding (EGVB). The prognosis of EGVB has been improved significantly over the past few decades, and endoscopic variceal ligation combined with drug therapy is now recommended as the first-line treatment regimen for this disease. The latest research advances in the management of EGVB over the past decade have focused on the relatively new concept of "early" or "pre-emptive" TIPS, that is to say, early TIPS (within 72 hours after admission, ideally within 24 hours) is recommended for patients with EGVB who are at a relatively high risk of failure in standard treatment. This article briefly introduces the effect of early TIPS on controlling bleeding, mortality rate, and hepatic encephalopathy, the high-risk population for early TIPS, timing of intervention, cost effectiveness, the applications of early TIPS in a real-world setting, and recommendations for early TIPS in international guidelines and consensus statements.
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We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia (BPH) on the efficacy of transurethral prostatectomy. Symptomatic, imaging, and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University (Chengdu, China) from July 2019 to December 2021 were collected. Follow-up data included the quality of life (QoL), International Prostate Symptom Score (IPSS), and IPSS storage and voiding (IPSS-s and IPSS-v). Moreover, urinary creatinine (Cr), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin estradiol (PGE2) were measured in 30 patients with BPH and 30 healthy participants. Perioperative indicators were determined by subgroup analyses and receiver operating characteristic (ROC) curve analysis. Among the 313 patients with BPH included, patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms. Similarly, good bladder sensation, compliance, and detrusor contractility (DC) were predictors of low postoperative IPSS and QoL. The urinary concentrations of BDNF/Cr, NGF/Cr, and PGE2/Cr in patients were significantly higher than those in healthy participants (all P < 0.001). After evaluation, only DC was significantly related to both urinary indicators and postoperative recovery of patients. Patients with good DC, as predicted by urinary indicators, had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively (both P < 0.05). In summary, patients with impaired bladder function had poor recovery. The combined levels of urinary BDNF/Cr, NGF/Cr, and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladder function and postoperative recovery.
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OBJECTIVE@#To investigate the application of 3D printing percutaneous surgical guide plate in closed reduction and cannulated screw internal fixation of femoral neck fracture.@*METHODS@#The clinical data of 12 patients with femoral neck fracture from March 2019 to March 2022 were retrospectively analyzed. Patients were divided into observation group and control group according to different operation plans, with 6 cases in each group. The observation group received percutaneous operation guide plate assisted closed reduction and hollow screw internal fixation, while the control group received closed reduction and hollow compression screw internal fixation. The operation time, intraoperative blood loss, fluoroscopy times, and Kirschner needle puncture times were compared between two groups. The location of screws were recordedon postoperative X-ray films, follow-up time, time of complete fracture healing, Harris score of hip joint and the incidence of complications were recorded on postoperative X-ray films.@*RESULTS@#The operation time of observation group (32.17±6.18) min was shorter than that of control group (53.83±7.31) min (P<0.05). The amount of intraoperative bleeding in the observation group (18.33±2.94) ml was less than that in the control group (38.17±5.56) ml(P<0.05). The times of fluoroscopy in the observation group (7.50±1.05) were less than those in the control group (21.00±4.82) (P<0.05). The number of Kirschner needle punctures (8.00±0.63) in observation group was less than that in control group (32.67±3.08) (P<0.05). The follow-up time was(12.88±0.74) months in observation group and (12.83±0.72) months in control group, there was no significant difference between two groups (P>0.05). One year after operation, Harris score of hip joint in the observation group was(82.00±4.52) points, while that in the control group was(81.00±3.41) points, there was no significant difference between two groups(P>0.05). The time of complete fracture healing in the observation group was (7.50±1.05) months, while that in the control group was (7.67±1.21) months, there was no significant difference between two groups(P>0.05). The parallelism of the screws in the observation group was (0.50±0.11) ° and (0.76±0.15) °, which were lower than that in the control group (1.57±0.31) ° and (1.87±0.21) ° (P<0.05). The screw distribution area ratio (0.13±0.02) cm2 in the observation group was higher than that in the control group (0.08±0.01) cm2 (P<0.05). No complications such as necrosis of femoral head, nonunion of fracture, shortening of femoral neck and withdrawal of internal fixation occurred in both groups.@*CONCLUSION@#The application of 3D printing percutaneous surgical guide plate improves the accuracy and safety of closed reduction and cannulated screw internal fixation for femoral neck fracture. It has the advantages of minimally invasive, reducing radiation exposure, fast and accurate, shortening the operation time and reducing intraoperative bleeding.
Subject(s)
Humans , Retrospective Studies , Treatment Outcome , Femoral Neck Fractures/surgery , Fracture Fixation, Internal , Bone Screws , Printing, Three-DimensionalABSTRACT
Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Facial Paralysis/etiology , Diagnosis, Differential , Jugular Foramina , Retrospective Studies , Cough , Hoarseness , Neoplasm Recurrence, Local , Chondrosarcoma/surgeryABSTRACT
BACKGROUND: Primary spinal cord (PSC) glioblastoma (GB) is an extremely rare but fatal primary tumor of the central nervous system and associated with a poor prognosis. While typical tumor imaging features are generally easy to recognize, glioblastoma multiforme can have a wide range of imaging findings. Atypical GB is often misdiagnosed, which usually delays the optimal time for treatment. In this article, we discuss a clinical case of pathologically confirmed PSC GB under the guise of benign tumor imaging findings, as well as the most recent literature pertaining to PSC GB. CASE SUMMARY: A 70-year-old female complained of limb weakness lasting more than 20 d. Irregular masses were observed inside and outside the left foramina of the spinal canal at C7-T1 on medical imaging. Based on the imaging features, radiologists diagnosed the patient with schwannoma. Tumor resection was performed under general anesthesia. The final histopathological findings revealed a final diagnosis of PSC GB, world health organization Grade IV. The patient subsequently underwent a 4-wk course of radiotherapy (60 Gy in 20 fractions) combined with temozolomide chemotherapy. The patient was alive at the time of submission of this manuscript. CONCLUSION: Atypical GB presented unusual imaging findings, which led to misdiagnosis. Therefore, a complete recognition of imaging signs may facilitate early accurate diagnosis.
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Ammonia lyases have great application potential in food and pharmaceuticals owing to their unique ammonia addition reaction and atom economy. A novel methylaspartate ammonia-lyase, EcMAL, from E. coli O157:H7 showed high catalytic activity. To further strengthen its thermostability and activity, disulfide bond and backbone cyclization (cyclase) variants were constructed by rational design, respectively. Among them, variant M3, with a disulfide bond introduced, exhibited a 2.3-fold increase in half-life at 50 °C, while cyclase variant M8 showed better performance, with 25.9-fold increases. The synergistic promotion effect of this combinational strategy on activity and stability was also investigated, and the combined mutant M9 exhibited a 1.1-fold improvement in catalytic efficiency while maintaining good thermostability. Circular dichroism analysis and molecular dynamics simulation confirmed that the main sources of improved thermostability were reduced atomic fluctuation and a more stable secondary structure. To our knowledge, this is the first example of combining the introduction of disulfide bonds with cyclase construction to improve enzyme stability, which was characterized by modification away from the enzyme active center, and provided a new method for adjusting enzyme thermostability.
Subject(s)
Ammonia-Lyases , Escherichia coli , Ammonia , Cyclization , Disulfides/chemistry , Enzyme Stability , Pharmaceutical Preparations , TemperatureABSTRACT
Using data mining technology, the rules of acupoint selection of acupuncture and moxibustion were explored in treatment of stroke-related pneumonia. The clinical articles of acupuncture and moxibustion in treatment of stroke-related pneumonia were retrieved from CNKI, SinoMed, Wanfang and VIP databases from their inception through to January l 2021, and then, the acupuncture-moxibustion prescription database was set up for stroke-related pneumonia. SPSS Modeler 18.0 Apriori algorithm was adopted to analyze the association rules of acupoints and draw complex network diagrams. SPSS26.0 was used in clustering analysis of acupoints. Finally, a total of 44 articles were included, with 51 acupoint prescriptions and 82 acupoints extracted. The total frequency of acupoints was 340 times. The high-frequency acupoints in treatment with acupuncture and moxibustion for stroke-related pneumonia were Feishu (BL 13), Fenglong (ST 40), Hegu (LI 4), etc. These acupoints were mainly distributed on the limbs and back and mostly from yang meridians. Of these extracted acupoints, the five-shu points, convergent points and back-shu points were selected specially. Regarding acupoint combination, the association of Quchi (LI 11) had the highest support with Hegu (LI 4) and Zusanli (ST 36). The core prescription of acupuncture-moxibustion treatment for stroke-related pneumonia could be composed of Quchi (LI 11), Hegu (LI 4), Zusanli (ST 36), Fenglong (ST 40) and Taichong (LR 3).
Subject(s)
Humans , Acupuncture Points , Acupuncture Therapy , Meridians , Moxibustion , Pneumonia/therapy , Stroke/therapyABSTRACT
Based on the difference between disease and syndrome differentiation of acupuncture and moxibustion and each department of TCM, i.e. internal medicine, external medicine, gynecology and pediatrics, it is believed that "differentiation of disease location" is the key of disease and syndrome differentiation of acupuncture and moxibustion. According to the disease location, in the section "treatment" of Science of Acupuncture and Moxibustion, the disorders/illness are classified as zangfu disorder, disorders of limbs and meridians, dermatological disorder, ophthalmological and otorhinolaryngological disorder, gynecological disorder, as well as qi, blood and body fluid disorder. Besides, the rules of disease and syndrome differentiation, as well as treatment characteristics of each category are explained separately. It is considered that the clinical diagnosis and treatment system of acupuncture and moxibustion should be constructed by focusing on "differentiation of disease location".
Subject(s)
Child , Humans , Acupuncture , Acupuncture Therapy , Meridians , Moxibustion , SyndromeABSTRACT
Arterial spin labeling (ASL) perfusion MRI is a non-invasive technique for quantifying and mapping cerebral blood flow (CBF). Depending on the tissue signal change after magnetically labeled arterial blood enters the brain tissue, ASL MRI signal can be affected by several factors, including the volume of arrived arterial blood, signal decay of labeled blood, physiological fluctuations of the brain and CBF, and head motion, etc. Some of them can be controlled using sophisticated state-of-art ASL MRI sequences, but the others can only be resolved with post-processing strategies. Over the decades, various post-processing methods have been proposed in the literature, and many post-processing software packages have been released. This self-contained review provides a brief introduction to ASL MRI, recommendations for typical ASL MRI data acquisition protocols, an overview of the ASL data processing pipeline, and an introduction to typical methods used at each step in the pipeline. Although the main focus is on traditional heuristic model-based methods, a brief introduction to recent machine learning-based approaches is provided too.
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The brain relies on the blood-brain barrier (BBB) for the selective absorption of nutrients and the exclusion of other big molecules from the circulating blood. Therefore, the integrity of BBB is critical to brain health, and assessing BBB condition is of great clinical importance. BBB is often examined using exogenous tracers that can travel across the BBB, but the tracers might cause severe side effects. To avoid the use of external tracers, researchers have used magnetically labeled arterial blood as the endogenous tracer to assess the water permeability of BBB as a surrogate index of BBB. This paper reviews the three major types of arterial spin labelling-based BBB water permeability assessment techniques and their applications in brain diseases such as Alzheimer’s disease.
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Antireflective performance is critical for most optical devices, such as the efficient solar energy utilization in photovoltaic cells of an aerospace craft and optical displays of scientific precise equipment. Therein, outstanding broad-band antireflection is one of the most crucial properties for antireflection films (ARFs). Unfortunately, it is still a challenging work to realize perfect "broader-band" antireflection because both the low refractive indices materials and time-consuming nanotexturing technologies are required in the fabricating process. Even in this case, a broader-band and flexible ARF with hierarchical structures is successfully developed, which is inspired by butterfly wing scales. First, the butterfly wings surface is treated with acid and stuck on a clean glass. Now, all the scales on the wings will form a strong adhesion with the glass substrate. Then, the wings are removed and the scales are left on the glass slide. Now the backside of scales is facing outward, the backside structures of the scales are coincidentally used as the template. Finally, the structure is replicated and the ARF with a controllable thickness is successfully fabricated by rotating PDMS on the biological template. In this work, the bionic ARFs realize the transmission of nearly 90% and more than 90% in the visible light and infrared region. It enhanced transmission to 13% under standard illumination compared with flat PDMS films of the same thickness. Furthermore, the ARF is flexible enough that it could bend nearly 180° to meet the special antireflection requirements in some extreme conditions. It is expected that this bioinspired AR film could revolutionize the technologies of broader-band antireflective materials and impact numerous applications from glass displays to optoelectronic devices.
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Objective:To observe the effect of modified Shengjiangsan on renal fibrosis in rats with membranous nephropathy （MN） and to explore the mechanism of its complications of renal fibrosis. Method:Rats were injected with cationized bovine serum albumin（C-BSA）in the tail vein to establish a rat model of membranous nephropathy. The normal group，model group，modified Shengjiangsan group （27.3 g·kg<sup>-1</sup>）and benazepril group（10 mg·kg<sup>-1</sup>）were established in this study. Each group was given corresponding dosage of the drug once a day for 4 weeks of continuous intervention. After the administration，we observed the pathological changes of rat kidneys by the technology of Masson staining， silverhexylamine iodate （PASM） staining， transmission electron microscopy （TEM）， immunofluorescence technology （IF） was used to detect immunoglobulin（Ig）G deposition in rat kidneys. The levels of interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， interleukin-6 （IL-6）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） in rat serum were detected by enzyme-linked immunosorbent assay （ELISA） method. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and immunohistochemistry （IHC） were used to detect the mRNA and protein expression levels of monocyte chemotactic protein 1 （MCP-1）， intercellular adhesion molecule 1 （ICAM-1）， nuclear factor kappa B （NF-<italic>κ</italic>B）， Toll-like receptor 4 （TLR4）， plasminogen activator inhibitor 1 （PAI-1）， transforming growth factor-<italic>β</italic><sub>1</sub> （TGF-<italic>β</italic><sub>1</sub>）， <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMΑ） and type Ⅳ Collagen （Collagen Ⅳ） in rat kidney tissues. Result:Compared with normal group， the kidney tissue of the model group was obviously fibrotic， the serum levels of IL-1<italic>β</italic>， IL-6， and TNF-<italic>α</italic> were significantly increased（<italic>P</italic><0.05）， and the expressions of MCP-1， ICAM-1， NF-<italic>κ</italic>B， TLR4， PAI-1， TGF-<italic>β</italic><sub>1</sub>， <italic>α</italic>-SMA and Collagen Ⅳ mRNA and protein in kidney tissue were significantly increased（<italic>P</italic><0.05）. Compared with model group， modified Shengjiangsan and benazepril significantly improved renal fibrosis in rats， reduced the levels of IL-1<italic>β</italic>， IL-6， and TNF-<italic>α</italic> in the serum of MN rats（<italic>P</italic><0.05）， down-regulated MCP-1， ICAM-1， NF-<italic>κ</italic>B， TLR4， PAI-1， TGF-<italic>β</italic><sub>1</sub>， <italic>α</italic>-SMA and Collagen Ⅳ mRNA and protein expression in kidney tissue（<italic>P</italic><0.05）. Conclusion:Modified Shengjiangsan can reduce the release and expression of inflammatory factors by down-regulating the TLR4/NF-<italic>κ</italic>B signaling pathway， inhibit renal fibrosis， and reduce renal damage in MN rats.
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Objective:The purpose of this article was to observe the effect of modified Shengjiangsan on podocyte apoptosis in membranous nephropathy （MN） rats， to explore the molecular mechanism of its treatment of MN and to provide experimental basis for its clinical application. Method:The MN rat model was established by injection of cationic bovine serum albumin into the tail vein of rats. The successfully modeled rats were then randomly divided into model group （equal volume of normal saline）， modified Shengjiangsan group （27.3 g·kg<sup>-1</sup>） and benazepril group （10 mg·kg<sup>-1</sup>）， with corresponding drug dosage once a day for 4 weeks of continuous intervention. After drug administration， the 24-hour urine protein （UTP） was detected. Real time fluorescent quantitative polymerase chain reaction （Real-time PCR） and immunohistochemical （IHC） methods were used to detect Podocalyxin， Nephrin， Podocin， Synaptopodin mRNA and protein expression levels in rat kidney tissue. terninal-deoxynucleoitidyl transferase medsated nick and labeling （TUNEL） method was used to detect cell apoptosis rate in rat kidney tissue， and Western blot was used to detect Notch1， Hes1， B lymphoblastoma-2 （Bcl-2） associated X protein （Bax）， and Bcl-2 protein expression levels in rat kidney tissue. Result:Compared with the normal group， UTP in the model group increased significantly， renal tissue cell apoptosis increased significantly， podocyte marker proteins podocalyxin， Nephrin， Podocin， Synaptopodin mRNA and protein expression levels decreased significantly， and Notch1， Hes1， Bax protein expression increased significantly， and Bcl-2 protein expression was significantly reduced（<italic>P</italic><0.05）. Compared with the model group， UTP levels in MN rats were significantly reduced in modified Shengjiangsan and benazepril groups， with reduced rate of renal cell apoptosis， increased mRNA and protein expression levels of podocalyxin， Nephrin， Podocin， and Synaptopodin in renal tissue， decreased Notch1， Hes1， Bax protein expression， and increased Bcl-2 protein expression（<italic>P</italic><0.05）. Conclusion:Modified Shengjiangsan can inhibit the Notch signaling pathway， reduce the apoptosis of rat kidney tissue podocytes， and reduce the kidney injury of MN rats.
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Glioblastoma is the most common intracranial primary malignant tumor, which leads to the poor quality of life of patients and has a high recurrence rate. Chemotherapy is a vital part in the treatment of this disease. Tetrandrine(Tet) is an active ingredient extracted from the root of the Chinese medicinal plant Stephania tetrandra, which has been proved with a wide range of pharmacological effects including anti-tumor. However, there are few studies regarding the effect of Tet on glioma. In this study, MTT and BrdU assays were employed to detect the effect of Tet on the proliferation of LN229 glioblastoma cells; flow cytometry was used to analyze the cycle distribution and apoptosis; plate cloning assay and soft agar colony formation assay were performed to study the colony formation ability of LN229 cells exposed to Tet; scratch assay and Transwell assay were conducted to detect the ability of migration and invasion; Western blot was adopted to the exploration of the molecular mechanism. The MTT and BrdU assays showed that Tet inhibited the proliferation of LN229 cells in a time-and dose-dependent manner. The plate cloning assay and soft agar colony formation assay showed that Tet weakened the colony formation of LN229 cells in vitro; cytometry assay showed that Tet blocked cells in the G_1 phase and promoted cell apoptosis; scratch and Transwell assays proved that Tet inhibited the migration and invasion of LN229 cells; Western blot results showed that Tet down-regulated the expression levels of CDK2, CDK6, cyclin D1, cyclin E1, snail, slug, vimentin, and N-cadherin, while up-regulated the level of E-cadherin. The results indicate that Tet has a certain inhibitory effect on the proliferation, migration, and invasion of LN229 glioblastoma cells, and such effect may be related to the participation of Tet in the regulation of c-Myc/p27 axis and snail signaling pathway.
Subject(s)
Humans , Apoptosis , Benzylisoquinolines , Cell Line, Tumor , Cell Movement , Cell Proliferation , Glioblastoma/genetics , Quality of LifeABSTRACT
Through analyzing the indication distribution of the different acupoints located at the upper limbs recorded in