Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses ...Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment.展开更多
Loss of self-tolerance and expansion of auto-reactive lymphocytes are the basis for autoimmunity. Apoptosis and the rapid clearance of apoptotic cells by phagocytes usually occur as coordinated processes that ensure r...Loss of self-tolerance and expansion of auto-reactive lymphocytes are the basis for autoimmunity. Apoptosis and the rapid clearance of apoptotic cells by phagocytes usually occur as coordinated processes that ensure regulated cellularity and stress response with non-pathological outcomes. Defects in clearance of apoptotic ceils would contribute to the generation of self-reactive lymphocytes, which drive autoimmune disorders such as rheumatoid arthritis （RA） and systemic lupus erythematosus （SLE）. The IL-12 family of cytokines （IL-12, IL-23, and IL-27） and IL-10 are produced by phagocytic macrophages and play critical roles in the regulation of antigen-presenting cells （APCs） and effector lymphocytes during an immune response to pathogens. Inappropriate expression of these cytokines and their dysregulated activities have been strongly implicated in the pathogenesis of several autoimmune diseases. The production of pro- and anti-inflammatory cytokines by phagocytic APCs is delicately regulated during the ingestion of apoptotic cells as part of an intrinsic mechanism to prevent inflammatory autoimmune reactions. How apoptotic cell-derived signals regulate cytokine production is poorly understood. A recent study by our group demonstrated that phagocytosis of apoptotic cells by activated macrophages results in strong inhibition of IL-12 p35 gene expression by activating a novel transcription repressor, which we named GC-binding protein （GC-BP）, through tyrosine dephosphorylation. We are also beginning to understand the molecular mechanisms underlying apoptotic cell-triggered production of IL-10 by phagocytes. These studies will help to elucidate some novel immune regulatory mechanisms and explore the regulation of immune responses to autoantigens with potentials to discover new therapeutic targets for the treatment of autoimmune disorders.展开更多
Objective To examine the role of Cd-induced reactive oxygen species（ROS） generation in the apoptosis of neuronal cells. Methods Neuronal cells（primary rat cerebral cortical neurons and PC12 cells） were incubated w...Objective To examine the role of Cd-induced reactive oxygen species（ROS） generation in the apoptosis of neuronal cells. Methods Neuronal cells（primary rat cerebral cortical neurons and PC12 cells） were incubated with or without Cd post-pretreatment with rapamycin（Rap） or N-acetyl-L-cysteine（NAC）. Cell viability was determined by MTT assay, apoptosis was examined using flow cytometry and fluorescence microscopy, and the activation of phosphoinositide 3’-kinase/protein kinase B（Akt）/mammalian target of rapamycin（m TOR） and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays. Results Cd-induced activation of Akt/m TOR signaling, including Akt, m TOR, p70 S6 kinase（p70 S6K）, and eukaryotic initiation factor 4E binding protein 1（4E-BP1）. Rap, an m TOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/m TOR signaling and apoptosis of neuronal cells. Furthermore, NAC blocked the decrease of B-cell lymphoma 2/Bcl-2 associated X protein（Bcl-2/Bax） ratio, release of cytochrome c, cleavage of caspase-3 and poly（ADP-ribose） polymerase（PARP）, and nuclear translocation of apoptosis-inducing factor（AIF） and endonuclease G（Endo G）. Conclusion Cd-induced ROS generation activates Akt/m TOR and mitochondrial pathways, leading to apoptosis of neuronal cells. Our findings suggest that m TOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.展开更多
Hypocrellin A（ HA）, a photosensitive perylenequinone compound of Hypocrella bambusae, inhibited the proliferation of several tumor cell lines. Human cervical cancer cells, HeLa ceils, were used as a model to elucida...Hypocrellin A（ HA）, a photosensitive perylenequinone compound of Hypocrella bambusae, inhibited the proliferation of several tumor cell lines. Human cervical cancer cells, HeLa ceils, were used as a model to elucidate the molecular mechanisms of HA-induced tumor cell death. The results show that HA can induce the oligonucleosomal fragmentation of DNA in HeLa cells and also can increase the expression of apoptosis inducer Bax mRNA and that it decreases the expression of apoptosis suppressor, Bcl-2 mRNA, in mitochondria. It can be concluded from the data that HA-induced apoptosis is related to the balance between Bcl-2 and Bax gene expressions.展开更多
Resveratrol(3,5,4’-trihydroxystilbene,RSV) has been widely used in mammalian cells,but whether it can be used during freezing boar semen is still unknown.The effects of RSV treatment during boar semen freezing on its...Resveratrol(3,5,4’-trihydroxystilbene,RSV) has been widely used in mammalian cells,but whether it can be used during freezing boar semen is still unknown.The effects of RSV treatment during boar semen freezing on its anti-freezing ability,apoptosis,and possible apoptotic pathways were observed in this study.Sperm motility,mitochondrial membrane potential(ΔΨm),adenosine triphosphate(ATP) content,terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive apoptotic state,and messenger RNA(mRNA) expression levels of apoptotic genes involved in different apoptotic pathways after freezing with or without RSV treatment were tested.The results showed that:(1) Compared with fresh sperm,the motility,normal acrosome rate,and plasma membrane integrity rate of frozen boar sperm decreased significantly(P<0.05),and RSV did not significantly increase the sperm motility(0.44 vs.0.40,P>0.05),but it did significantly improve the normal acrosome rate(57.65% vs.47.00%,P<0.05) and plasma membrane integrity rate(46.67% vs.38.85%,P<0.05).(2) After freezing,most boar sperm showed low mitochondrial ΔΨm.RSV treatment could increase the rate of high mitochondrial ΔΨm of boar sperm.(3) RSV treatment significantly decreased reactive oxygen species(ROS) levels(58.65% vs.88.41%,P<0.05)and increased the ATP content(0.49 μmol/L vs.0.25 μmol/L,P<0.05) of boar sperm during freezing.(4) The apoptotic rate of the freezing group(80.41%) with TUNEL detection increased significantly compared to the fresh group(9.70%,P<0.05),and RSV treatment greatly decreased the apoptotic rate(68.32%,P<0.05).(5) Real-time polymerase chain reaction(RT-PCR) showed that not only the genes from the death receptor-mediated apoptotic pathway(tumor necrosis factor-α(TNF-α),Fas ligand(FasL),and Caspase-8),but also the genes from the mitochondria-mediated apoptotic pathway(manganese superoxide dismutase(MnSOD),B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),and Caspase-9) were both significantly changed after freezing.RSV treatment during freezing greatly changed their expression levels.Although RSV treatment during boar semen freezing did not significantly increase motility after thawing,it still played an efficient antioxidant role,which could enhance the mitochondrial function and decrease the apoptotic level induced by both the death receptor-and mitochondria-mediated apoptotic pathways.展开更多
Hepatocellular carcinoma(HCC)is a malignant tumor with high morbidity and mortality globally.It accounts for the majority of primary liver cancer cases.Amyloid precursor protein(APP),a cell membrane protein,plays a vi...Hepatocellular carcinoma(HCC)is a malignant tumor with high morbidity and mortality globally.It accounts for the majority of primary liver cancer cases.Amyloid precursor protein(APP),a cell membrane protein,plays a vital role in the pathogenesis of Alzheimer’s disease,and has been found to be implicated in tumor growth and metastasis.Therefore,to understand the relationship between APP and 5-fluorouracil(5-FU)resistance in liver cancer,Cell Counting Kit-8,apoptosis and cell cycle assays,western blotting,and reverse transcription-quantitative polymerase chain reaction(q PCR)analysis were performed.The results demonstrated that APP expression in Bel7402-5-FU cells was significantly up-regulated,as compared with that in Bel7402 cells.Through successful construction of APP-silenced(si APP)and overexpressed(OE)Bel7402 cell lines,data revealed that the Bel7402-APP751-OE cell line was insensitive,while the Bel7402-si APP cell line was sensitive to 5-FU in comparison to the matched control group.Furthermore,APP overexpression decreased,while APP silencing increased 5-FU-induced apoptosis in Bel7402 cells.Mechanistically,APP overexpression and silencing can regulate the mitochondrial apoptotic pathway and the expression of apoptotic suppressor genes(B-cell lymphoma-2(Bcl-2)and B-cell lymphoma-extra large(Bcl-xl)).Taken together,these results preliminarily revealed that APP overexpression contributes to the resistance of liver cancer cells to 5-FU,providing a new perspective for drug resistance.展开更多
Focal ischemic stroke（FIS）results from the lack of blood flow in a particular region of the brain and accounts for about 80%of all human strokes.Although tremendous efforts have been made in translational research,t...Focal ischemic stroke（FIS）results from the lack of blood flow in a particular region of the brain and accounts for about 80%of all human strokes.Although tremendous efforts have been made in translational research,the treatment strategies are still limited.Tissue plasminogen activator is the only FDA-approved drug currently available for acute stroke treatment,展开更多
AIM To systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer(CRC).METHODS A systematic literature search was conducted using Pub Med,Web of Science and EMBASE databases. Any eligib...AIM To systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer(CRC).METHODS A systematic literature search was conducted using Pub Med,Web of Science and EMBASE databases. Any eligible study must meet the following criteria:(1) bcl-2 expression was evaluated in human CRC tissues by immunohistochemistry;(2) assessment of the relationships between bcl-2 expression and overall survival(OS),disease free survival(DFS),recurrent free survival(RFS) or clinic-pathological characteristics of CRC was included;(3) sufficient information was provided to estimate the hazard ratio(HR) or odds ratio and their 95% confidence intervals(CIs); and(4) the study was published in English. The impact of Bcl-2 expression on survival of CRC patients were evaluated through this meta-analysis.RESULTS A total of 40 eligible articles involving 7658 patients were enrolled in our final analysis. We drew the conclusion that Bcl-2 high expression was significantly correlated with favorable OS(pooled HR = 0.69,95%CI: 0.55-0.87,P = 0.002) and better DFS/RFS(pooled HR = 0.65,95%CI: 0.50-0.85,P = 0.001). Additionally,the subgroup analysis suggested that Bcl-2 overexpression was significantly associated withprognosis(OS) especially in patients came from Europe and America but not Asian and patients who did not receive any adjuvant therapy before surgery. Finally,our present results indicated that expression of bcl-2 protein was associated with high differentiation grade and A/B Ducks' stage. CONCLUSION Bcl-2 high expression was significantly correlated with favorable OS and better DFS/RFS. Hence,we propose that Bcl-2 may be a valuable prognostic-predictive marker in CRC.展开更多
Previous investigations of retrograde survival signaling by nerve growth factor （NGF） and other neurotrophins have supported diverse mechanisms, but all proposed mechanisms have in common the generation of survival ...Previous investigations of retrograde survival signaling by nerve growth factor （NGF） and other neurotrophins have supported diverse mechanisms, but all proposed mechanisms have in common the generation of survival signals retrogradely transmitted to the neuronal cell bodies. We report the finding of a retrograde apoptotic signal in axons that is suppressed by local NGF signaling. NGF withdrawal from distal axons alone was sufficient to activate the pro-apoptotic transcription factor, c-jun, in the cell bodies. Providing NGF directly to cell bodies, thereby restoring a source of NGF-induced survival signals, could not prevent c-jun activation caused by NGF withdrawal from the distal axons. This is evidence that c-jun is not activated due to loss of survival signals at the cell bodies. Moreover, blocking axonal transport with colchicine inhibited c-jun activation caused by NGF deprivation suggesting that a retrogradely transported pro-apoptotic signal, rather than loss of a retrogradely transported survival signal, caused c-jun activation. Additional experiments showed that activation of c-jun, pro-caspase-3 cleavage, and apoptosis were blocked by the protein kinase C inhibitors, rottlerin and chelerythrine, only when applied to distal axons suggesting that they block the axon-specific pro-apoptotic signal. The rottlerin-sensitive mechanism was found to regulate glyco- gen synthase kinase 3 （GSK3） activity. The effect of siRNA knockdown, and pharmacological inhibition of GSK3 suggests that GSK3 is required for apoptosis caused by NGF deprivation and may function as a retrograde carrier of the axon apoptotic signal. The existence of a retrograde death signaling system in axons that is suppressed by neurotro- phins has broad implications for neurodevelopment and for discovering treatments for neurodegenerative diseases and neurotrauma.展开更多
AIM: To investigate the effect of Physalis angulata leaf extract on apoptotic and proliferation of retinoblastoma cells. Despite several previous studies evidencing the anticancer potential of Physalis angulata;howeve...AIM: To investigate the effect of Physalis angulata leaf extract on apoptotic and proliferation of retinoblastoma cells. Despite several previous studies evidencing the anticancer potential of Physalis angulata;however, certain study that proves its benefits in retinoblastoma cancer cells has been limited.METHODS: This study utilizes an in-vitro experimental study by applying Y79 human retinoblastoma cell line culture obtained from the American Type Culture Collection(ATCC;10801 University Boulevard Manassas, VA 20110, USA). The cell was divided into 4 groups. Group I was the control group without the administration of Physalis angulata leaf extract. Whereas, group II, II and IV are engaged with 25, 50, and 100 μg/mL of Physalis angulata leaf extract respectively. After a 24 h incubation, an examination with microtetrazolium(MTT) cell proliferation assay and Annexin V apoptosis detection was conducted. Statistical analysis was performed with the Tukey test.RESULTS: Physalis angulata leaf extract improved apoptosis and significantly reduced the number of living cells in retinoblastoma cells, along with the increase in the given dose. Based on the Tukey test, a significant difference was found in the treatment group at 50 μg/mL(P=0.025) and 100 μg/mL(P=0.001) in the measurement of apoptosis. Proliferation measurements also indicated a significant decrease in the number of living cells in the 50μg/m L treatment group(P=0.004), and in the 100 μg/mL treatment group(P=0.000). Meanwhile, a dose of 25 μg/mL indicated insignificant difference in the two measurements. Improved apoptosis and decreased number of living cells occured at a dose of 100 μg/mL. Decreased number of living cells(in the measurement of proliferation) was due to the inhibited proliferation or improved apoptosis.CONCLUSION: Physalis angulata leaf extract improve apoptosis in retinoblastoma cell culture, requiring further research to inhibit proliferation.展开更多
Brain cell death after intracerebral hemorrhage may be mediated in part by an apoptotic mechanism Colostrum is the first milk produced by mammals for their young. It plays an important role in protection and developme...Brain cell death after intracerebral hemorrhage may be mediated in part by an apoptotic mechanism Colostrum is the first milk produced by mammals for their young. It plays an important role in protection and development by providing various antibodies, growth factors and nutrients, and has been used for various diseases in many countries. In the present study, we investigated the anti-apoptotic effects of bovine colostrum using organotypic hippocampal slice cultures and an intracerebral hemorrhage animal model. We performed densitometric measurements of propidium iodide uptake, a step-down avoidance task, Nissl staining, and caspase-3 immunohistochemistry. The present results revealed that colostrum treatment significantly suppressed N-methyI-D-aspartic acid-induced neuronal cell death in the rat hippocampus. Moreover, colostrum treatment improved short-term memory by suppressing hemorrhage-induced apoptotic neuronal cell death and decreasing the volume of the lesion induced by intracerebral hemorrhage in the rat hippocampus. These results suggest that colostrum may have a beneficial role in recovering brain function following hemorrhagic stroke by suppressing apoptotic cell death.展开更多
Objective: To investigate the anti-inflammatory properties of methanolic extract of Clausena excavata in lipopolysaccharide(LPS)-activated macrophages(J774 A.1) and the effect on skin wound in a rat model through dete...Objective: To investigate the anti-inflammatory properties of methanolic extract of Clausena excavata in lipopolysaccharide(LPS)-activated macrophages(J774 A.1) and the effect on skin wound in a rat model through determining cytokine levels and gene expressions. Methods: The effects of methanolic extract of Clausena excavata on in vitro viability and TNF-α, IL-6, IL-10, and nitric oxide release by LPS-activated J774 A.1 cells were determined. In addition, relative expressions of BAX, BCL-2 and COX-2 genes were examined in healed wounds of rats. Results: The methanolic extract of Clausena excavata was not toxic to J774 A.1 cells at the highest dose of 400 μg/m L. It decreased levels of TNF-α and IL-6, while increasing IL-10 level in LPSactivated J774 A.1 cells and in the healed wounds of rats. The methanolic extract of Clausena excavata also inhibited nitric oxide production in LPS-activated J774 A.1 cells. The BAX and COX-2 genes were downregulated while the BCL-2 gene was upregulated in the healed wound of rats. Conclusions: The methanolic extract of Clausena excavata promotes wound healing via its anti-inflammatory and anti-apoptotic activities.展开更多
The influence of mild hypothermia on neural cell apoptosis remains poorly understood. Therefore, the present study established rat models of diffuse axonal injury （DAI） at 33℃. Morris water maze results demonstrate...The influence of mild hypothermia on neural cell apoptosis remains poorly understood. Therefore, the present study established rat models of diffuse axonal injury （DAI） at 33℃. Morris water maze results demonstrated significantly better learning and memory functions in DAI rats with hypothermia compared with DAI rats with normothermia. Expression of apoptotic protease activating factor-1 in the hippocampal CA1 region was significantly lower in the DAI hypothermia group compared with the DAI normothermia group. Expression of apoptotic protease activating factor-1 positively correlated with latency, but negatively correlated with platform location times and time of swimming in the quadrant area. Results suggested that post-traumatic mild hypothermia in a rat model of DAI could provide cerebral protection by attenuating expression of apoptotic protease activating factor-1.展开更多
Objective: To investigate the apoptotic threshold of adriamycin (ADM) and cisplatin (CDDP) on hepatocellular carcinoma (HCC). Methods: Sensitivities of ADM and CDDP on HCC were studied by primary cell culture. Results...Objective: To investigate the apoptotic threshold of adriamycin (ADM) and cisplatin (CDDP) on hepatocellular carcinoma (HCC). Methods: Sensitivities of ADM and CDDP on HCC were studied by primary cell culture. Results: The apoptotic threshold of ADM and CDDP were 1.0 μg/ml and 1.5μg/ml respectively (its clinical dosage was 20 mg and 30 mg respectively). Conclusion: Understanding apoptotic threshold of anticancer drugs may reduce clinical dosages of anticancer drugs and reduce the incidence of multidrug resistance (MDR).展开更多
AIM:To evaluate the safety and the short term apoptotic activity of intravitreai bevacizumab in rabbit eyes by histopathological analysis.METHODS:Twenty-eight eyes of 14 rabbits were divided into three groups:8 rabbit...AIM:To evaluate the safety and the short term apoptotic activity of intravitreai bevacizumab in rabbit eyes by histopathological analysis.METHODS:Twenty-eight eyes of 14 rabbits were divided into three groups:8 rabbits in group 1 and 3rabbits in each of group 2 and group 3.Intravitreai bevacizumab(1.25mg/0.05mL)was applied to the right eyes of each subject in group 1 and group 2(11 eyes)and the same volume of saline was applied to the left eyes of each subject in group 1 and group 3(11 eyes).The left eyes in group 2 and the right eyes in group 3were left untreated and used as control.Enucleated eyes were used for histopathologic analyses.RESULTS:After immunohistochemical staining with caspase-3 and p53,there was no histological evidence of toxicity to the retina and the optic nerve in any of the sections that were analyzed in all three groups.In addition,vascular endothelial cells located at the retina and the optic nerve tissues in all groups showed a similar staining pattern with caspase-3 and p53.CONCLUSION:Our study showed that intravitreai bevacizumab with the dose of 1.25mg/0.05mL caused no histological signs of toxicity or apoptotic activity on the rabbit retina.展开更多
Objective It was reported that p53 apoptotic peptide (N37) could inhibit p73 gene through being bound with iASPP,which could induce tumor cell apoptosis. To further explore the function of N37,we constructed the cloni...Objective It was reported that p53 apoptotic peptide (N37) could inhibit p73 gene through being bound with iASPP,which could induce tumor cell apoptosis. To further explore the function of N37,we constructed the cloning plasmid of DNA fragment encoding p53 (N37) apoptotic peptide by using DNA synthesis and molecular biology methods. Methods According to human p53 sequence from the GenBank database,the primer of p53(N37) gene was designed using Primer V7.0 software. The DNA fragment encoding p53 (N37) apoptotic peptide was amplified by using self-complementation polymerase chain reaction (PCR) method and cloned into the pGEM-T Easy vector. The constructed plasmid was confirmed by endonuclease analysis and sequencing. Results The insertion of objective DNA fragment was confirmed by plasmid DNA enzyme spectrum analysis. p53(N37)gene was successfully synthesized chemically in vitro. The sequencing result of positive clone was completely identical to the human p53(N37) sequence in GenBank using BLAST software (http://www.ncbi.nlm.nih.gov/cgi-bin /BLASTn). Conclusion The cloning of DNA fragment encoding p53(N37) apoptotic peptide was constructed by using DNA synthesis and pGEM-T Easy cloning methods. With the constructed plasmid,we could further investigate the function of N37 peptide.展开更多
Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focu...Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focused on identifying new protective substances that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of S100b, a neurotrophic factor and neuronal survival protein, that is highly expressed by reactive astrocytes in close vicinity of beta-amyloid deposits, against amyloid beta (1-42)-dependent toxicity. Our results show that at nanomolar concentrations, S100b protects cells against Aβmediated cytotoxicity, as assessed by MTS vitality test. The protective mechanism seems to be related to the effect on bcl-2 (an anti-apoptotic gene) expression, which is highly down-regulated by amyloid beta (1-42) treatment, while resulted more expressed in the presence of S100b. On the contrary, Bax, a proapoptotic gene, resulted down-regulated by the treatment with S100 compared with the results obtained in the presence of amyloid beta (1-42) peptide. However, at micromolar doses, S100b is toxic for IMR-32 cells and its toxicity adds to that of the Aβpeptide, suggesting that additional molecular mechanisms may be involved in theneurotoxic process.展开更多
Objective: To study the effect on apoptosis of CD 4 +T、CD 19 +B in spleen of BXSB mice with systemic lupus erythematosus treated with Langchuangjing Granule (LCJG, and to probe into the mechanism of the tr ea...Objective: To study the effect on apoptosis of CD 4 +T、CD 19 +B in spleen of BXSB mice with systemic lupus erythematosus treated with Langchuangjing Granule (LCJG, and to probe into the mechanism of the tr eatment. Methods: The apoptosis was examined by the flow cytometric analysis and immunofluorescence double-staining method. Results: Apoptosis of male BXSB mice speeds up. LCJG can restrain the excessive apoptosis of CD 4 +T and CD 19 +B cells in spleen. Conclusion: LCJG treated systemic lupus erythematosus by restraining the excessive apoptosis of T, B lymphocytes, probably restraining the release of excessive amount of apoptotic DNA fragments, so decreasing abnormal proliferation of B cells and the produce of autoantibodies.展开更多
We present the case of an adolescent who presented with rhabdomyolysis due to severe hypokalemia arising from chronic diarrhea. Initial evaluation for celiac disease, known to present in this manner, was negative. Fur...We present the case of an adolescent who presented with rhabdomyolysis due to severe hypokalemia arising from chronic diarrhea. Initial evaluation for celiac disease, known to present in this manner, was negative. Further evaluation with colonoscopy showed a normal appearing colon but biopsies showed a significant number of apoptotic cells in the mucosal crypts supporting a diagnosis of apoptotic colitis. Investigation into the cause of apoptotic colitis resulted in a diagnosis of common variable immune deficiency due to a defect in the inducible T-cell costimulator (ICOS) gene. Physicians should be aware of this uncommon condition and the importance of mucosal biopsy despite the presence of normal appearing mucosa.展开更多
Objective: To study the effects of Kang Ai injection + conventional chemotherapy on tumor markers, apoptotic molecules and immune response in patients with advanced non-small cell lung cancer (NSCLC). Methods: Patient...Objective: To study the effects of Kang Ai injection + conventional chemotherapy on tumor markers, apoptotic molecules and immune response in patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients diagnosed as advanced NSCLC in our hospital during March 2015 - October 2017 were randomly divided into the experimental group receiving Kang Ai injection + conventional chemotherapy and the control group receiving conventional chemotherapy. The contents of tumor markers, apoptotic molecules and immunologic cytokines in serum and the contents of immune cells in peripheral blood were determined before and after chemotherapy. Results: after chemotherapy, the content of CEA, CYFRA21-1, SCC-Ag, GDF15 and Livin in the serum of the two groups decreased significantly, and the content of PDCD5, P53 and Bax increased significantly, and the content of CEA, CYFRA21-1, SCC-Ag, GDF15, Livin in the serum of the experimental group were lower than those of the control group, and the content of PDCD5, P53 and Bax were higher than those of the control group;the content of CD3+ and CD4+ cells in peripheral blood and the content of IFN-γ, IL-2 in serum of control group significantly decreased, whereas the content of CD8+ cells in peripheral blood and the content of IL-4, IL-5 in serum significantly increased after chemotherapy;while the content of CD3+ and CD4+ cells in peripheral blood and the content of IFN-γ, IL-2 in serum of experimental group significantly increased, whereas the content of CD8+ cells in peripheral blood and the content of IL-4, IL-5 in serum significantly decreased after chemotherapy. Conclusion: Kang Ai injection + conventional chemotherapy in the treatment of advanced NSCLC can more significantly decrease the serum tumor markers, regulate the secretion of apoptotic molecules and anti-tumor immune response than conventional chemotherapy.展开更多
文摘Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment.
文摘Loss of self-tolerance and expansion of auto-reactive lymphocytes are the basis for autoimmunity. Apoptosis and the rapid clearance of apoptotic cells by phagocytes usually occur as coordinated processes that ensure regulated cellularity and stress response with non-pathological outcomes. Defects in clearance of apoptotic ceils would contribute to the generation of self-reactive lymphocytes, which drive autoimmune disorders such as rheumatoid arthritis （RA） and systemic lupus erythematosus （SLE）. The IL-12 family of cytokines （IL-12, IL-23, and IL-27） and IL-10 are produced by phagocytic macrophages and play critical roles in the regulation of antigen-presenting cells （APCs） and effector lymphocytes during an immune response to pathogens. Inappropriate expression of these cytokines and their dysregulated activities have been strongly implicated in the pathogenesis of several autoimmune diseases. The production of pro- and anti-inflammatory cytokines by phagocytic APCs is delicately regulated during the ingestion of apoptotic cells as part of an intrinsic mechanism to prevent inflammatory autoimmune reactions. How apoptotic cell-derived signals regulate cytokine production is poorly understood. A recent study by our group demonstrated that phagocytosis of apoptotic cells by activated macrophages results in strong inhibition of IL-12 p35 gene expression by activating a novel transcription repressor, which we named GC-binding protein （GC-BP）, through tyrosine dephosphorylation. We are also beginning to understand the molecular mechanisms underlying apoptotic cell-triggered production of IL-10 by phagocytes. These studies will help to elucidate some novel immune regulatory mechanisms and explore the regulation of immune responses to autoantigens with potentials to discover new therapeutic targets for the treatment of autoimmune disorders.
基金supported by the National Natural Science Foundation of China(No.31101866 and 31302058)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China Postdoctoral Science Foundation funded project(2015M581874)Jiangsu Planned Projects for Postdoctoral Research Funds(1501072A)
文摘Objective To examine the role of Cd-induced reactive oxygen species（ROS） generation in the apoptosis of neuronal cells. Methods Neuronal cells（primary rat cerebral cortical neurons and PC12 cells） were incubated with or without Cd post-pretreatment with rapamycin（Rap） or N-acetyl-L-cysteine（NAC）. Cell viability was determined by MTT assay, apoptosis was examined using flow cytometry and fluorescence microscopy, and the activation of phosphoinositide 3’-kinase/protein kinase B（Akt）/mammalian target of rapamycin（m TOR） and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays. Results Cd-induced activation of Akt/m TOR signaling, including Akt, m TOR, p70 S6 kinase（p70 S6K）, and eukaryotic initiation factor 4E binding protein 1（4E-BP1）. Rap, an m TOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/m TOR signaling and apoptosis of neuronal cells. Furthermore, NAC blocked the decrease of B-cell lymphoma 2/Bcl-2 associated X protein（Bcl-2/Bax） ratio, release of cytochrome c, cleavage of caspase-3 and poly（ADP-ribose） polymerase（PARP）, and nuclear translocation of apoptosis-inducing factor（AIF） and endonuclease G（Endo G）. Conclusion Cd-induced ROS generation activates Akt/m TOR and mitochondrial pathways, leading to apoptosis of neuronal cells. Our findings suggest that m TOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.
基金Supported by the Department of Science and Technology of Jilin Province(No.20020502).
文摘Hypocrellin A（ HA）, a photosensitive perylenequinone compound of Hypocrella bambusae, inhibited the proliferation of several tumor cell lines. Human cervical cancer cells, HeLa ceils, were used as a model to elucidate the molecular mechanisms of HA-induced tumor cell death. The results show that HA can induce the oligonucleosomal fragmentation of DNA in HeLa cells and also can increase the expression of apoptosis inducer Bax mRNA and that it decreases the expression of apoptosis suppressor, Bcl-2 mRNA, in mitochondria. It can be concluded from the data that HA-induced apoptosis is related to the balance between Bcl-2 and Bax gene expressions.
基金Project supported by the Jiangsu Agri-animal Husbandry Vocational College Academy Research Project(No.NSF201509)the Jiangsu University Brand Speciality Construction Work Founded Project(No.PPZY2015C230),China。
文摘Resveratrol(3,5,4’-trihydroxystilbene,RSV) has been widely used in mammalian cells,but whether it can be used during freezing boar semen is still unknown.The effects of RSV treatment during boar semen freezing on its anti-freezing ability,apoptosis,and possible apoptotic pathways were observed in this study.Sperm motility,mitochondrial membrane potential(ΔΨm),adenosine triphosphate(ATP) content,terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive apoptotic state,and messenger RNA(mRNA) expression levels of apoptotic genes involved in different apoptotic pathways after freezing with or without RSV treatment were tested.The results showed that:(1) Compared with fresh sperm,the motility,normal acrosome rate,and plasma membrane integrity rate of frozen boar sperm decreased significantly(P<0.05),and RSV did not significantly increase the sperm motility(0.44 vs.0.40,P>0.05),but it did significantly improve the normal acrosome rate(57.65% vs.47.00%,P<0.05) and plasma membrane integrity rate(46.67% vs.38.85%,P<0.05).(2) After freezing,most boar sperm showed low mitochondrial ΔΨm.RSV treatment could increase the rate of high mitochondrial ΔΨm of boar sperm.(3) RSV treatment significantly decreased reactive oxygen species(ROS) levels(58.65% vs.88.41%,P<0.05)and increased the ATP content(0.49 μmol/L vs.0.25 μmol/L,P<0.05) of boar sperm during freezing.(4) The apoptotic rate of the freezing group(80.41%) with TUNEL detection increased significantly compared to the fresh group(9.70%,P<0.05),and RSV treatment greatly decreased the apoptotic rate(68.32%,P<0.05).(5) Real-time polymerase chain reaction(RT-PCR) showed that not only the genes from the death receptor-mediated apoptotic pathway(tumor necrosis factor-α(TNF-α),Fas ligand(FasL),and Caspase-8),but also the genes from the mitochondria-mediated apoptotic pathway(manganese superoxide dismutase(MnSOD),B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),and Caspase-9) were both significantly changed after freezing.RSV treatment during freezing greatly changed their expression levels.Although RSV treatment during boar semen freezing did not significantly increase motility after thawing,it still played an efficient antioxidant role,which could enhance the mitochondrial function and decrease the apoptotic level induced by both the death receptor-and mitochondria-mediated apoptotic pathways.
基金Project supported by the International Science&Technology Cooperation Program of China(No.2016G02).
文摘Hepatocellular carcinoma(HCC)is a malignant tumor with high morbidity and mortality globally.It accounts for the majority of primary liver cancer cases.Amyloid precursor protein(APP),a cell membrane protein,plays a vital role in the pathogenesis of Alzheimer’s disease,and has been found to be implicated in tumor growth and metastasis.Therefore,to understand the relationship between APP and 5-fluorouracil(5-FU)resistance in liver cancer,Cell Counting Kit-8,apoptosis and cell cycle assays,western blotting,and reverse transcription-quantitative polymerase chain reaction(q PCR)analysis were performed.The results demonstrated that APP expression in Bel7402-5-FU cells was significantly up-regulated,as compared with that in Bel7402 cells.Through successful construction of APP-silenced(si APP)and overexpressed(OE)Bel7402 cell lines,data revealed that the Bel7402-APP751-OE cell line was insensitive,while the Bel7402-si APP cell line was sensitive to 5-FU in comparison to the matched control group.Furthermore,APP overexpression decreased,while APP silencing increased 5-FU-induced apoptosis in Bel7402 cells.Mechanistically,APP overexpression and silencing can regulate the mitochondrial apoptotic pathway and the expression of apoptotic suppressor genes(B-cell lymphoma-2(Bcl-2)and B-cell lymphoma-extra large(Bcl-xl)).Taken together,these results preliminarily revealed that APP overexpression contributes to the resistance of liver cancer cells to 5-FU,providing a new perspective for drug resistance.
基金supported by NIH NS069726 and NS094539America Heart Association 13GRANT17020004(to SD)
文摘Focal ischemic stroke（FIS）results from the lack of blood flow in a particular region of the brain and accounts for about 80%of all human strokes.Although tremendous efforts have been made in translational research,the treatment strategies are still limited.Tissue plasminogen activator is the only FDA-approved drug currently available for acute stroke treatment,
文摘AIM To systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer(CRC).METHODS A systematic literature search was conducted using Pub Med,Web of Science and EMBASE databases. Any eligible study must meet the following criteria:(1) bcl-2 expression was evaluated in human CRC tissues by immunohistochemistry;(2) assessment of the relationships between bcl-2 expression and overall survival(OS),disease free survival(DFS),recurrent free survival(RFS) or clinic-pathological characteristics of CRC was included;(3) sufficient information was provided to estimate the hazard ratio(HR) or odds ratio and their 95% confidence intervals(CIs); and(4) the study was published in English. The impact of Bcl-2 expression on survival of CRC patients were evaluated through this meta-analysis.RESULTS A total of 40 eligible articles involving 7658 patients were enrolled in our final analysis. We drew the conclusion that Bcl-2 high expression was significantly correlated with favorable OS(pooled HR = 0.69,95%CI: 0.55-0.87,P = 0.002) and better DFS/RFS(pooled HR = 0.65,95%CI: 0.50-0.85,P = 0.001). Additionally,the subgroup analysis suggested that Bcl-2 overexpression was significantly associated withprognosis(OS) especially in patients came from Europe and America but not Asian and patients who did not receive any adjuvant therapy before surgery. Finally,our present results indicated that expression of bcl-2 protein was associated with high differentiation grade and A/B Ducks' stage. CONCLUSION Bcl-2 high expression was significantly correlated with favorable OS and better DFS/RFS. Hence,we propose that Bcl-2 may be a valuable prognostic-predictive marker in CRC.
文摘Previous investigations of retrograde survival signaling by nerve growth factor （NGF） and other neurotrophins have supported diverse mechanisms, but all proposed mechanisms have in common the generation of survival signals retrogradely transmitted to the neuronal cell bodies. We report the finding of a retrograde apoptotic signal in axons that is suppressed by local NGF signaling. NGF withdrawal from distal axons alone was sufficient to activate the pro-apoptotic transcription factor, c-jun, in the cell bodies. Providing NGF directly to cell bodies, thereby restoring a source of NGF-induced survival signals, could not prevent c-jun activation caused by NGF withdrawal from the distal axons. This is evidence that c-jun is not activated due to loss of survival signals at the cell bodies. Moreover, blocking axonal transport with colchicine inhibited c-jun activation caused by NGF deprivation suggesting that a retrogradely transported pro-apoptotic signal, rather than loss of a retrogradely transported survival signal, caused c-jun activation. Additional experiments showed that activation of c-jun, pro-caspase-3 cleavage, and apoptosis were blocked by the protein kinase C inhibitors, rottlerin and chelerythrine, only when applied to distal axons suggesting that they block the axon-specific pro-apoptotic signal. The rottlerin-sensitive mechanism was found to regulate glyco- gen synthase kinase 3 （GSK3） activity. The effect of siRNA knockdown, and pharmacological inhibition of GSK3 suggests that GSK3 is required for apoptosis caused by NGF deprivation and may function as a retrograde carrier of the axon apoptotic signal. The existence of a retrograde death signaling system in axons that is suppressed by neurotro- phins has broad implications for neurodevelopment and for discovering treatments for neurodegenerative diseases and neurotrauma.
文摘AIM: To investigate the effect of Physalis angulata leaf extract on apoptotic and proliferation of retinoblastoma cells. Despite several previous studies evidencing the anticancer potential of Physalis angulata;however, certain study that proves its benefits in retinoblastoma cancer cells has been limited.METHODS: This study utilizes an in-vitro experimental study by applying Y79 human retinoblastoma cell line culture obtained from the American Type Culture Collection(ATCC;10801 University Boulevard Manassas, VA 20110, USA). The cell was divided into 4 groups. Group I was the control group without the administration of Physalis angulata leaf extract. Whereas, group II, II and IV are engaged with 25, 50, and 100 μg/mL of Physalis angulata leaf extract respectively. After a 24 h incubation, an examination with microtetrazolium(MTT) cell proliferation assay and Annexin V apoptosis detection was conducted. Statistical analysis was performed with the Tukey test.RESULTS: Physalis angulata leaf extract improved apoptosis and significantly reduced the number of living cells in retinoblastoma cells, along with the increase in the given dose. Based on the Tukey test, a significant difference was found in the treatment group at 50 μg/mL(P=0.025) and 100 μg/mL(P=0.001) in the measurement of apoptosis. Proliferation measurements also indicated a significant decrease in the number of living cells in the 50μg/m L treatment group(P=0.004), and in the 100 μg/mL treatment group(P=0.000). Meanwhile, a dose of 25 μg/mL indicated insignificant difference in the two measurements. Improved apoptosis and decreased number of living cells occured at a dose of 100 μg/mL. Decreased number of living cells(in the measurement of proliferation) was due to the inhibited proliferation or improved apoptosis.CONCLUSION: Physalis angulata leaf extract improve apoptosis in retinoblastoma cell culture, requiring further research to inhibit proliferation.
文摘Brain cell death after intracerebral hemorrhage may be mediated in part by an apoptotic mechanism Colostrum is the first milk produced by mammals for their young. It plays an important role in protection and development by providing various antibodies, growth factors and nutrients, and has been used for various diseases in many countries. In the present study, we investigated the anti-apoptotic effects of bovine colostrum using organotypic hippocampal slice cultures and an intracerebral hemorrhage animal model. We performed densitometric measurements of propidium iodide uptake, a step-down avoidance task, Nissl staining, and caspase-3 immunohistochemistry. The present results revealed that colostrum treatment significantly suppressed N-methyI-D-aspartic acid-induced neuronal cell death in the rat hippocampus. Moreover, colostrum treatment improved short-term memory by suppressing hemorrhage-induced apoptotic neuronal cell death and decreasing the volume of the lesion induced by intracerebral hemorrhage in the rat hippocampus. These results suggest that colostrum may have a beneficial role in recovering brain function following hemorrhagic stroke by suppressing apoptotic cell death.
基金financially supported by the University of Malaya PPP Grant no.PG059-2013A.
文摘Objective: To investigate the anti-inflammatory properties of methanolic extract of Clausena excavata in lipopolysaccharide(LPS)-activated macrophages(J774 A.1) and the effect on skin wound in a rat model through determining cytokine levels and gene expressions. Methods: The effects of methanolic extract of Clausena excavata on in vitro viability and TNF-α, IL-6, IL-10, and nitric oxide release by LPS-activated J774 A.1 cells were determined. In addition, relative expressions of BAX, BCL-2 and COX-2 genes were examined in healed wounds of rats. Results: The methanolic extract of Clausena excavata was not toxic to J774 A.1 cells at the highest dose of 400 μg/m L. It decreased levels of TNF-α and IL-6, while increasing IL-10 level in LPSactivated J774 A.1 cells and in the healed wounds of rats. The methanolic extract of Clausena excavata also inhibited nitric oxide production in LPS-activated J774 A.1 cells. The BAX and COX-2 genes were downregulated while the BCL-2 gene was upregulated in the healed wound of rats. Conclusions: The methanolic extract of Clausena excavata promotes wound healing via its anti-inflammatory and anti-apoptotic activities.
基金a grant from Department of Public Health of Heibei Province, No. 20100134
文摘The influence of mild hypothermia on neural cell apoptosis remains poorly understood. Therefore, the present study established rat models of diffuse axonal injury （DAI） at 33℃. Morris water maze results demonstrated significantly better learning and memory functions in DAI rats with hypothermia compared with DAI rats with normothermia. Expression of apoptotic protease activating factor-1 in the hippocampal CA1 region was significantly lower in the DAI hypothermia group compared with the DAI normothermia group. Expression of apoptotic protease activating factor-1 positively correlated with latency, but negatively correlated with platform location times and time of swimming in the quadrant area. Results suggested that post-traumatic mild hypothermia in a rat model of DAI could provide cerebral protection by attenuating expression of apoptotic protease activating factor-1.
文摘Objective: To investigate the apoptotic threshold of adriamycin (ADM) and cisplatin (CDDP) on hepatocellular carcinoma (HCC). Methods: Sensitivities of ADM and CDDP on HCC were studied by primary cell culture. Results: The apoptotic threshold of ADM and CDDP were 1.0 μg/ml and 1.5μg/ml respectively (its clinical dosage was 20 mg and 30 mg respectively). Conclusion: Understanding apoptotic threshold of anticancer drugs may reduce clinical dosages of anticancer drugs and reduce the incidence of multidrug resistance (MDR).
文摘AIM:To evaluate the safety and the short term apoptotic activity of intravitreai bevacizumab in rabbit eyes by histopathological analysis.METHODS:Twenty-eight eyes of 14 rabbits were divided into three groups:8 rabbits in group 1 and 3rabbits in each of group 2 and group 3.Intravitreai bevacizumab(1.25mg/0.05mL)was applied to the right eyes of each subject in group 1 and group 2(11 eyes)and the same volume of saline was applied to the left eyes of each subject in group 1 and group 3(11 eyes).The left eyes in group 2 and the right eyes in group 3were left untreated and used as control.Enucleated eyes were used for histopathologic analyses.RESULTS:After immunohistochemical staining with caspase-3 and p53,there was no histological evidence of toxicity to the retina and the optic nerve in any of the sections that were analyzed in all three groups.In addition,vascular endothelial cells located at the retina and the optic nerve tissues in all groups showed a similar staining pattern with caspase-3 and p53.CONCLUSION:Our study showed that intravitreai bevacizumab with the dose of 1.25mg/0.05mL caused no histological signs of toxicity or apoptotic activity on the rabbit retina.
文摘Objective It was reported that p53 apoptotic peptide (N37) could inhibit p73 gene through being bound with iASPP,which could induce tumor cell apoptosis. To further explore the function of N37,we constructed the cloning plasmid of DNA fragment encoding p53 (N37) apoptotic peptide by using DNA synthesis and molecular biology methods. Methods According to human p53 sequence from the GenBank database,the primer of p53(N37) gene was designed using Primer V7.0 software. The DNA fragment encoding p53 (N37) apoptotic peptide was amplified by using self-complementation polymerase chain reaction (PCR) method and cloned into the pGEM-T Easy vector. The constructed plasmid was confirmed by endonuclease analysis and sequencing. Results The insertion of objective DNA fragment was confirmed by plasmid DNA enzyme spectrum analysis. p53(N37)gene was successfully synthesized chemically in vitro. The sequencing result of positive clone was completely identical to the human p53(N37) sequence in GenBank using BLAST software (http://www.ncbi.nlm.nih.gov/cgi-bin /BLASTn). Conclusion The cloning of DNA fragment encoding p53(N37) apoptotic peptide was constructed by using DNA synthesis and pGEM-T Easy cloning methods. With the constructed plasmid,we could further investigate the function of N37 peptide.
文摘Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focused on identifying new protective substances that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of S100b, a neurotrophic factor and neuronal survival protein, that is highly expressed by reactive astrocytes in close vicinity of beta-amyloid deposits, against amyloid beta (1-42)-dependent toxicity. Our results show that at nanomolar concentrations, S100b protects cells against Aβmediated cytotoxicity, as assessed by MTS vitality test. The protective mechanism seems to be related to the effect on bcl-2 (an anti-apoptotic gene) expression, which is highly down-regulated by amyloid beta (1-42) treatment, while resulted more expressed in the presence of S100b. On the contrary, Bax, a proapoptotic gene, resulted down-regulated by the treatment with S100 compared with the results obtained in the presence of amyloid beta (1-42) peptide. However, at micromolar doses, S100b is toxic for IMR-32 cells and its toxicity adds to that of the Aβpeptide, suggesting that additional molecular mechanisms may be involved in theneurotoxic process.
文摘Objective: To study the effect on apoptosis of CD 4 +T、CD 19 +B in spleen of BXSB mice with systemic lupus erythematosus treated with Langchuangjing Granule (LCJG, and to probe into the mechanism of the tr eatment. Methods: The apoptosis was examined by the flow cytometric analysis and immunofluorescence double-staining method. Results: Apoptosis of male BXSB mice speeds up. LCJG can restrain the excessive apoptosis of CD 4 +T and CD 19 +B cells in spleen. Conclusion: LCJG treated systemic lupus erythematosus by restraining the excessive apoptosis of T, B lymphocytes, probably restraining the release of excessive amount of apoptotic DNA fragments, so decreasing abnormal proliferation of B cells and the produce of autoantibodies.
文摘We present the case of an adolescent who presented with rhabdomyolysis due to severe hypokalemia arising from chronic diarrhea. Initial evaluation for celiac disease, known to present in this manner, was negative. Further evaluation with colonoscopy showed a normal appearing colon but biopsies showed a significant number of apoptotic cells in the mucosal crypts supporting a diagnosis of apoptotic colitis. Investigation into the cause of apoptotic colitis resulted in a diagnosis of common variable immune deficiency due to a defect in the inducible T-cell costimulator (ICOS) gene. Physicians should be aware of this uncommon condition and the importance of mucosal biopsy despite the presence of normal appearing mucosa.
文摘Objective: To study the effects of Kang Ai injection + conventional chemotherapy on tumor markers, apoptotic molecules and immune response in patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients diagnosed as advanced NSCLC in our hospital during March 2015 - October 2017 were randomly divided into the experimental group receiving Kang Ai injection + conventional chemotherapy and the control group receiving conventional chemotherapy. The contents of tumor markers, apoptotic molecules and immunologic cytokines in serum and the contents of immune cells in peripheral blood were determined before and after chemotherapy. Results: after chemotherapy, the content of CEA, CYFRA21-1, SCC-Ag, GDF15 and Livin in the serum of the two groups decreased significantly, and the content of PDCD5, P53 and Bax increased significantly, and the content of CEA, CYFRA21-1, SCC-Ag, GDF15, Livin in the serum of the experimental group were lower than those of the control group, and the content of PDCD5, P53 and Bax were higher than those of the control group;the content of CD3+ and CD4+ cells in peripheral blood and the content of IFN-γ, IL-2 in serum of control group significantly decreased, whereas the content of CD8+ cells in peripheral blood and the content of IL-4, IL-5 in serum significantly increased after chemotherapy;while the content of CD3+ and CD4+ cells in peripheral blood and the content of IFN-γ, IL-2 in serum of experimental group significantly increased, whereas the content of CD8+ cells in peripheral blood and the content of IL-4, IL-5 in serum significantly decreased after chemotherapy. Conclusion: Kang Ai injection + conventional chemotherapy in the treatment of advanced NSCLC can more significantly decrease the serum tumor markers, regulate the secretion of apoptotic molecules and anti-tumor immune response than conventional chemotherapy.
