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Non-infectious chronic diseases in human including diabetes, non-alcoholic fatty liver disease (NAFLD), atherosclerosis (AS), neurodegenerative diseases, osteoporosis, as well as malignant tumors may have some common pathogenic mechanisms such as non-resolved inflammation (NRI), gut microbiota dysfunction, endoplasmic reticulum stress, mitochondria dysfunction, and abnormality of the mammalian target of rapamycin (mTOR) pathway. These pathogenic mechanisms could be the basis for "homotherapy for heteropathy" in clinic. Some commonly used clinical drugs, such as metformin, berberine, aspirin, statins, and rapamycin may execute therapeutic effect on their targeted diseases,and also have the effect of "homotherapy for heteropathy". The mechanisms of the above drugs may include anti-inflammation, modulation of gut microbiota, suppression of endoplasmic reticulum stress, improvement of mitochondria function, and inhibition of mTOR. For virus infectious diseases, as some viruses need certain commonly used replicases, the inhibitors of the replicases become examples of "homotherapy for heteropathy" for antiviral therapy in clinic (for example tenofovir for both AIDS and HBV infection). Especially, in case of outbreak of new emerging viruses, these viral enzyme inhibitors such as azvudine and sofibuvir, could be rapidly used in controlling viral epidemic or pandemic, based on the principle of "homotherapy for heteropathy". In this review article, we show the research progress of the biological basis for "homotherapy for heteropathy" and the possible mechanisms of some well-known drugs, in order to provide insights and new references for innovative drug R&D.
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The purpose of this study is to investigate the effect of Reduning injection (RI) on influenza A virus (IAV) and its mechanism. We evaluated the cytotoxicity of RI in A549 and MDCK cells by cell counting kit-8 (CCK-8) assay. Western blot and cytopathic effect (CPE) assays were applied to test the effects of RI on viral protein, CPE and virus virulence to evaluate its inhibitory effect. The proteins level of heme oxygenase 1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), phosphorylation of P38 mitogen-activated protein kinases (MAPK) and extracellular signal-regulated kinases 1/2 (ERK1/2) were detected by Western blot. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the RNA expression of interferon-α/β (IFN-α/β). The relative luciferase reporter assay was used to analyze the promoter activity and transcriptional regulation of Nrf2. The results indicated that RI inhibited IAV-induced MDCK cytopathies in a dose-dependent manner, decreased M2 protein of influenza virus and viral titer, indicating that it has definite effect on inhibiting IAV. RI promotes the phosphorylation of P38 MAPK and ERK1/2, activates the activity of Nrf2 nuclear transcription factor, increases the expression of Nrf2 protein in the nucleus, thus up-regulates the expression of HO-1 protein, and ultimately increases the IFN-α/β mRNA level. In summary, our results demonstrated that RI inhibits the replication of IAV by activating MAPK/Nrf2/HO-1 signaling pathway, revealing a new mechanism of RI against influenza virus, and providing theoretical basis for clinical treatment of influenza virus.
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Two new ursane triterpenoids along with twelve known compounds were isolated from 80% ethanol extract of Agastache rugosa (Fisch. et. Mey.) O. Kuntze by using silica gel column, MCI column, ODS column and HPLC. The structures of the new compounds were identified as 2α,3α-dihydroxy-24-nor-urs-4(23),12(13)-dien-28-oic acid (1) and 2α,3α-dihydroxy-24-nor-urs-4(23),12(13),20(30) -trien-28-oic acid (2) by HR-ESI-MS, NMR and ECD spectral data, named agasursacid A and agasursacid B. In addition, compounds 3, 4, 6, 8 showed anti-coxsackievirus B3 (CVB3) activities with a IC50 as 4.77, 1.59, 11.11 and 25.87 μmol·L-1, resepectively.
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To investigate the effect of Fufang yinhua jiedu (FFYH) granules against coronavirus and its potential mechanism, we used Huh7, Huh7.5, H460, and C3A cell lines as in vitro models to evaluate the cytotoxicity and antiviral activity of FFYH by observation of cell pathogenic effect (CPE); and then the inhibitory effect of FFYH on the transcription expression of coronavirus RNA and inflammatory factor mRNA were evaluated by quantitive reverse transcription PCR (qRT-PCR); finally, the inhibitory effect of FFYH on the expression of coronavirus protein and its underlying mechanism against coronavirus were investigated by Western blot and immunofluorescence. Our results indicated that 50% toxic concentration (TC50) FFYH on Huh7, Huh7.5, H460, and C3A cells were 2 035.21, 5 245.69, 2 935.28 and 520 µg·mL-1, respectively; 50% inhibitory concentration (IC50) of FFYH on HCoV-229E in Huh7 and Huh7.5 cells were 438.16 and 238.54 µg·mL-1 with safety index (SI) of 4.64 and 21.99, respectively; IC50 of FFYH on HCoV-OC43 in H460 cells was 165.13 µg·mL-1 with SI of 17.78. Moreover, FFYH not only could inhibit the replication of coronaviruses (HCoV-OC43 and HCoV-229E) through inhibiting the transcription of viral RNA and the expression of viral protein, but also effectively suppress the expression of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8) at mRNA level caused by coronaviruses, which might be associated with the inhibitory effect of FFYH on mitogen-activated protein kinase (MAPK) pathway and the nuclear translocation of nuclear transcription factor-κB (NF-κB). In summary, our results demonstrated that FFYH exhibited a good in vitro anti-coronavirus effect, which provides a theoretical basis for its clinical use in the treatment of anti-coronavirus pneumonia.
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Qing-Fei-Pai-Du decoction (QFPDD) is a combination of traditional Chinese medicine and plays an important role in the treatment of coronavirus disease 2019 (COVID-19). This study investigated the inhibitory effect of QFPDD on coronavirus replication and antiviral mechanism. The cytotoxicity of QFPDD was determined by PrestoBlue cell viability assay. Quantitive reverse transcription PCR (qRT-PCR) and immunofluorescence assay (IF) were used to detect the inhibitory effects of QFPDD on coronavirus at RNA and protein levels. qRT-PCR was used to detect the adsorption and penetration of coronavirus after QFPDD treatment. The effects of QFPDD on interferon (IFN) and interferon-stimulated genes (ISGs) were also detected by qRT-PCR. The results showed that QFPDD inhibited coronavirus at RNA and protein levels in a dose-dependent manner at non-toxic concentration, and QFPDD targeted in the early stages of coronavirus infection cycle. Preliminary mechanism studies have shown that QFPDD can directly block the virus entry into the cell by inhibiting virus adsorption, and QFPDD can also play an antiviral role by up-regulating the expression of IFN and ISGs. These results indicate QFPDD as a drug potential to treat coronavirus infection.
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Compound houttuynia mixture belongs to OTC class A medicine, which is made from Houttuynia cordata, Scutellaria baicalensis, Radix Isatidis, Forsythia, and Lonicera. As a kind of compound preparation of traditional Chinese medicine, houttuynia cordata mixture has extensive pharmacological effects, for example, clearing away heat and detoxifying, thus it is used for the sore throat, acute pharyngitis, and tonsillitis with wind-heat syndrome. In this study, the antiviral activity against influenza viruses and the primary mechanism of compound houttuynia mixture was evaluated. The antiviral effect of compound houttuynia mixture was determined by cytopathic effects (CPE), Western blot, quantitive reverse transcription PCR (qRT-PCR), and virus titer assays. The effect of houttuynia mixture on the replication cycle of influenza virus was evaluated by time-of-addition assay. In conclusion, the results showed that the compound houttuynia mixture had a broad-spectrum effect against influenza virus, including the international common influenza virus strains, the drug-resistant strains and the highly pathogenic avian influenza viruses H5N1 and H7N9. It mainly impairs the early stage of the viral replication.
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<p><b>OBJECTIVE</b>To study the anatomical measurement of goat lumbar vertebrae and to compare with human lumbar vertebrae, so as to build the foundation for establishing animal models of lumbar prosthesis.</p><p><b>METHODS</b>The anatomical parameters of the vertebral body, pedicle and intervertebral disc in the fresh lumbar vertebrae of Boer goat and the lumbar vertebrae of healthy adults were collected by computer aided software Mimics16.0, and the anatomical characteristics of the two lumbar vertebrae were compared with the statistical software.</p><p><b>RESULTS</b>The anterior vertebral body height(VBHa) of goat lumbar was less than the middle vertebral body height(VBHm), which was less than the posterior vertebral body height(VBHp), and the maximum values were (38.7±2.9), (40.1±2.6) and (40.7±2.7) mm respectively. Its endplate width was greater than its depth, with the whole shaped like a heart or a kidney. The cranial endplate of goats was convex while the caudal endplate was depressed and the depression was small, with a maximum value of (1.6±0.6) mm. The pedicle height of goats increased from L₁1 to L̀ with the maximum of (30.5±1.9) mm; its pedicle width and angle increased firstly and then decreased with the increase of vertebra level and the minimum values were (6.7±0.4) mm and(45.9±2.6)° respectively. The anterior intervertebral disc height was larger than the middle which was larger than the posterior and all varied slightly with the changes of intervertebral spaces; the height and width of intervertebral foramen separately waved at (12.9±0.3) to (14.3±1.0) mm and (5.7±1.0) to (6.7±0.9) mm. The comparative results showed that the vertebral body height, pedicle height and angle of goats were greater than those of humans (<0.05) while the width and depth of the endplate, the intervertebral disc height, and etc. were significantly smaller than those of humans (<0.05). In addition, some structures, such as the height of pedicle and intervertebral disc, also showed different changing laws with the increase of vertebra level.</p><p><b>CONCLUSIONS</b>Although there are similarities in goat lumbar spine in some aspects, such as endplate and foramen foramen, there are still many differences in many aspects. Understanding the anatomical characteristics of goat lumbar vertebrae and the difference between goat and human is of great guiding significance for the research of goat prosthesis and related technology.</p>
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<p><b>OBJECTIVE</b>To systematically evaluate the clinical effect of high frequency repeated transcranial magnetic stimulation(HF rTMS)therapy on dyskinesia in patients with incomplete spinal cord injury.</p><p><b>METHODS</b>Randomized controlled trials(RCTs) about HF rTMS therapy on patients with motor incomplete spinal cord injury were searched electronically in PubMed, Google scholar, Cochrane library, Clinical trial, Medline, Web of science, CNKI, VIP, and Wanfang database before October 2016. Two reviewers independently screened the literatures according to the inclusion and exclusion criteria, as well as extracted the data and assessed the methodological quality. The observed outcomes included ASIA motor score, ASIA lower extremities motor score(LEMS), Modified Ashworth score (MAS), Ten-meter walking test (10MWT) and Walking index for SCI II(WISCI II), and the outcomes were analyzed using RevMan5.2 software provided by the Cochrane information management system.</p><p><b>RESULTS</b>Five RCTs involved 103 patients were included, and 61 patients(experimental group) accepted real rTMS and physical rehabilitation care for SCI, 51 patients(control group) accepted only physical rehabilitation care. There were significant differences in ASIA motor score, LEMS and 10MWT between two groups after HF rTMS therapy (statistics were=2.96,=0.003;=3.04,=0.002;=2.16,=0.03; respectively). When stimulating the leg motor cortex, there was significant difference in MAS between two groups(=2.79,=0.005), and when stimulating the vertex, there was no significant difference(=0.09,=0.93). There was no significant difference in WISCI IIscore after HF rTMS therapy between two groups(=0.90,=0.37).</p><p><b>CONCLUSIONS</b>HF rTMS can raise motor score in patients with incomplete spinal cord injury, improve the spasticity of the lower extremities, and increase the motor ability.</p>
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<p><b>OBJECTIVE</b>To study the change trend of cervical range of motion(ROM) after single-level anterior cervical corpectomy and fusion(ACCF) in treating cervical spondylotic myelopathy.</p><p><b>METHODS</b>The clinical data of 23 patients with cervical spondylotic myelopathy was retrospectively analyzed from February 2015 to April 2016. There were 11 males and 12 females, with an average age of (54.6±13.3) years. All the patients were diagnosed as cervical spondylotic myelopathy by interrogation, physical examination and radiology, and were treated by ACCF. The Coda motion system was applied to assess the cervical range of motion pre-and post-operation. JOA and VAS scores were used to evaluate the clinical outcomes.</p><p><b>RESULTS</b>The mean follow-up time was (9.4±1.6) months. Cervical ROM in all directions at 3 months postoperatively were significantly lower except for the left rotation(<0.05). There was significant difference of cervical ROM in all directions between preoperative and 6 months postoperatively(>0.05). The right lateral bending and the left rotation at 9 months postoperatively increased significantly(<0.05). Postoperative extension at 6 months was significantly better than that of 3 months postoperatively(<0.05). The extension, left and right lateral bending and left rotation at 9 months postoperatively were significantly better than of 6 months postoperatively(<0.05). Postoperative JOA scores at each time points were significantly higher than that of preoperative(<0.05) and VAS scores at each time points were significantly lower than that of preoperative(<0.05).</p><p><b>CONCLUSIONS</b>The change trend of three-dimensional cervical ROM after single-level ACCF revealed that the ROM decreased in short term, and later increased and was better than the preoperative level. Meanwhile, the neurological function improved significantly. But the short-term and long-term change trend of ROM postoperatively and the change trend of ROM after multi-level ACCF need to be further studied.</p>
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<p><b>OBJECTIVE</b>To study whether lithium agent produces neuroprotective effect by inhibiting the nerve cell apoptosis of rats after spinal cord injury.</p><p><b>METHODS</b>Forty-two male SD rats weighing 200 to 250 g were randomly divided into 3 groups: blank control group(=6) without surgery, normal saline(NS) group(=18) with intraperitoneal injection of NS (40 mg/kg); and Lithium chloride (Licl) group (=18) with intraperitoneal injection of Licl (40 mg/kg). After Allen method modeling, Licl group started intraperitoneal injection of Licl solution (40 mg·kg⁻¹·d⁻¹) within 15 min after operation to the second week. NS group, during the same interval, was injected with a same amount of NS. Postoperative 3, 7, 14 d, BBB scores in each group were measured;the expression of Bcl-2 and Bax protein were observed by immunohistochemisty staining;TUNEL staining was used to observe the nerve cell apoptosis.</p><p><b>RESULTS</b>The BBB scores in blank control group were 21. Postoperative 7, 14 d, BBB scores of Licl group were higher than that of NS group(<0.05). As for the Bcl-2 protein expression, black control group has a level of 0.081±0.003;7 d and 14 d postoperatively, the level in Licl group was 0.151±0.003, 0.163±0.003 and in NS group, 0.143±0.003, 0.154±0.002, respectively. Licl group showed significantly increased Bcl-2 protein expression(<0.05). As for the Bax protein expression, black control group showed a level of 0.071±0.003; 7 d and 14 d postoperatively, the level in Licl group was 0.121±0.002, 0.106±0.002 and in NS group was 0.126±0.001, 0.120±0.002, respectively. The Bax protein expression is significantly inhibited in the Licl group(<0.05). In nerve cell apoptosis by TUNEL staining, the positive cells were fewer in the black control group with apoptosis index (AI) of 1.98±0.19;while 7d and 14d postoperatively, the AI of Licl group was 13.12±0.69, 4.29±1.00 and of NS group, 18.26±0.87, 5.48±0.70, respectively. Licl group showed significant inhibition of the cell apoptosis(<0.05).</p><p><b>CONCLUSIONS</b>Licl can promote the Bcl-2 protein expression and inhibit the Bax proteins expression in nerve cells of rat after SCI, thereby playing a role in the inhibition of nerve cell apoptosis. This may be one of the mechanisms that Licl can promote the recovery of motor function of rats after SCI.</p>
Subject(s)
Animals , Male , Rats , Apoptosis , Lithium , Pharmacology , Neurons , Cell Biology , Neuroprotective Agents , Pharmacology , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Random Allocation , Rats, Sprague-Dawley , Spinal Cord Injuries , Drug Therapy , bcl-2-Associated X Protein , MetabolismABSTRACT
Objective To evaluate renal function in congenital spinal deformities patients with urinary malformations.Methods We prospectively enrolled patients diagnosed with congenital spinal deformities combined with urinary malformation as well as age- and weight-matched healthy individuals and divided them into three groups:renal malformations group,urinary tract malformations group,and healthy control group.Serum creatinine,blood urea,blood uric acid,serum cystatin C,and estimate glomerular filtration rate(eGFR)level were used to evaluate general renal function.Urinary microalbumin(mALB),urinary alpha-1-microglobulin(α1-MG), beta-2-microglobulin(β2-MG),and N-acetyl-beta-D-glucosaminidase(NAG)level were determined to evaluate early renal function.Results We enrolled totally 16 patients with renal malformations,14 patients with urinary tract malformations group,and 20 healthy individuals as controls.The concentration of serum creatinine,blood urea, blood uric acid,serum cystatin C,and the value of eGFR in the three groups were within normal reference values, with no significant difference(P>0.05).There were significant differences in the urinary levels of mALB,α1-MG and NAG in the three groups(P<0.05),but not for the concentration of β2-MG(P>0.05).Urinary levels of mALB and NAG were significantly higher in renal malformations group than in urinary tract malformations group (P<0.05),but not for the concentration of α1-MG(P> 0.05).Conclusion Early renal function impairment occurs in congenital spinal deformities children with urinary malformation.Moreover,it appears more severe in patients with renal malformations than in those with urinary tract malformations.
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Tribbles homologous protein 3 (TRB3) has a wide range of biological functions, such as involvement in tumor regulation, the occurrence of insulin resistance, endoplasmic reticulum stress response, inflammation regulation and the regulation of cell growth and differentiation. TRB3, as a key "pressure regulating switch", is involved in the regulation of numerous diseases and serves as a biomarker and potential therapeutic target for many diseases. This paper gives an overview of the research on the biological function of TRB3 in recent years, in order to provide a theoretical basis for further research on TRB3 function.
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OBJECTIVE@#To study and measure the anatomic structure of lumbar vertebral endplate structure in healthy adults by computed tomography(CT) technique in order to provide a useful guidance for the optimal design and clinical application of lumbar prostheses.@*METHODS@#Sixty healthy adults (male and female equals) were recruited for full-waist CT scan after signing the informed consent form in the imaging department of the Second Affiliated Hospital of Xi'an Jiaotong University. The scanning data was imported into the computer aided software Mimics 16.0 for 3D reconstruction and measurement. The acquisition indexes included median sagittal diameter, maximum coronal diameter, concavity depth, median sagittal depression angle, coronal depression angle and so on. Finally, the collected data were statistically analyzed by the statistical software.@*RESULTS@#The median sagittal diameter and the maximum coronal diameter of the upper and lower endplates were not only different between the different sexes(0.05), but had a little change from L₁ to L₅, fluctuating from 1.5 to 2.0 mm and from 2.2 to 3.9 mm, respectively. In the same sequence, the concavity depth of lower endplate in males was greater than that of upper endplate, and the difference was statistically significant(0.05). Sagittal concavity angle and coronal concavity angle of upper and lower endplates changed slightly with the increase of vertebral order, and there was no gender difference in sagittal and coronal concavity angle of most vertebral sequences (>0.05). Statistics showed that the largest concavity near the caudal lumbar endplate was located on the dorsal side of the endplate plane.@*CONCLUSIONS@#The anatomical structure of the lumbar endplate is very complicated. It is important to master the anatomical parameters of the endplate and make full use of CT before operation for the development and clinical application of the lumbar prosthesis.
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Female , Humans , Male , Lumbar Vertebrae , Lumbosacral Region , Prostheses and Implants , Tomography, X-Ray ComputedABSTRACT
Artificial vertebral body has achieved good results in treating spinal tumors, tuberculosis, fracture and other diseases. Currently, artificial vertebral body with variety of kinds and pros and cons, is generally divided into two types: fusion type and movable type. The former according to whether the height could be adjusted and strength of self-stability is divided into three types: support-fixed type, adjust-fixed type and self-fixed type. Whether the height of self-fixed type could be adjusted is dependent on structure of collar thread rotation. The latter is due to mobile device of ball-and-socket joints or hollow structures instead of the disc which retains the activity of the spine to some extent. Materials of artificial vertebral body include metals, ceramics, biomaterials, polymer composites and other materials. Titanium with a dominant role in the metal has developed to the third generation, but there are still defects such as poor surface bioactivity; ceramics with the representative of hydroxyapatite composite, magnetic bioceramics, polycrystalline alumina ceramics and so on, which have the defects of processing complex and uneven mechanical properties; biological material is mainly dominated by xenogeneic bone, which is closest to human bone in structure and properties, but has defects of low toughness and complex production; polymer composites according to biological characteristics in general consists of biodegradable type and non-biodegradable type which are respectively represented by poly-lactide and polyethylene, each with advantages and disadvantages. Although the design and materials of prosthesis have made great progress, it is difficult to fully meet requirements of spinal implants and they need be further optimized. 3D printing technology makes process of the complex structure of prosthesis and individual customization possible and has broad development prospects. However, long production cycles and high cost of defect should be overcome. Although artificial vertebral body has achieved curative effect in treating spinal disease, there were reports of implant loosening or displacement. Combining with evaluation standards not unified, short follow-up time, its exact effect needs further observation.
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12-N-m-Cyanobenzenesulfonyl matrinic butyl methyl ether is a potent anti-coxsackievirus B3(CVB3) agent bearing a novel structure skeleton. Taking this compound as a lead, totally 15 novel target compounds have been synthesized and evaluated for the anti-CVB3 activities using CPE method. Structureactivity relationship (SAR) demonstrated that the shorten-length of 11-side chain was not helpful for keeping the good anti-virus activity. Among the newly synthesized compounds, compound c1 displayed a good anti-CVB3 activity with the IC50 of 7.1 μmol·L-1 and SI of 35.5, similar to that of the lead. The SAR results provided useful information for further optimization of these compounds in the molecular structure.
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12-N-Benzenesulfonyl-11-matrinic acid derivatives are a new class of anti-CVB3 compounds, but the mechanism of action is still unknown. Therein, two kinds of molecule probes were designed and constructed in this study, including matrinic amines that might be applied to the BIAcore fishing technique and biotin-tagged matrinic derivatives, which could be applied in the biotin affinity chromatography. Moreover, their anti-CVB3 activities were evaluated. Among them, 10a displayed a good activity with an IC50 value of 0.8 μmol·L-1. This active molecule probe provides a key chemical tool for exploration of the anti-CVB3 mechanism of this type of compounds.
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The challenge of the emergence of drug-resistant influenza strains, which is caused by wide spread utilization of direct-acting antivirals (DAAs), accelerates the research and exploration towards host targeted agents. In contrast to DAAs targeting viral replication components, host targeted agents, which regulate host factors and pathways linked to viral replication, can interfere the replication of influenza. Additionally, the innate immune system is activated by influenza during the early stage of infection, so manipulating the innate immune response may prevent the viral infection. However, the excessive inflammatory response induced at the late phase of influenza infection would lead to severe tissue injures. Thus, it is very important to explore drugs with anti-inflammatory actions to suppress these immune imbalances and tissue injures. Here we overview the current progresses about host targets related to anti-influenza drugs.
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Humans , Anti-Inflammatory Agents , Pharmacology , Antiviral Agents , Pharmacology , Immunity, Innate , Influenza, Human , Drug Therapy , Virus ReplicationABSTRACT
This study is to investigate the effect of recombinant human interferon alpha 2b against broad-spectrum respiratory viruses in vitro. At the cellular level, the effect of the recombinant human interferon alpha 2b on influenza A virus was detected using real-time fluorescence quantitative RT-PCR. The effects of the recombinant human interferon alpha 2b on influenza B virus, parainfluenza virus, respiratory syncytial virus (RSV) and coronavirus were detected using cytopathic effect (CPE) method. In this study, the therapeutic index of recombinant human interferon alpha 2b anti-HPIV was 1476.63, the therapeutic index of recombinant human interferon alpha 2b anti-RSV was 141.37, the therapeutic index of recombinant human interferon alpha 2b anti-coronavirus was more than 2820.76, and the antiviral effect of recombinant human interferon alpha 2b was better than ribavirin (RBV). Recombinant human interferon alpha 2b has a stronger inhibitory effect on different influenza A virus RNA than drug control. The therapeutic index of recombinant human interferon alpha 2b anti-influenza B virus was 2.74, with modest effect. Recombinant human interferon alpha 2b in vitro has broad spectrum antiviral activities, low toxicity and high therapeutic index. Recombinant human interferon alpha 2b is expected to become the efficient medicine in clinical against respiratory viruses, as well as provide better services for prevention and treatment of respiratory viruses' infections.
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Humans , Antiviral Agents , Pharmacology , Influenza A virus , Influenza B virus , Interferon-alpha , Pharmacology , Parainfluenza Virus 1, Human , Recombinant Proteins , Pharmacology , RibavirinABSTRACT
Thirty-three compounds were isolated from the root decoction of Isatis indigotica by using a combination of various chromatographic techniques including silica gel, macroporous adsorbent resin, Sephadex LH-20, and reversed-phase HPLC. Their structures were elucidated by spectroscopic data as (+)-dehydrovomifoliol (1), (S)-(+)-abscisic acid (2), vomifoliol (3), cyclo (L-Phe-L-Leu) (4), cyclo(L-Phe-L-Tyr) (5), cyclo(L-Tyr-L-Leu) (6), cyclo(L-Pro-L-Tyr) (7), evofolin B (8), (+)-syringaresinol (9), (-)-(7R,7'R,8S,8'S)-4,4'-dihydroxy-3-methoxy-7,9';7',9-diepoxy-lignan (10), (-)-medioresinol (11), (+) -(7R,7'R,8S,8'S) -neo-olivil (12), (-) -5-methoxyisolariciresinol (13), 1,3-dihydro-2H-indol-2-one (14), isalexin (15), dihydroneoascorbigen (16), indican (17), (-) -(S) -cyanomethyl-3-hydroxyoxindole (18), isoformononetein (19), calycosin (20), stigamast-5-ene-3beta-ol-7-one (21), acetovanillone (22), 3, 5-dimethoxy-4-hydroxyacetophenone (23), dihydroconiferyl alcohol (24), dihyroferulic acid (25), 3-hydroxy-1-(4-hydroxyphenyl) propan-1-one (26), beta-hydroxypropiovanillone (27), 4-aminobenzoic acid (28), 3-(4-hydroxyphenyl) propan-1-ol (29), 4-(2-hydroxyethyl) phenol (30), 2-methoxy-4-vinylphenol (31), pyrocatechol (32), and 4-pentenamide (33). These compounds were isolated from the root of I. indigotica for the first time. In preliminary in vitro assays, compound 19 showed activity against the influenza virus A/Hanfang/359/95 (H3N2), the herpes simplex virus 1 (HSV-1), and Coxsackie virus B3 (Cox-B3), with IC50 values of 2.06, 6.84, and 8.70 micromol x L(-1), respectively, but other compounds were in-active at a concentration of 1.0 x 10 x (-5) mol x L(-1).
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Animals , Humans , Cell Line , Isatis , Chemistry , Plant Extracts , Chemistry , Pharmacology , Toxicity , Plant Roots , ChemistryABSTRACT
Animal model is very important for anti-EV71 (enterovirus 71) drug and vaccine development. 1-day-old suckling EV71 mouse model is the main in vivo model used in China. 1-day-old suckling EV71 mouse is too small to perform antiviral experiment. And the route of administration and dosage capacity are also restricted. A strong virulence EV71 virus strain was selected after screening from five EV71 strains with 1-day-old suckling mice. A mouse-adapted EV71 strain with increased virulence in 12-day-old suckling mice, EV71-M5, was generated after five serial passages of the parental EV71 strain in mice. Virus titers of EV71 infected mice heart, liver, spleen, lung, kidney, small intestine, brain and muscle tissue were determined by cytopathic effect (CPE) assay. The virus used in this model is the first isolated EV71 strain in China. And 2-week-old suckling mice were used in this model. This is a supplement for the EV71 animal model in China. Establishment of this EV71 model will provide an attractive platform for anti-EV71 vaccine and drug development.