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1.
Orthop Surg ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33821557

RESUMO

OBJECTIVE: The purpose of the present study was to discuss a new surgical strategy that combines percutaneous endoscopic transforaminal discectomy (PETD) with percutaneous endoscopic interlaminar discectomy (PEID) for L4/5 and L5/S1 two-level disc herniation. METHODS: This was a retrospective study. A total of 19 patients with L4/5 and L5/S1 two-level lumbar disc herniation (LDH) who underwent percutaneous endoscopic lumbar discectomy (PELD) in our hospital from January 2015 to June 2016 were retrospectively examined. The average age of these 19 patients was 42.21 ± 14.88 years old, including 12 men and 7 women. One experienced surgeon who had carried out more than 3000 lumbar surgeries performed PELD for these patients. During the PELD surgery, the transforaminal approach was adopted for L4/5 level disc herniation and the interlaminar approach was adopted for L5/S1 level disc herniation. The demographic data, operation time (min), fluoroscopy times, hospital stay (days), and complications were recorded and analyzed. The visual analogue scale (VAS), Oswestry disability index (ODI) scores, and the modified MacNab criteria were used to evaluate the surgical outcomes. MRI was conducted to evaluate the radiographic improvement. RESULTS: All patients underwent PELD via the transforaminal approach combined with the interlaminar approach successfully and achieved satisfactory efficacy. The follow-up points were 3, 12, and 18 months. The average hospital stay (days) and the average follow up (months) were 3.32 ± 0.98 and 18.63 ± 3.84, respectively. The operation time and fluoroscopy times were 85.79 ± 12.90 min and 39.05 ± 4.59 times, respectively. The fluoroscopy times (frequency) for L4/5 and L5/S1 were 26.95 ± 6.41 and 12.11 ± 3.49 (t = 7.00, P < 0.05). Furthermore, there was no significant difference for fluoroscopy times between male and female patients (t = 0.89, P = 0.99). The preoperative back pain (VAS-Back) and the last follow-up VAS-Back were 5.58 ± 2.01 and 2.37 ± 1.01, respectively (t = 7.14, P < 0.05). The preoperative leg pain (VAS-Leg) and the last follow-up VAS-Leg were 7.00 ± 1.56 and 1.63 ± 1.01, respectively (t = 20.97, P < 0.05). There were significant differences between preoperative VAS-Back and the last follow-up VAS-Back in men (t = 4.61, P < 0.05) and women (t = 6.57, P < 0.05). In addition, there was significant differences between preoperative VAS-Leg and the last follow-up VAS-Leg in men (t = 13.48, P < 0.05) and women (t = 26.87, P < 0.05). There were significant differences between preoperative ODI scores (44.84 ± 10.82%) and the last follow-up ODI scores (11.12 ± 5.80%) (t = 10.92, P < 0.05). Preoperative ODI scores and the last follow-up ODI scores were significantly different for men (t = 8.80, P < 0.05) and women (t = 6.63, P < 0.05). All patients received significant pain relief and functional improvement after the surgery. Except for two cases of postoperative dysesthesia and one dural tear, no severe complications occurred. The dysesthesia symptoms of these two patients disappeared within 1 week with the application of dexamethasone and neurotrophic drugs and the dural tear case also recovered well as the dural laceration was small. No poor results were reported and 89.47% of patients achieved excellent or good recovery. CONCLUSION: Percutaneous endoscopic lumbar discectomy via the transforaminal approach combined with the interlaminar approach under epidural anesthesia can treat L4/5 and L5/S1 two-level disc herniation safely and effectively.

2.
Molecules ; 26(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810025

RESUMO

Protein kinases are key enzymes in many signal transduction pathways, and play a crucial role in cellular proliferation, differentiation, and various cell regulatory processes. However, aberrant function of kinases has been associated with cancers and many other diseases. Consequently, competitive inhibition of the ATP binding site of protein kinases has emerged as an effective means of curing these diseases. Over the past three decades, thousands of protein kinase inhibitors (PKIs) with varying molecular frames have been developed. Large-scale data mining of the Protein Data Bank resulted in a database of 2139 non-redundant high-resolution X-ray crystal structures of PKIs bound to protein kinases. This provided us with a unique opportunity to study molecular determinants for the molecular recognition of PKIs. A chemoinformatic analysis of 2139 PKIs resulted in findings that PKIs are "flat" molecules with high aromatic ring counts and low fractions of sp3 carbon. All but one PKI possessed one or more aromatic rings. More importantly, it was found that the average weighted hydrogen bond count is inversely proportional to the number of aromatic rings. Based on this linear relationship, we put forward the exchange rule of hydrogen bonding interactions and non-bonded π-interactions. Specifically, a loss of binding affinity caused by a decrease in hydrogen bonding interactions is compensated by a gain in binding affinity acquired by an increase in aromatic ring-originated non-bonded interactions (i.e., π-π stacking interactions, CH-π interactions, cation-π interactions, etc.), and vice versa. The very existence of this inverse relationship strongly suggests that both hydrogen bonding and aromatic ring-originated non-bonded interactions are responsible for the molecular recognition of PKIs. As an illustration, two representative PKI-kinase complexes were employed to examine the relative importance of different modes of non-bonded interactions for the molecular recognition of PKIs. For this purpose, two FDA-approved PKI drugs, ibrutinib and lenvatinib, were chosen. The binding pockets of both PKIs were thoroughly examined to identify all non-bonded intermolecular interactions. Subsequently, the strengths of interaction energies between ibrutinib and its interacting residues in tyrosine kinase BTK were quantified by means of the double hybrid DFT method B2PLYP. The resulting energetics for the binding of ibrutinib in tyrosine kinase BTK showed that CH-π interactions and π-π stacking interactions between aromatic rings of the drug and hydrophobic residues in its binding pocket dominate the binding interactions. Thus, this work establishes that, in addition to hydrogen bonding, aromatic rings function as important molecular determinants for the molecular recognition of PKIs. In conclusion, our findings support the following pharmacophore model for ATP-competitive kinase inhibitors: a small molecule features a scaffold of one or more aromatic rings which is linked with one or more hydrophilic functional groups. The former has the structural role of acting as a scaffold and the functional role of participating in aromatic ring-originated non-bonded interactions with multiple hydrophobic regions in the ATP binding pocket of kinases. The latter ensure water solubility and form hydrogen bonds with the hinge region and other hydrophilic residues of the ATP binding pocket.

3.
Chin J Integr Med ; 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33837482

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). METHODS: A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. RESULTS: The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case. CONCLUSION: The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].

4.
Zhen Ci Yan Jiu ; 46(3): 194-200, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33798291

RESUMO

OBJECTIVE: To explore the effect of moxibustion at "Zusanli"(ST36) and "Shenshu"(BL23) on synovitis, and expressions of miR-155, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), interlukine(IL-1) receptor-associated kinase (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor κB (NF-κB), IL-1ß, tumor necrosis factor receptor (TNF)-α and IL-6 mRNA and protein of synovial membrane in rheumatoid arthritis (RA) rats, so as to explore its mechanism underlying improvement of RA. METHODS: A total of 48 male Wistar rats were randomly divided into normal control, model, moxibustion and antagonist groups (n=12 rats in each group). The RA model was replicated by placing the rats in a wind, cold and wet environment and injection of Freund's complete adjuvant (CFA, 0.5 mL) into the right hindlimb foot plantar. Moxibustion was applied to bilateral ST36 and BL23 for 30 min, once daily for 21 consecutive days. Rats of the antagonist group was treated by injection of TLR4 antagonist (TAK-242, 1 mg/mL, 0.1 mg/kg) via tail vein, once per day for consecutive 21 d. The joint swelling degree (JSD) and arthritis index (AI, red swelling scale) were determined, and the expression levels of various indicators of miR-155, and TLR4, myeloid MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein were assayed by quantitative real time-PCR and Western blot, separately. RESULTS: Compared with the normal control group, the JSD and AI, and the expression levels of synovial miR-155, TLR4, MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein were significantly increased in the model group (P<0.01). Compared with the model group, the increased levels of JSD and AI, and the expression levels of synovial miR-155, TLR4, MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein were notably down-regulated in both moxibustion and antagonist groups (P<0.01). The effects of moxibustion were evidently superior to the antagonist in down-regulating the abovementioned indexes (P<0.01), except TLR4 mRNA and protein. CONCLUSION: Moxibustion at ST36 and BL23 can reduce the synovitis of RA rats, which is related to its effects in suppressing the expressions of miR-155, TLR4, MyD88, IRAK1, TRAF6, NF-κB, IL-1ß, TNF-α and IL-6 mRNA and protein (i.e., inhibition of miR-155/TLR4/NF-κB signaling).


Assuntos
Artrite Reumatoide , MicroRNAs , Moxibustão , Sinovite , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/terapia , Masculino , MicroRNAs/genética , NF-kappa B/genética , Ratos , Ratos Wistar , Receptor 4 Toll-Like/genética
5.
Anal Chem ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797890

RESUMO

The multiple-metal-nanoparticle tagging strategy has generally been applied to the multiplexed detection of multiple analytes of interest such as microRNAs (miRNAs). Herein, it was used for the first time to improve both the specificity and sensitivity of a novel mass spectroscopic platform for miRNA detection. The mass spectroscopic platform was developed through the integration of the ligation reaction, hybridization chain reaction amplification, multiple-metal-nanoparticle tagging, and inductively coupled plasma mass spectrometry. The high specificity resulted from the adoption of the ligation reaction is further enhanced by the multiple-metal-nanoparticle tagging strategy. The combination of hybridization chain reaction amplification and metal nanoparticle tagging endows the proposed platform with the feature of high sensitivity. The proposed mass spectrometric platform achieved quite satisfactory quantitative results for Let-7a in real-world cell line samples with accuracy comparable to that of the real-time quantitative reverse-transcriptase polymerase chain reaction method. Its limit of detection and limit of quantification for Let-7a were experimentally determined to be about 0.5 and 10 fM, respectively. Furthermore, due to the unique way of utilizing the multiple-metal-nanoparticle tagging strategy, the proposed platform can unambiguously discriminate between the target miRNA and nontarget ones with single-nucleotide polymorphisms based on their response patterns defined by the relative mass spectral intensities among the multiple tagged metal elements and can also provide location information of the mismatched bases. Its unique advantages over conventional miRNA detection methods make the proposed platform a promising and alternative tool in the fields of clinical diagnosis and biomedical research.

6.
ACS Infect Dis ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33834753

RESUMO

Carbapenem-resistant Klebsiella pneumoniae has been classified as an Urgent Threat by the Centers for Disease Control and Prevention (CDC). The combination of two "old" antibiotics, polymyxin and chloramphenicol, displays synergistic killing against New Delhi metallo-ß-lactamase (NDM)-producing K. pneumoniae. However, the mechanism(s) underpinning their synergistic killing are not well studied. We employed an in vitro pharmacokinetic/pharmacodynamic model to mimic the pharmacokinetics of the antibiotics in patients and examined bacterial killing against NDM-producing K. pneumoniae using a metabolomic approach. Metabolomic analysis was integrated with an isolate-specific genome-scale metabolic network (GSMN). Our results show that metabolic responses to polymyxin B and/or chloramphenicol against NDM-producing K. pneumoniae involved the inhibition of cell envelope biogenesis, metabolism of arginine and nucleotides, glycolysis, and pentose phosphate pathways. Our metabolomic and GSMN modeling results highlight the novel mechanisms of a synergistic antibiotic combination at the network level and may have a significant potential in developing precision antimicrobial chemotherapy in patients.

7.
Int Urol Nephrol ; 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33713287

RESUMO

BACKGROUND: L-carnitine is an amino acid derivative that is thought to be helpful for treating renal anemia in hemodialysis patients. However, the mechanism remains to be fully elucidated. METHODS: A literature search was performed on PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) and conduct a meta-analysis for investigating the effect of L-carnitine in the treatment of renal anemia in participants receiving hemodialysis. RESULTS: A total of 18 eligible trials with 1090 participants were included in this study. L-carnitine can significantly increase plasma free L-carnitine levels (mean difference [MD]: 140.53, 95% confidence interval [CI] 102.22-178.85; P < 0.00001), decrease the erythropoietin responsiveness index (ERI; MD: -2.72, 95% CI -3.20 to -2.24; P < 0.00001) and the required erythropoiesis-stimulating agent (ESA) doses (MD: -1.70, 95% CI -2.04 to -1.36; P < 0.00001). However, the use of L-carnitine was not associated with a higher hemoglobin level (MD: 0.18, 95% CI -0.20 to 0.55; P = 0.35) and hematocrit level (MD: 1.07, 95% CI -0.73 to 2.87; P = 0.24). In subgroup analyses, the effects of L-carnitine supplementation on renal anemia in patients on hemodialysis were independent of the treatment duration and intervention routes. CONCLUSION: The present meta-analysis indicated that L-carnitine therapy significantly increased plasma L-carnitine concentrations, improved the response to ESA, decreased the required ESA doses in patients receiving hemodialysis, and maintained hemoglobin and hematocrit levels. L-carnitine supplementation should be supported in hemodialysis patients. However, the relationship between L-carnitine treatment and long-term outcomes is still unclear. Further high-quality RCTs are needed to verify our findings.

8.
Genomics ; 113(3): 1482-1490, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33771636

RESUMO

Retinal ischemia-reperfusion (I/R) is involved in the pathogenesis of many vision-threatening diseases. circRNAs act as key players in gene regulation and human diseases. However, the global circRNA expression profile in retinal I/R injury has not been fully uncovered. Herein, we established a murine model of retinal I/R injury and performed circRNA microarrays to identify I/R-related circRNAs. 1265 differentially expressed circRNAs were identified between I/R retinas and normal retinas. Notably, the detection of cWDR37 level in aqueous humor could discriminate glaucoma patients from cataract patients (AUC = 0.9367). cWdr37 silencing protected against hypoxic stress- or oxidative stress-induced retinal ganglion cell (RGC) injury. cWdr37 silencing alleviated IR-induced retinal neurodegeneration as shown by increased NeuN staining, reduced retinal reactive gliosis, and decreased retinal apoptosis. Collectively, this study provides a novel insight into the pathogenesis of retinal I/R injury. cWdr37 is a promising target for the diagnosis or treatment of I/R-related ocular diseases.

9.
Orthop Surg ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33783979

RESUMO

OBJECTIVE: To investigate the epidemiological characteristics of major intra-articular fractures. METHODS: This retrospective study enrolled patients with major intra-articular fractures who were treated in the Third Hospital of Hebei Medical University from January 2015 to December 2019. A total of 11,084 patients (7,338 [66.20%] males and 3,746 [33.80%] females) meeting the inclusion and exclusion criteria were included. The distribution characteristics of intra-articular fractures involving shoulder, elbow, wrist, hip, knee, ankle, and subtalar joints were identified.The potential associations between fractures and various other factors, such as age, gender, sites, were explored. RESULTS: There were 74 cases (0.67%) of shoulder fractures, 1,941 cases (17.51%) of elbow fractures, 1,155 cases (10.42%) of wrist fractures, 520 cases (4.69%) of hip fractures, 3,118 cases (28.13%) of knee fractures, 2,156 cases (19.45%) of ankle fractures, and 2,120 cases (19.13%) of subtalar fractures. The overall male-to-female ratio was 1.96:1. The highest proportion age group of major intra-articular fractures included the ages 45-54 years. For males, the highest proportion age group was 45-54 years, for females, it was 55-64 years. The knee joint fracture was the most common type, accounting for 28.13%. For male and female patients, knee fractures accounted for 26.19% and 31.93%, respectively, with a male to female ratio of 1.13:1. The proportion of shoulder fractures was the smallest among this investigation, accounting for 0.67%. For male and female patients, shoulder fractures accounted for 0.44% and 1.12%, respectively, with a male to female ratio of 0.76:1. The age group with the highest proportion of shoulder joint fractures was ≥65 year olds (41.89%), with a male to female ratio of 0.76:1. The age group with the highest risk of elbow, wrist, hip, knee, ankle, and subtalar joint fracture was 5-14 year olds (33.59%) with a male to female ratio of 3.29:1, 5-14 year olds (23.98%) with a male to female ratio of 6.91:1, 45-54 year olds (26.92%) with a male to female ratio of 5.67:1, 45-54 year olds (24.60%) with a male to female ratio of 1.68:1, 25-34 year olds (20.36%) with a male to female ratio of 2.30:1, 45-54 year olds (27.41%) with a male to female ratio of 9.02:1, respectively. The most common site of intra-articular fractures in different age groups was corresponding as follows: 0-4 year olds (elbow), 5-14 year olds (elbow), 15-24 year olds (ankle), 25-34 year olds (subtalar joint), 35-44 year olds (subtalar joint), 45-54 year olds (knee), 55-64 year olds (knee), 65-74 year olds (knee), and ≥75 year olds (knee). CONCLUSION: The current study revealed the age- and gender-specific epidemiological characteristics of major intra-articular fractures, providing a basis for clinical evaluation and practices.

10.
Sleep ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33768250

RESUMO

Chronic short sleep (CSS) is prevalent in modern societies and has been proposed as a risk factor for Alzheimer's disease (AD). In support, short-term sleep loss acutely increases levels of amyloid ß (Aß) and tau in wild type (WT) mice and humans, and sleep disturbances predict cognitive decline in older adults. We have shown that CSS induces injury to and loss of locus coeruleus neurons (LCn), neurons with heightened susceptibility in AD. Yet whether CSS during young adulthood drives lasting Aß and/or tau changes and/or neural injury later in life in the absence of genetic risk for AD has not been established. Here we examined the impact of CSS exposure in young adult WT mice on late-in-life Aß and tau changes and neural responses in two AD-vulnerable neuronal groups, LCn and hippocampal CA1 neurons. Twelve months following CSS exposure, CSS-exposed mice evidenced reductions in CA1 neuron counts and volume, spatial memory deficits, CA1 glial activation, and loss of LCn. Aß42 and hyperphosphorylated tau were increased in the CA1; however, amyloid plaques and tau tangles were not observed. Collectively the findings demonstrate that CSS exposure in the young adult mouse imparts late-in-life neurodegeneration and persistent derangements in amyloid and tau homeostasis. These findings occur in the absence of a genetic predisposition to neurodegeneration and demonstrate for the first time that CSS can induce lasting, significant neural injury consistent with some, but not all, features of late onset AD.

11.
Vet Med Sci ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780162

RESUMO

BACKGROUND: Litter size is an important factor that significantly affects the development of the sheep industry. Our previous TMT proteomics analysis found that three key proteins in the ovarian steroidogenesis pathway, STAR, HSD3B1, and CYP11A1, may affect the litter size trait of Small Tail Han sheep. OBJECTIVE: The purpose of this study was to better understand the relationship between polymorphisms of these three genes and litter size. MATERIAL AND METHOD: Sequenom MassARRAY detected genetic variance of the three genes in 768 sheep. Real-time qPCR of the three genes was used to compare their expression in monotocous and polytocous sheep in relevant tissues. Finally, bioinformatics analysis predicted the protein sequences of the different SNP variants. RESULT: Association analysis showed that there was a significant difference in litter size among the genotypes at two loci of the CYP11A1 gene (p < 0.05), but no significant difference was observed in litter size among all genotypes at all loci of the STAR and HSD3B1 genes (p > 0.05). However, STAR expression was significantly different in polytocous and monotocous sheep in the pituitary (p < 0.01). Tissue-specific expression in the ovary was observed for HSD3B1 (p < 0.05), but its expression was not different between polytocous and monotocous sheep. Bioinformatics analysis showed that the g.33217408C > T mutation of CYP11A1 resulted in major changes to the secondary and tertiary structures. In contrast, gene polymorphisms in STAR and HSD3B1 had minimal impacts on their protein structures. DISCUSSION: This may explain why the CYP11A1 variant impacted litter size while the others did not. The single nucleotide polymorphism of the CYP11A1 gene would serve as a good molecular marker when breeding to increase litter size in sheep. Our study provides a basis for further revealing the function of the ovarian steroidogenesis pathway in sheep reproduction and sheep breeding.

12.
Zhongguo Zhong Yao Za Zhi ; 46(1): 6-14, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645045

RESUMO

Hypertension is a clinical syndrome characterized by elevated systemic arterial blood pressure, which may be accompanied by functional or organic damage of heart, brain, kidney and other organs. The pathogenesis and development of hypertension are affected by genetic, environmental, epigenetic, intestinal microbiota and other factors. They are the result of multiple factors that promote the change of blood pressure level and vascular resistance. G protein coupled receptors(GPCRs) are the largest and most diverse superfamily of transmembrane receptors that transmit signals across cell membranes and mediate a large number of cellular responses required by human physiology. A variety of GPCRs are involved in the control of blood pressure and the maintenance of normal function of cardiovascular system. Hypertension contributes to the damages of heart, brain, kidney, intestine and other organs. Many GPCRs are expressed in various organs to regulate blood pressure. Although many GPCRs have been used as therapeutic targets for hypertension, their efficacy has not been fully studied. The purpose of this paper is to elucidate the role of GPCRs in blood pressure regulation and its distribution in target organs. The relationship between GPCRs related to intestinal microorganisms and blood pressure is emphasized. It is proposed that traditional Chinese medicine may be a new way to treat hypertension by regulating the related GPCRs via intestinal microbial metabolites.


Assuntos
Microbioma Gastrointestinal , Hipertensão , Pressão Sanguínea , Proteínas de Ligação ao GTP , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo
13.
Stem Cell Rev Rep ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33661471

RESUMO

BACKGROUND: Previous studies have showed the beneficial effects of mesenchymal stem cells (MSCs) on experimental intracerebral hemorrhage (ICH) animal. Enhancement of the treatment efficacy of MSCs in ICH is essential, considering the diseases association with high rates of disability and mortality. Some auxiliary methods to enhance the beneficial efficacy of MSCs have been introduced. However, the effect of electroacupuncture (EA) on the therapeutic efficacy of MSCs transplantation in hemorrhagic stroke and its potential mechanism is not explored. METHODS: ICH rat models were established using collagenase and heparin. 48 h after ICH induction, the rats were randomly divided into model control (MC), MSCs transplantation (MSCs), EA stimulation (EA) and MSCs transplantation combined with EA stimulation (MSCs + EA) groups. We used mNSS test and gait analysis to assess neurological function of rats, and PET/CT to evaluate the volume of hemorrhage focus and level of glucose uptake. The concentrations of MDA, SOD, NSE, S100B and MBP in serum or plasma were examined with ELISA. Neural differentiation of MSCs, and the expressions of Bcl-2, Bax, Arg-1 and iNOS proteins around hematoma were detected by immunofluorescence and immunohistochemistry staining respectively. Western blot was carried out to analyze the expression levels of COX4, OGDH, PDH-E1α, Bcl-2 and Bax proteins. TUNEL staining was used to estimate cell apoptosis and transmission electron microscopy (TEM) was used to observe the ultrastructure and number of mitochondria. RESULTS: Our data showed that EA promoted neuron-like differentiation of transplanted MSCs and the expressions of BDNF and NGF proteins in ICH rats. The score of mNSS and the gait analysis showed that the recovery of the neurological function in the MSCs + EA group was better than that in the MSCs and EA groups. EA improved the structure of brain tissue, and alleviated brain injury further after MSCs transplantation in ICH rats. When compared with the MSCs and EA groups, the level of glucose uptake and numbers of mitochondria and Arg-1 positive cells in MSCs + EA group increased significantly, but the numbers of apoptotic cells and iNOS positive cells and volume of hemorrhage focus reduced. The expressional levels of COX4, OGDH, PDH-E1α and Bcl-2 proteins increased, while the expressional level of Bax protein decreased compared with those in the MSCs and EA groups. CONCLUSIONS: Our results reveal that EA improve therapeutic efficacy of MSCs transplantation in ICH rats.

14.
Front Immunol ; 12: 613907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679754

RESUMO

Idiopathic pulmonary fibrosis (IPF) is serious chronic lung disease with limited therapeutic approaches. Inflammation and immune disorders are considered as the main factors in the initiation and development of pulmonary fibrosis. Inspired by the key roles of macrophages during the processes of inflammation and immune disorders, here, we report a new method for direct drug delivery into the in-situ fibrotic tissue sites in vitro and in vivo. First, liposomes containing dexamethasone (Dex-L) are prepared and designed to entry into the macrophages in the early hours, forming the macrophages loaded Dex-L delivery system (Dex-L-MV). Chemokine and cytokine factors such as IL-6, IL-10, Arg-1 are measured to show the effect of Dex-L to the various subtypes of macrophages. Next, we mimic the inflammatory and anti-inflammatory microenvironment by co-culture of polarized/inactive macrophage and fibroblast cells to show the acute inflammation response of Dex-L-MV. Further, we confirm the targeted delivery of Dex-L-MV into the inflammatory sites in vivo, and surprisingly found that injected macrophage containing Dex can reduce the level of macrophage infiltration and expression of the markers of collagen deposition during the fibrotic stage, while causing little systematic toxicity. These data demonstrated the suitability and immune regulation effect of Dex-L-MV for the anti-pulmonary process. It is envisaged that these findings are a step forward toward endogenous immune targeting systems as a tool for clinical drug delivery.

15.
Food Res Int ; 140: 110085, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33648303

RESUMO

Ultraviolet-C (UV-C) light is a non-thermal method for improving the safety and shelf-life of cold-pressed juices with minimal impact on quality and nutrition. Most previous studies have investigated fruit juices as opposed to particulate dense leafy green juices with very low UV transmittance (UVT). Pure kale juice is a common juice ingredient and represents the worst-case scenario in terms of low UVT green juices. This study validated the use of continuous benchtop UV-C treatment at 253.7 nm for 5-log reduction of non-pathogenic Escherichia coli P36 in kale juice. An average absorbed fluence of 108.3 mJ cm-2 resulted in a 5.8 log reduction of E. coli P36. At a fluence comparable to that reported for commercial juice processing (74.0 mJ cm-2), kale juice exhibited a decrease in absorption coefficient, while sedimentation, supernatant browning and pectin methylesterase activity increased with no effect on the chlorophyll content, colour, viscosity or antioxidant content.

16.
Phytomedicine ; 85: 153514, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33676083

RESUMO

BACKGROUND: Prostate cancer (PCa) is a major cause of morbidity and mortality in men in both developed and developing countries. Androgens and the androgen receptor (AR) play predominant roles in the progression of PCa. Neoisoliquiritin (NEO) belongs to the class of licorice (Glycyrrhiza) flavonoids, which have a variety of biological activities including anti-depressant, anti-tumor-promoting, and anti-inflammation properties. Licorice root has cancer chemopreventive effects and has been given to PCa patients as an ingredient of PC-SPES, a commercially available combination of eight herbs. Therefore, we determined if NEO can suppress the proliferation of PCa cells. PURPOSE: We investigated whether and how NEO exerts its anti-neoplastic activity against PCa. METHODS: The Cell Counting Kit 8 and flow cytometry were used to evaluate the effects of NEO on the proliferation and cell cycle progression of AR-dependent (LNCaP) and AR-independent (PC3) PCa cells. RNA sequencing was employed to examine the genome-wide changes in responsiveness to NEO in LNCaP cells. Quantitative PCR, Western blotting, docking, chromatin immunoprecipitation, and dual-luciferase reporter assays were conducted to determine the mechanism of action of NEO and its potential cross-talk with AR. A LNCaP xenograft nude mouse model was used to determine the inhibitory effects of NEO on AR-dependent PCa tumors in vivo. RESULTS: NEO inhibited LNCaP cell proliferation in vitro by inducing G0/G1 phase cell cycle arrest. Conversely, NEO treatment had no effect on PC3 cells. Transcriptomic analysis indicated that AR signaling might be the key target of NEO in preventing PCa. NEO regulated AR-mediated cell growth suppression and AR-sensitized cell cycle arrest in LNCaP cells. NEO also blocked several key steps in the AR signaling pathway, including proposed targeting to the ligand binding pocket of AR by computer modeling, modulating AR-androgen response element DNA-binding activity, inhibiting the expression and transcriptional activity of AR, and suppressing downstream AR signaling. CONCLUSIONS: NEO negatively regulates AR expression and activity, thus supporting the tumor suppressive role for NEO in AR-dependent PCa.

18.
Medicine (Baltimore) ; 100(13): e25181, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787598

RESUMO

ABSTRACT: This retrospective study aimed to explore the effect of orthodontic treatment (ODT) on anterior tooth displacement (ATD) caused by periodontal disease (PD).A total of 72 patients were selected and were divided into a control group (n = 36) and an experimental group (n = 36). Patients in both groups received conventional periodontal treatment. In addition, patients in the experimental group also received ODT. Outcomes include probing depth, percentage of bleeding sites, clinical attachment loss, clinical crown length, tooth root length, and periodontal tissue of the affected tooth (alveolar bone height, periodontal pocket depth, bleeding index).After treatment, the patients in the experimental group achieved more improvements in probing depth (P < .01), percentage of bleeding sites (P < .01), clinical attachment loss (P < .01), clinical crown length (P = .04), and periodontal tissue of the affected tooth (periodontal pocket depth (P < .01), and bleeding index (P < .01)), than those of patients in the control group.This study suggests that ODT is beneficial for ATD caused by PD. Future studies are still needed to verify the findings of this study.

19.
Dalton Trans ; 50(13): 4713-4719, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33729226

RESUMO

Two types of Cu(ii)-AMP-4,4'-bipy coordination polymers, {[Cu(AMP)(4,4'-bipy)(H2O)3]·5H2O}n (1) and {[Cu2(HAMP)2(4,4'-bipy)2(H2O)4]·2NO3·11H2O}n (2) (Na2AMP = adenosine 5'-monophosphate disodium salt), were synthesised through pH control. X-ray single-crystal diffraction analysis revealed that 1 and 2 are one-dimensional (1D) coordinating coordination polymers. The nucleotide in 1 was not protonated whereas that in 2 was protonated. With the protonated NO3- in 2 entering the crystal lattice, it plays a role in balancing the charge. The chirality was studied using solid-state circular dichroism (CD) spectroscopy based on the analysis of crystal structures.

20.
Clin Nephrol ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33749583

RESUMO

AIMS: The therapeutic effect of plasma exchange (PLEX) combined with conventional treatment in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. MATERIALS AND METHODS: We searched PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure for randomized controlled trials (RCTs) and cohort studies that compared PLEX added to conventional therapy with conventional therapy only in active AAV. RESULTS: 19 studies were included for the meta-analysis. Compared with the conventional therapy group, the PLEX group had a significantly reduced risk of end-stage renal disease (ESRD) at 3 months (odds ratio (OR) = 0.32, 95% confidence interval (CI) = 0.16 - 0.66, p = 0.002, I2 = 0%), and the ANCA titerwas also decreased (OR = 40.99, 95% Cl = 23.56 - 58.43, p < 0.00001, I2 = 42%). The plasma and non-plasma exchange groups had no substantial differences in terms of short- and long-term outcomes, including all-cause mortality, ESRD risk at 12 months and 5 years, remission rate, serum creatine levels, or serious adverse events. CONCLUSION: PLEX therapy was not associated with favorable long-term outcomes, although the results showed benefits in the incidence of ESRD rate at 3 months and ANCA titers in patients with AAV. No advantage of PLEX added to conventional therapy on mortality and complete remission was observed in patients with diffuse alveolar hemorrhage. Further high-quality multicenter RCTs with a high number of participants are required to assess the potential efficacy of PLEX in active AAV.

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