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PubMed1995

Glass-ceramic-coated titanium hip endoprosthesis. Experimental study in rabbits.

Titanium alloy hip endoprostheses coated with a bioactive glass ceramic (BGC) were followed in rabbits. All test endoprostheses remained stable, and image analysis showed an average of 78% bonding of the BGC-coated implants to bone at 52 weeks. The uncoated Ti-alloy controls demonstrated an average of 37% bone coverage after 52 weeks. By scanning electron microscopy the thickness of the BGC reaction layer was found to stabilize at 60 microns after bioactive bone bonding. The results indicate that the BGC coating must be thicker than the reaction layer to prevent detachment from the core metal.

Alloys↗
PubMed2026

Fine-grained structural classification of biosynthetic gene cluster-encoded products.

MOTIVATION: Biosynthetic gene clusters (BGCs) are responsible the biosynthesis of many natural products, including a multitude of effective therapeutics and their precursors. Advances in genomic data collection as well as computational techniques have made it possible to identify BGCs at scale. However, accurately determining the types of BGC-encoded products from genomic content remains elusive. RESULTS: Here, we introduce BGC annotation tool (BGCat), a machine learning method for fine-grained structural classification of BGC-encoded products, leveraging the NPClassifier natural product nomenclature. Our method leverages a pre-trained protein language model for creating meaningful gene representations and a deep neural network for class label prediction. We show the method outperforms state-of-the-art approaches in coarse-grained product classification and is effective for detailed classification. We implement a clustering-based augmentation strategy for BGC-product relationships, addressing a crucial gap in the available datasets. We then introduce the concept of product class profiles of gene cluster families (GCFs), associating each GCF with a probabilistic distribution of product types and offering a new perspective on GCF functions. Lastly, we use BGCat to provide new product class labels for over 100k BGCs in antiSMASH DB that presently have minimal information about their products. AVAILABILITY AND IMPLEMENTATION: The source code and trained model weights are freely available at https://github.com/HassounLab/BGCat.

Multigene Family↗
PubMed1989

Alveolar ridge augmentation with bioactive glass ceramics: a histological study.

A particulate BGC (bioactive glass ceramics), has been developed as a new bone graft biomaterial for alveolar ridge augmentation and has been evaluated by simulated animal models. Five beagle dogs were used in this investigation. Prior to augmentation the mandibular posterior teeth of the animals were extracted. Three months after the extractions, the porous BGC particles were packed into the subperiosteal tunnels in the ridges with a special syringe. The animals were killed at different time intervals and the specimens were examined by light microscopy, scanning electron microscopy (SEM), and X-ray energy dispersive analysis (EDAX), respectively. The results of this study indicate that the BGC particles are firmly combined with the adjacent hard and soft tissues by the bone bonding interface between the implants and the alveolar bone, and by the ingrowth of bone or fibrous connective tissue into the interspaces and the pores of the particles. The results have demonstrated that particulate BGC with pores is an excellent implant material for alveolar ridge augmentation because of its very good biocompatibility.

Alveolar Process↗
PubMed1988

Significance of basal ganglia calcification on computed tomography in children.

We reviewed 6,428 head computed tomography (CT) scans performed on 4,283 children at our institution over a 3-year period and found basal ganglia calcification (BGC) in 48 (1.1%) of the patients. Their mean age at the time of detection was 5.3 years (range: 0.5-20 years); 16 (33%) patients had cancer, 14 (29%) had tuberous sclerosis or congenital infection and 18 (38%) had other medical conditions. All patients with cancer had been treated with radiation therapy, receiving a mean dose of 4,583 cGy (range: 1,800-5,500 cGy) to the diencephalon, and calcifications first became apparent at a median of 10 months after treatment. Other medical conditions included neonatal asphyxia (3), metabolic disease (3) (Kearns Sayre, MELAS, Krabbe's), congenital anomalies (3), meningitis (2), Fahr's disease (1) and others (6). Neurologic symptoms were common in children of all groups, but could not be correlated to BGC changes. Calcium and phosphorus metabolism was evaluated in 19 patients and was abnormal in 1. We conclude that BGC on CT in childhood occur primarily as an aftermath of the cancer treatment or in children with generalized neurologic dysfunction. Many children with BGC are delayed in their development, but calcifications are not directly related to specific forms of neurologic dysfunction. Rather, ther appear to serve as markers for more extensive brain damage.

Adolescent↗
PubMed2005

Association between endogenous gene expression and growth regulation induced by TGF-beta1 in human gastric cancer cells.

AIM: To investigate the association between endogenous gene expression and growth regulation including proliferation and apoptosis induced by transforming growth factor-beta1 (TGF-beta1) in human gastric cancer (GC) cells. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the main components of the TGF-beta1/Smads signal pathway in human poorly differentiated GC cell line BGC-823. Localization of Smad proteins was also determined using immunofluorescence. Then, the BGC-823 cells were cultured in the presence or absence of TGF-beta1 (10 ng/mL) for 24 and 48 h, and the effects of TGF-beta1 on proliferation and apoptosis were measured by cell growth curve and flow cytometry (FCM) analysis. The ultrastructural features of BGC-823 cells with or without TGF-beta1 treatment were observed under transmission electron microscope. The apoptotic cells were visualized by means of the terminal deoxynucleotidyl transferase (TdT)-mediated dTUP in situ nick end-labeling (TUNEL) method. Meanwhile, the expression levels of endogenous p15, p21 and Smad7 mRNA and the corresponding proteins in the cells were detected at 1, 2 and 3 h after culture in the presence or absence of TGF-beta1 (10 ng/mL) by semi-quantitative RT-PCR and Western blot, respectively. RESULTS: The TGF-beta1/Smad signaling was found to be intact and functional in BGC-823 cells. The growth curve revealed the most evident inhibition of cell proliferation by TGF-beta1 at 48 h, and FCM assay showed G1 arrest accompanied with apoptosis induced by TGF-beta1. The typical morphological changes of apoptosis were observed in cells exposed to TGF-beta1. The apoptosis index (AI) in TGF-beta1-treated cells was significantly higher than that in the untreated controls (10.7+/-1.3% vs 0.32+/-0.06%, P<0.01). The levels of p15, p21 and Smad7 mRNA and corresponding proteins in cells were significantly up-regulated at 1 h, but gradually returned to basal levels at 3 h following TGF-beta1 (10 ng/mL) treatment. CONCLUSION: TGF-beta1 affects both proliferation and apoptosis of GC cells through the regulation of p15 and p21, and induces transient expression of Smad 7 as a negative feedback modulation of TGF-beta1 signal. Our results suggest a novel functional role of p21 as an accelerant of TGF-beta1-mediated apoptosis in GC cells.

Adenocarcinoma↗
PubMed2001

The effect pathway of retinoic acid through regulation of retinoic acid receptor alpha in gastric cancer cells.

AIM: To evaluate the role of RARalpha gene in mediating the growth inhibitory effect of all-trans retinoic acid (ATRA) on gastric cancer cells. METHODS: The expression levels of retinoic acid receptors (RARs) in gastric cancer cells were detected by Northern blot. Transient transfection and chlorophenicol acetyl transferase (CAT) assay were used to show the transcriptional activity of beta retinoic acid response element (betaRARE) and AP-1 activity. Cell growth inhibition was determined by MTT assay and anchorage-independent growth assay, respectively. Stable transfection was performed by the method of Lipofectamine, and the cells were screened by G418. RESULTS: ATRA could induce expression level of RARalpha in MGC80-3, BGC-823 and SGC-7901 cells obviously, resulting in growth inhibition of these cell lines. After sense RARalpha gene was transfected into MKN-45 cells that expressed rather low level of RARalpha and could not be induced by ATRA, the cell growth was inhibited by ATRA markedly. In contrast, when antisense RARalpha gene was transfected into BGC-823 cells, a little inhibitory effect by ATRA was seen, compared with the parallel BGC-823 cells. In transient transfection assay, ATRA effectively induced transcriptional activity of betaRARE in MGC80-3, BGC-823, SGC-7902 and MKN/RARalpha cell lines, but not in MKN-45 and BGC/aRARalpha cell lines. Similar results were observed in measuring-antiAP-1 activity by ATRA in these cancer cell lines. CONCLUSION: ATRA inhibits the growth of gastric cancer cells by up-regulating the level of RARalpha RARalpha is the major mediator of ATRA action in gastric cancer cells; and adequate level of RARalpha is required for ATRA effect on gastric cancer cells.

Agar↗
PubMed2000

Effect of all-trans retinoic acid on growth of xenograft tumor and its metastasis in nude mice.

OBJECTIVE: To study the effect of all-trans retinoic acid on growth of xenograft tumor and its metastasis in nude mice. METHODS: Human gastric cancer BGC-823 and MKN-45 cells were inoculated into spleen subcapsule of nude mice, respectively. The nude mice were subsequently administered with all-trans retinoic acid every other day. Food consuming and body weight of nude mice were measured weekly. Six weeks later, the nude mice were killed. Xenograft tumors in spleen and metastatic tumors in liver were pathologically examined. Microvessel density in the tumors was detected immunohistochemically, and serum carcinoembryonic antigen was measured by radioimmunoassay. RESULTS: After the nude mice were fed with all-trans retinoic acid, the growth of splenic tumor and its liver metastasis were inhibited and the metastatic rates decreased by 50% (BGC-823) and 33.3% (MKN-45), respectively. The microvessel density in splenic and hepatic tumors reduced by 28.58% and 35.47% (BGC-823), 19.45% and 14.52% (MKN-45), respectively. The concentration of carcinoembryonic antigen decreased by 50.24% (BGC-823) and 48.10% (MKN-45). CONCLUSION: All-trans retinoic acid may effectively inhibit the growth of xenograft tumor in spleen and its metastasis to liver in nude mice, which can be corroborated by the decrease of carcinoembryonic antigen and microvessel density.

Animals↗
PubMed2003

[D-limonene induces apoptosis of gastric cancer cells].

OBJECTIVE: To investigate the apoptosis effect induced by D-limonene on BGC-823 gastric cancer cells. METHODS: The expression of p53, bc1-2 in BGC-823 cells and qualitative, quantitative index of cell apoptosis were detected with MTT, electron microscopy, flow cytometry and immunohistochemical method. RESULTS: D-limonene could induce the formation of apoptotic bodies in a dose- and time-dependent manner. The expression of bcl-2 protein decreased and p53 protein increased in BGC-823 cells treated with D-limonene, compared with the control cells. CONCLUSION: D-limonene exerts its cytotoxic effect on BGC-823 gastric cancer cells by inducing apoptosis.

Adenocarcinoma↗
PubMed2004

Influence of diazepam on blood glucose levels in nondiabetic and non-insulin-dependent diabetic subjects under dental treatment with local anesthesia.

The effect of diazepam on blood glucose concentration (BGC) was investigated in a double-blind cross-over study in 10 healthy and 10 non-insulin-dependent diabetic subjects taking oral hypoglycemic drugs. In the first session, fasting blood samples were taken for blood glucose and glycosylated hemoglobin estimation and at 60, 80, 95, 125, and 155 minutes thereafter for glucose estimation. In another 2 sessions, a venous sample was taken immediately before premedication (5 mg diazepam or placebo randomly given during breakfast). One hour later a blood sample was taken, and the volunteers were submitted to periodontal treatment after injection of 1.8 mL of 2% mepivacaine with 1:100,000 adrenaline. Venous blood samples were taken at 15, 30, 60, and 90 minutes after injection. The changes in BGC were analyzed using analysis of variance (ANOVA) for repeated measures; the means were compared using Tukey test (P = .05). Statistically significant differences in the BGC were observed between diabetic and nondiabetic groups (P = .00003). However, there were no significant differences among the sessions of the same group (P = .29). The results of this study show that a single dose of 5 mg diazepam before dental treatment does not influence BGC in nondiabetic and non-insulin-dependent diabetic subjects.

Analysis of Variance↗
PubMed1987

[Expression of the surface antigen in human gastric cancer cells and the relation to cell cycles--correlated analysis with flow cytometry].

Expression of tumor-associated antigen in different gastric cancer cell lines and different phases of cell cycle was studied cytochemically. The antigen was recognized by the monoclonal antibody (McAb) PC1 against gastric cancer cells. By using the McAb PC1 as first antibody, the indirect immunofluorescence stain and the peroxidase-anti-peroxidase (PAP) stain were done on the gastric cancer cell lines (MGC 803, SGC 7901 and BGC 823). It was shown that PC1 antigen was mainly expressed on the membrane of these cells and only a certain percentage of the cells gave the positive reaction with different intensities. It was obvious that the expression of PC1 antigen was heterogeneous in nature. The heterogeneity of the PC1 antigen expression in gastric cancer cells might be due to either various subpopulations in the cell lines or different phases of cell cycle. In order to go further into the question, we studied quantitatively the expression of PC1 antigen in gastric cancer cell lines (MGC 803, STC 7901 and BGC 823) and the relationship between the antigen expression and cell cycle by double fluorescence stain and two-dimensional flow cytometry. It was found that expression levels of PC1 antigen in these cell lines were in the following order: MGC 803 greater than SGC 7901 greater than BGC 823. The PC1 antigen predominantly expressed on G1 phase for MGC 803 and G1, G2-M phase for SGC 7901 respectively. And uniform low level of PC1 antigen expression was found for BGC 823 throughout the cell cycle. Therefore, the PC1 antigen expression is dependent on cell cycle in MGC 803 and SGC 7901 cell lines.

Antigens, Neoplasm↗
PubMed2025

Genetic background of neurological disorders with basal ganglia calcification.

BACKGROUND: Bilateral basal ganglia calcifications (BGCs), if severe, are known hallmarks for idiopathic BGC disease (IBGC), but if milder, are often considered radiological findings of unknown significance. In previous studies, only a minority of patients with BGC had monogenic forms of IBGC. METHODS: We studied consecutive patients from a tertiary neurology clinic with bilateral BGCs of variable severity, and their families. We analyzed known IBGC genes, and an extended panel of genes linked to monogenic stroke and metabolic conditions. Clinical, radiological, and genetic data were collected, including vascular risk factors, cerebrovascular events, imaging findings (total calcification score, white matter hyperintensities, ischemic/hemorrhagic lesions), and relevant family history. RESULTS: Twenty-four families with BGCs and neurological symptoms were analyzed. Disease-causing variants were identified in 14 families (58.3%). Eight patients had IBGC (variants in SLC20A2, PDGFB, MYORG), 4 had mitochondrial disease (MT-TL1), and 2 had monogenic vascular conditions (GAL, MAP3K6). Three variants were novel. BGC severity was highest in IBGC cases, while vascular and mitochondrial cases had milder calcifications. White matter hyperintensities were seen in 94.7% of cases and correlated highly with the total calcification score. Clinical vascular events had occurred in 41.7% cases. No monogenic cause was found in 10 patients, although many of these showed clinical or radiological features suggestive of monogenic disease. CONCLUSIONS: Bilateral BGCs can occur in many neurogenetic disorders apart from IBGCs, and a broader genetic search increases the diagnostic yield. Patients with BGCs frequently had clinical cerebrovascular events, which emphasizes the role of cerebrovascular pathology in BGCs.

Humans↗
PubMed2004

Resolution of overlapped non-absorbing and absorbing solutes using either an absorption null-balance detection window or multivariate deconvolution applied to capillary electrophoresis of anionic surfactants.

Non-absorbing alkyl ether sulfates (AES) can be separated using anthraquinone-2-carboxylic acid (AQCA) as a probe; however, absorbing alkyl benzene sulfonates (ABS), if present, interfere indirect detection of most AES oligomers. Overcoming of this interference, as well as the simultaneous characterisation and evaluation of AES, fatty acids and ABS, was accomplished by using a diode-array detector and the procedures here discussed. First, it was shown that ABS can be made undetectable by using a 9 nm wide and 227 nm centred charge-absorptivity null-balance detection window (NBDW), where its contribution to the absorbance cancels the dilution effects that its presence induces on the signal of the background chromophore (BGC). Two other procedures, not requiring any prior knowledge on the nature of the absorbing interference, were also addressed. In the first one, the NBDW procedure was emulated by software, by treating the time-wavelength data matrix stored during the experimental run, and in the second one, both the ABS and BGC spectra, and the concentration profiles of ABS and the non-absorbing solutes, were recovered by orthogonal projection approach (OPA) and alternating least squares (ALS). The OPA-ALS processing provided the deconvolved signals and the wavelengths required to implement the experimental and software-emulated NBDW procedures. A composite ABS spectrum and a mixed concentration profile of the non-absorbing solutes, that involves mutual ABS-BGC dilution effects are enclosed in the OPA-ALS straightforward solutions. The pure spectra and concentration profiles were finally retrieved by crossed orthogonalisation. For the NBDW procedures, the limits of detection (S/N = 3) for AES oligomers overlapped by 1500 microg ml(-1) ABS were of ca. 10 microM AES. Using decyl sulfate as internal standard, the relative standard deviation for AES in an ABS containing industrial sample was 4.5%. The procedures here described are useful to remove the interference produced by any absorbing solute when overlapped with indirectly detected solutes in both capillary electrophoresis (CE) and HPLC.

Anions↗
PubMed2005

Basal ganglia calcification and psychosis in 22q11.2 deletion syndrome.

Intracerebral calcifications are a facultative symptom of hypoparathyreoidism in 22q11.2 deletion syndrome (22qDS). We describe a patient with 22qDS, basal ganglia calcification (BGC) and psychotic symptoms and discuss the etiological connection of BGC with psychiatric symptoms. Future work needs to determine the prevalence of BGC in 22qDS and psychiatric disorders.

Adult↗
PubMed2005

Basal ganglia calcification in BB/E rats with diabetes.

Human diabetes is associated with cognitive impairment and structural abnormalities in the brain such as cerebral atrophy. The aetiology of these abnormalities is not known. The BB/E rat is a well-established model of type 1 (insulin dependent) diabetes. A cohort of 34 BB/E rats with diabetes was divided into three sub-groups according to age (and duration of diabetes). Basal ganglia calcification (BGC) was present in the brains of more than 50% of diabetic animals, but not in any of 37 non-diabetic BB/E rats. BGC occurred more commonly in those animals which had the longest duration of diabetes (p=0.001), such that BGC was present in only 8% of animals with diabetes for 20 weeks, but in 100% of animals with diabetes for 60 weeks. There were no other significant light microscopic neuropathologic changes in diabetic animals. It will be important to investigate the mechanism of brain calcification, whether a similar process occurs in humans with diabetes, and its possible relationship to cognitive decline.

Actins↗
PubMed1997

Effects of acute prenatal ethanol exposure on Bergmann glia cells early postnatal development.

The effects of acute ethanol exposure during the prenatal phase of Bergmann glia cell (Bgc) generation were evaluated in three postnatal days. Ethanol exposed rats showed Bgc with reduced soma size, decreased number and width of their fibers, and increased fiber length, when compared with control animals. These differences, however, were significant at postnatal day 12. Our results demonstrate that acute, prenatal exposure to ethanol during critical stages of brain development disrupts Bgc early postnatal development.

Animals↗
PubMed2003

Biased gene conversion: implications for genome and sex evolution.

Classical genetic studies show that gene conversion can favour some alleles over others. Molecular experiments suggest that gene conversion could favour GC over AT basepairs, leading to the concept of biased gene conversion towards GC (BGC(GC)). The expected consequence of such a process is the GC-enrichment of DNA sequences under gene conversion. Recent genomic work suggests that BGC(GC) affects the base composition of yeast, invertebrate and mammalian genomes. Hypotheses for the mechanisms and evolutionary origin of such a strange phenomenon have been proposed. Most BGC(GC) events probably occur during meiosis, which has implications for our understanding of the evolution of sex and recombination.

Animals↗
PubMed2026

Biosynthesis and Glycosylation of Antarlides, the Polyene Macrolides Possessing Androgen Receptor Antagonistic Activity.

Antarlides (ATLs) are tetraene macrolides discovered from Streptomyces spp. They demonstrated excellent antagonist activities toward mutated androgen receptors (ARs) related to the drug resistances in AR-targeted prostate cancer treatment. Herein, a biosynthetic gene cluster (BGC) of type I modular polyketide synthases (PKSs) from S. conglobatus ATCC 31005 was verified to be responsible for the biosynthesis of ATLs in the heterologous host S. lividans SBT5. The atl BGC was also activated in situ in S. conglobatus by equipping a strong promoter for the PKS genes operon. Unexpectedly, a new glycosylated product, ATL D1, was produced in the heterologous expression. ATL D1 was also generated in the S. conglobatus mutant bearing activated atl BGC through the introduction of a GT1 family glycosyltransferase gene mgt from S. lividans. Enzymatic analysis showed that the protein MGT catalyzed the glycosylation of ATL D to yield ATL D1 by attaching a &#x3b2;-d-glucose to the C11-hydroxyl position. Moreover, site-directed mutation of MGT resulted in an iterative glycosylation to yield ATL D2 bearing a disaccharide at the C11-hydroxyl. These results offer a platform for constructing efficient biosynthetic pathway of ATLs, and the O-glycosylation could be applied to improve the pharmaceutical properties of ATLs.

Glycosylation↗
PubMed2025

Multichassis Expression of Cyanobacterial and Other Bacterial Biosynthetic Gene Clusters.

Heterologous expression of biosynthetic gene clusters (BGCs) is a powerful strategy for natural product (NP) discovery, yet achieving consistent expression across microbial hosts remains challenging. Here, we developed cross-phyla vector systems enabling the expression of BGCs from cyanobacteria and other bacterial origins in Gram-negative Escherichia coli, Gram-positive Bacillus subtilis, and two model cyanobacterial strains including unicellular Synechocystis PCC 6803 and filamentous Anabaena sp. PCC 7120. Following validation using constitutive and inducible expression of the enhanced yellow fluorescent protein (eYFP), we applied these vectors to express the shinorine and violacein BGCs in all four hosts. Promoter tuning, substrate feeding, BGC refactoring, and inducible control enhanced NP production and mitigated host toxicity. Notably, we demonstrated that B. subtilis can serve as a chassis for cyanobacterial NP BGC expression. Our results provide versatile expression platforms for probing BGC function and accelerating natural product discovery from diverse cyanobacterial and other bacterial lineages.

Multigene Family↗