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Introduction: Acupuncture analgesia (AA) is widely used in clinical practice. The autonomic nervous system (ANS) may be an important pathway for acupuncture signal transduction. However, real-time changes in autonomic function during AA and the effect of "needle sensation" remain unclear. Methods: We established a human pain model in healthy adults and randomly assigned 128 participants to the model, sham acupuncture, and acupuncture groups in a 1:1:2 ratio. Heart rate variability (HRV), including total power (TP), low-frequency power (LF), high-frequency power (HF), ratio of LF to HF (LF/HF), standard deviation of the normal-normal intervals (SDNN), and root mean square of successive interval differences (RMSSD), were used to assess autonomic function. The visual analog scale (VAS) and efficiency were used to assess the analgesic effect of acupuncture. The Massachusetts General Hospital acupuncture sensation scale (MASS) was used to indicate the intensity of the needle sensation. Anxiety levels were also measured. Finally, the correlation of MASS with HRV, VAS, and anxiety levels was analyzed. Results: VAS decreased after 10 min of needling and 5 min after needle withdrawal in the acupuncture group compared with those in the model group (p = 0.038, p = 0.020). The efficacy rates were 82.0, 50.0, and 61.3% in the acupuncture, model, and sham groups, respectively. These represent significant differences between the acupuncture group and the model and sham acupuncture groups (p < 0.001 in each case). No differences were observed between the model and sham acupuncture groups. HF, TP, SDNN, and RMSSD were all increased in the acupuncture group compared with those in the model group (p = 0.045, p = 0.041, p = 0.002, p = 0.006, respectively). No differences were observed in the sham acupuncture group compared to the model group (p = 0.632, p = 0.542, p = 0.093, p = 0.222, respectively). The LF and LF/HF did not differ among all three groups. A positive correlation was observed between MASS and RMSSD2, LF2, RMSSD4, TP4, VAS5, and anxiety levels. Conclusion: AA was associated with enhanced vagal activity. The intensity of needle sensation was positively correlated with vagal and sympathetic nerve activities. Acupuncture is an effective means of regulating autonomic function, and needle sensation may be an important modulator.
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BACKGROUND: Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published. OBJECTIVE: This overview aims to assess the quality of related SRs and MAs. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022. INCLUSION CRITERIA: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included. DATA EXTRACTION AND ANALYSIS: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted. RESULTS: Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores. CONCLUSION: GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS. Please cite this article as: Meng TT, You YP, Li M, Guo JB, Song XB, Ding JY, Xie XL, Li AQ, Li SJ, Yin XJ, Wang P, Wang Z, Wang BL, He QY. Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses. J Integr Med. 2024;22(2): 163-179.
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Medicamentos Herbarios Chinos , Ginkgo biloba , Accidente Cerebrovascular Isquémico , Revisiones Sistemáticas como Asunto , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Metaanálisis como Asunto , Fitoterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Extractos Vegetales/uso terapéutico , Extracto de GinkgoRESUMEN
Ovarian cancer (OC) is one of the most common types of cancer in women with a high mortality rate, and the treatment of OC is prone to high recurrence rates and side effects. Scutellaria baicalensis (SB) is a herbal medicine with good anti-cancer activity, and several studies have shown that SB and its flavonoids have some anti-OC properties. This paper elucidated the common pathogenesis of OC, including cell proliferation and cell cycle regulation, cell invasion and metastasis, apoptosis and autophagy, drug resistance and angiogenesis. The mechanisms of SB and its flavonoids, wogonin, baicalein, baicalin, Oroxylin A, and scutellarein, in the treatment of OC, are revealed, such as wogonin inhibits proliferation, induces apoptosis, inhibits invasion and metastasis, and increases the cytotoxicity of the drug. Baicalein also inhibits vascular endothelial growth factor (VEGF) expression etc. Analyzing their advantages and disadvantages in treating OC provides a new perspective on the role of SB and its flavonoids in OC treatment. It serves as a resource for future OC research and development.
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Flavanonas , Neoplasias Ováricas , Femenino , Humanos , Scutellaria baicalensis , Factor A de Crecimiento Endotelial Vascular , Flavanonas/farmacología , Flavanonas/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Extractos Vegetales/farmacología , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.
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Bupleurum , Hígado , Animales , Ratones , Aspartato AminotransferasasRESUMEN
OBJECTIVE: To investigate the clinical value of laparoscopic cytoreductive surgery (CRS) in treating of appendiceal pseudomyxoma peritonei with limited disease and low tumor burden. METHODS: The clinical data of patients with appendiceal pseudomyxoma peritonei treated by surgery with CRS at the Aerospace Center Hospital from January 2018 to December 2021 were retrospectively analyzed. The patients were divided into laparoscopic or open CRS groups according to the operation method. A propensity score-matched (PSM) analysis (1:1) was performed, the related clinical variables were compared between the two groups, and the effect on progression-free survival (PFS) was also analyzed. RESULTS: One hundred and eight patients were included in this study. After PSM, 33 patients were selected from each group and the age and peritoneal cancer index were matched between the two groups. There were significant differences in operation time (P < 0.001), intraoperative bleeding (P < 0.001), intraoperative blood transfusion (P = 0.007), hospital stay (P < 0.001). The analysis of PFS showed that there was no significant difference between the two operation methods. After multivariate analysis, the pathologic subtype (P = 0.012) was identified as an independent prognostic factor for PFS. CONCLUSION: The curative effect of laparoscopic CRS is like that of open operation, which can significantly shorten the operation time and hospital stay and reduce intraoperative bleeding and blood transfusion event. The laparoscopic CRS is safe and feasible in strictly selected patients. The pathologic subtype is an independent factor affecting the prognosis for PFS.
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Hipertermia Inducida , Laparoscopía , Neoplasias Peritoneales , Seudomixoma Peritoneal , Humanos , Seudomixoma Peritoneal/cirugía , Estudios Retrospectivos , Procedimientos Quirúrgicos de Citorreducción/métodos , Carga Tumoral , Hipertermia Inducida/métodos , Terapia Combinada , Tasa de SupervivenciaRESUMEN
Aspergillus terreus is a fungus responsible for various infections in human beings; however, spine involvement is uncommon. Herein, we report a case of A. terreus spondylodiscitis following acupuncture and acupotomy in an immunocompetent Chinese patient. Admission lumbar magnetic resonance imaging (MRI) revealed infection at the L4/5 level without significant vertebral destruction. After unsuccessful symptomatic and anti-tuberculosis treatments, A. terreus was identified through culture, microscopy of isolate, histological examination and VITEK system. Intravenous voriconazole was then given; however, the patient's spinal condition deteriorated rapidly, resulting in evident destruction of the L4/5 vertebral bodies. Surgeries including L4/5 intervertebral disc debridement, spinal canal decompression, posterior lumbar interbody fusion (PLIF) with allogeneic fibula ring fusion cages, and posterior pedicle screw fixation were then performed. Imaging findings at one-month and six-month follow-up suggested that the patient was successfully treated. This case highlighted two important points: firstly, although acupuncture and acupotomy are generally regarded as safe conservative treatments for pain management, they can still lead to complications such as fungal spinal infection. Therefore, vigilance is necessary when considering these treatments; secondly, PLIF with allogeneic fibula ring fusion cages may be beneficial for A. terreus spondylodiscitis patients with spinal instability.
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Terapia por Acupuntura , Discitis , Fusión Vertebral , Humanos , Discitis/terapia , Discitis/microbiología , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Aspergillus , Terapia por Acupuntura/efectos adversos , Resultado del TratamientoRESUMEN
Enrichment of rare cancer cells from various cell mixtures for subsequent analysis or culture is essential for understanding cancer formation and progression. In particular, maintaining the viability of captured cancer cells and gently releasing them for relevant applications remain challenging for many reported methods. Here, a physically cross-linked deoxyribozyme (DNAzyme)-based hydrogel strategy was developed for the specific envelopment and release of targeted cancer cells, allowing the aptamer-guided capture, 3D envelopment, and Zn2+-dependent release of viable cancer cells. The DNAzyme hydrogel is constructed through the intertwinement and hybridization of two complementary DNAzyme strands located on two rolling circle amplification-synthesized ultralong DNA chains. The enveloping and separation of target cells were achieved during the formation of the DNAzyme hydrogel (sol-gel transition). Triggered by Zn2+, the encapsulated cells can be gently released from the dissociated DNAzyme hydrogel with high viability (gel-sol transition). Successful isolations of target cells from cancer cell mixtures and peripheral blood mononuclear cells (PBMC) were demonstrated. This method offers an attractive approach for the separation of target cancer cells for various downstream applications that require viable cells.
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Células Inmovilizadas/citología , ADN Catalítico/química , Hidrogeles/química , Transición de Fase , Aptámeros de Nucleótidos/química , Línea Celular Tumoral , Células Inmovilizadas/química , Humanos , Neoplasias/patología , Zinc/químicaRESUMEN
Firstly discovered in 1980s, human immunodeficiency virus (HIV) continues to affect more and more people. However, there is no effective drug available for the therapy of HIV infection. Betulinic acid existing in various medicinal herbs and fruits exhibits multiple biological effects, especially its outstanding anti-HIV activity, which has drawn the attentions of many pharmacists. Among the derivatives of betulinic acid, some compounds exhibited inhibitory activities at the nanomolar concentration, and have entered phase II clinical trials. This paper summarizes the current investigations on the anti-HIV activity of betulinic acid analogues, and provides valuable data for subsequent researches.
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Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , VIH-1/efectos de los fármacos , Triterpenos/química , Triterpenos/farmacología , Animales , Humanos , Triterpenos Pentacíclicos , Relación Estructura-Actividad , Replicación Viral/efectos de los fármacos , Ácido BetulínicoRESUMEN
AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A-positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling. Besides, excitatory amino acid transporter-2 (EAAT2) expression levels were significantly decreased, accompanied by impaired glutamate clearance ability, in mut-SOD1 astrocytes; yin yang 1 (YY1), a transcriptional inhibitor for EAAT2, increased in nucleus of mut-SOD1 astrocytes. AEG-1 silence inhibited translocation of YY1 to nucleus, increased EAAT2 expression levels, and enhanced astrocytic ability of glutamate clearance, ultimately exerted the neuronal protection. Findings from this study implicate potential function of AEG-1 in mut-SOD1 related astrogliosis and the accompanied excitatory cytotoxic mechanism in ALS.
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BACKGROUND: Glia-mediated neuroinflammation is related to brain injury exacerbation after cerebral ischemia/reperfusion (I/R) injury. Astrocytic hemichannels or gap junctions, which were mainly formed by connexin-43, have been implicated in I/R damage. However, the exact roles of astrocytic hemichannels and gap junction in neuroinflammatory responses induced by I/R injury remain unknown. METHODS: Primary cultured astrocytes were subjected to OGD/R injury, an in vitro model of I/R injury. Salvianolic acid B (SalB) or carbenoxolone (CBX) were applied for those astrocytes. Besides, Cx43 mimetic peptides Gap19 or Gap26 were also applied during OGD/R injury; Cx43 protein levels were determined by western blot and cytoimmunofluorescene staining, hemichannel activities by Ethidium bromide uptake and ATP concentration detection, and gap junction intercellular communication (GJIC) permeability by parachute assay. Further, astrocyte-conditioned medium (ACM) was collected and incubated with microglia. Meanwhile, ATP or apyrase were applied to explore the role of ATP during OGD/R injury. Microglial activation, M1/M2 phenotypes, and M1/M2-related cytokines were detected. Also, microglia-conditioned medium (MEM) was collected and incubated with astrocytes to further investigate its influence on astrocytic hemichannel activity and GJIC permeability. Lastly, effects of ACM and MCM on neuronal viability were detected by flow cytometry. RESULTS: We found that OGD/R induced abnormally opened hemichannels with increased ATP release and EtBr uptake but reduced GJIC permeability. WB tests showed decreased astrocytic plasma membrane's Cx43, while showing an increase in cytoplasma. Treating OGD/R-injured microglia with ATP or OGD/R-ACM induced further microglial activation and secondary pro-inflammatory cytokine release, with the M1 phenotype predominating. Conversely, astrocytes incubated with OGD/R-MCM exhibited increased hemichannel opening but reduced GJIC coupling. Both SalB and CBX inhibited abnormal astrocytic hemichannel opening and ATP release and switched the activated microglial phenotype from M1 to M2, thus providing effective neuroprotection. Application of Gap19 or Gap26 showed similar results with CBX. We also found that OGD/R injury caused both plasma membrane p-Cx43(Ser265) and p-Src(Tyr416) significantly upregulated; application of SalB may be inhibiting Src kinase and attenuating Cx43 internalization. Meanwhile, CBX treatment induced obviously downregulation of p-Cx43(Ser368) and p-PKC(Ser729) protein levels in plasma membrane. CONCLUSIONS: We propose a vicious cycle exists between astrocytic hemichannel and microglial activation after OGD/R injury, which would aggravate neuroinflammatory responses and neuronal damage. Astrocytic Cx43, hemichannels, and GJIC play critical roles in OGD/R injury-induced neuroinflammatory responses; treatment differentially targeting astrocytic Cx43, hemichannels, and GJIC may provide novel avenues for therapeutics during cerebral I/R injury.
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Astrocitos/metabolismo , Benzofuranos/farmacología , Carbenoxolona/farmacología , Hipoxia de la Célula/efectos de los fármacos , Conexina 43/metabolismo , Uniones Comunicantes/fisiología , Glucosa/deficiencia , Animales , Animales Recién Nacidos , Antígenos CD/metabolismo , Astrocitos/efectos de los fármacos , Comunicación Celular/efectos de los fármacos , Polaridad Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Medicamentos Herbarios Chinos/farmacología , Uniones Comunicantes/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Oxígeno/metabolismo , QuinolinasRESUMEN
The family Flaviviridae consists of four genera, Flavivirus, Pestivirus, Pegivirus, and Hepacivirus, and comprises important pathogens of human and animals. Although the construction of recombinant viruses carrying reporter genes encoding fluorescent and bioluminescent proteins has been reported, the stable insertion of foreign genes into viral genomes retaining infectivity remains difficult. Here, we applied the 11-amino-acid subunit derived from NanoLuc luciferase to the engineering of the Flaviviridae viruses and then examined the biological characteristics of the viruses. We successfully generated recombinant viruses carrying the split-luciferase gene, including dengue virus, Japanese encephalitis virus, hepatitis C virus (HCV), and bovine viral diarrhea virus. The stability of the viruses was confirmed by five rounds of serial passages in the respective susceptible cell lines. The propagation of the recombinant luciferase viruses in each cell line was comparable to that of the parental viruses. By using a purified counterpart luciferase protein, this split-luciferase assay can be applicable in various cell lines, even when it is difficult to transduce the counterpart gene. The efficacy of antiviral reagents against the recombinant viruses could be monitored by the reduction of luciferase expression, which was correlated with that of viral RNA, and the recombinant HCV was also useful to examine viral dynamics in vivo Taken together, our findings indicate that the recombinant Flaviviridae viruses possessing the split NanoLuc luciferase gene generated here provide powerful tools to understand viral life cycle and pathogenesis and a robust platform to develop novel antivirals against Flaviviridae viruses.IMPORTANCE The construction of reporter viruses possessing a stable transgene capable of expressing specific signals is crucial to investigations of viral life cycle and pathogenesis and the development of antivirals. However, it is difficult to maintain the stability of a large foreign gene, such as those for fluorescence and bioluminescence, after insertion into a viral genome. Here, we successfully generated recombinant Flaviviridae viruses carrying the 11-amino-acid subunit derived from NanoLuc luciferase and demonstrated that these viruses are applicable to in vitro and in vivo experiments, suggesting that these recombinant Flaviviridae viruses are powerful tools for increasing our understanding of viral life cycle and pathogenesis and that these recombinant viruses will provide a robust platform to develop antivirals against Flaviviridae viruses.
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Flaviviridae/genética , Expresión Génica , Genes Reporteros , Recombinación Genética , Animales , Antivirales/farmacología , Línea Celular , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Evaluación Preclínica de Medicamentos , Flaviviridae/efectos de los fármacos , Genoma Viral , Hepacivirus/genética , Humanos , Ratones , Mutagénesis InsercionalRESUMEN
Firstly discovered in 1980s,human immunodeficiency virus (HIV) continues to affect more and more people.However,there is no effective drug available for the therapy of HIV infection.Betulinic acid existing in various medicinal herbs and fruits exhibits multiple biological effects,especially its outstanding anti-HIV activity,which has drawn the attentions of many pharmacists.Among the derivatives of betulinic acid,some compounds exhibited inhibitory activities at the nanomolar concentration,and have entered phase Ⅱ clinical trials.This paper summarizes the current investigations on the anti-HIV activity of betulinic acid analogues,and provides valuable data for subsequent researches.
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Firstly discovered in 1980s,human immunodeficiency virus (HIV) continues to affect more and more people.However,there is no effective drug available for the therapy of HIV infection.Betulinic acid existing in various medicinal herbs and fruits exhibits multiple biological effects,especially its outstanding anti-HIV activity,which has drawn the attentions of many pharmacists.Among the derivatives of betulinic acid,some compounds exhibited inhibitory activities at the nanomolar concentration,and have entered phase Ⅱ clinical trials.This paper summarizes the current investigations on the anti-HIV activity of betulinic acid analogues,and provides valuable data for subsequent researches.
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A first phenalenon derivative with an acetyl side chain at C-8, 8-acetyl-9-hydroxy-3-methoxy-7-methyl-1-phenalenon (compound 1), and a pair of new sesquilignan epimers at C-7â³ of hedyotol C and hedyotol D analogs, hedyotol C 7â³-O-ß-d-glucopyranoside (compound 2) and hedyotol D 7â³-O-ß-d-glucopyranoside (compound 3) were isolated from the aerial parts of Helicteres angustifolia together with nine known compounds (4-12). Their structures were elucidated on the basis of spectroscopic methods, including mass spectroscopy, and 1D and 2D nuclear magnetic resonance. Eleven isolates exhibited anti-complementary activity. In particular, compounds 4 and 5 exhibited potent anti-complementary activities against the classical and alternative pathways with CH50 values of 0.040 ± 0.009 and 0.009 ± 0.002 mM, and AP50 values of 0.105 ± 0.015 and 0.021 ± 0.003 mM, respectively. The targets of compounds 4 and 5 in the complement activation cascade were also identified. In conclusion, the anti-complementary components of H. angustifolia possessed chemical diversity and consisted mostly of flavonoids and lignans in this study.
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Activación de Complemento/efectos de los fármacos , Proteínas del Sistema Complemento/inmunología , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Malvaceae/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hemólisis/efectos de los fármacos , Hemólisis/inmunología , Humanos , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX) using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5) and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5), PTX-NC (n = 10), and PTX-HC (n = 10), respectively). Serum parathyroid hormone levels decreased to non-detectable levels in all PTX groups. All animals in the PTX-FC group died within 4 days after the operation. All animals survived when supplied calcium in the diet. However, serum calcium levels were higher in the PTX-HC than the SHAM group. The PTX-NC group demonstrated the most representative modeling of primary hypothyroidism. Serum calcium levels decreased and phosphorus levels increased, and bone volume was increased. All animals survived without further treatment and did not show nephrotoxicity including calcium deposits. These findings demonstrate that PTX animal models produced by using the fluorescent-identification method, and fed a 0.5% calcium diet, are appropriate for hypoparathyroidism treatment studies.
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Hipoparatiroidismo/sangre , Hipoparatiroidismo/fisiopatología , Animales , Biomarcadores , Peso Corporal , Huesos/metabolismo , Huesos/patología , Calcio/sangre , Calcio/orina , Dieta/efectos adversos , Modelos Animales de Enfermedad , Hipoparatiroidismo/diagnóstico , Hipoparatiroidismo/etiología , Riñón/metabolismo , Riñón/patología , Masculino , Hormona Paratiroidea/sangre , Paratiroidectomía , Fósforo/sangre , Fósforo/orina , Ratas , Microtomografía por Rayos XRESUMEN
To analyze the compatibility regularity of compound traditional Chinese medicine (TCM) patents for treating dyslipidemia, and provide basis for the clinical development and research of new TCM for treating dyslipidemia. Totally 243 compound traditional Chinese medicine patents for treating dyslipidemia were collected from the national patent database from September 1985 to March 2014 and analyzed by using drug frequency, association rules, complex network and entropy method of Traditional Chinese Medicine Inheritance System (V1.1). The commonest single medicine in the treatment of dyslipidemia is Crataegi Fructus 109 (44.86%). The commonest pair medicine is Crataegi Fructus-Salviae Miltiorrhizae Radix et Rhizoma 53 (21.81%). The commonest corner drug is Crataegi Fructus-Cassiae Semen-Polygoni Multiflori Radix 25 (10.29%). The common prescriptions on basis of association rules are Prunellae Spica-->Salviae Miltiorrhizae Radix et Rhizoma (0.833), Rhei Radix et Rhizoma, Alismatis Rhizoma-->Polygoni Multiflori Radix (1.00), Salviae Miltiorrhizae Radix et Rhizoma, Cassiae Semen, Alismatis Rhizoma-->Polygoni Multiflori Radix (0.929). The core drugs based on complex networks are Salviae Miltiorrhizae Radix et Rhizoma and Crataegi Fructus. The new prescriptions extracted by entropy method are Atractylodis Macrocephalae Rhizoma-Glycyrrhizae Radix et Rhizoma-Platycladi Semen-Stephaniae Tetrandrae Radix; Citri Reticulatae Pericarpium-Poria-Coicis Semen-Pinelliae Rhizoma. This study shows the regularity in the compatibility of compound TCM patents treating dyslipidemia, suggesting that future studies on new traditional Chinese medicines treating dyslipidemia should focus on the following six aspects: (1) Single medicine should be preferred: e. g. Crataegi Fructus; (2) Pair medicines should be preferred: e. g. Crataegi Fructus-Salviae Miltiorrhizae Radix et Rhizoma; (3) Corner drugs should be preferred: e. g. Crataegi Fructus, Cassiae Semen, Polygoni Multiflori Radix; (4) The compatibility among drugs shall be given attention, and highly correlated drugs should be preferred: e. g. Prunellae Spica, Salviae Miltiorrhizae Radix et Rhizoma; Rhei Radix et Rhizoma, Alismatis Rhizoma, Polygoni Multiflori Radix; Salviae Miltiorrhizae Radix et Rhizoma, Cassiae Semen, Alismatis Rhizoma, Polygoni Multiflori Radix; (5) Core drugs should be dominant and compatible, e. g. in the digestion catharsis method, the core drugs is Crataegi Fructus and compatible with Salviae Miltiorrhizae Radix et Rhizoma; (6) Application of new prescriptions: Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Platycladi Semen, Stephaniae Tetrandrae Radix; Citri Reticulatae Pericarpium, Poria, Coicis Semen, Pinelliae Rhizoma.
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Dislipidemias/tratamiento farmacológico , Entropía , Medicina Tradicional China , Humanos , Patentes como AsuntoRESUMEN
This study aimed to investigate the clinical effect of transplantation of CD133⺠peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133⺠peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133⺠cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 µmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent.
Asunto(s)
Hiperamonemia/cirugía , Trasplante de Células Madre , Antígeno AC133 , Amoníaco/sangre , Antígenos CD/análisis , Arginina/sangre , Citrulina/sangre , Femenino , Glicoproteínas/análisis , Arteria Hepática , Humanos , Hiperamonemia/sangre , Lactante , Masculino , Péptidos/análisisRESUMEN
OBJECTIVE: Improvement in lung function was reported after acupuncture treatment of chronic obstructive pulmonary disease (COPD), but little is known about the underlying mechanisms. Because an immune response imbalance could be seen in COPD, we hypothesize that electroacupuncture (EA) may play a role in regulating inflammatory cytokines and contribute to lung protection in a rat model of smoke-induced COPD. METHODS: A COPD model using male Sprague-Dawley rats exposed to cigarette smoke was established. The rats were randomly divided into four groups (control, sham, COPD, and COPD plus EA), and COPD model was evaluated by measuring pulmonary pathological changes and lung function. EA was applied to the acupuncture point Zusanli (ST36) for 30 min/d for 14 d in sham and COPD rats. Bronchoalveolar lavage fluid (BALF) was used to measure levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and malonaldehyde (MDA). RESULTS: Compared with the control rats, COPD rats had significant changes in lung resistance (RL) and lung compliance (CL) (both P<0.01), bronchi and bronchiole airway obstruction (P<0.01), and levels of MDA, TNF-α, and IL-1ß (P<0.01). There were no significant differences between the control and the sham groups. Compared with the COPD rats, the COPD plus EA rats had decreased RL and increased CL (both P<0.05), and reduced bronchi and bronchiole airway obstruction (P<0.05, P<0.01, respectively), while levels of TNF-α, IL-1ß, and MDA in BALF were lowered (P<0.05 and P<0.01, respectively). However, TNF-α and IL-1ß levels of the EA group rats remained higher than those of the control group (P<0.05). CONCLUSION: EA at ST36 can reduce lung injury in a COPD rat model, and beneficial effects may be related to down-regulation of inflammatory cytokines. The anti-inflammatory and antioxidant effects may prolong the clinical benefit of EA.
Asunto(s)
Puntos de Acupuntura , Electroacupuntura , Interleucina-1beta/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Fumar/efectos adversos , Factor de Necrosis Tumoral alfa/inmunología , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Modelos Animales de Enfermedad , Humanos , Masculino , Enfermedad Pulmonar Obstructiva Crónica/etiología , Ratas , Ratas Sprague-DawleyRESUMEN
Overexpression of ABCB1 is one of major barriers for multidrug resistance in chemotherapy and limits drug oral bioavailability. Inhibition of ABCB1 would sensitize multidrug resistance in clinical cancer chemotherapy. With this aim, a 3D pharmacophore model was created based on known ABCB1 inhibitors with correlation coefficient of 0.94, comprising three hydrophobic features and one hydrogen bond acceptor. It was further validated and used to search our in-house 3D database for potential ABCB1 inhibitors. The inhibitory activities of the best hits were evaluated by several biological assays, such as rhodamine 123 accumulation assay, chemosensitization assay, multidrug resistance 1-Madin-Darby canine kidney cells/Madin-Darby canine kidney cells permeability assay. Finally, compounds YZ-3 and YZ-16 were identified as potential leads to be developed in the designing of novel potent ABCB1 inhibitors.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Aminoquinolinas/química , Benzotiazoles/química , Diseño de Fármacos , Compuestos Heterocíclicos con 3 Anillos/química , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Aminoquinolinas/metabolismo , Aminoquinolinas/toxicidad , Animales , Benzotiazoles/metabolismo , Benzotiazoles/toxicidad , Supervivencia Celular/efectos de los fármacos , Bases de Datos Factuales , Perros , Evaluación Preclínica de Medicamentos , Resistencia a Antineoplásicos/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/metabolismo , Compuestos Heterocíclicos con 3 Anillos/toxicidad , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Células K562 , Células de Riñón Canino Madin Darby , Modelos Químicos , Permeabilidad/efectos de los fármacos , Relación Estructura-Actividad Cuantitativa , Quinolonas/química , Quinolonas/metabolismo , Quinolonas/toxicidad , Rodamina 123/química , Rodamina 123/metabolismoRESUMEN
<p><b>OBJECTIVE</b>Improvement in lung function was reported after acupuncture treatment of chronic obstructive pulmonary disease (COPD), but little is known about the underlying mechanisms. Because an immune response imbalance could be seen in COPD, we hypothesize that electroacupuncture (EA) may play a role in regulating inflammatory cytokines and contribute to lung protection in a rat model of smoke-induced COPD.</p><p><b>METHODS</b>A COPD model using male Sprague-Dawley rats exposed to cigarette smoke was established. The rats were randomly divided into four groups (control, sham, COPD, and COPD plus EA), and COPD model was evaluated by measuring pulmonary pathological changes and lung function. EA was applied to the acupuncture point Zusanli (ST36) for 30 min/d for 14 d in sham and COPD rats. Bronchoalveolar lavage fluid (BALF) was used to measure levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and malonaldehyde (MDA).</p><p><b>RESULTS</b>Compared with the control rats, COPD rats had significant changes in lung resistance (RL) and lung compliance (CL) (both P<0.01), bronchi and bronchiole airway obstruction (P<0.01), and levels of MDA, TNF-α, and IL-1β (P<0.01). There were no significant differences between the control and the sham groups. Compared with the COPD rats, the COPD plus EA rats had decreased RL and increased CL (both P<0.05), and reduced bronchi and bronchiole airway obstruction (P<0.05, P<0.01, respectively), while levels of TNF-α, IL-1β, and MDA in BALF were lowered (P<0.05 and P<0.01, respectively). However, TNF-α and IL-1β levels of the EA group rats remained higher than those of the control group (P<0.05).</p><p><b>CONCLUSION</b>EA at ST36 can reduce lung injury in a COPD rat model, and beneficial effects may be related to down-regulation of inflammatory cytokines. The anti-inflammatory and antioxidant effects may prolong the clinical benefit of EA.</p>