The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bon...The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.展开更多
Objective:To evaluate the efficacy and safety of Jiawei Simiao powder(JWSMP)combined with celecoxib for the treatment of acute gouty arthritis by conducting a meta-analysis of randomized controlled trials(RCTs).Method...Objective:To evaluate the efficacy and safety of Jiawei Simiao powder(JWSMP)combined with celecoxib for the treatment of acute gouty arthritis by conducting a meta-analysis of randomized controlled trials(RCTs).Methods: The Chinese National Knowledge Infrastructure Databases,Chinese Scientific Journal Database,Wanfang,Cochrane Library,EMBASE,PubMed,and Web of Science databases were searched from inception until December 2023.Continuous variables were analyzed using the mean difference(MD)for analysis,and dichotomous variables were used as risk ratios.Data with similar characteristics were pooled for meta-analysis,and heterogeneity was assessed using I2.The Cochrane Handbook was used to assess the risk of bias and quality.RevMan 5.3 software was used to perform the meta-analysis.Results: Thirteen RCTs involving 1007 patients were included in the study.The quality of the included studies was low(unclear randomization processes and insufficient blinding reporting).The group receiving JWSMP combined with celecoxib showed significantly lower levels of serum uric acid(SUA,MD=−66.32,95%confidence interval(CI):−80.97 to−51.67,P<.001),erythrocyte sedimentation rate(ESR,MD=−6.05,95%CI:−8.29 to−3.82,P<.001),C-reactive protein(CRP,MD=−7.39,95%CI:−11.15,−3.63,P<.001),and joint pain score(VAS score,MD=−2.14,95%CI:−2.4 to−1.88,P<.001)compared to celecoxib alone.Additionally,the JWSMP combined group had a higher total effective rate(risk ratio=1.22,95%CI:1.14 to 1.29,P<.001)and fewer adverse compared to celecoxib alone.Conclusions: JWSMP combined with celecoxib is more effective than celecoxib alone in improving the total efficacy rate,alleviating joint pain,and improving SUA,ESR,and CRP levels.JWSMP also reduced the occurrence of adverse events caused by celecoxib.However,the quality of the included studies was low,highlighting the need for further high-quality research with larger sample sizes and robust methodologies,such as double-blind randomization,to confirm these findings.展开更多
AIM: To determine whether midkine (M/O and its truncated form (tMK) contribute to gastric tumorigenesis using in vitro and in vivo models. METHODS: Human MK and tMt( plasmids were constructed and expressed in BG...AIM: To determine whether midkine (M/O and its truncated form (tMK) contribute to gastric tumorigenesis using in vitro and in vivo models. METHODS: Human MK and tMt( plasmids were constructed and expressed in BGC823 (a gastric adenocarcinoma cell line) to investigate the effect of over-expressed MK or tMK on cell growth and turmorigenesis in nude mice. RESULTS: The growth of MK-transfected or tMK- transfected cells was significantly increased compared with that of the control cells, and tMK-transfected cells grew more rapidly than MK-transfected cells. The number of colony formation of the cells transfected with MK or tMK gene was larger than the control cells. In nude mice injected with MK-transfected or tMK-transfected cells, visible tumor was observed earlier and the tumor tissues were larger in size and weight than in control animals that were injected with cells without the transfection of either genes. CONCLUSION: Over-expressed MK or tMtC can promote human gastric cancer cell growth in vitro and in vivo, and bMK has greater effect than MK. tMK may be a more promising gene therapeutic target compared with MK for treatment of malignant tumors.展开更多
AIM: To investigate the possible mechanism by which hepatitis B virus X protein (HBx) mediates apoptosis of HepG2 cells. METHODS: HBx expression vector pcDNA3.1-X was transfected into HepG2 cells to establish an H...AIM: To investigate the possible mechanism by which hepatitis B virus X protein (HBx) mediates apoptosis of HepG2 cells. METHODS: HBx expression vector pcDNA3.1-X was transfected into HepG2 cells to establish an HBx high- expression cellular model as pcDNA3.1-X transfected group. The pcDNA3.1-X and pSilencer3.1-shHBX (HBx antagonist) were cotransfected into HepG2 cells to es- tablish an HBx low-expression model as RNAi group. Untransfected HepG2 cells and HepG2 cells transfected with negative control plasmid were used as controls. Apoptosis rate, the expression of Fas/FasL signaling pathway-related proteins and the phosphorylation lev- els of MLK3, MKK7 and JNKs, which are upstream molecules of death receptor pathways and belong to the family of mitogen-activated protein kinases (MAPKs),were measured in each group RESULTS: Compared with HepG2 cell group and RNAi group, apoptosis rate, the expression of Fas and FasL proteins, and the activation of MLK3, MKK7 and 3NKs were increased in the pcDNA3.1-X transfected group. The activation of JNKs and expression of FasL protein were inhibited in the pcDNA3.1-X transfected group when treated with a known JNK inhibitor, SP600125. When authors treated pcDNA3.1-X transfected group with K252a, a known MLK3 inhibitor, the activation of MLK3, MKK7 and 3NKs as well as expression of FasL protein was inhibited. Furthermore, cell apoptosis rate was also significantly declined in the presence of K252a in the pcDNA3.1-X transfected group. CONCLUSION: HBx can induce HepG2 cell apoptosis via a novel active MLK3-MKK7-JNKs signaling module to upregulate FasL protein expression.展开更多
Black soybeans [Glycine max(L.) Merrill] were fermented with various GRAS(generally recognized as safe) microorganisms,including Aspergillus sp.,Bacillus sp.and yeast(Issatchenkia orientalis) at 30°C for 3 ...Black soybeans [Glycine max(L.) Merrill] were fermented with various GRAS(generally recognized as safe) microorganisms,including Aspergillus sp.,Bacillus sp.and yeast(Issatchenkia orientalis) at 30°C for 3 d.The antioxidant contents,including total phenolics and total flavonoids,and the antioxidant activities of 1,1-diphenyl-2-picrylhydrazine(DPPH),ferric reducing antioxidant power(FRAP) and HO.scavenging were analyzed in preparations of fermented black soybeans.Fermented cultures proved to yield significant levels of antioxidants compared with non-fermented cultures(P 〈 0.05).Fermented black soybean preparations possessed antioxidant activities could be attributed to the total phenolics and flavonoids present.展开更多
Syzygium cumini(S.cumini)(L.) Skeels(jambolan) is one of the widely used medicinal plants in the treatment of various diseases in particular diabetes.The present review has been primed to describe the existing data on...Syzygium cumini(S.cumini)(L.) Skeels(jambolan) is one of the widely used medicinal plants in the treatment of various diseases in particular diabetes.The present review has been primed to describe the existing data on the information on botany,phytochemical constituents,traditional uses and pharmacological actions of 5.cumini(L.) Skeels(jambolan).Electronic database search was conducted with the search terms of Eugenia jambolana,S.cumini,jambolan,common plum and java plum.The plant has been viewed as an antidiabetic plant since it became commercially available several decades ago.During last four decades,numerous folk medicine and scientific reports on the antidiabetic effects of this plant have been cited in the literature.The plant is rich in compounds containing anthocyanins,glucoside,ellagic acid,isoquercetin,kaemferol and myrecetin.The seeds are claimed to contain alkaloid,jambosine,and glycoside jambolin or antimellin,which halts the diastalic conversion of starch into sugar.The vast number of literatures found in the database revealed that the extracts of different parts of jambolan showed significant pharmacological actions.We suggest that there is a need for further investigation to isolate active principles which confer the pharmacological action.Hence identification of such active compounds is useful for producing safer drugs in the treatment of various ailments including diabetes.展开更多
Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across dif...Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.展开更多
This study investigated the chromium(Cr)detoxification mechanism-induced changes in growth and antioxidant defence enzyme activities in Chrysopogon zizanioides.Plant growth decreased by 36.8%and 45.0%in the shoots and...This study investigated the chromium(Cr)detoxification mechanism-induced changes in growth and antioxidant defence enzyme activities in Chrysopogon zizanioides.Plant growth decreased by 36.8%and 45.0%in the shoots and roots,respectively,in the 50 mg/L Cr treatment.Cr accumulation was higher in root(9807μg/g DW)than in shoots(8730μg/g DW).Photosynthetic pigments and malondialdehyde content increased up to the 30 mg/L Cr treatment,whereas they declined at higher doses.The activity of superoxide dismutase(SOD),catalase(CAT)and peroxidase(POX)were increased significantly with increasing of Cr dose but slightly declined at higher doses.Isozyme banding patterns revealed the expression of multiple bands for SOD,CAT and POX enzymes,and the band intensity decreased at high doses of Cr exposure.These results indicate that higher Cr doses increased the oxidative stress by over production of reactive oxygen species(ROS)in vetiver that had potential tolerance mechanism to Cr as evidenced by enhanced level of antioxidative enzymes,photosynthetic pigments,MDA contents.Therefore,vetiver has evolved a mechanism for detoxification and accumulates higher concentration of toxic Cr.This study provides a better understanding of how vetiver detoxifies Cr.展开更多
The pandemic of novel coronavirus disease 2019(COVID-19)is an infectious disease caused by+ve strand RNA virus(SARS-CoV-2,severe acute respiratory syndrome coronavirus 2)that belongs to the corona viridae family.In Ma...The pandemic of novel coronavirus disease 2019(COVID-19)is an infectious disease caused by+ve strand RNA virus(SARS-CoV-2,severe acute respiratory syndrome coronavirus 2)that belongs to the corona viridae family.In March,the World Health Organization declared the outbreak of novel coronavirus for the public health emergency.Although SARS-CoV-2 infection presents with respiratory symptoms,it affects other organs such as the kidneys,liver,heart and brain.Early-stage laboratory disease testing shows many false positive or negative outcomes such as less white blood cell count and a low number of lymphocyte count.However,radiological examination and diagnosis are among the main components of the diagnosis and treatment of COVID-19.In particular,for COVID-19,chest computed tomography developed vigorous initial diagnosis and disease progression assessment.However,the accuracy is limited.Although realtime reverse transcription-polymerase chain reaction is the gold standard method for the diagnosis of COVID-19,sometimes it may give false-negative results.Due to the consequences of the missing diagnosis.This resulted in a discrepancy between the two means of examination.Conversely,based on currently available evidence,we summarized the possible understanding of the various pathophysiology,radio diagnostic methods in severe COVID-19 patients.As the information on COVID-19 evolves rapidly,this review will provide vital information for scientists and clinicians to consider novel perceptions for the comprehensive knowledge of the diagnostic approaches based on current experience.展开更多
The novel coronavirus disease-2019(COVID-19)is caused by a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family.In March 2019 the World Health Organization declared that COVID-19 was a pa...The novel coronavirus disease-2019(COVID-19)is caused by a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family.In March 2019 the World Health Organization declared that COVID-19 was a pandemic.COVID-19 patients typically have a fever,dry cough,dyspnea,fatigue,and anosmia.Some patients also report gastrointestinal(GI)symptoms,including diarrhea,nausea,vomiting,and abdominal pain,as well as liver enzyme abnormalities.Surprisingly,many studies have found severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)viral RNA in rectal swabs and stool specimens of asymptomatic COVID-19 patients.In addition,viral receptor angiotensin-converting enzyme 2 and transmembrane protease serine-type 2,were also found to be highly expressed in gastrointestinal epithelial cells of the intestinal mucosa.Furthermore,SARS-CoV-2 can dynamically infect and replicate in both GI and liver cells.Taken together these results indicate that the GI tract is a potential target of SARS-CoV-2.Therefore,the present review summarizes the vital information available to date on COVID-19 and its impact on GI aspects.展开更多
For better understanding the chemical or biological information of ZNF191 (243-368), we expressed the fusion protein of GST and ZNF191 (243-368), and used it to obtain the binding DNA sequence of this zinc finger ...For better understanding the chemical or biological information of ZNF191 (243-368), we expressed the fusion protein of GST and ZNF191 (243-368), and used it to obtain the binding DNA sequence of this zinc finger protein. But in the process of expression and purification, we found this fusion protein slowly degradated. For resolving this problem, we simultaneously added charged amino acids L-Arg and L-Glu to the solution of fusion protein, and demonstrated that this method can dramatically increase the stability of this fusion protein. This method can make the fusion protein suitable for the continuous works, especially for situations where high protein concentration and long-term stability without precipitate and degradation of protein are required.展开更多
Objective:To investigate the effects of Gymnema montanum leaf extract against endoplasmic reticulum(ER)stress-induced toxicity in endothelial cells.Methods:The immortalized endothelial hybrid cell,EA.hy926 was treated...Objective:To investigate the effects of Gymnema montanum leaf extract against endoplasmic reticulum(ER)stress-induced toxicity in endothelial cells.Methods:The immortalized endothelial hybrid cell,EA.hy926 was treated with different concentrations of Gymnema montanum leaf extract(0–100μg/mL)and the ER stress inducer,tunicamycin.The cytotoxicity was assessed by MTT as well as lactate dehydrogenase and malondialdehyde levels were determined.The levels of ER stress markers,GRP78 and CHOP were analysed by Western blot assay.The Gymnema montanum leaf extract-mediated activation of nuclear factor erythroid 2-related factor 2(Nrf2)was assessed by cell-based luciferase enzyme fragment complementation assay and antioxidant responsive element driven luciferase reporter assay.The levels of phosphoproteins of the MAPK pathway were analyzed using the Bioplex system.Results:A dose-dependent cytoprotective effect of Gymnema montanum leaf extract was observed in tunicamycin-induced toxicity.Gymnema montanum leaf extract significantly reduced lactate dehydrogenase activity and malondialdehyde levels in ER stress-induced endothelial cells.It also suppressed ER stress markers dose dependently and inhibited the phosphorylation of JNK,ERK,MEK and p38 MAPK in tunicamycin-induced endothelial cells.Moreover,Gymnema montanum leaf extract increased the expression of Nrf2 and its downstream targets in endothelial cells.Conclusions:Gymnema montanum leaf extract attenuates ER stress by increasing the expression of Nrf2 and its downstream genes.展开更多
Breast cancer is one of the leading causes of cancer-related deaths in women worldwide.It is a cancer that originates from the mammary ducts and involves mutations in multiple genes.Recently,the treatment of breast ca...Breast cancer is one of the leading causes of cancer-related deaths in women worldwide.It is a cancer that originates from the mammary ducts and involves mutations in multiple genes.Recently,the treatment of breast cancer has become increasingly challenging owing to the increase in tumor heterogeneity and aggressiveness,which gives rise to therapeutic resistance.Epidemiological,populationbased,and hospital-based case-control studies have demonstrated an association between high intake of certain Allium vegetables and a reduced risk in the development of breast cancer.Diallyl disulfide(DADS)and diallyl trisulfide(DATS)are the main allyl sulfur compounds present in garlic,and are known to exhibit anticancer activity as they interfere with breast cancer cell proliferation,tumor metastasis,and angiogenesis.The present review highlights multidrug resistance mechanisms and their signaling pathways in breast cancer.This review discusses the potential anticancer activities of DADS and DATS,with emphasis on drug resistance in triple-negative breast cancer(TNBC).Understanding the anticancer activities of DADS and DATS provides insights into their potential in targeting drug resistance mechanisms of TNBC,especially in clinical studies.展开更多
The rapid degradation of Mg alloy was reduced by incorporating titanate on a fluorine-based anodized layer.The coating shows(i)excellent biomineralization ability,(ii)improved local and periodical corrosion behavior a...The rapid degradation of Mg alloy was reduced by incorporating titanate on a fluorine-based anodized layer.The coating shows(i)excellent biomineralization ability,(ii)improved local and periodical corrosion behavior and(iii)enhanced expression of osteogenic factors(Runx2,Col 1,OCN and OPN)along with(iv)the antibacterial property.The fluoride and magnesium ions dissolution from the anodized layer is responsible for the better expression of osteogenic factors and antibacterial behavior.The preparation of the titanate incorporated anodized Mg alloy(Ti-AMg)is a facile solution to overcome the implant-associated bacterial infections with required biological functions including progression of bone ingrowth and biocompatibility.展开更多
Objective:To isolate the larvicidal component from the fruits of Piper longum(P.longum) against the filariasis vector,Culex quinquefasciatus(C.quinquefasciatus).Methods:Pulverized fruits of P.longum were subjected...Objective:To isolate the larvicidal component from the fruits of Piper longum(P.longum) against the filariasis vector,Culex quinquefasciatus(C.quinquefasciatus).Methods:Pulverized fruits of P.longum were subjected to soxhlet extraction using series of organic solvents of increasing polarity.All the solvent extracts were verified for their larvicidal efficacy against 4th instar larvae of C.quinquefasciatus employing standard WHO procedure.Bioassayguided fractionation through column chromatography lead to the isolation of a bioactive amide, pipyahyine from the petroleum ether extract.Results:Petroleum ether extract was found to be the most active fraction among all the extracts tested with LC<sub>50</sub> and LC<sub>90</sub> being 1.03 and 2.04 ppm respectively.Whereas,pipyahyine,an isolated component of the same fraction was found to be even more effective than the parent extract in terms of LC<sub>50</sub> being 0.58 and 1.88 ppm respectively. Conclusions:From the results,it is evident that P.longum can be considered as a powerful arsenal for the control of mosquito population.展开更多
AIM: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice. METHODS: Two sets of experiments were designed. In the first set, recently weaned mice were eith...AIM: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice. METHODS: Two sets of experiments were designed. In the first set, recently weaned mice were either orally administered ferrous (Fe2+) iron salt or ferric (Fe3+) microencapsulated iron for 6 wk. The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced. In the second set, juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments. In both sets of experiments, animals were sacrificed 7 d after TNBS instillation. Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (MPO) activity. Alteration of the microflora profile was estimated usingquantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora, Bacteroidetes, Firmicutes and enterobacteria. RESULTS: Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain. Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27 MPO U/mg proteinvs 2.47 ± 0.22 MPO U/mg protein in colitic mice). In contrast, ferric iron significantly prevented the increase of MPO activity (1.64 ± 0.14 MPO U/mg protein) in TNBS-induced colitis. Moreover, this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po - 6 wk). In the study we also compared, in both rats and mice, the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po - 6 wk) on TNBS-induced colitis and its related dysbiosis. We confirmed that ferric iron limited the TNBS-induced increase of MPO activity in both the rodent species. Furthermore, we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis. At first, we needed to optimize the isolation and quantify DNA copy numbers using standard curves to perform by qPCR this interspecies comparison. Using this approach, we determined that total microflora was similar in control rats and mice and was mainly composed of Firmicutes and Bacteroidetes at a ratio of 10/1. Ferric juvenile administration did not modify the microflora profile in control animals. Total microflora numbers remained unchanged whichever experimental conditions studied. Following TNBS-induced colitis, the Firmicutes/Bacteroidetes ratio was altered resulting in a decrease of the Firmicutes numbers and an increase of the Bacteroidetes numbers typical of a gut inflammatory reaction. In parallel, the subdominant population, the enterobacteria was also increased. However, ferric iron supplementation for the juvenile period prevented the increase of Bacteroidetes and of enterobacteria numbers consecutive to the colitis in both the studied species at adulthood.CONCLUSION: Rats and mice juvenile chronic ferric iron ingestion prevents colitis and dysbiosis at adulthood as assessed by the first interspecies comparison.展开更多
Apocytochrome b5 with a typical heme-binding motif of HPGG, and its variants with mutated motifs, GPGG, GPGH, HVGG, and HPGP, have been subjected to molecular dynamics simulation. Comparison of the dynamic consequence...Apocytochrome b5 with a typical heme-binding motif of HPGG, and its variants with mutated motifs, GPGG, GPGH, HVGG, and HPGP, have been subjected to molecular dynamics simulation. Comparison of the dynamic consequences has revealed the crucial role of HPGG in assembling the heine group of cytochrome b5 and in modulating protein structure, property and function.展开更多
Objective: Midkine (MK), a new member of the heparin-binding growth factor family, has been found recently to have a high expression level in many tumor specimens including lung carcinoma. Estrogens may be involved...Objective: Midkine (MK), a new member of the heparin-binding growth factor family, has been found recently to have a high expression level in many tumor specimens including lung carcinoma. Estrogens may be involved in lung carcinogenesis, and estrogen receptors, mainly estrogen receptor-β (ER-β), are present and functional in normal lung and tumor cell lines and tissues. In addition, estrogens and growth factors may promote the progression of human non-small cell lung cancer (NSCLC). Previously, we have immunohistochemically demonstrated that MK and ER-β proteins were overexpressed in NSCLC and their expression levels were both significantly negatively correlated with the pathological classification. The purpose of this study was to further verify their expression and its correlation with NSCLC. Methods: Taking NSCLC tissues and their corresponding paraneoplastic and normal lung as research objects, we further examined the expression of MK and ER-β by meas of RT-PCR, in situ hybridization and Western blot analyses at the levels of messenger RNA (mRNA) and protein, respectively. Results: The increased MK and ER-β mRNA expression was found in NSCLC by RT-PCR and in situ hybridization analyses. Furthermore, Western blot analysis also displayed increased expression of MK and ER-β proteins in NSCLC. Finally, their correlation analysis at the levels of mRNA and protein expression in NSCLC demonstrated that MK protein level was significantly correlated to estrogen receptor-β (P〈0.01, rs=0.535); in spite of their correlation at the mRNA level, there was no remarkable difference between MK and ER-β (P〉0.05, rs=0.178). Conclusion: All these results in the present study confirmed that MK and ER-β were overexpressed in human NSCLC.展开更多
The linkage between Qi and mitochondria was investigated by exploring the effect of Traditional Chinese Medicine (TCM) Qi-invigorating herbs on mitochondrial function at the biochemical and molecular levels. Three Chi...The linkage between Qi and mitochondria was investigated by exploring the effect of Traditional Chinese Medicine (TCM) Qi-invigorating herbs on mitochondrial function at the biochemical and molecular levels. Three Chinese herbs (<i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;">,</span><i><span style="font-family:Verdana;"> Herba cistanche</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">Panax ginseng</span></i><span style="font-family:Verdana;"></i>) were used to treat cultured mouse kidney cells and the generation of adenosine triphosphate (ATP) was measured. The Qi-invigorating herb, <i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;"></i>, was selected for further </span></span><span style="font-family:""><span style="font-family:Verdana;">study using additional biological and molecular parameters, including ATP, reactive oxygen species (ROS), mitochondrial membrane potential (MMP),</span><span><span style="font-family:Verdana;"> mtDNA copies, superoxide dismutase (SOD), glutathione (GSH), cell growth, cell viability and transcriptomes. We also chose two concentrations of <i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;"></i> to study the hormetic effect. The results indicated that: 1) Qi-invigorating herbs have significant effects on the function of mitochondria, with ATP production and the antioxidant capacity being significantly enhanced, and ROS le</span></span><span style="font-family:Verdana;">vels being reduced, allowing for a more optimal oxidation environment. The effect of the herbs followed a hormetic curve with a stimulating effect at lower</span><span> </span><span style="font-family:Verdana;">doses but an inhibiting effect at high doses;2) The growth of the cells was not</span><span> </span><span style="font-family:Verdana;">affected despite numerous biochemical changes associated with mitochondrial</span><span> </span><span style="font-family:Verdana;">function, indicating the powerful ability of mitochondria to maintain cellular homeostasis;3) The up-regulation of NOCT gene, related to nicotinamide adenine dinucleotide (NADH) synthesis, offers a molecular basis for the ATP-promoting effect of the Qi-invigorating herbs. This work provides additional insight into the efficacy of TCM herbs from a western perspective.展开更多
基金Supported by the National Key Research and Development Program of China,No.2023YFC2508806Key Research and Development Project in Henan Province,No.231111310500+4 种基金Young Elite Scientists Sponsorship Program by CAST,No.2021-QNRC2-A06Scientific Research Project of Henan Zhongyuan Medical Science and Technology Innovation and Development Foundation,No.ZYYC2023ZDYouth Science Award Project of the Provincial-Level Joint Fund for Science and Technology Research and Development Project in Henan Province,No.225200810084Special Project on Training Top Talents in Traditional Chinese Medicine in Henan Province,No.2022ZYBJ242023 Hunan University of Chinese Medicine Postgraduate Innovation Project,No.2023CX64。
文摘The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.
基金supported by the National Administration of Traditional Chinese Medicine Young Qi Huang Scholars support project.
文摘Objective:To evaluate the efficacy and safety of Jiawei Simiao powder(JWSMP)combined with celecoxib for the treatment of acute gouty arthritis by conducting a meta-analysis of randomized controlled trials(RCTs).Methods: The Chinese National Knowledge Infrastructure Databases,Chinese Scientific Journal Database,Wanfang,Cochrane Library,EMBASE,PubMed,and Web of Science databases were searched from inception until December 2023.Continuous variables were analyzed using the mean difference(MD)for analysis,and dichotomous variables were used as risk ratios.Data with similar characteristics were pooled for meta-analysis,and heterogeneity was assessed using I2.The Cochrane Handbook was used to assess the risk of bias and quality.RevMan 5.3 software was used to perform the meta-analysis.Results: Thirteen RCTs involving 1007 patients were included in the study.The quality of the included studies was low(unclear randomization processes and insufficient blinding reporting).The group receiving JWSMP combined with celecoxib showed significantly lower levels of serum uric acid(SUA,MD=−66.32,95%confidence interval(CI):−80.97 to−51.67,P<.001),erythrocyte sedimentation rate(ESR,MD=−6.05,95%CI:−8.29 to−3.82,P<.001),C-reactive protein(CRP,MD=−7.39,95%CI:−11.15,−3.63,P<.001),and joint pain score(VAS score,MD=−2.14,95%CI:−2.4 to−1.88,P<.001)compared to celecoxib alone.Additionally,the JWSMP combined group had a higher total effective rate(risk ratio=1.22,95%CI:1.14 to 1.29,P<.001)and fewer adverse compared to celecoxib alone.Conclusions: JWSMP combined with celecoxib is more effective than celecoxib alone in improving the total efficacy rate,alleviating joint pain,and improving SUA,ESR,and CRP levels.JWSMP also reduced the occurrence of adverse events caused by celecoxib.However,the quality of the included studies was low,highlighting the need for further high-quality research with larger sample sizes and robust methodologies,such as double-blind randomization,to confirm these findings.
基金Supported by The Scientific Research Fund of Graduate School of Nanjing University, the Fund for Key Program of Ministry of Education, No. 02111the 985-Ⅱ Program of Nanjing University
文摘AIM: To determine whether midkine (M/O and its truncated form (tMK) contribute to gastric tumorigenesis using in vitro and in vivo models. METHODS: Human MK and tMt( plasmids were constructed and expressed in BGC823 (a gastric adenocarcinoma cell line) to investigate the effect of over-expressed MK or tMK on cell growth and turmorigenesis in nude mice. RESULTS: The growth of MK-transfected or tMK- transfected cells was significantly increased compared with that of the control cells, and tMK-transfected cells grew more rapidly than MK-transfected cells. The number of colony formation of the cells transfected with MK or tMK gene was larger than the control cells. In nude mice injected with MK-transfected or tMK-transfected cells, visible tumor was observed earlier and the tumor tissues were larger in size and weight than in control animals that were injected with cells without the transfection of either genes. CONCLUSION: Over-expressed MK or tMtC can promote human gastric cancer cell growth in vitro and in vivo, and bMK has greater effect than MK. tMK may be a more promising gene therapeutic target compared with MK for treatment of malignant tumors.
基金Supported by Natural Science Foundation of Jiangsu Province,No.10KJD310002The Graduate Innovation Program in Science and Technology of Xuzhou Medical College,No.XYCX201005
文摘AIM: To investigate the possible mechanism by which hepatitis B virus X protein (HBx) mediates apoptosis of HepG2 cells. METHODS: HBx expression vector pcDNA3.1-X was transfected into HepG2 cells to establish an HBx high- expression cellular model as pcDNA3.1-X transfected group. The pcDNA3.1-X and pSilencer3.1-shHBX (HBx antagonist) were cotransfected into HepG2 cells to es- tablish an HBx low-expression model as RNAi group. Untransfected HepG2 cells and HepG2 cells transfected with negative control plasmid were used as controls. Apoptosis rate, the expression of Fas/FasL signaling pathway-related proteins and the phosphorylation lev- els of MLK3, MKK7 and JNKs, which are upstream molecules of death receptor pathways and belong to the family of mitogen-activated protein kinases (MAPKs),were measured in each group RESULTS: Compared with HepG2 cell group and RNAi group, apoptosis rate, the expression of Fas and FasL proteins, and the activation of MLK3, MKK7 and 3NKs were increased in the pcDNA3.1-X transfected group. The activation of JNKs and expression of FasL protein were inhibited in the pcDNA3.1-X transfected group when treated with a known JNK inhibitor, SP600125. When authors treated pcDNA3.1-X transfected group with K252a, a known MLK3 inhibitor, the activation of MLK3, MKK7 and 3NKs as well as expression of FasL protein was inhibited. Furthermore, cell apoptosis rate was also significantly declined in the presence of K252a in the pcDNA3.1-X transfected group. CONCLUSION: HBx can induce HepG2 cell apoptosis via a novel active MLK3-MKK7-JNKs signaling module to upregulate FasL protein expression.
基金supproted by a grant from the Korea Institute of Planning and Evaluation for Technology of Food,Agriculture,Forestry and Fishes (i PET)
文摘Black soybeans [Glycine max(L.) Merrill] were fermented with various GRAS(generally recognized as safe) microorganisms,including Aspergillus sp.,Bacillus sp.and yeast(Issatchenkia orientalis) at 30°C for 3 d.The antioxidant contents,including total phenolics and total flavonoids,and the antioxidant activities of 1,1-diphenyl-2-picrylhydrazine(DPPH),ferric reducing antioxidant power(FRAP) and HO.scavenging were analyzed in preparations of fermented black soybeans.Fermented cultures proved to yield significant levels of antioxidants compared with non-fermented cultures(P 〈 0.05).Fermented black soybean preparations possessed antioxidant activities could be attributed to the total phenolics and flavonoids present.
基金fianancially supported by University Grants Commission,New Delhi[grant No.F.4-2/2006(BSR)/13-98/2008(BSR)]
文摘Syzygium cumini(S.cumini)(L.) Skeels(jambolan) is one of the widely used medicinal plants in the treatment of various diseases in particular diabetes.The present review has been primed to describe the existing data on the information on botany,phytochemical constituents,traditional uses and pharmacological actions of 5.cumini(L.) Skeels(jambolan).Electronic database search was conducted with the search terms of Eugenia jambolana,S.cumini,jambolan,common plum and java plum.The plant has been viewed as an antidiabetic plant since it became commercially available several decades ago.During last four decades,numerous folk medicine and scientific reports on the antidiabetic effects of this plant have been cited in the literature.The plant is rich in compounds containing anthocyanins,glucoside,ellagic acid,isoquercetin,kaemferol and myrecetin.The seeds are claimed to contain alkaloid,jambosine,and glycoside jambolin or antimellin,which halts the diastalic conversion of starch into sugar.The vast number of literatures found in the database revealed that the extracts of different parts of jambolan showed significant pharmacological actions.We suggest that there is a need for further investigation to isolate active principles which confer the pharmacological action.Hence identification of such active compounds is useful for producing safer drugs in the treatment of various ailments including diabetes.
基金supported by Georgia Research Alliance and the National Natural Science Foundation of China(Grant Nos.81320108025,61402194,61572227)the Science-Technology Development Project from Jilin Province(Nos.20160101259JC,20160204022GX,20170520063JH)
文摘Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.
基金Project(41771512)supported by the National Natural Science Foundation of ChinaProject(2018RS3004)supported by Hunan Science&Technology Innovation Program,China
文摘This study investigated the chromium(Cr)detoxification mechanism-induced changes in growth and antioxidant defence enzyme activities in Chrysopogon zizanioides.Plant growth decreased by 36.8%and 45.0%in the shoots and roots,respectively,in the 50 mg/L Cr treatment.Cr accumulation was higher in root(9807μg/g DW)than in shoots(8730μg/g DW).Photosynthetic pigments and malondialdehyde content increased up to the 30 mg/L Cr treatment,whereas they declined at higher doses.The activity of superoxide dismutase(SOD),catalase(CAT)and peroxidase(POX)were increased significantly with increasing of Cr dose but slightly declined at higher doses.Isozyme banding patterns revealed the expression of multiple bands for SOD,CAT and POX enzymes,and the band intensity decreased at high doses of Cr exposure.These results indicate that higher Cr doses increased the oxidative stress by over production of reactive oxygen species(ROS)in vetiver that had potential tolerance mechanism to Cr as evidenced by enhanced level of antioxidative enzymes,photosynthetic pigments,MDA contents.Therefore,vetiver has evolved a mechanism for detoxification and accumulates higher concentration of toxic Cr.This study provides a better understanding of how vetiver detoxifies Cr.
文摘The pandemic of novel coronavirus disease 2019(COVID-19)is an infectious disease caused by+ve strand RNA virus(SARS-CoV-2,severe acute respiratory syndrome coronavirus 2)that belongs to the corona viridae family.In March,the World Health Organization declared the outbreak of novel coronavirus for the public health emergency.Although SARS-CoV-2 infection presents with respiratory symptoms,it affects other organs such as the kidneys,liver,heart and brain.Early-stage laboratory disease testing shows many false positive or negative outcomes such as less white blood cell count and a low number of lymphocyte count.However,radiological examination and diagnosis are among the main components of the diagnosis and treatment of COVID-19.In particular,for COVID-19,chest computed tomography developed vigorous initial diagnosis and disease progression assessment.However,the accuracy is limited.Although realtime reverse transcription-polymerase chain reaction is the gold standard method for the diagnosis of COVID-19,sometimes it may give false-negative results.Due to the consequences of the missing diagnosis.This resulted in a discrepancy between the two means of examination.Conversely,based on currently available evidence,we summarized the possible understanding of the various pathophysiology,radio diagnostic methods in severe COVID-19 patients.As the information on COVID-19 evolves rapidly,this review will provide vital information for scientists and clinicians to consider novel perceptions for the comprehensive knowledge of the diagnostic approaches based on current experience.
文摘The novel coronavirus disease-2019(COVID-19)is caused by a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family.In March 2019 the World Health Organization declared that COVID-19 was a pandemic.COVID-19 patients typically have a fever,dry cough,dyspnea,fatigue,and anosmia.Some patients also report gastrointestinal(GI)symptoms,including diarrhea,nausea,vomiting,and abdominal pain,as well as liver enzyme abnormalities.Surprisingly,many studies have found severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)viral RNA in rectal swabs and stool specimens of asymptomatic COVID-19 patients.In addition,viral receptor angiotensin-converting enzyme 2 and transmembrane protease serine-type 2,were also found to be highly expressed in gastrointestinal epithelial cells of the intestinal mucosa.Furthermore,SARS-CoV-2 can dynamically infect and replicate in both GI and liver cells.Taken together these results indicate that the GI tract is a potential target of SARS-CoV-2.Therefore,the present review summarizes the vital information available to date on COVID-19 and its impact on GI aspects.
文摘For better understanding the chemical or biological information of ZNF191 (243-368), we expressed the fusion protein of GST and ZNF191 (243-368), and used it to obtain the binding DNA sequence of this zinc finger protein. But in the process of expression and purification, we found this fusion protein slowly degradated. For resolving this problem, we simultaneously added charged amino acids L-Arg and L-Glu to the solution of fusion protein, and demonstrated that this method can dramatically increase the stability of this fusion protein. This method can make the fusion protein suitable for the continuous works, especially for situations where high protein concentration and long-term stability without precipitate and degradation of protein are required.
基金supported by the Indian Council of Medical Research(grant no.59/57/2011/BMS/TRM),Government of India
文摘Objective:To investigate the effects of Gymnema montanum leaf extract against endoplasmic reticulum(ER)stress-induced toxicity in endothelial cells.Methods:The immortalized endothelial hybrid cell,EA.hy926 was treated with different concentrations of Gymnema montanum leaf extract(0–100μg/mL)and the ER stress inducer,tunicamycin.The cytotoxicity was assessed by MTT as well as lactate dehydrogenase and malondialdehyde levels were determined.The levels of ER stress markers,GRP78 and CHOP were analysed by Western blot assay.The Gymnema montanum leaf extract-mediated activation of nuclear factor erythroid 2-related factor 2(Nrf2)was assessed by cell-based luciferase enzyme fragment complementation assay and antioxidant responsive element driven luciferase reporter assay.The levels of phosphoproteins of the MAPK pathway were analyzed using the Bioplex system.Results:A dose-dependent cytoprotective effect of Gymnema montanum leaf extract was observed in tunicamycin-induced toxicity.Gymnema montanum leaf extract significantly reduced lactate dehydrogenase activity and malondialdehyde levels in ER stress-induced endothelial cells.It also suppressed ER stress markers dose dependently and inhibited the phosphorylation of JNK,ERK,MEK and p38 MAPK in tunicamycin-induced endothelial cells.Moreover,Gymnema montanum leaf extract increased the expression of Nrf2 and its downstream targets in endothelial cells.Conclusions:Gymnema montanum leaf extract attenuates ER stress by increasing the expression of Nrf2 and its downstream genes.
基金supported by UGC-DAE-CSR,Kolkata(Grant No.:KC/CRS/19/RB-04/1047).
文摘Breast cancer is one of the leading causes of cancer-related deaths in women worldwide.It is a cancer that originates from the mammary ducts and involves mutations in multiple genes.Recently,the treatment of breast cancer has become increasingly challenging owing to the increase in tumor heterogeneity and aggressiveness,which gives rise to therapeutic resistance.Epidemiological,populationbased,and hospital-based case-control studies have demonstrated an association between high intake of certain Allium vegetables and a reduced risk in the development of breast cancer.Diallyl disulfide(DADS)and diallyl trisulfide(DATS)are the main allyl sulfur compounds present in garlic,and are known to exhibit anticancer activity as they interfere with breast cancer cell proliferation,tumor metastasis,and angiogenesis.The present review highlights multidrug resistance mechanisms and their signaling pathways in breast cancer.This review discusses the potential anticancer activities of DADS and DATS,with emphasis on drug resistance in triple-negative breast cancer(TNBC).Understanding the anticancer activities of DADS and DATS provides insights into their potential in targeting drug resistance mechanisms of TNBC,especially in clinical studies.
基金One of the authors K.Saranya is thankful to the Department of Science and Technology(DST),New Delhi,India for financial assistance under women scientist scheme(WOS-A)(Ref.No:SR/WOS-A/ET-17/2017).
文摘The rapid degradation of Mg alloy was reduced by incorporating titanate on a fluorine-based anodized layer.The coating shows(i)excellent biomineralization ability,(ii)improved local and periodical corrosion behavior and(iii)enhanced expression of osteogenic factors(Runx2,Col 1,OCN and OPN)along with(iv)the antibacterial property.The fluoride and magnesium ions dissolution from the anodized layer is responsible for the better expression of osteogenic factors and antibacterial behavior.The preparation of the titanate incorporated anodized Mg alloy(Ti-AMg)is a facile solution to overcome the implant-associated bacterial infections with required biological functions including progression of bone ingrowth and biocompatibility.
基金Department of Science and Technology,New Delhi,India for providing financial assistance under women scientist scheme-B
文摘Objective:To isolate the larvicidal component from the fruits of Piper longum(P.longum) against the filariasis vector,Culex quinquefasciatus(C.quinquefasciatus).Methods:Pulverized fruits of P.longum were subjected to soxhlet extraction using series of organic solvents of increasing polarity.All the solvent extracts were verified for their larvicidal efficacy against 4th instar larvae of C.quinquefasciatus employing standard WHO procedure.Bioassayguided fractionation through column chromatography lead to the isolation of a bioactive amide, pipyahyine from the petroleum ether extract.Results:Petroleum ether extract was found to be the most active fraction among all the extracts tested with LC<sub>50</sub> and LC<sub>90</sub> being 1.03 and 2.04 ppm respectively.Whereas,pipyahyine,an isolated component of the same fraction was found to be even more effective than the parent extract in terms of LC<sub>50</sub> being 0.58 and 1.88 ppm respectively. Conclusions:From the results,it is evident that P.longum can be considered as a powerful arsenal for the control of mosquito population.
基金Supported by Institut Polytechnique LaSalle Beauvais
文摘AIM: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice. METHODS: Two sets of experiments were designed. In the first set, recently weaned mice were either orally administered ferrous (Fe2+) iron salt or ferric (Fe3+) microencapsulated iron for 6 wk. The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced. In the second set, juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments. In both sets of experiments, animals were sacrificed 7 d after TNBS instillation. Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (MPO) activity. Alteration of the microflora profile was estimated usingquantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora, Bacteroidetes, Firmicutes and enterobacteria. RESULTS: Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain. Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27 MPO U/mg proteinvs 2.47 ± 0.22 MPO U/mg protein in colitic mice). In contrast, ferric iron significantly prevented the increase of MPO activity (1.64 ± 0.14 MPO U/mg protein) in TNBS-induced colitis. Moreover, this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po - 6 wk). In the study we also compared, in both rats and mice, the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po - 6 wk) on TNBS-induced colitis and its related dysbiosis. We confirmed that ferric iron limited the TNBS-induced increase of MPO activity in both the rodent species. Furthermore, we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis. At first, we needed to optimize the isolation and quantify DNA copy numbers using standard curves to perform by qPCR this interspecies comparison. Using this approach, we determined that total microflora was similar in control rats and mice and was mainly composed of Firmicutes and Bacteroidetes at a ratio of 10/1. Ferric juvenile administration did not modify the microflora profile in control animals. Total microflora numbers remained unchanged whichever experimental conditions studied. Following TNBS-induced colitis, the Firmicutes/Bacteroidetes ratio was altered resulting in a decrease of the Firmicutes numbers and an increase of the Bacteroidetes numbers typical of a gut inflammatory reaction. In parallel, the subdominant population, the enterobacteria was also increased. However, ferric iron supplementation for the juvenile period prevented the increase of Bacteroidetes and of enterobacteria numbers consecutive to the colitis in both the studied species at adulthood.CONCLUSION: Rats and mice juvenile chronic ferric iron ingestion prevents colitis and dysbiosis at adulthood as assessed by the first interspecies comparison.
基金supported by the initial foundation for Ph.D.introduced into University of South China(No.506XJQ06001).
文摘Apocytochrome b5 with a typical heme-binding motif of HPGG, and its variants with mutated motifs, GPGG, GPGH, HVGG, and HPGP, have been subjected to molecular dynamics simulation. Comparison of the dynamic consequences has revealed the crucial role of HPGG in assembling the heine group of cytochrome b5 and in modulating protein structure, property and function.
基金supported by a grant from General Program of the National Natural Science Foundation of China(No.30872941)the Scientific Research Foundation of Graduate School of Nanjing University(2008CL06)
文摘Objective: Midkine (MK), a new member of the heparin-binding growth factor family, has been found recently to have a high expression level in many tumor specimens including lung carcinoma. Estrogens may be involved in lung carcinogenesis, and estrogen receptors, mainly estrogen receptor-β (ER-β), are present and functional in normal lung and tumor cell lines and tissues. In addition, estrogens and growth factors may promote the progression of human non-small cell lung cancer (NSCLC). Previously, we have immunohistochemically demonstrated that MK and ER-β proteins were overexpressed in NSCLC and their expression levels were both significantly negatively correlated with the pathological classification. The purpose of this study was to further verify their expression and its correlation with NSCLC. Methods: Taking NSCLC tissues and their corresponding paraneoplastic and normal lung as research objects, we further examined the expression of MK and ER-β by meas of RT-PCR, in situ hybridization and Western blot analyses at the levels of messenger RNA (mRNA) and protein, respectively. Results: The increased MK and ER-β mRNA expression was found in NSCLC by RT-PCR and in situ hybridization analyses. Furthermore, Western blot analysis also displayed increased expression of MK and ER-β proteins in NSCLC. Finally, their correlation analysis at the levels of mRNA and protein expression in NSCLC demonstrated that MK protein level was significantly correlated to estrogen receptor-β (P〈0.01, rs=0.535); in spite of their correlation at the mRNA level, there was no remarkable difference between MK and ER-β (P〉0.05, rs=0.178). Conclusion: All these results in the present study confirmed that MK and ER-β were overexpressed in human NSCLC.
文摘The linkage between Qi and mitochondria was investigated by exploring the effect of Traditional Chinese Medicine (TCM) Qi-invigorating herbs on mitochondrial function at the biochemical and molecular levels. Three Chinese herbs (<i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;">,</span><i><span style="font-family:Verdana;"> Herba cistanche</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">Panax ginseng</span></i><span style="font-family:Verdana;"></i>) were used to treat cultured mouse kidney cells and the generation of adenosine triphosphate (ATP) was measured. The Qi-invigorating herb, <i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;"></i>, was selected for further </span></span><span style="font-family:""><span style="font-family:Verdana;">study using additional biological and molecular parameters, including ATP, reactive oxygen species (ROS), mitochondrial membrane potential (MMP),</span><span><span style="font-family:Verdana;"> mtDNA copies, superoxide dismutase (SOD), glutathione (GSH), cell growth, cell viability and transcriptomes. We also chose two concentrations of <i></span><i><span style="font-family:Verdana;">Astragali radix</span></i><span style="font-family:Verdana;"></i> to study the hormetic effect. The results indicated that: 1) Qi-invigorating herbs have significant effects on the function of mitochondria, with ATP production and the antioxidant capacity being significantly enhanced, and ROS le</span></span><span style="font-family:Verdana;">vels being reduced, allowing for a more optimal oxidation environment. The effect of the herbs followed a hormetic curve with a stimulating effect at lower</span><span> </span><span style="font-family:Verdana;">doses but an inhibiting effect at high doses;2) The growth of the cells was not</span><span> </span><span style="font-family:Verdana;">affected despite numerous biochemical changes associated with mitochondrial</span><span> </span><span style="font-family:Verdana;">function, indicating the powerful ability of mitochondria to maintain cellular homeostasis;3) The up-regulation of NOCT gene, related to nicotinamide adenine dinucleotide (NADH) synthesis, offers a molecular basis for the ATP-promoting effect of the Qi-invigorating herbs. This work provides additional insight into the efficacy of TCM herbs from a western perspective.