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Epidemiology and Infection Apr 2024This paper retrospectively analysed the prevalence of macrolide-resistant (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145...
This paper retrospectively analysed the prevalence of macrolide-resistant (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 μg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 μg/ml and ≤ 1 μg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.
Topics: Mycoplasma pneumoniae; Humans; China; Macrolides; Retrospective Studies; Child; Anti-Bacterial Agents; Drug Resistance, Bacterial; Child, Preschool; Adolescent; Adult; Female; Male; Pneumonia, Mycoplasma; Middle Aged; Young Adult; Microbial Sensitivity Tests; Aged; Infant; Prevalence; RNA, Ribosomal, 23S; Aged, 80 and over
PubMed: 38634450
DOI: 10.1017/S0950268824000323 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Aug 2023Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The... (Review)
Review
Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.
Topics: Tacrolimus; Immunosuppressive Agents; Fermentation; Macrolides; Anti-Bacterial Agents
PubMed: 37622350
DOI: 10.13345/j.cjb.220994 -
Journal of Neuroscience Research Jan 2024Ivermectin (IVM), a semi-synthetic macrolide parasiticide, has demonstrated considerable effectiveness in combating internal and external parasites, particularly... (Review)
Review
Ivermectin (IVM), a semi-synthetic macrolide parasiticide, has demonstrated considerable effectiveness in combating internal and external parasites, particularly nematodes and arthropods. Its remarkable ability to control parasites has earned it significant recognition, culminating in Satoshi Omura and William C. Campbell's receipt of the 2015 Nobel Prize in Physiology or Medicine for their contributions to the development of IVM. In recent years, investigations have revealed that IVM possesses antitumor properties. It can suppress the growth of various cancer cells, including glioma, through a multitude of mechanisms such as selective targeting of tumor-specific proteins, inducing programmed cell death, and modulation of tumor-related signaling pathways. Hence, IVM holds tremendous potential as a novel anticancer drug. This review seeks to provide an overview of the underlying mechanisms that enable IVM's capacity to suppress glioma. Furthermore, it aims to elucidate the challenges and prospects associated with utilizing IVM as a new anticancer agent.
Topics: Humans; Ivermectin; Glioma; Antineoplastic Agents; Nobel Prize; Apoptosis
PubMed: 37814994
DOI: 10.1002/jnr.25254 -
Frontiers in Cellular and Infection... 2023With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as , (including , ), , , and , have shown varying... (Review)
Review
With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as , (including , ), , , and , have shown varying degrees of drug resistance. In order to provide such problem and related evidence for rational use of antibiotics in clinic, we reviewed the drug resistance of common bacteria to macrolides in children recent 20 years.
Topics: Drug Resistance, Bacterial; Macrolides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Humans; Child; China
PubMed: 37637457
DOI: 10.3389/fcimb.2023.1181633 -
The Medical Clinics of North America Mar 2024Mycoplasma genitalium (MG) is an emerging sexually transmitted infection, which appears to be a cause of urethritis and cervicitis and has been associated with pelvic... (Review)
Review
Mycoplasma genitalium (MG) is an emerging sexually transmitted infection, which appears to be a cause of urethritis and cervicitis and has been associated with pelvic inflammatory disease (PID), epididymitis, proctitis, infertility, complications during pregnancy, and human immunodeficiency virus (HIV) transmission. Three Food and Drug Administration (FDA) approved tests are available. Testing should be focused to avoid inappropriate antibiotic use. The Center of Disease Control and Prevention (CDC) guidelines recommend testing for persistent male urethritis, cervicitis, and proctitis and state that testing should be considered in cases of PID. Testing is also recommended for sexual contacts of patients with MG. Testing is not recommended in asymptomatic patients, including pregnant patients, who do not have a history of MG exposure. Although resistance-guided therapy is recommended, there are currently no FDA approved tests for MG macrolide resistance, and tests are not widely available in the United States. The CDC recommends 2-step treatment with doxycycline followed by azithromycin or moxifloxacin. Moxifloxacin is recommended if resistance testing is unavailable or testing demonstrates macrolide resistance..
Topics: Pregnancy; Female; Humans; Male; Anti-Bacterial Agents; Urethritis; Mycoplasma genitalium; Moxifloxacin; Uterine Cervicitis; Macrolides; Mycoplasma Infections; Drug Resistance, Bacterial; Pelvic Inflammatory Disease; Proctitis; Primary Health Care
PubMed: 38331481
DOI: 10.1016/j.mcna.2023.07.004 -
The Lancet. Healthy Longevity Feb 2024Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its... (Review)
Review
Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies. Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with ageing-related diseases. Overall, no significant effects on the endocrine, muscular, or neurological systems were found. The effects of rapamycin or its derivatives on the respiratory, digestive, renal, and reproductive systems were not assessed. No serious adverse events attributed to rapamycin and its derivatives were reported in healthy individuals; however, there were increased numbers of infections and increases in total cholesterol, LDL cholesterol, and triglycerides in individuals with ageing-related diseases. Future studies should assess the remaining unexamined systems and test the effects of long-term exposure to rapamycin and its derivatives.
Topics: Humans; Aging; Sirolimus
PubMed: 38310895
DOI: 10.1016/S2666-7568(23)00258-1 -
Investigative Ophthalmology & Visual... Jul 2023The mechanism underlying axial elongation during myopia progression remains unknown. Epidermal growth factor receptor (EGFR) signaling is associated with axial...
PURPOSE
The mechanism underlying axial elongation during myopia progression remains unknown. Epidermal growth factor receptor (EGFR) signaling is associated with axial elongation. We explored whether mammalian target of rapamycin complex 1 (mTORC1) signaling acts as the downstream pathway of EGFR and participates in negative lens-induced axial elongation (NLIAE).
METHODS
Three-week-old male pigmented guinea pigs underwent binocular NLIAE. (1) To investigate whether EGFR is the upstream regulator of mTORC1, an EGFR inhibitor (20 µg erlotinib) was intravitreally injected once a week for three weeks. (2) To assess the effect of mTORC1 inhibition on NLIAE, an mTORC1 inhibitor (2 µg, 10 µg, and 20 µg everolimus) was intravitreally injected once a week for three weeks. (3) To explore the long-term effect of mTORC1 overactivation on axial elongation, an mTORC1 agonist (4 µg MHY1485) was intravitreally injected once a week for three months. Biometric measurements included axial length and choroidal thickness were performed.
RESULTS
Compared with the guinea pigs without NLIAE, NLIAE was associated with activation of mTORC1 signaling, which was suppressed by intravitreal erlotinib injection. Intravitreally injected everolimus suppressed NLIAE-induced axial elongation, mTORC1 activation, choroidal thinning, and hypoxia-inducible factor-1α expression in the sclera. Immunofluorescence revealed that the retinal pigment epithelium was the primary location of mTORC1 activation during NLIAE. Combining NLIAE and MHY1485 intravitreal injections significantly promoted axial elongation, choroidal thinning, and peripapillary choroidal atrophy.
CONCLUSIONS
The mTORC1 signaling is associated with increased axial elongation, as in NLIAE, raising the possibility of inhibiting mTORC1 as a novel treatment for slowing myopia progression.
Topics: Male; Animals; Guinea Pigs; Erlotinib Hydrochloride; Everolimus; Myopia; Intravitreal Injections; ErbB Receptors; Mammals
PubMed: 37466949
DOI: 10.1167/iovs.64.10.24 -
Antimicrobial Agents and Chemotherapy Nov 2023Rifampicin is recommended for the treatment of complex pulmonary disease alongside azithromycin and ethambutol. We evaluated the azithromycin-ethambutol backbone with...
Rifampicin is recommended for the treatment of complex pulmonary disease alongside azithromycin and ethambutol. We evaluated the azithromycin-ethambutol backbone with and without rifampicin in an intracellular hollow fiber model and performed RNA sequencing to study the differences in adaptation. In an hollow fiber experiment, we simulated epithelial lining fluid pharmacokinetic profiles of the recommended 3-drug (rifampicin, ethambutol, and azithromycin) or a 2-drug (ethambutol and azithromycin) treatment. THP-1 cells infected with ATCC700898 were exposed to these regimens for 21 days. We determined intra- and extra-cellular bacterial load- and THP-1 cell densities on days 0, 3, 7, 14, and 21, alongside RNA sequencing. The emergence of macrolide resistance was studied by inoculating intra- and extra-cellular fractions of azithromycin-containing Middlebrook 7H10 agar plates. Complete pharmacokinetic profiles were determined at days 0 and 21. Both therapies maintained stasis of both intra- and extra-cellular bacterial populations for 3 days, whilst regrowth coinciding with the emergence of a macrolide-resistant subpopulation was seen after 7 days. THP-1 cell density remained static. Similar transcriptional profiles were observed for both therapies that were minimally influenced by exposure duration. Transcriptional response was slightly larger during 2-drug treatment. Rifampicin did not add to the antimycobacterial effect to the 2-drug therapy or suppression of emergence resistance. RNA transcription was not greatly altered by the addition of rifampicin, which may be due to strong transcriptional influence of azithromycin and host cells. This questions the role of rifampicin in the currently recommended therapy. These findings should be confirmed in clinical trials.
Topics: Humans; Rifampin; Mycobacterium avium; Anti-Bacterial Agents; Ethambutol; Azithromycin; Macrolides; Drug Resistance, Bacterial; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Lung Diseases
PubMed: 37877693
DOI: 10.1128/aac.00874-23 -
Revue Medicale Suisse Apr 2024
Topics: Humans; Macrolides; Anti-Bacterial Agents; Community-Acquired Infections; Pneumonia
PubMed: 38568069
DOI: 10.53738/REVMED.2024.20.868.727 -
Organic Letters Nov 2023A convergent route for the asymmetric total synthesis of antibacterial macrolide sorangiolide A has been developed for the first time. The key feature of this synthesis...
A convergent route for the asymmetric total synthesis of antibacterial macrolide sorangiolide A has been developed for the first time. The key feature of this synthesis includes Krische iridium-catalyzed -diastereoselective carbonyl crotylation, Crimmins acetate aldol, Yamaguchi esterification, Julia-Kocienski olefination, Horner-Wadsworth-Emmons olefination, and ring-closing metathesis. The origin of the low intensity of the C{H} NMR signals of the C1 and C2 centers of the natural product has been investigated, disclosing possible forms of existence for the natural product in the solution phase.
Topics: Macrolides; Stereoisomerism; Esterification; Anti-Bacterial Agents; Biological Products; Molecular Structure
PubMed: 37856450
DOI: 10.1021/acs.orglett.3c03066