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The International Journal of Behavioral... Feb 2024Knowledge regarding the health impacts of daily eating frequency (DEF) and nighttime fasting duration (NFD) on mortality is very limited.
BACKGROUND
Knowledge regarding the health impacts of daily eating frequency (DEF) and nighttime fasting duration (NFD) on mortality is very limited.
OBJECTIVE
This study aimed to examine whether DEF and NFD are associated with CVD and all-cause mortality.
METHODS
This was a prospective cohort study of a nationally representative sample from the United States, including 30,464 adults who participated in the National Health and Nutrition Examination Survey 2003-2014. Using 24-h dietary recall, DEF was assessed by the number of eating episodes, and NFD was calculated by the first and last eating time across a day. Death information was obtained from the National Death Index up to 2019. Weighted Cox proportional hazards regression models were used to assess survival relationships of DEF and NFD with mortality.
RESULTS
During 307,686 person-years of follow-up, 4560 deaths occurred, including 1824 CVD cases. After adjustment for confounders, compared to DEF at 4-6 times, participants whose DEF was less than 3 times had greater CVD [hazard-ratio (HR) = 1.33, 95% confidence-interval (CI): 1.06-1.67] and all-cause (HR = 1.16, 95% CI: 1.01-1.33) mortality risks. Furthermore, compared to NFD of 10 to 11 h, participants whose NFD was shorter than 10 h had HRs of 1.30 (95% CI: 1.08-1.55) for CVD mortality and 1.23 (95% CI: 1.08-1.39) for all-cause mortality. NFD longer than 14 h was also related to CVD mortality (HR = 1.37, 95% CI: 1.12-1.67) and all-cause mortality (HR = 1.36, 95% CI: 1.19-1.54). Similar results for the association of NFD and DEF with heart-specific and stroke-specific mortality were observed.
CONCLUSION
This study found that DEF less than 3 times and NFD shorter than 10 h or longer than 14 h were independently associated with greater cardiovascular and all-cause mortality.
Topics: Adult; Humans; United States; Cardiovascular Diseases; Nutrition Surveys; Prospective Studies; Feeding Behavior; Fasting; Carubicin
PubMed: 38409117
DOI: 10.1186/s12966-023-01556-5 -
The Journal of Antibiotics Jan 1984The absolute configurations of rubeomycins A and A1 (corresponding to carminomycins II and III) and rubeomycins B and B1 (corresponding to 4-hydroxybaumycinols A1 and...
The absolute configurations of rubeomycins A and A1 (corresponding to carminomycins II and III) and rubeomycins B and B1 (corresponding to 4-hydroxybaumycinols A1 and A2), except at the C-1" position, were determined by comparison of the optical rotations and other spectral data of rubeomycin derivatives with those of daunomycin and L-(+)-lactic acid.
Topics: Anthracyclines; Anti-Bacterial Agents; Carbohydrate Conformation; Carubicin; Daunorubicin; Gas Chromatography-Mass Spectrometry; Lactates; Lactic Acid; Models, Chemical; Naphthacenes; Optical Rotation
PubMed: 6698886
DOI: 10.7164/antibiotics.37.44 -
Malaria Journal Mar 2024Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy...
Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021.
BACKGROUND
Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021.
METHODS
A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1).
RESULTS
Sequencing success was ≥ 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%.
CONCLUSION
This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT.
Topics: Humans; Lumefantrine; Plasmodium falciparum; Antimalarials; Tanzania; Artemisinins; Artemether; Multidrug Resistance-Associated Proteins; Artemether, Lumefantrine Drug Combination; Malaria, Falciparum; Biomarkers; Drug Resistance; Protozoan Proteins; Carubicin
PubMed: 38461239
DOI: 10.1186/s12936-024-04896-0 -
British Journal of Cancer Feb 1999The effects of 4-demethoxydaunorubicin (idarubicin, IDA) and MX2, a new morpholino-anthracycline, on up-regulation of the MDR1 gene in the low-level multidrug resistant... (Comparative Study)
Comparative Study
The effects of 4-demethoxydaunorubicin (idarubicin, IDA) and MX2, a new morpholino-anthracycline, on up-regulation of the MDR1 gene in the low-level multidrug resistant (MDR) cell line CEM/A7R were compared at similar concentrations (IC10, IC50 and IC90) over a short time exposure (4 and 24 h). The chemosensitivity of each drug was determined by a 3-day cell growth inhibition assay. Compared with epirubicin (EPI), IDA and MX2 were 17- and eightfold more effective in the CEM/A7R line respectively. No cross-resistance to 5-FU was seen in the CEM/A7R line. Verapamil (5 microM) and PSC 833 (1 microM), which dramatically reversed resistance to EPI in the CEM/A7R line, had no sensitizing effect on the resistance of this line to MX2, but slightly decreased resistance to IDA. The sensitivity to 5-FU was unchanged by these modulators. The induction of MDR1 mRNA expression by IDA, MX2 and 5-FU was analysed by Northern blotting and semiquantitatively assessed by scanning Northern blots on a phosphorimager. The relative level of MDR1 expression was expressed as a ratio of MDR1 mRNA to the internal RNA control glyceraldehyde-3-phosphate dehydrogenase (GAPDH). IDA, MX2 and 5-FU differentially up-regulated MDR1 mRNA in the CEM/A7R line in a dose-dependent manner. Both IDA and MX2 induced MDR1 expression within 4 h. 5-FU up-regulated MDR1 expression only when drug exposure was prolonged to 24 h. Based on MRK 16 binding, flow cytometric analysis of P-glycoprotein (Pgp) expression paralleled the increase in MDR1 mRNA levels. For the three anthracyclines, the increase in MDR1 expression was stable in cells grown in the absence of drug for more than 3 weeks after drug treatment. The induction of MDR1 expression by 5-FU was transient, associated with a rapid decrease in the increased Pgp levels which returned to baseline 72 h after the removal of 5-FU. This study demonstrates that MDR1 expression can be induced by analogues of anthracyclines not pumped by Pgp, and that this induction appears to be stable despite a 3-week drug-free period.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Anthracyclines; Antibiotics, Antineoplastic; Carubicin; Cell Survival; Clone Cells; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Gene Expression Regulation, Neoplastic; Humans; Idarubicin; Kinetics; Leukemia, T-Cell; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 10070877
DOI: 10.1038/sj.bjc.6690133 -
British Journal of Cancer Apr 2005KRN 8602 (MX2) is a novel morpholino anthracycline derivative having the chemical structure 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. To... (Comparative Study)
Comparative Study
KRN 8602 (MX2) is a novel morpholino anthracycline derivative having the chemical structure 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. To investigate the mechanisms of resistance to MX2, we established an MX2-resistant phenotype (K562/MX2) of the human myelogeneous leukaemia cell line (K562/P), by continuously exposing a suspension culture to increasing concentrations of MX2. K562/MX2 cells were more resistant to MX2 than the parent cells, and also showed cross-resistance to etoposide and doxorubicin. Topoisomerase (Topo) IIalpha protein levels in K562/MX2 cells were lower of those in K562/P cells on immunoblot analysis and decreased expression of Topo IIalpha mRNA was seen in K562/MX2 cells. Topoisomerase II catalytic activity was also reduced in the nuclear extracts from K562/MX2 cells when compared with K562/P cells. Aberrant methylated CpG of Topo IIalpha gene was observed in K562/MX2 cells when compared with the parent line on methylation-specific restriction enzyme analysis. To overcome the drug resistance to MX2 and etoposide, we investigated treatment with 5-Aza-2'-deoxycytidine (5AZ), which is a demethylating agent, in K562/MX2 cells. 5-Aza-2'-deoxycytidine treatment increased Topo IIalpha mRNA expression in K562/MX2 cells, but not in K562/P cells, and increased the cytotoxicity of MX2 and etoposide. Methylated CpG was decreased in K562/MX2 cells after 5AZ treatment. We concluded that the mechanism of drug resistance to MX2 and etoposide in K562/MX2 cells might be the combination of decreased expression of Topo IIalpha gene and increased methylation, and that 5AZ could prove to be a novel treatment for etoposide-resistant cell lines, such as K562/MX2.
Topics: Antigens, Neoplasm; Antineoplastic Agents; Azacitidine; Blotting, Northern; Carubicin; Cell Line, Tumor; CpG Islands; DNA Methylation; DNA Topoisomerases, Type II; DNA-Binding Proteins; Decitabine; Drug Resistance, Neoplasm; Etoposide; Flow Cytometry; Humans; Immunoblotting; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 15798770
DOI: 10.1038/sj.bjc.6602498 -
Cancer Research Jan 2011Clear cell renal cell carcinoma (CCRCC) evolves due to mutations in the Von Hippel-Lindau (VHL) tumor suppressor gene. Although the loss of VHL enables survival and...
Clear cell renal cell carcinoma (CCRCC) evolves due to mutations in the Von Hippel-Lindau (VHL) tumor suppressor gene. Although the loss of VHL enables survival and proliferation of CCRCC cells, it is also expected to introduce vulnerabilities that may be exploited for therapeutics discovery. To this end, we developed a high-throughput screen to identify small molecules derived from plants, microorganisms, and marine organisms to which CCRCC cells are sensitive. Screening over 8,000 compounds using this approach, we report here the identification of the microbially derived compound carminomycin I (CA) as an effective inhibitor of VHL-defective (VHL(-/-)) CCRCC cell proliferation. CA also induced apoptosis in CCRCC cells by a mechanism independent of p53 or hypoxia-inducible factor 2. We found that P-glycoprotein (P-gp) sequestered CA within the Golgi complex. Interestingly, Golgi sequestration was critical for the antiproliferative effects of CA and P-gp inhibitors abrogated this activity. Furthermore, CA induced cleavage of the Golgi protein p115 and the translocation of its C-terminal fragment to the nucleus. Finally, examination of the activity of the VHL-interacting Golgi protein, endoplasmic reticulum-Golgi intermediate compartment, ERGIC-53 showed that VHL could mediate protection from CA in CCRCC cells. Our natural product-based screening approach has revealed the P-gp-mediated localization of anticancer compounds within the Golgi in CCRCC cells as a potential strategy of targeting VHL-deficient CCRCC cells.
Topics: Antibiotics, Antineoplastic; Apoptosis; Base Sequence; Blotting, Western; Carcinoma, Renal Cell; Carubicin; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Golgi Apparatus; Humans; Immunohistochemistry; Kidney Neoplasms; RNA Interference; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 21199801
DOI: 10.1158/0008-5472.CAN-10-0757 -
The Journal of Antibiotics Mar 1979The conversion of epsilon-rhodomycinone to its 11-methyl ether via selective hydrolysis of the 4,6,7,11-tetraacetate is described. This series of reactions was used as a...
The conversion of epsilon-rhodomycinone to its 11-methyl ether via selective hydrolysis of the 4,6,7,11-tetraacetate is described. This series of reactions was used as a model for the conversion of carminomycin to its 11-methyl ether. The anti-tumor activity of the latter compound was less than that of both carminomycin and its 4-methyl ether (daunomycin).
Topics: Anti-Bacterial Agents; Antibiotics, Antineoplastic; Carubicin; Chemical Phenomena; Chemistry; Magnetic Resonance Spectroscopy; Methylation; Naphthacenes
PubMed: 457585
DOI: 10.7164/antibiotics.32.247 -
The Journal of Antibiotics Feb 2004The new hydrophilic derivatives of 14-hydroxycarminomycin were obtained using 13-dimethyl ketal of 14-bromocarminomycin (6) as the starting compound. The reductive...
The new hydrophilic derivatives of 14-hydroxycarminomycin were obtained using 13-dimethyl ketal of 14-bromocarminomycin (6) as the starting compound. The reductive alkylation of 6 with melibiose or D-galactose followed by hydrolysis of the corresponding intermediate bromoketals 9 and 11 produced 3'-N-[-alpha-D-(galactopyranosyl-(1 --> 6)-O-D-1-desoxyglucit-1-yl]-14-hydroxycarminomycin (10) and 3'-N-(1-desoxy-D-galactit-1-yl)-14-hydroxycarminomycin (12), respectively. These novel derivatives 10 and 12 were less toxic than carminomycin or 14-hydroxycarminomycin for leukemia (K562) and breast carcinoma (MCF-7) cells. Importantly, carminomycin, 14-hydroxycarminomycin and compounds 10 and 12 were similarly active for wild type cells and their multidrug resistant (MDR) sublines, K562i/S9 and MCF-7Dox.
Topics: ATP Binding Cassette Transporter, Subfamily B; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Cell Survival; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Genes, MDR; Humans; Leukemia; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 15112963
DOI: 10.7164/antibiotics.57.143 -
Journal of Bacteriology Apr 1997We recently determined the function of the gene product of Streptomyces sp. strain C5 doxA, a cytochrome P-450-like protein, to be daunorubicin C-14 hydroxylase (M. L....
We recently determined the function of the gene product of Streptomyces sp. strain C5 doxA, a cytochrome P-450-like protein, to be daunorubicin C-14 hydroxylase (M. L. Dickens and W. R. Strohl, J. Bacteriol. 178: 3389-3395, 1996). In the present study, we show that DoxA also catalyzes the hydroxylation of 13-deoxycarminomycin and 13-deoxydaunorubicin to 13-dihydrocarminomycin and 13-dihydrodaunorubicin, respectively, as well as oxidizing the 13-dihydro-anthracyclines to their respective 13-keto forms. The Streptomyces sp. strain C5 dauP gene product also was shown unequivocally to remove the carbomethoxy group of the epsilon-rhodomycinone-glycoside (rhodomycin D) to form 10-carboxy-13-deoxycarminomycin. Additionally, Streptomyces sp. strain C5 DauK was found to methylate the anthracyclines rhodomycin D, 10-carboxy-13-deoxycarminomycin, and 13-deoxy-carminomycin, at the 4-hydroxyl position, indicating a broader substrate specificity than was previously known. The products of Streptomyces sp. strain C5 doxA, dauK, and dauP were sufficient and necessary to confer on Streptomyces lividans TK24 the ability to convert rhodomycin D, the first glycoside in daunorubicin and doxorubicin biosynthesis, to doxorubicin.
Topics: Anthracyclines; Bacterial Proteins; Carubicin; Cytochrome P-450 Enzyme System; Daunorubicin; Doxorubicin; Esterases; Genes, Bacterial; Hydroxylation; Methyltransferases; Models, Chemical; Multigene Family; Recombinant Fusion Proteins; Restriction Mapping; Streptomyces; Substrate Specificity
PubMed: 9098063
DOI: 10.1128/jb.179.8.2641-2650.1997 -
Japanese Journal of Cancer Research :... Aug 1990The antitumor activity and pharmacokinetics of (7R, 8S, 10S)-10-((3-deamino- 3-(4-morpholino)-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-8- ethyl-...
The antitumor activity and pharmacokinetics of (7R, 8S, 10S)-10-((3-deamino- 3-(4-morpholino)-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-8- ethyl- 7,8,9,10-tetrahydro-1,6,7,8,11-pentahydroxy-5,12-naphthacenedione hydrochloride (KRN8602) were evaluated using five human breast carcinoma xenografts in nude mice. The maximum non-toxic dose of KRN8602 was 2 mg/kg by q4d x 3 intraperitoneal and peroral administration. KRN8602 showed significant antitumor activity against MX-1, which is less sensitive to adriamycin, with the chemotherapeutic indices of 13.0 for po administration and 9.5 for ip injection. Although KRN8602 also inhibited the growth of T-61 significantly, the antitumor activity of this agent against the other three breast carcinoma xenografts was limited. To elucidate this discrepancy, pharmacokinetic analysis and MTT assay were conducted using the KRN8602-sensitive MX-1 and KRN8602-insensitive R-27. While no differences were observed in the area under the curve and the peak concentration of KRN8602 for each tumor, a difference in the sensitivity of the tumor strains was obvious in MTT assay. The efficacy of this agent seemed to depend on the sensitivity of each type of tumor cell rather than the concentration of agent in tumor tissues. If it were possible to select patients with sensitive tumor cells to this agent by the MTT assay, the phase II trial might be completed within a short period by reducing the number of studied patients.
Topics: Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Daunorubicin; Drug Administration Schedule; Drug Screening Assays, Antitumor; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Specific Pathogen-Free Organisms
PubMed: 2144515
DOI: 10.1111/j.1349-7006.1990.tb02652.x