[Clinical analysis of dual enhanced antiplatelet therapy after cerebrovascular intervention for reducing the risk of cerebral infarction recurrence].

To investigate the clinical assessment of dual-enhanced antiplatelet therapy after cerebrovascular intervention to reduce the risk of cerebral infarction recurrence, and to provide a reference for the prevention and treatment of cerebral infarction recurrence risk. 202 patients with cerebral infarction who underwent cerebrovascular intervention in Tianjin Fifth Central Hospital from January 2018 to October 2022 were selected as study subjects. The patients were divided into a treatment group (n=104) based on randomized controlled single-blind method with 61 males and 43 females with a mean age of (62.33±2.57) years old and a control group (n=98) with 56 males and 42 females with a mean age of (62.49±2.36) years old. The control group was given aspirin mono-antiplatelet therapy, and the treatment group was given clopidogrel doublet augmented antiplatelet therapy on the basis of the control group, and both groups continued the treatment for 2 months. Platelet counts, coagulation indexes and inflammatory factors were compared between the two groups before and after treatment, and the America National Institutes of Health Stroke Scale (NIHSS) score was used to assess the neurological functions of the two groups before and after treatment, and the recurrence of cerebral infarction in the two groups was counted within 6 months after treatment. In addition, the patients in the treatment group were divided into the cerebral infarction recurrence group and the cerebral infarction non-recurrence group according to whether they had cerebral infarction recurrence within 6 months after treatment, and the clinical data of the patients in the treatment group were collected to analyze the influencing factors of the dual-enhancement antiplatelet therapy for the recurrence of cerebral infarction in patients with cerebral infarction after cerebral vascular intervention by multifactorial logistic regression. The results showed that after treatment, patients in the treatment group had an international normalized ratio (INR) of (1.76±0.38), a platelet activation rate of (39.52±4.79)%, a platelet aggregation rate of (48.54±5.21)%, a tumor necrosis factor-alpha (TNF-alpha) of (28.37±4.47)ng/L, an interleukin 6 (IL-6) of (24.77±3.52)ng/L, a high-sensitivity C-reactive protein (hs-CRP) of (7.39±1.53)mg/L and an NIHSS score of (6.11±1.39) were lower than those of the control group (2.32±0.41), (44.81±6.37)%, (51.39±5.58)%, (39.66±4.51) ng/L, (29.25±4.04) ng/L, (9.03±1.78) mg/L and (9.93±1.46) points (all P<0.05). At 6-month follow-up of all patients, cerebral infarction recurred in 16 (15.38%) patients in the treatment group and in 33 (33.67%) patients in the control group (χ2=9.185, P<0.05). Kaplan-Meier results showed a statistically significant difference in the rate of recurrence without cerebral infarction in the treatment group compared with the control group(LogRank χ2=4.595,P<0.05). Logistic regression analysis showed that smoking history, cervical vascular plaque, post-treatment NIHSS score, post-treatment stenosis score, post-treatment INR, post-treatment hs-CRP and CYP2C19 gene polymorphism were independent influences on the recurrence of cerebral infarction in cerebral infarction patients with cerebral vascular interventions followed by doublet augmentation of antiplatelet therapy (all P<0.05). In conclusion, dual-enhanced antiplatelet therapy may be an effective measure to reduce the risk of cerebral infarction recurrence after cerebrovascular intervention in patients with cerebral infarction, but it is still influenced by more factors.

[Left occipital dural arteriovenous fistulas presenting as right red eye: a case report].

A 63-year-old male with a healthy history presented with a red and swollen right eye for 3 months. Neuro-ophthalmic examination showed slight bulging of the right eyeball, and multiple spiral conjunctival vessels were visible on the surface of the right conjunctiva, suggesting a right carotid cavernous fistula. Cerebral angiography showed left occipital dural arteriovenous fistulas. After endovascular embolization treatment, the patient's abnormal craniocerebral venous drainage and right eye syndrome resolved, and there was no recurrence during the one-month clinical follow-up after surgery.

[Prevalence and risk factors of diabetes and prediabetes in adults in Jingyuan Ningxia].

Objective: To investigate the prevalence and risk factors of diabetes and prediabetes in Jingyuan County in Ningxia. Methods: A cross-sectional survey including 10 639 participants (18-88 years of age) with a multistage sampling was conducted in Jingyuan County between January, 2014 and April, 2015. Questionnaires, physical examinations, and laboratory tests were included in the survey. Results: Among all the subjects, 10 491 participants (men: 4 826, women: 5 665) with complete data were included in the analysis. The standardized prevalence of diabetes and prediabetes was 4.2% (men: 3.9%, women: 4.5%) and 8.8% (men: 7.6%, women 10.3%), respectively, in which the standardized prevalence of diabetes was higher in Hui (4.5%) than that in Han (3.5%) (P< 0.05). Logistic regression analyses showed that age, family history of diabetes, overweight/obesity, hypertriglyceridemia and hypertension were positively associated with prediabetes and diabetes with the odds ratios being 1.60 and 2.14 (age, P< 0.001), 1.40 and 3.32 (family history, P< 0.05), 1.47 and 1.57 (overweight/obesity, P< 0.001), 1.88 and 2.55 (hypertriglyceridemia, P< 0.001), 1.44 and 1.89 (hypertension, P< 0.001), respectively. Conclusions: The prevalence of diabetes was relatively low in the rural area in Ningxia. However, it is still essential to take active interventions in people at high risk of diabetes in order to prevent the incident diabetes.

[The prevalence of metabolic syndrome among adults in rural areas of Ningxia Hui autonomous region].

Objective: To investigate the prevalence of metabolic syndrome (MS) among adults in rural areas of Ningxia Hui autonomous region. Methods: A cross-sectional study was conducted in 10 639 adults enrolled with a multistage method from Jingyuan County. The MS was identified according to Chinese type 2 diabetes prevention guide (2013). Results: Among all the subjects, 17.4% of them met the MS definition with the standardized prevalence of 14.7% after adjustment of sex and age. The prevalence and standardized rate of MS in men were 19.9% and 17.3%, and in women were 15.3% and 13.5%.The prevalence of MS in men was higher than that in women(P<0.001) and increased with aging in both genders. The prevalence and standardized rate of abdominal obesity, hyperglycemia, hypertension, high triglycerides, and low HDL-C were 19.5% and 16.7%, 15.0% and 12.9%, 42.0% and 37.1%, 25.8% and 23.1%, 28.5% and 27.7%, respectively. The rate of abdominal obesity was higher in women than in men (20.5% vs 18.2%, P=0.004), whereas the rate of hypertension, high triglycerides, and low HDL-C were higher in men than in women (all P<0.01). The prevalence of having one parameter of the MS was 68.4%. Conclusion: The prevalence of MS is higher in rural areas of Ningxia Hui autonomous region, suggesting that a series of comprehensive prevention measures should be carried out to prevent and control the MS so as to improve the public health conditions in rural areas.

Association of genetic variations in miR-146a rs2910164 and miR-149 rs11614913 with the development of classic Kaposi sarcoma.

Classic Kaposi sarcoma is a type of vascular proliferative inflammatory disease. Previous studies have reported significant associations between microRNAs expression and the development of classic Kaposi sarcoma. Here, we conducted a case-control study to investigate the association between miR-146a and miR-149 genetic polymorphisms and risk of classic Kaposi sarcoma in a Chinese population. Both classic Kaposi sarcoma patients and healthy controls were recruited between December 2013 and October 2015. Genotyping of miR-146a and miR-149 was performed by polymerase chain reaction-coupled with restriction fragment length polymorphism. Results showed that the GG genotype of miR-146a was associated with increased risk to classic Kaposi sarcoma (OR = 6.00, 95%CI = 1.19-30.12), as compared with the CC genotype. In the recessive model, we found that the GG genotype carried a 4.55-fold increased risk to classic Kaposi sarcoma as compared with the CC + CG genotype (OR = 2.06, 95%CI = 1.04-20.29). In conclusion, our study demonstrated that miR-146a, but not miR-149 polymorphism, is associated with risk to classic Kaposi sarcoma in the Chinese population.

Pluronic-PEI copolymers enhance exon-skipping of 2'-O-methyl phosphorothioate oligonucleotide in cell culture and dystrophic mdx mice.

A series of small-size polyethylenimine (PEI)-conjugated pluronic polycarbamates (PCMs) have been investigated for the ability to modulate the delivery of 2'-O-methyl phosphorothioate RNA (2'-OMePS) in vitro and in dystrophic mdx mice. The PCMs retain strong binding capacity to negatively charged oligomer as demonstrated by agarose gel retardation assay, with the formation of condensed polymer/oligomer complexes at a wide-range weight ratio from 1:1 to 20:1. The condensed polymer/oligomer complexes form 100-300 nm nanoparticles. Exon-skipping effect of 2'-OMePS was dramatically enhanced with the use of the most effective PCMs in comparison with 2'-OMePS alone in both cell culture and in vivo, respectively. More importantly, the effective PCMs, especially those composed of moderate size (2k-5kDa) and intermediate hydrophilic-lipophilic balance (7-23) of pluronics, enhanced exon-skipping of 2'-OMePS with low toxicity as compared with Lipofectamine-2000 in vitro or PEI 25k in vivo. The variability of individual PCM for delivery of antisense oligomer and plasmid DNA indicate the complexity of interaction between polymer and their cargos. Our data demonstrate the potential of PCMs to mediate delivery of modified antisense oligonucleotides to the muscle for treating muscular dystrophy or other appropriate myodegenerative diseases.

Exon skipping restores dystrophin expression, but fails to prevent disease progression in later stage dystrophic dko mice.

Antisense therapy with both chemistries of phosphorodiamidate morpholino oligomers (PMOs) and 2'-O-methyl phosphorothioate has demonstrated the capability to induce dystrophin expression in Duchenne muscular dystrophy (DMD) patients in phase II-III clinical trials with benefit in muscle functions. However, potential of the therapy for DMD at different stages of the disease progression is not understood. In this study, we examined the effect of peptide-conjugated PMO (PPMO)-mediated exon skipping on disease progression of utrophin-dystrophin-deficient mice (dko) of four age groups (21-29, 30-39, 40-49 and 50+ days), representing diseases from early stage to advanced stage with severe kyphosis. Biweekly intravenous (i.v.) administration of the PPMO restored the dystrophin expression in nearly 100% skeletal muscle fibers in all age groups. This was associated with the restoration of dystrophin-associated proteins including functional glycosylated dystroglycan and neuronal nitric synthase. However, therapeutic outcomes clearly depended on severity of the disease at the time the treatment started. The PPMO treatment alleviated the disease pathology and significantly prolonged the life span of the mice receiving treatment at younger age with mild phenotype. However, restoration of high levels of dystrophin expression failed to prevent disease progression to the mice receiving treatment when disease was already at advanced stage. The results could be critical for design of clinical trials with antisense therapy to DMD.

Effective Resistance to Wheat Stripe Rust in a Region with High Disease Pressure.

Stripe rust is a major fungal disease of wheat. It frequently becomes epidemic in southeastern Gansu province, a stripe rust hot spot in China. Evaluations of wheat germplasm response are crucial for developing cultivars to control the disease. In total, 57 wheat cultivars and lines from Europe and other countries, comprising 36 cultivars with documented stripe rust resistance genes and 21 with unknown genes, were tested annually with multiple races of Puccinia striiformis f. sp. tritici in the field at Tianshui in Gansu province from 1993 to 2013. Seven wheat lines were highly resistant, with infection type (IT) 0 during the entire period; 16 were moderately resistant (IT 0;-2); and 26 were moderately susceptible (IT 0;-4), with low maximum disease severity compared with the susceptible control Huixianhong. 'Strampelli' and 'Libellula', with three and five quantitative trait loci, respectively, for stripe rust resistance have displayed durable resistance in this region for four decades. Ten cultivars, including 'Lantian 15', 'Lantian 26', and 'Lantian 31', with stripe rust resistance derived from European lines, were developed in our breeding program and have made a significant impact on controlling stripe rust in southeastern Gansu. Breeding resistant cultivars with multiple adult-plant resistance genes seems to be a promising strategy in wheat breeding for managing stripe rust in this region and other hot spots.

Effect analysis of sacral canal therapy combined with Fufang Wulingzhi Tangjiang in the treatment of residual root pain after lumbar surgery.

OBJECTIVE: To observe the clinical effect of a combination of traditional Chinese and western medicine (sacral canal therapy combined with compound Fufang Wulingzhi Tangjiang) in the treatment of residual root pain after lumbar surgery. PATIENTS AND METHODS: From January 2019 to December 2020, 538 patients with residual root pain due to lumbar degenerative diseases were treated in our hospital [open decompression discectomy (ODD), Percutaneous Endoscopic Lumbar Discectomy (PELD) or Transforminal Lumbar Interbody Fusion (TLIF)]. They were randomly divided into control group (basic treatment + celecoxib), observation group 1 (basic treatment + compound Fufang Wulingzhi Tangjiang), observation group 2 (basic treatment + sacral canal therapy) and observation group 3 (basic treatment + sacral canal therapy + Fufang Wulingzhi Tangjiang). Follow-up 3-12 months. The therapeutic effect, VAS score, JOA score, treatment cost, complications, serum interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-α) were recorded and compared before treatment, 1 week after treatment, 2 weeks after treatment, 1 month after treatment, and the last follow-up. RESULTS: The treatment effect, VAS score, JOA, and treatment cost in the observation group were better than those in the control group (p < 0.05). There were significant differences in the above-mentioned indexes between the observation group 3 and the control group, observation group 1, and observation group 2 (p < 0 01). Inflammatory factors (IL-6, IL1, TNF-α) in the observation group were lower than those in the control group (p < 0 05). Inflammatory factors in observation group 3 were significantly lower than those in the control group, observation group 1, and observation group 2 (p < 0 01). CONCLUSIONS: Sacral canal injection combined with Fufang Wulingzhi Tangjiang can be effective in the treatment of postoperative root pain of lumbar degenerative diseases, which can reduce inflammatory factors such as IL-6, IL-1ß and TNF-α. It has the advantages of quick effect, short treatment time, low cost, high safety, in line with the concept of ERAS, easily accepted by patients and their families, and worthy of further popularizing and applying in clinic.

Dose-dependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino.

We have earlier shown that antisense morpholino oligomers are able to restore dystrophin expression by systemic delivery in body-wide skeletal muscles of dystrophic mdx mice. However, the levels of dystrophin expression vary considerably and, more importantly, no dystrophin expression has been achieved in cardiac muscle. In this study, we investigate the efficiency of morpholino-induced exon skipping in cardiomyoblasts and myocytes in vitro, and in cardiac muscle in vivo by dose escalation. We showed that morpholino induces targeted exon skipping equally effectively in both skeletal muscle myoblasts and cardiomyoblasts. Effective exon skipping was achieved in cardiomyocytes in culture. In the mdx mice, morpholino rescues dystrophin expression dose dependently in both skeletal and cardiac muscles. Therapeutic levels of dystrophin were achieved in cardiac muscle albeit at higher doses than in skeletal muscles. Up to 50 and 30% normal levels of dystrophin were induced by single systemic delivery of 3 g kg(-1) of morpholino in skeletal and cardiac muscles, respectively. High doses of morpholino treatment reduced the serum levels of creatine kinase without clear toxicity. These findings suggest that effective rescue of dystrophin in cardiac muscles can be achieved by morpholino for the treatment of Duchenne muscular dystrophy.

Sc-coated Si@Al(12) as high-capacity hydrogen storage medium.

Hydrogen molecules adsorption and storage in Sc coated Si@Al(12) cluster were investigated using density functional theory methods. Scandium atoms can bind strongly to the surfaces of Si@Al(12) due to the charge transfer between Sc and Si@Al(12), and do not suffer from clustering on the substrate. Si@Al(12) cluster coated with three and four Sc atoms can adsorb 16 and 18 H(2) molecules with a binding energy of 0.28-0.63 eV/H(2), corresponding to hydrogen storage capacity of 6.0 and 6.3 wt %, respectively. The stable Si@Al(12) can be applied as one of candidates for hydrogen storage materials at ambient conditions.

Decreased long noncoding RNA ADIPOQ promoted cell proliferation and metastasis via miR-219c-3p/TP53 pathway in colorectal carcinoma.

OBJECTIVE: To investigate the expression of Long non-coding RNA ADIPOQ and its facilitating effects on proliferation and invasion of colorectal cancer by modulating the expression of TP53 via sponging with miR-219c-3p. PATIENTS AND METHODS: qRT-PCR was performed to detect the expressions of ADIPOQ and TP53 in human colorectal cancer tissues and cells. CCK-8 assay was performed to evaluate the Caco-2 cells proliferation and transwell assay was performed to evaluate the Caco-2 cells migration. The relationship between ADIPOQ and miR-219c-3p was detected by statistical analysis. Target prediction and Luciferase activity assay were conducted to investigate the binding site and interaction between ADIPOQ and miR-219c-3p. Further, we cloned the mice TP53 3'-UTR into the Luciferase reporter vector and constructed miR-219c-3p binding mutants to verify the inhibited regulation of miR-219c-3p to the TP53 expression. RESULTS: The results suggested that the expression of ADIPOQ and TP53 was downregulated in human colorectal cancer tissues and Caco-2 cells. qRT-PCR and CCK-8 assay showed that ADIPOQ expression is correlated with the proliferation of colorectal cancer cells. Transwell assay showed that ADIPOQ regulated the migration ability of colorectal cancer cells. The bioinformatics prediction and Luciferase assay demonstrated that ADIPOQ serves as ceRNA for miR-219c-3p to further regulate the expression of TP53. CONCLUSIONS: For the first time, we found that lncRNA-ADIPOQ was downregulated in human colorectal cancer cells, which could facilitate tumor proliferation, migration and invasion as a ceRNA by sponging with miR-219c-3p.

Microwave irradiation enhances gene and oligonucleotide delivery and induces effective exon skipping in myoblasts.

Microwave (MW) energy consists of electric and magnetic fields and is able to penetrate deep into biological materials. We investigated the effect of MW (2450 MHz) irradiation on gene delivery in cultured mouse myoblasts and observed enhanced transgene expression. This effect is, however, highly variable and critically dependent on the power levels, duration and cycle conditions of MW exposure. MW irradiation greatly enhances delivery of 2'O methyl-phosphorothioate antisense oligonucleotide (AON) targeting mouse dystrophin exon 23 and induces specific exon skipping in cultured myoblasts. Effective delivery of AON by MW irradiation is able to correct the dystrophin reading frame disrupted by a nonsense point mutation in the H2K mdx myoblasts, resulting in the restoration of dystrophin expression. MW-mediated nucleic acid delivery does not directly link to the increase in system temperature. The high variability in gene and oligonucleotide delivery is most likely the result of considerable irregularity in the distribution of the energy and magnetic field produced by MW with the current device. Therefore, achieving effective delivery of the therapeutic molecules would require new designs of MW devices capable of providing controllable and evenly distributed energy for homogenous exposure of the target cells.

bcl-2 overexpression inhibits cell death and promotes the morphogenesis, but not tumorigenesis of human mammary epithelial cells.

Overexpression of the B cell leukemia/lymphoma-2 (bcl-2) gene has been shown to confer a survival advantage on cells by inhibiting apoptosis. In epithelia, the bcl-2 gene is also related to development and differentiation, and the protein is strongly expressed in the embryo in the epithelial cells of the developing mammary gland. To investigate directly the effect of bcl-2 on human epithelial cells, we used an amphotropic recombinant retrovirus to introduce the gene into nontumorigenic cell lines developed from luminal epithelial cells cultured from milk. Here we demonstrate that while bcl-2 overexpression does not directly induce the tumorigenic phenotype, it provides a survival advantage to the mammary epithelial cells by inhibiting cell death at confluence or under conditions of serum starvation, bcl-2 can also affect the phenotype of the original epithelial cells, and promote epithelial-mesenchymal conversion, accompanied by loss of the cell adhesion molecules E-cadherin and alpha 2 beta 1 integrin. The extent of the epithelial-mesenchymal conversion varies with small differences in the phenotype of the parental line and with the level of expression of Bcl-2 and in some cases cell lines emerge with a mixed phenotype. The increased survival of Bcl-2-expressing cells at confluence results in multilayering, and the development of three- dimensional structures. Where a mixed phenotype is observed these structures consist of an outer layer of polarized epithelial cells separated by a basement membrane-like layer from an inner mass of fibroblastoid cells. Branching morphogenesis of bcl-2 transfectants is also observed in collagen gels (in the absence of fibroblast growth factors). The results strongly indicate that by increasing their survival under restrictive growth conditions, and by modifying the epithelial phenotype, bcl-2 can influence the specific morphogenetic behavior of mammary epithelial cells.

Massive idiosyncratic exon skipping corrects the nonsense mutation in dystrophic mouse muscle and produces functional revertant fibers by clonal expansion.

Conventionally, nonsense mutations within a gene preclude synthesis of a full-length functional protein. Obviation of such a blockage is seen in the mdx mouse, where despite a nonsense mutation in exon 23 of the dystrophin gene, occasional so-called revertant muscle fibers are seen to contain near-normal levels of its protein product. Here, we show that reversion of dystrophin expression in mdx mice muscle involves unprecedented massive loss of up to 30 exons. We detected several alternatively processed transcripts that could account for some of the revertant dystrophins and could not detect genomic deletion from the region commonly skipped in revertant dystrophin. This, together with exon skipping in two noncontiguous regions, favors aberrant splicing as the mechanism for the restoration of dystrophin, but is hard to reconcile with the clonal idiosyncrasy of revertant dystrophins. Revertant dystrophins retain functional domains and mediate plasmalemmal assembly of the dystrophin-associated glycoprotein complex. Physiological function of revertant fibers is demonstrated by the clonal growth of revertant clusters with age, suggesting that revertant dystrophin could be used as a guide to the construction of dystrophin expression vectors for individual gene therapy. The dystrophin gene in the mdx mouse provides a favored system for study of exon skipping associated with nonsense mutations.

Theoretical study of hydrogenated Mg, Ca@Al12 clusters.

The studies on the structure and electronic properties of hydrogenated metal embedded Al(12) cage clusters have been performed by density functional theory calculations. We have investigated aluminum cluster hydrides with 12 and 14 hydrogen atoms, respectively. Insertion of the Mg, Ca alkali metals remarkably enhances the stability of the aluminum clusters. The hydrogen atom prefers to occupy on-top sites along the surface of the clusters. Mulliken population analysis indicates that significant charge transfer occurs between the Mg and Ca atoms and the Al atoms. Our computations suggest that these clusters appear to be physically and chemically stable.

Seedling and Slow Rusting Resistance to Stripe Rust in Chinese Common Wheats.

Identification of seedling and slow stripe rust resistance genes is important for gene pyramiding, gene deployment, and developing slow-rusting wheat cultivars to control the disease. A total of 98 Chinese lines were inoculated with 26 pathotypes of Puccinia striiformis f. sp. tritici for postulation of stripe rust resistance genes effective at the seedling stage. A total of 135 wheat lines were planted at two locations to characterize their slow rusting responses to stripe rust in the 2003-2004 and 2004-2005 cropping seasons. Genes Yr2, Yr3a, Yr4a, Yr6, Yr7, Yr9, Yr26, Yr27, and YrSD, either singly or in combinations, were postulated in 72 lines, whereas known resistance genes were not identified in the other 26 accessions. The resistance genes Yr9 and Yr26 were found in 42 and 19 accessions, respectively. Yr3a and Yr4a were detected in two lines, and four lines may contain Yr6. Three lines were postulated to possess YrSD, one carried Yr27, and one may possess Yr7. Thirty-three lines showed slow stripe rusting resistance at two locations in both seasons.

A new blocking method for application of murine monoclonal antibody to mouse tissue sections.

Antigen detection with primary antibody of the same species as the test tissue is complicated by high levels of background staining when indirect immunohistochemical detection methods are used. This severely limits the use of murine monoclonal antibodies on tissues of the mouse, the most widely used experimental model system; no method for blocking this is fully satisfactory. Here we show that background staining encountered in this system results largely from the binding of secondary antibodies via both Fc and Fab to endogenous immunoglobulins and other tissue components. A simple and efficient blocking strategy was established, employing papain-digested whole fragments of unlabeled secondary anti-mouse Igs enriched with Fc fragment of the same Igs. We have used this method to visualize dystrophin, an antigen expressed at low level, in revertant fibers of mdx mouse by both immunoperoxidase and immunofluorescence methods. In combination with the use of a biotin-streptavidin immunohistochemical detection protocol with biotinylated anti-mouse F(ab')2 as second layer, we eliminated the heavy background in this system and achieved strong signal amplification to demonstrate the specific antigen clearly. Double labeling with one mouse antibody and one antibody from another species was performed without signal interference. This principle can be adapted for wider applications, such as antibodies of other species on homologous tissues and perhaps where high background is found with heterologous antibodies. (J Histochem Cytochem 46:977-983, 1998)

bcl-2: role in epithelial differentiation and oncogenesis.

The precise regulation and maintenance of balance between cell proliferation and cell death in multicellular organisms is critical for tissue homeostasis. bcl-2 initiates a new gene family involved in the regulation of cell death and survival without affecting cell proliferation. Expression of Bcl-2 has been reported in a wide range of hematopoietic cells, nonneoplastic epithelia (both hormone-responsive and nonresponsive), and epithelial malignancies. Although the major group of epithelial cells expressing Bcl-2 protein are in the proliferating zones, expression is not directly related to cell proliferation. Bcl-2 is also associated with stem cells committed to differentiation and morphogenesis. The survival advantage provided by Bcl-2 prolongs the life span of epithelial cells with differentiation potential and allows proliferation, differentiation, and morphogenesis to proceed. The gene expression in hormone-responsive organs may contribute to the sustained life of those terminally differentiated epithelial cells and a decrease in Bcl-2 levels leads to cell death by apoptosis. Overexpression of bcl-2 protects epithelial cells from death, but it is neither able to immortalize normal cells, nor to cause tumorigenic transformation of immortalized epithelial cells. Heterogeneous expression of Bcl-2 in epithelial malignancies suggests that the gene is differentially regulated. Furthermore, its expression in association with precancerous lesions suggests a role in the early stage of tumorigenesis. The effects of Bcl-2 expression on sensitivity of epithelial cells to drug, radiation, and hormone therapies vary depending on the typed of tumor. Expression of Bcl-2 is associated with resistance to hormone therapy and recurrence in prostate carcinomas, whereas in lung and breast carcinomas it is associated with a better prognosis. Studies now being performed should clarify the underlying mechanisms of differential gene regulation in different tissues and show the clinical significance of the expression of bcl-2 and other members of the bcl-2 gene family.