Biomedical subjects

Bo Zhang

Publications and source records attributed to Bo Zhang.

At least 109 records · Page 6Linked to original sources

PubMed2005

[The clinical effect of anti-rotation reduction internal fixator on the treatment of fresh thoracolumbar spine fracture].

OBJECTIVE: To evaluate the effect of self-designed anti-rotation reduction internal fixator (ARRIF) on treating different spine segment fracture. METHODS: From August 1999 to March 2003, 76 patients(48 males and 28 females, aged from 22 to 59 with an average of 34.1) with thoracolumbar fracture were operatively treated by ARRIF. The follow-up period ranged from 6 to 21 months (15 months in average). Classification according to injury segment: flexion compression fracture 27 cases, burst fracture 42 cases, flexion distraction injury 3 cases, flexion revolving type fracture dislocation 2 cases, shear force type dislocation 2 cases. Classification according Frankel's grade: A grade 16 cases, B grade 15 cases, C grade 27 cases, D grade 10 cases, E grade 8 cases. Operation duration, volume of bleeding, incidence post-operation complication and effect of reduction-fixation were observed. RESULTS: The operation duration of ARRIF was 1.2 h in average, and there was about 200 ml volume of bleeding during operation. The nerve function showed one Frankel's grade improvement after operation were as follows: A grade 8 cases (50%), B grade 11 cases (73.3%), C grade 20 cases (74.1%), D grade 3 cases (30%); 2 Frankel's E cases have no nerve function changes. The nerve function damage have no aggravation in all the patients, the postoperation Cobb's angle was averagely corrected 22 degrees. The horizontal displacement of dislocation vertebrae was averagely corrected 28% in sagittal plane, the statistical analysis had significant variance (P < 0.01). ARRIF had no complications of the breakage of screws and rods. CONCLUSION: ARRIF proves to be a valid internal fixator in reducing and fixing different thoracic lumbar segment spine fracture.

Adult↗

PubMed2005

[Expression of enhanced green fluorescent protein in rat brain transduced by recombinant adeno-associated viruses type 1 and type 2].

OBJECTIVE: To explore the expression of enhanced green fluorescent protein (EGFP) transduced into the brain via recombinant adeno-associated virus (rAAV) type 1 and rAAV type 2 vectors so as to select the better rAAV serotype and feasible gene transfer route to central nervous system (CNS). METHODS: Twenty-four SD male adult rats were randomly divided into 4 equal groups: rAAV1 intra-hippocampus injection group, rAAV1 intra-ventricular injection group, rAAV2 intra-hippocampus injection group, and rAAV2 intra-ventricular injection group to be injected stereotactically with titer and volume matched rAAV1-EGFP and rAAV2-EGFP vectors respectively. The rats were sacrificed respectively 2 and 4 weeks after injection and their brains were removed to be made into serial frozen coronal sections. Fluorescence microscopy was used to observe the expression of EGFP in the brain and to calculate the expression volume of EGFP in different parts of the brain. RESULTS: Two weeks after injection EGFP was expressed in a small amount or not expressed in all groups. Four weeks after injection the EGFP expression volume were (7.00 +/- 0.98) mm(3) and (0.81 +/- 0.28) mm(3) in the rAAV1 and rAAV2 intra-hippocampus injection groups respectively (P < 0.01), and were (12.72 +/- 0.28) mm(3) and (0.24 +/- 0.13) mm(3) in the rAAV1 and rAAV2 intra-ventricular injection groups respectively (P < 0.001). CONCLUSION: As gene-transducing vector in CNS rAAV1 is superior to rAAV2. High expression can be achieved by intra-ventricular injection with rAAV1 vectors.

Animals↗

PubMed2005

The Genomes of Oryza sativa: a history of duplications.

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.

Base Sequence↗

PubMed2005

[Using ANN and serum protein pattern models in liver cancer diagnosis].

OBJECTIVE: To set up a method for the detection of the serum protein fingerprint pattern by using the protein chip technology for exploration of serum protein fingerprint pattern models based on the artificial neural network in diagnosis of liver cancer. METHODS: One hundred and six serum samples form subjects with liver cancer, hepatocirrhosis, and healthy individuals were detected with protein biochip surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) for protein fingerprint pattern, and analyzed with the artificial neural network. The 106 samples were randomly put into a training group (n = 70, 35 patients with liver cancer, 14 patients with hepatocirrhosis, and 21 healthy individuals) and a blind test group (n = 36, 17 patients with liver cancer, 8 patients with hepatocirrhosis, and 11 healthy individuals). RESULTS: The serum protein fingerprint pattern model obtained by the artificial neural network from training group was used to detect the 36 unknown serum samples. The sensitivity and specificity of this method in detection of liver cancer were 88.2% (15/17) and 94.6% (18/19) respectively. CONCLUSION: In comparison with the traditional methods, this new method has higher sensitivity and specificity in diagnosis of liver cancer and should be further studied.

Adult↗

PubMed2005

Kinetic studies of iron deposition catalyzed by recombinant human liver heavy and light ferritins and Azotobacter vinelandii bacterioferritin using O2 and H2O2 as oxidants.

The discrepancy between predicted and measured H(2)O(2) formation during iron deposition with recombinant heavy human liver ferritin (rHF) was attributed to reaction with the iron protein complex [Biochemistry 40 (2001) 10832-10838]. This proposal was examined by stopped-flow kinetic studies and analysis for H(2)O(2) production using (1) rHF, and Azotobacter vinelandii bacterial ferritin (AvBF), each containing 24 identical subunits with ferroxidase centers; (2) site-altered rHF mutants with functional and dysfunctional ferroxidase centers; and (3) recombinant human liver light ferritin (rLF), containing no ferroxidase center. For rHF, nearly identical pseudo-first-order rate constants of 0.18 s(-1) at pH 7.5 were measured for Fe(2+) oxidation by both O(2) and H(2)O(2), but for rLF, the rate with O(2) was 200-fold slower than that for H(2)O(2) (k = 0.22 s(-1)). A Fe(2+)/O(2) stoichiometry near 2.4 was measured for rHF and its site altered forms, suggesting formation of H(2)O(2). Direct measurements revealed no H(2)O(2) free in solution 0.5-10 min after all Fe(2+) was oxidized at pH 6.5 or 7.5. These results are consistent with initial H(2)O(2) formation, which rapidly reacts in a secondary reaction with unidentified solution components. Using measured rate constants for rHF, simulations showed that steady-state H(2)O(2) concentrations peaked at 14 muM at approximately 600 ms and decreased to zero at 10-30 s. rLF did not produce measurable H(2)O(2) but apparently conducted the secondary reaction with H(2)O(2). Fe(2+)/O(2) values of 4.0 were measured for AvBF. Stopped-flow measurements with AvBF showed that both H(2)O(2) and O(2) react at the same rate (k = 0.34 s(-1)), that is faster than the reactions with rHF. Simulations suggest that AvBF reduces O(2) directly to H(2)O without intermediate H(2)O(2) formation.

Azotobacter vinelandii↗

PubMed2005

DNA damage in mice treated with sulfur dioxide by inhalation.

Sulfur dioxide (SO2) is a ubiquitous air pollutant produced by the burning of fossil fuels. In this study, single-cell gel electrophoresis (the Comet assay) was used to evaluate the DNA damage produced by inhalation exposure of mice to SO2. Male and female mice were housed in exposure chambers and treated with 14.00 +/- 1.25, 28.00 +/- 1.98, 56.00 +/- 3.11, and 112.00 +/- 3.69 mg/m3 SO2 for 6 hr/day for 7 days, while control groups were exposed to filtered air. Comet assays were performed on blood lymphocytes and cells from the brain, lung, liver, spleen, kidney, intestine, and testicles of the animals. SO2 caused significant, dose-dependent increases in DNA damage, as measured by Olive tail moment, in all the cell types analyzed from both sexes of mice. The results indicate that inhalation exposure to SO2 damages the DNA of multiple organs in addition to the lung, and suggests that this damage could result in mutation, cancer, and other diseases related to DNA damage. Further work will be required to understand the ultimate toxicological significance of this damage. These data also suggest that detecting DNA damage in blood lymphocytes, using the Comet assay, may serve as a useful tool for evaluating the impact of pulmonary SO2 exposure in human biomonitoring studies.

Air Pollutants↗

PubMed2005

Matrix metalloproteinase-2 (MMP-2) expression and regulation by tumor necrosis factor alpha (TNFalpha) in the bovine corpus luteum.

Angiogenesis and tissue remodeling events in the corpus luteum (CL) are mediated by matrix metalloproteinases (MMPs). We have recently reported the cloning of bovine membrane-type 1 metalloproteinase (MT1-MMP) and have shown that active MT1-MMP is correlated to MMP-2 activity in the CL during the estrous cycle. Given the important role that MMP-2 plays in neovascularization, we became interested in understanding the role of this enzyme in the CL, a system in which angiogenesis is exquisitely regulated in the course of its lifespan. The aims of the present study were to clone bovine MMP-2 cDNA, to investigate its temporal and spatial expression in three stages of CL during the estrous cycle and to study its regulation by TNFalpha, a key cytokine regulator of CL physiology. Bovine MMP-2 cDNA was isolated from a UNI-ZAP II bovine capillary endothelial cell cDNA library and sequenced. This gene encoded a protein of 662 amino acids. Luteal tissues were collected from non-lactating dairy cows on days 4, 10, and 16 of the estrous cycle. Northern and Western blotting revealed that the levels of MMP-2 mRNA (3.1 kb) and immunoreactive pro-MMP-2 protein (68 kDa) did not differ (P > 0.05) in any age of CL examined. In addition to large luteal cells, MMP2 was localized to endothelial cells in all ages of CL by immunohistochemistry. Studies using in vitro luteal cell cultures showed that MMP-2 mRNA, protein expression and activity was upregulated by TNFalpha in a dose- and time-dependent manner. The present study suggests that MMP-2 is predominantly produced by large luteal cells and endothelial cells, and that it plays an essential role in luteal remodeling and angiogenesis. These data also suggest that cytokines such as TNFalpha may modulate these processes by regulating MMP-2 expression.

Animals↗

PubMed2005

Smoking cessation and lung cancer mortality in a cohort of middle-aged Canadian women.

PURPOSE: To determine the impact of smoking cessation on lung cancer mortality among women. METHODS: Survival analysis is used to assess the effect of smoking cessation on lung cancer death in the dietary cohort of 49,165 women aged 40 to 59 years enrolled in the Canadian National Breast Screening Study. RESULTS: During an average of 10.3 years of follow-up, 106 women died of lung cancer. The risk of lung cancer mortality among women who quit before age 50 (HR=0.26; 95% CI, 0.13-0.55 among women who quit at ages 40-49) or quit in the previous 10 years (HR=0.39; 95% CI, 0.22-0.69) is substantially lower than the risk among current smokers. Women who quit after age 40 or have quit for less than 20 years are at substantially higher risk of lung cancer mortality compared with never smokers. Both duration of smoking cessation and age at quitting have independent effects on lung cancer mortality, after controlling for number of cigarettes smoked per day and number of years smoked, as well as other potential confounding variables. CONCLUSION: These findings suggest that programs and policies to promote early cessation of smoking and prevention of relapse should be a public health priority.

Adult↗

PubMed2005

Correlation of high density lipoprotein (HDL)-associated sphingosine 1-phosphate with serum levels of HDL-cholesterol and apolipoproteins.

BACKGROUND: Extracellular sphingosine 1-phosphate (S1P) has been shown to contribute to the action of high density lipoprotein (HDL) on endothelial and smooth muscle cells. We examined the relationship of lipoprotein-associated S1P concentrations with cholesterol (C) and apolipoprotein (apo) contents of lipoprotein and lipoprotein subfractions characterized by capillary isotachophoresis (cITP). METHODS: Blood samples were drawn from 16 volunteers. S1P concentrations were quantified by bioassay based on the ability of S1P to stimulate its receptor. cITP was performed using plasma that had been prestained with NBD-ceramide. RESULTS: In plasma, S1P was concentrated in HDL and associated with LDL at a much lower concentration. HDL-S1P was the major determinant of the plasma S1P concentration. HDL-S1P was strongly and positively (p<0.001) correlated with serum levels of HDL-C (r=0.82), apo A-I (r=0.91) and apo A-II (r=0.92). HDL-S1P was strongly and positively (p<0.01) correlated with the apo A-I- and apo A-I/apo A-II-containing cITP HDL subfractions [fast HDL-C (r=0.66) and intermediate HDL-C (r=0.80)], but was not significantly correlated with apo E-containing slow HDL, suggesting that S1P is associated with both apo A-I HDL and apo A-I/A-II HDL. LDL-S1P was positively correlated (p<0.01) with levels of LDL-C (r=0.65) and apo B (r=0.85). CONCLUSION: Lipoprotein-associated S1P was related to the lipoprotein composition of cholesterol and apolipoproteins, suggesting that extracellular S1P may play different roles depending on the particles with which it is associated.

Aged↗

PubMed2005

C-reactive protein in atherosclerotic lesions: its origin and pathophysiological significance.

C-reactive protein (CRP) is frequently deposited in the lesions of the arterial intima; however, the origin and pathological significance of CRP in these lesions are not completely understood. In this study, we measured CRP levels in the plasma of hypercholesterolemic rabbits and investigated CRP expression at both the mRNA and protein levels using rabbit and human atherosclerotic specimens. CRP levels were significantly elevated in both cholesterol-fed and Watanabe heritable hyperlipidemic rabbits, and CRP levels were clearly correlated with aortic atherosclerotic lesion size. Immunohistochemical staining coupled with Western blotting analysis revealed that CRP-immunoreactive proteins were found at all stages of atherosclerosis from the early to advanced lesions. CRP was present extracellularly and co-localized with apolipoprotein B but was rarely associated with the cytoplasm of macrophages and foam cells. Real-time reverse transcriptase-polymerase chain reaction analysis revealed that CRP mRNA in atherosclerotic lesions was barely detectable, and isolated macrophages did not express CRP mRNA, suggesting that CRP proteins found in the lesions were essentially derived from the circulation rather than synthesized de novo by vascular cells. These results suggest that there is a link between plasma CRP and the degree of atherosclerosis and that inhibition of plasma CRP may represent a therapeutic modality for the treatment of cardiovascular disease.

Animals↗

PubMed2005

A unified framework for image retrieval using keyword and visual features.

In this paper, a unified image retrieval framework based on both keyword annotations and visual features is proposed. In this framework, a set of statistical models are built based on visual features of a small set of manually labeled images to represent semantic concepts and used to propagate keywords to other unlabeled images. These models are updated periodically when more images implicitly labeled by users become available through relevance feedback. In this sense, the keyword models serve the function of accumulation and memorization of knowledge learned from user-provided relevance feedback. Furthermore, two sets of effective and efficient similarity measures and relevance feedback schemes are proposed for query by keyword scenario and query by image example scenario, respectively. Keyword models are combined with visual features in these schemes. In particular, a new, entropy-based active learning strategy is introduced to improve the efficiency of relevance feedback for query by keyword. Furthermore, a new algorithm is proposed to estimate the keyword features of the search concept for query by image example. It is shown to be more appropriate than two existing relevance feedback algorithms. Experimental results demonstrate the effectiveness of the proposed framework.

Algorithms↗

PubMed2005

Severe acute respiratory syndrome associated coronavirus is detected in intestinal tissues of fatal cases.

OBJECTIVES: A significant percentage of confirmed severe acute respiratory syndrome (SARS) patients experienced gastrointestinal symptoms, and the viral sequence was detectable in the stool of most patients. At present, the knowledge of the pathology of the digestive system in SARS patients is limited. Because a resurgence of the SARS epidemic is constantly possible, there is an urgent need to understand the involvement of the digestive system in this new disease. METHODS: We performed seven SARS autopsies in which samples of alimentary tract and digestive glands were examined with routine pathology, electron microscopy (EM), in situ hybridization (ISH), immunohistochemistry, and real-time polymerase chain reaction (PCR). RESULTS: The main histopathological finding was atrophy of the mucosal lymphoid tissue. A few mucosal epithelial cells and lymphocytes in the intestine were positively stained for coronavirus with ISH. SARS-coronavirus (CoV)-like particles were found in the mucosal epithelial cells under EM and mild focal inflammation was detected in the alimentary tract. One patient who experienced severe diarrhea had pseudomembranous enteritis of the ileum. Fatty degeneration and central lobular necrosis were observed in the liver. No evidence of direct viral infection was found in the esophagus, the stomach, the salivary gland, the liver, or the pancreas. CONCLUSIONS: In addition to the lungs, the gastrointestinal tract is another target of SARS-CoV infection, as the intestinal epithelial cells and mucosal lymphoid tissue are infected. The findings provide possible explanations for the gastrointestinal symptoms and the presence of virus in the stool of SARS patients.

Adult↗

PubMed2005

Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis.

The activation and entry of antigen-specific CD8(+) T cells into the central nervous system is an essential step towards clearance of West Nile virus (WNV) from infected neurons. The molecular signals responsible for the directed migration of virus-specific T cells and their cellular sources are presently unknown. Here we demonstrate that in response to WNV infection, neurons secrete the chemokine CXCL10, which recruits effector T cells via the chemokine receptor CXCR3. Neutralization or a genetic deficiency of CXCL10 leads to a decrease in CXCR3(+) CD8(+) T-cell trafficking, an increase in viral burden in the brain, and enhanced morbidity and mortality. These data support a new paradigm in chemokine neurobiology, as neurons are not generally considered to generate antiviral immune responses, and CXCL10 may represent a novel neuroprotective agent in response to WNV infection in the central nervous system.

Animals↗

PubMed2005

Construction of a novel peptide nucleic acid piezoelectric gene sensor microarray detection system.

A novel 2 x 5 clamped style piezoelectric gene sensor microarray has been successfully constructed. Every crystal unit of the fabricated gene sensor can oscillate independently without interfering with each other. The bis-peptide nucleic acid (bis-PNA) probe, which can combine with target DNA or RNA sequences more effectively and specifically than a DNA probe, was designed and immobilized on the surface of the gene sensor microarray to substitute the conventional DNA probe for direct detection of the hepatitis B virus (HBV) genomic DNA. Detection conditions were then explored and optimized. Results showed that PBS buffer of pH 6.8, an ion concentration of 20 mmol/liter, and a probe concentration of 1.5 micromol/liter were optimal for the detection system. Under such optimized experimental conditions, the specificity of bis-PNA was proved much higher than that of DNA probe. The relationship between quantity of target and decrease of frequency showed a typical saturation curve when concentrations of target HBV DNA varied from 10 pg/liter to 100 microg/liter, and 10 microg/liter was the watershed, with a statistic linear regression equation of I gC = -2.7455 + 0.0691 deltaF and the correlating coefficient of 0.9923. Fortunately, this is exactly the most ordinary variant range of the HBV virus concentration in clinical hepatitis samples. So, a good technical platform is successfully constructed and it will be applied to detect HBV quantitatively in clinical samples.

Base Sequence↗

PubMed2005

Comparison of 2 mapping strategies for pulmonary vein isolation.

BACKGROUND: Pulmonary vein (PV) isolation using a circular catheter (CC) creates an entrance block from the left atrium (LA) to PV to eliminate paroxysmal atrial fibrillation (PAF). We describe a new approach for PV isolation during distal PV pacing using a basket catheter (BC). The purpose of the present study was to compare 2 mapping strategies for PV isolation. METHODS AND RESULTS: Of 100 consecutive patients with PAF, 50 underwent CC-guided PV isolation and 50 underwent BC-guided PV isolation. During CC-guided ablation, the endpoint was the elimination of PV potentials based on the entrance block from the LA to PV. During BC-guided ablation during distal PV pacing, the endpoint was the elimination of bidirectional PV-LA conduction. At 12 months, 62% of patients who underwent CC ablation and 80% of patients who underwent BC ablation were free of symptomatic PAF without the use of antiarrhythmic drugs (p<0.05). The incidence of mild (<50%) PV stenosis in BC ablation was significantly lower than that in CC ablation (12 vs 24%, p<0.01). CONCLUSIONS: This new approach for PV isolation during distal PV pacing using BC is useful for confirming a bidirectional PV-LA conduction block and is more effective than CC ablation.

Aged↗

PubMed2005

Hybrid therapy with pilsicainide and pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Pulmonary vein (PV) isolation is commonly performed in patients with drug-refractory atrial fibrillation (AF) and in cases of unsuccessful ablation, antiarrhythmic agents that were ineffective before the ablation sometimes become effective afterward. Therefore, the effects and mechanisms of hybrid therapy with pilsicainide and PV isolation for AF were assessed in the present study. METHODS AND RESULTS: Seventy-four patients with paroxysmal AF in whom pilsicainide was ineffective underwent PV isolation. If AF recurred, a second procedure was performed and if AF recurred again, pilsicainide was re-administered. After the first procedure, AF recurred in 42 patients, and a second procedure was performed in 31 patients, of whom 28 had recovery of left atrial (LA)-PV conduction and non-PV foci were identified in 3. After the second session, ablation eliminated AF without drugs in 53 (72%) patients. Pilsicainide suppressed the conduction properties at the LA-PV junction. In 21 patients with recurrence of AF, pilsicainide was re-administered and eliminated AF in 11 patients (success with pilsicainide: 86%). CONCLUSIONS: In cases of unsuccessful PV isolation, pilsicainide may prevent AF by modifying the LA-PV conduction properties. Hybrid therapy with pilsicainide and PV isolation may be an effective therapeutic approach for AF.

Anti-Arrhythmia Agents↗

PubMed2005

Potent capillary isotachophoresis (cITP) for analyzing a marker of coronary heart disease risk and electronegative low-density lipoprotein (LDL) in small dense LDL fraction.

BACKGROUND: The potency and usefulness of capillary isotachophoresis (cITP) for assessing whole-serum lipoprotein profiles and quantifying electronegative low-density lipoprotein (LDL) has been previously reported. METHODS AND RESULTS: A new cITP method to measure electronegative LDL in the small dense LDL fraction has been established. Both electronegative LDL and electronegative LDL in the small dense LDL fraction decreased after treatment with fenofibrate. CONCLUSIONS: This method appears to be useful for analyzing a marker of coronary heart disease risk and may be suitable for evaluating the effects of hypolipidemic agents.

Biomarkers↗

PubMed2005

Involvement of peroxiredoxin I in protecting cells from radiation-induced death.

Peroxiredoxin I (Prx-I), a key member of the peroxiredoxin family, reduces peroxides and equivalents through the thioredoxin system. Our previous work has shown that expression of Prx-I in mammalian cells increases following ionizing radiation (IR), indicating that Prx-I actively responds to IR-induced reactive oxygen species (ROS) and suggesting that Prx-I plays an important role in protecting cells from IR-induced death. To test this hypothesis, we suppressed the expression of Prx-I in SW480 cells by RNA interference. Our results show that IR induces the expression of Prx-I in SW480 cells in a dose- and time-dependent manner. The recombinant siRNA vector targeting Prx-I dramatically reduced the expression of Prx-I in SW480 cells. When Prx-I was knocked down in SW480 cells, the cells exhibited a decreased growth rate, a reduced antioxidant capability following IR and became more sensitive to IR-induced apoptosis. Together, our results demonstrate that Prx-I plays an important role in protecting cells from IR-induced cell death, which might be through scavenging IR-induced ROS in the cells.

Apoptosis↗