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International Journal of Molecular... Dec 2023Statins have been used in the treatment of hyperlipidemia, both as monotherapy and in combination therapy. Natural fermentation processes of fungi such as spp., spp.,... (Review)
Review
Statins have been used in the treatment of hyperlipidemia, both as monotherapy and in combination therapy. Natural fermentation processes of fungi such as spp., spp., , and have given rise to natural statins. Compactin (mevastatin), the original naturally occurring statin, is the primary biotransformation substrate in the manufacturing process of marketed drugs. Statins are classified into natural, semi-synthetic derivatives of natural statins, and synthetic ones. Synthetic statins differ from natural statins in their structural composition, with the only common feature being the HMG-CoA-like moiety responsible for suppressing HMG-CoA reductase. Statins do not differ significantly regarding their pleiotropic and adverse effects, but their characteristics depend on their pharmacokinetic parameters and chemical properties. This paper focuses on describing the processes of obtaining natural statins, detailing the pharmacokinetics of available statins, divided into natural and synthetic, and indicating their pleiotropic effects.
Topics: Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacy; Fungi; Lovastatin
PubMed: 38203637
DOI: 10.3390/ijms25010466 -
Nature Microbiology Jul 2023Although the interaction between prokaryotic and eukaryotic microorganisms is crucial for the functioning of ecosystems, information about the processes driving...
Although the interaction between prokaryotic and eukaryotic microorganisms is crucial for the functioning of ecosystems, information about the processes driving microbial interactions within communities remains scarce. Here we show that arginine-derived polyketides (arginoketides) produced by Streptomyces species mediate cross-kingdom microbial interactions with fungi of the genera Aspergillus and Penicillium, and trigger the production of natural products. Arginoketides can be cyclic or linear, and a prominent example is azalomycin F produced by Streptomyces iranensis, which induces the cryptic orsellinic acid gene cluster in Aspergillus nidulans. Bacteria that synthesize arginoketides and fungi that decode and respond to this signal were co-isolated from the same soil sample. Genome analyses and a literature search indicate that arginoketide producers are found worldwide. Because, in addition to their direct impact, arginoketides induce a secondary wave of fungal natural products, they probably contribute to the wider structure and functioning of entire soil microbial communities.
Topics: Polyketides; Ecosystem; Soil; Streptomyces; Aspergillus nidulans; Biological Products
PubMed: 37322111
DOI: 10.1038/s41564-023-01382-2 -
Journal of Clinical Medicine Feb 2024The modern history of cholesterol-lowering drugs started in 1972 when Dr. Akira Endo identified an active compound (compactin) that inhibited cholesterol biosynthesis... (Review)
Review
The modern history of cholesterol-lowering drugs started in 1972 when Dr. Akira Endo identified an active compound (compactin) that inhibited cholesterol biosynthesis from the culture broth of blue-green mold ( Pen-51). Since 1987, statins have represented the milestone for the treatment of atherosclerotic cardiovascular disease. A new therapy for the treatment of hypercholesterolemia since the discovery of statins is ezetimibe, the first and only agent inhibiting intestinal cholesterol absorption. Ezetimibe was approved by the FDA in October 2002. A year later, the association between gain-of-function PCSK9 genetic mutations and hypercholesterolemia was reported, and this discovery opened a new era in lipid-lowering therapies. Monoclonal antibodies and small-interfering RNA approaches to reduce PCSK9 were developed and approved for clinical use in 2015 and 2022, respectively. Finally, the newly approved bempedoic acid, an oral adenosine triphosphate citrate lyase inhibitor that lowers LDL-C, is able to reduce major adverse cardiovascular events in both primary and secondary prevention. In the present narrative review, we summarize the pharmacological properties and the clinical efficacy of all these agents currently used for a tailored therapy of hypercholesterolemia in patients with atherosclerotic cardiovascular disease.
PubMed: 38398257
DOI: 10.3390/jcm13040943 -
Scientific Reports Nov 2023Microorganisms present in mosquitoes and their interactions are key factors affecting insect development. Among them, Wolbachia is closely associated with the host and... (Review)
Review
Microorganisms present in mosquitoes and their interactions are key factors affecting insect development. Among them, Wolbachia is closely associated with the host and affects several fitness parameters. In this study, the bacterial and fungal microbiota from two laboratory Culex quinquefasciatus isolines (wild type and tetracycline-cured) were characterized by metagenome amplicon sequencing of the ITS2 and 16S rRNA genes at different developmental stages and feeding conditions. We identified 572 bacterial and 61 fungal OTUs. Both isolines presented variable bacterial communities and different trends in the distribution of diversity among the groups. The lowest bacterial richness was detected in sugar-fed adults of the cured isoline, whereas fungal richness was highly reduced in blood-fed mosquitoes. Beta diversity analysis indicated that isolines are an important factor in the differentiation of mosquito bacterial communities. Considering composition, Penicillium was the dominant fungal genus, whereas Wolbachia dominance was inversely related to that of Enterobacteria (mainly Thorsellia and Serratia). This study provides a more complete overview of the mosquito microbiome, emphasizing specific highly abundant components that should be considered in microorganism manipulation approaches to control vector-borne diseases.
Topics: Animals; Aedes; Bacteria; Culex; Microbiota; Mosquito Vectors; RNA, Ribosomal, 16S; Wolbachia
PubMed: 37923779
DOI: 10.1038/s41598-023-46067-2 -
Toxins Jul 2023Mycotoxins are toxic secondary metabolites produced by filamentous fungi belonging, in particular, to the , , and genera [...].
Mycotoxins are toxic secondary metabolites produced by filamentous fungi belonging, in particular, to the , , and genera [...].
Topics: Mycotoxins; Food Microbiology; Fungi; Aspergillus; Edible Grain; Fusarium; Penicillium; Food Contamination
PubMed: 37505714
DOI: 10.3390/toxins15070445 -
Toxins Sep 2023Ochratoxins are the secondary metabolites of and , among which ochratoxin A (OTA) is the most toxic molecule. OTA is widely found in food and agricultural products. Due... (Review)
Review
Ochratoxins are the secondary metabolites of and , among which ochratoxin A (OTA) is the most toxic molecule. OTA is widely found in food and agricultural products. Due to its severe nephrotoxicity, immunotoxicity, neurotoxicity, and teratogenic mutagenesis, it is essential to develop effective, economical, and environmentally friendly methods for OTA decontamination and detoxification. This review mainly summarizes the application of technology in OTA prevention, removal, and detoxification from physical, chemical, and biological aspects, depending on the properties of OTA, and describes the advantages and disadvantages of each method from an objective perspective. Overall, biological methods have the greatest potential to degrade OTA. This review provides some ideas for searching for new strains and degrading enzymes.
Topics: Ochratoxins; Agriculture; Food; Mutagenesis
PubMed: 37755991
DOI: 10.3390/toxins15090565 -
Signal Transduction and Targeted Therapy Nov 2023The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infected a substantial proportion of Chinese population, and understanding...
The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.
Topics: Humans; COVID-19; SARS-CoV-2; Respiration, Artificial; Lung; Pneumonia; Microbiota; Bacteria
PubMed: 37949875
DOI: 10.1038/s41392-023-01684-1 -
ACS Omega Jan 2024The goal behind this work is to prepare, characterize, and study the antimicrobial behavior of zirconia (ZrO) nanoparticles (NPs). Various techniques, such as X-ray...
The goal behind this work is to prepare, characterize, and study the antimicrobial behavior of zirconia (ZrO) nanoparticles (NPs). Various techniques, such as X-ray diffraction (XRD), were used for studying the mineralogical structure and crystal size. The microstructure and chemical composition of the prepared particles were analyzed using a scanning electron microscope attached with an energy-dispersive X-ray analysis (EDAX) unit. The antagonistic ability against several Gram-negative and Gram-positive bacteria, including , and , was assessed using the well diffusion method. The results of XRD and scanning electron microscopy (SEM) analyses revealed that the prepared material exhibited the phase of zirconium nanoparticles with particle sizes ranging between 40 and 75 nm. The antimicrobial test results demonstrated that the inhibitory effect increased with the increase of concentration. The inhibitory effect was more pronounced against Gram-positive bacteria, as indicated by the larger size of the inhibitory zone. At a 9% dimethyl sulfoxide (DMSO) concentration, the inhibitory zone had a diameter of 3.50 mm for compared to a diameter of 3.40 mm for . The use of zirconium oxide nanoparticles reduced the diameter of the inhibitory zone when tested against at a 3% DMSO concentration (0.50 mm diameter) and against (0.40 mm diameter). Zirconia nanoparticles were also evaluated for their antifungal activity against several species, including , , and sp. The size of the inhibitory zone indicated the susceptibility of microorganisms to nanozirconium oxide, resulting in a stronger inhibition of sp. at a 100% DMSO concentration (4.50 mm diameter) compared to and (3.00 mm diameter). The results for sp. at a 3% DMSO concentration showed a diameter of the inhibitory zone of 0.90 mm, while for and , the diameter was 0.80 mm. Thus, our findings demonstrate that the zirconium oxide nanoparticles possess the capability to reduce the inhibition zone effectively for both bacterial and fungal activities.
PubMed: 38250396
DOI: 10.1021/acsomega.3c08580 -
Inflammatory Bowel Diseases Oct 2023Although gut fungi have been implicated in the immunopathogenesis of inflammatory bowel disease, the fungal microbiome has not been deeply explored across endohistologic...
BACKGROUND
Although gut fungi have been implicated in the immunopathogenesis of inflammatory bowel disease, the fungal microbiome has not been deeply explored across endohistologic activity and treatment exposure in ulcerative colitis.
METHODS
We analyzed data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry. We evaluated the fungal composition of fecal samples from 98 patients with ulcerative colitis across endoscopic activity (n = 43), endohistologic activity (n = 41), and biologic exposure (n = 82). Across all subgroups, we assessed fungal diversity and differential abundance of taxonomic groups.
RESULTS
We identified 500 unique fungal amplicon sequence variants across the cohort of 82 patients, dominated by phylum Ascomycota. Compared with endoscopic remission, patients with endoscopic activity had increased Saccharomyces (log2 fold change = 4.54; adjusted P < 5 × 10-5) and increased Candida (log2 fold change = 2.56; adjusted P < .03). After adjusting for age, sex, and biologic exposure among patients with endoscopic activity, Saccharomyces (log2 fold change = 7.76; adjusted P < 1 × 10-15) and Candida (log2 fold change = 7.28; adjusted P< 1 × 10-8) remained enriched during endoscopic activity compared with quiescence.
CONCLUSIONS
Endoscopic inflammation in ulcerative colitis is associated with an expansion of Saccharomyces and Candida compared with remission. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in ulcerative colitis should be evaluated.
Topics: Adult; Humans; Colitis, Ulcerative; Mycobiome; Prospective Studies; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Candida; Biological Products
PubMed: 37221272
DOI: 10.1093/ibd/izad082 -
PLoS Neglected Tropical Diseases Aug 2023Mycetoma is one of the six Neglected Tropical Diseases that are prevalent in Turkana County (northwest Kenya). The aim of the study was to estimate the prevalence of...
Mycetoma is one of the six Neglected Tropical Diseases that are prevalent in Turkana County (northwest Kenya). The aim of the study was to estimate the prevalence of mycetoma in the county, as well as to describe the main causative agents involved in the disease using methods affordable locally. Based on the data collected by the team of cooperative medicine Cirugia en Turkana (Surgery in Turkana), a specific study for mycetoma was started during the 16th humanitarian medicine campaign in February 2019. Patients with suspected mycetoma were studied at the Lodwar County Referral Hospital (LCRH). After informing the patient and getting their consent, the lesions were examined and sampled (mainly by biopsy) and clinical data were recorded. Samples were washed in sterile saline solution and cut in fragments. Some of these were inoculated on Sabouraud Dextrose Agar, Malt Extract Agar, and diluted Nutrient Agar plates. One fragment of each sample was used for DNA extraction. The DNA and the rest of the fragments of samples were kept at -20°C. All cultures were incubated at room temperature at the LCRH laboratory. The DNA obtained from clinical samples was submitted to PCR amplification of the ITS-5.8S and the V4-V5 16S rRNA gene region, for the detection and identification of fungi and bacteria respectively. From February 2019 till February 2022, 60 patients were studied. Most of them were men (43, 74,1%) between 13 and 78 y.o. (mean age 37). Half of the patients were herdsmen but, among women 40% (6) were housewives and 26.7% (4) charcoal burners. Lesions were mainly located at the feet (87.9%) and most of the patients (54; 93.1%) reported discharge of grains in the exudate, being 27 (46.6%) yellow or pale colored and 19 (32.8%) of them dark grains. Culture of clinical samples yielded 35 fungal and bacterial putative causative agents. Culture and molecular methods allowed the identification of a total of 21 causative agents of mycetoma (39.6% of cases studied). Most of them (17) corresponded to fungi causing eumycetoma (80.9%) being the most prevalent the genus Madurella (7; 41.2%), with two species involved (M. mycetomatis and M. fahalii), followed by Aspergillus (2; 11.8%). Other minority genera detected were Cladosporium, Fusarium, Acremonium, Penicillium, and Trichophyton (5.9% each of them). Actinobacteria were detected in 19.1% of samples, but only Streptomyces somaliensis was identified as a known agent of mycetoma, the rest being actinobacteria not previously described as causative agents of the disease, such as Cellulosimicrobium cellulans detected in two of the patients. Although Kenya is geographically located in the mycetoma belt, to our knowledge this is the first report on mycetoma in this country from 1973, and the first one for Turkana County.
Topics: Male; Humans; Female; Adult; Mycetoma; Kenya; Agar; RNA, Ribosomal, 16S; Polymerase Chain Reaction; Madurella
PubMed: 37578968
DOI: 10.1371/journal.pntd.0011327