BMC Complement Med Ther. 2024 Feb 15;24(1):89. doi: 10.1186/s12906-024-04378-5.

ABSTRACT

BACKGROUND: Evening primrose oil (EPO), extracted from the seeds of Oenothera biennis, has gained attention for its therapeutic effects in various inflammatory conditions.

METHOD: We performed a systematic search in multiple databases and defined the inclusion criteria based on the following PICOs: P: Patients with a form of inflammatory condition, I: EPO, C: Placebo or other therapeutic interventions, O: changes in inflammatory markers or patients' symptoms; S: randomized controlled trials. The quality of the RCTs was evaluated using Cochrane's RoB tool.

RESULTS: Several conditions were investigated in the literature. In rheumatoid arthritis, mixed results were observed, with some studies reporting significant improvements in symptoms while others found no significant impact. EPO showed some results in diabetes mellitus, atopic eczema, menopausal hot flashes, and mastalgia. However, it did not demonstrate effectiveness in chronic hand dermatitis, tardive dyskinesia, psoriatic arthritis, cystic fibrosis, hepatitis B, premenstrual syndrome, contact lens-associated dry eyes, acne vulgaris, breast cyst, pre-eclampsia, psoriasis, or primary Sjogren's syndrome. Some results were reported from multiple sclerosis after EPO consumption. Studies in healthy volunteers indicated no significant effect of EPO on epidermal atrophy, nevertheless, positive effects on the skin regarding hydration and barrier function were achieved.

CONCLUSION: Some evidence regarding the potential benefits of EPO in inflammatory disorders were reported however caution is due to the limitations of the current survey. Overall, contemporary literature is highly heterogeneous and fails to provide strong recommendations regarding the efficacy of EPO on inflammatory disorders. Further high-quality studies are necessitated to draw more definite conclusions and establish O. biennis oil effectiveness as an assuring treatment option in alleviating inflammatory conditions.

PMID:38360611 | DOI:10.1186/s12906-024-04378-5

J Cyst Fibros. 2024 Feb 14:S1569-1993(24)00015-8. doi: 10.1016/j.jcf.2024.02.001. Online ahead of print.

ABSTRACT

BACKGROUND: Sweat chloride (SC) concentrations in people with cystic fibrosis (PwCF) reflect relative CF transmembrane conductance regulator (CFTR) protein function, the primary CF defect. Populations with greater SC concentrations tend to have lesser CFTR function and more severe disease courses. CFTR modulator treatment can improve CFTR function within specific CF genotypes and is commonly associated with reduced SC concentration. However, SC concentrations do not necessarily fall to concentrations seen in the unaffected population, suggesting potential for better CFTR treatment outcomes. We characterized post-modulator SC concentration variability among CHEC-SC study participants by genotype and modulator.

METHODS: PwCF receiving commercially approved modulators for ≥90 days were enrolled for a single SC measurement. Clinical data were obtained from chart review and the CF Foundation Patient Registry (CFFPR). Variability of post-modulator SC concentrations was assessed by cumulative SC concentration frequencies.

RESULTS: Post-modulator SC concentrations (n = 3787) were collected from 3131 PwCF; most (n = 1769, 47 %) were collected after elexacaftor/tezacaftor/ivacaftor (ETI) treatment. Modulator use was associated with lower SC distributions, with post-ETI concentrations the lowest on average. Most post-ETI SC concentrations were <60 mmol/L (79 %); 26 % were <30 mmol/L. Post-ETI distributions varied by genotype. All genotypes containing at least one F508del allele had individuals with post-ETI SC ≥60 mmol/L, with the largest proportion being F508del/minimal function (31 %).

CONCLUSIONS: Post-modulator SC concentration heterogeneity was observed among all genotypes and modulators, including ETI. The presence of PwCF with post-modulator SC concentrations within the CF diagnostic range suggests room for additional treatment-associated CFTR restoration in this population.

PMID:38360461 | DOI:10.1016/j.jcf.2024.02.001

J Cyst Fibros. 2024 Feb 14:S1569-1993(23)01683-1. doi: 10.1016/j.jcf.2023.11.012. Online ahead of print.

ABSTRACT

BACKGROUND: Prescribers have an increasing range of inhaled antimicrobial formulations to choose from when prescribing both eradication and chronic suppression regimens in cystic fibrosis (CF). This study aimed to investigate the decision-making process behind prescribing of inhaled antimicrobials for Pseudomonas aeruginosa infections.

METHODS: A questionnaire was developed using Microsoft Forms and then forwarded to 57 Principal Investigators (PIs), at each of the CF centres within the European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN). Data collection occurred between November 2021 and February 2022.

RESULTS: The response rate was 90 % (n = 51/57 PIs), with at least 50 % of CF centers in each of the 17 countries represented in the ECFS-CTN. Physicians used a median of eight factors in their decision-making process with delivery formulations (92.2 %), adherence history (84.3 %), and antibiotic side-effect profile (76.5 %) often selected. Nebulised tobramycin or colistin were frequently selected as the inhaled antimicrobial in first-line eradication (n = 45, 88.2 %) and chronic suppression regimens (n = 42, 82.4 %). Combination regimens were more often chosen in eradication (first-line: n = 35, 68.6 %, second-line: n = 34, 66.7 %) and later chronic suppression regimens (third-line: n = 27, 52.9 %) than monotherapy. For pwCF also prescribed CFTR modulator therapies, most PIs did not alter inhaled antimicrobial regimens (n = 40, 78.4 %), with few pwCF (n = 18, 35.3 %) or PIs (n = 10, 19.6 %) deciding to stop inhaled antimicrobials.

CONCLUSIONS: The inhaled antimicrobial prescribing decision-making process is multifactorial. Nebulised tobramycin or colistin are often used in initial eradication and chronic suppression regimens. To date, CFTR modulator therapy has had a limited impact on the prescribing of inhaled antimicrobial regimens.

PMID:38360460 | DOI:10.1016/j.jcf.2023.11.012

JCI Insight. 2024 Feb 15:e165826. doi: 10.1172/jci.insight.165826. Online ahead of print.

ABSTRACT

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene lead to cystic fibrosis (CF), a life-threating autosomal recessive genetic disease. While recently approved Trikafta dramatically ameliorates CF lung diseases, there is still a lack of effective medicine to treat CF-associated liver disease (CFLD). To address this medical need, we used a recently established CF rabbit model to test if Sotagliflozin, a Sodium-Glucose cotransporter 1 and 2 (SGLT1/2) inhibitor drug that is approved to treat diabetes, can be repurposed to treat CFLD. Sotagliflozin treatment led to systemic benefits to CF rabbits, evidenced by increased appetite and weight gain as well as prolonged lifespan. For CF liver related phenotypes, the animals benefited from normalized blood chemistry and bile acid parameters. Further, Sotagliflozin alleviated non-alcoholic steatohepatitis (NASH)-like phenotypes including liver fibrosis. Intriguingly, Sotagliflozin treatment markedly reduced the otherwise elevated endoplasmic reticulum (ER) stress responses in the liver and other affected organs of CF rabbits. In summary, our work demonstrates that Sotagliflozin attenuates liver disorders in CF rabbits, and merits Sotagliflozin as a potential drug to treat CFLD.

PMID:38358827 | DOI:10.1172/jci.insight.165826

Am J Respir Crit Care Med. 2024 Feb 15. doi: 10.1164/rccm.202401-0181ED. Online ahead of print.

NO ABSTRACT

PMID:38358817 | DOI:10.1164/rccm.202401-0181ED

Pediatr Pulmonol. 2024 Feb 15. doi: 10.1002/ppul.26924. Online ahead of print.

NO ABSTRACT

PMID:38358024 | DOI:10.1002/ppul.26924

Med J Aust. 2024 Feb 15. doi: 10.5694/mja2.52233. Online ahead of print.

NO ABSTRACT

PMID:38357991 | DOI:10.5694/mja2.52233

Front Microbiol. 2024 Jan 31;15:1341179. doi: 10.3389/fmicb.2024.1341179. eCollection 2024.

ABSTRACT

The principal pathogen responsible for chronic urinary tract infections, immunocompromised hosts, and cystic fibrosis patients is Pseudomonas aeruginosa, which is difficult to eradicate. Due to the extensive use of antibiotics, multidrug-resistant P. aeruginosa has evolved, complicating clinical therapy. Therefore, a rapid and efficient approach for detecting P. aeruginosa strains and their resistance genes is necessary for early clinical diagnosis and appropriate treatment. This study combines recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats-association protein 13a (CRISPR-Cas13a) to establish a one-tube and two-step reaction systems for detecting the mexX gene in P. aeruginosa. The test times for one-tube and two-step RPA-Cas13a methods were 5 and 40 min (including a 30 min RPA amplification reaction), respectively. Both methods outperform Quantitative Real-time Polymerase Chain Reactions (qRT-PCR) and traditional PCR. The limit of detection (LoD) of P. aeruginosa genome in one-tube and two-step RPA-Cas13a is 10 aM and 1 aM, respectively. Meanwhile, the designed primers have a high specificity for P. aeruginosa mexX gene. These two methods were also verified with actual samples isolated from industrial settings and demonstrated great accuracy. Furthermore, the results of the two-step RPA-Cas13a assay could also be visualized using a commercial lateral flow dipstick with a LoD of 10 fM, which is a useful adjunt to the gold-standard qRT-PCR assay in field detection. Taken together, the procedure developed in this study using RPA and CRISPR-Cas13a provides a simple and fast way for detecting resistance genes.

PMID:38357344 | PMC:PMC10864651 | DOI:10.3389/fmicb.2024.1341179

North Clin Istanb. 2024 Jan 29;11(1):66-71. doi: 10.14744/nci.2023.25874. eCollection 2024.

ABSTRACT

OBJECTIVE: Herein, the results of the cases, who underwent surgical repair with or without ventral abdomino-rectosigmoidopexy through tube sigmoidostomy combined with Ekehorn's rectopexy due to recurrent rectal prolapse, were discussed.

METHODS: The demographic characteristics, surgical technique, and results of children who were operated in the department of Pediatric Surgery for rectal prolapse between 2004 and 2022 were retrospectively analyzed.

RESULTS: In 18 years, six pediatric cases (2 females [33%] and 4 males [67%]) were operated for persistent rectal prolapse. The mean operative age of the patients was 7.5 years (2.1-17), and all had severe rectal prolapse. Some of these patients were followed up in other centers and their rectal prolapse continued despite diet changes, toilet behavior training, and the treatment of sclerosing agents. Rectal trimming was applied to one of the first two patients who were operated for anal atresia and recurrence did not occur. In the second case who underwent laparoscopic colon pull-through, Ekehorn rectopexy was performed alone and no recurrence was observed also in this case. Considering that rectosigmoid colon adhesions formed on the anterior abdominal wall due to colostomy opening-closing may provide ventral sigmoidopexy, it was decided to offer the option of applying both methods together. Three of the next four cases were diagnosed with cystic fibrosis. All four underwent ventral abdomino-rectosigmoidopexy through tube sigmoidostomy combined with Ekehorn's rectopexy. Ekehorn's butterfly sutures were removed on 15th day and Foley catheters on 21st day. Three cases with cystic fibrosis were uneventful. However, a 14-year-old girl with a history of sexual abuse relapsed 6 months later.

CONCLUSION: Ventral abdomino-rectosigmoidopexy through tube sigmoidostomy combined with Ekehorn's rectopexy is a successful and unique method in terms of providing intestinal fixation. It may be the primary option for definitive surgical treatment of persistent rectal prolapse.

PMID:38357321 | PMC:PMC10861431 | DOI:10.14744/nci.2023.25874

ACS Pharmacol Transl Sci. 2024 Jan 25;7(2):533-543. doi: 10.1021/acsptsci.3c00354. eCollection 2024 Feb 9.

ABSTRACT

Pseudomonas aeruginosa is a notorious opportunistic pathogen associated with chronic biofilm-related infections, posing a significant challenge to effective treatment strategies. Quorum sensing (QS) and biofilm formation are critical virulence factors employed by P. aeruginosa, contributing to its pathogenicity and antibiotic resistance. Other than the homoserine-based QS systems, P. aeruginosa also possesses the quinolone-based Pseudomonas quinolone signal (PQS) QS signaling. Synthesis of the PQS signaling molecule is achieved by the pqsABCDEH operon, whereas the PQS signaling response was mediated by the PqsR receptor. In this study, we report the discovery of a novel natural compound, Juglone, with potent inhibitory effects on pqs QS and biofilm formation in P. aeruginosa. Through an extensive screening of natural compounds from diverse sources, we identified Juglone, a natural compound from walnut, as a promising candidate. We showed that Juglone could inhibit PqsR and the molecular docking results revealed that Juglone could potentially bind to the PqsR active site. Furthermore, Juglone could inhibit pqs-regulated virulence factors, such as pyocyanin and the PQS QS signaling molecule. Juglone could also significantly reduce both the quantity and quality of P. aeruginosa biofilms. Notably, this compound exhibited minimal cytotoxicity toward mammalian cells, suggesting its potential safety for therapeutic applications. To explore the clinical relevance of Juglone, we investigated its combinatorial effects with colistin, a commonly used antibiotic against P. aeruginosa infections. The Juglone-colistin combinatorial treatment could eliminate biofilms formed by wild-type P. aeruginosa PAO1 and its clinical isolates collected from cystic fibrosis patients. The Juglone-colistin combinatorial therapy dramatically improved colistin efficacy and reduced inflammation in a wound infection model, indicating its potential for clinical utility. In conclusion, the discovery of Juglone provides insights into the development of innovative antivirulence therapeutic strategies to combat P. aeruginosa biofilm-associated infections.

PMID:38357290 | PMC:PMC10863437 | DOI:10.1021/acsptsci.3c00354

Heliyon. 2024 Feb 1;10(3):e25241. doi: 10.1016/j.heliyon.2024.e25241. eCollection 2024 Feb 15.

ABSTRACT

Cystic Fibrosis (CF) is an autosomal recessive disease characterized by the production of thick and viscous mucus progressively affecting various organs and systems, with recurrent respiratory infections. The aim of this study was to learn about the oral health characteristics in CF patients.

METHODOLOGY: Data, such as sociodemographic, general and oral health, were collected from the medical records of CF patients aged 0 to 18 years old. The number of patients with tooth decay, prevalence of developmental defects of enamel (DDE), classification of dental occlusion, sialometry, salivary pH and oral microbial profile and respiratory secretions evaluations were recorded.

RESULTS: Most patients had pancreatic insufficiency (84.2%), malnutrition (60%), respiratory problems (75.4%) and genotyping of the F508del (66.7%). Regarding the medications used, 96.5% used vitamins and electrolyte replacement, 84,02% used pancreatic enzymes, 64.9% used dornase alfa and 47% were using antibiotics. The percentage of patients with tooth decay was 19.3%, 47% had DDE, low salivary flow and basic salivary pH. The most prevalent microorganisms found on tongue biofilm and respiratory secretions were SA and PA. There was a positive association between the presence of bacteria and fungi found on both the tongue and respiratory secretions. The presence of fungi on the tongue biofilm was significantly associated with the use of antibiotics.

CONCLUSIONS: These findings underscore the importance of dentists focusing on prevention and on the specific needs of the patient as well.

PMID:38356573 | PMC:PMC10865253 | DOI:10.1016/j.heliyon.2024.e25241

AAPS PharmSciTech. 2024 Feb 14;25(2):36. doi: 10.1208/s12249-024-02741-w.

ABSTRACT

Pulmonary drug delivery is a form of local targeting to the lungs in patients with respiratory disorders like cystic fibrosis, pulmonary arterial hypertension (PAH), asthma, chronic pulmonary infections, and lung cancer. In addition, noninvasive pulmonary delivery also presents an attractive alternative to systemically administered therapeutics, not only for localized respiratory disorders but also for systemic absorption. Pulmonary delivery offers the advantages of a relatively low dose, low incidence of systemic side effects, and rapid onset of action for some drugs compared to other systemic administration routes. While promising, inhaled delivery of therapeutics is often complex owing to factors encompassing mechanical barriers, chemical barriers, selection of inhalation device, and limited choice of dosage form excipients. There are very few excipients that are approved by the FDA for use in developing inhaled drug products. Depending upon the dosage form, and inhalation devices such as pMDIs, DPIs, and nebulizers, different excipients can be used to provide physical and chemical stability and to deliver the dose efficiently to the lungs. This review article focuses on discussing a variety of excipients that have been used in novel inhaled dosage forms as well as inhalation devices.

PMID:38356031 | DOI:10.1208/s12249-024-02741-w

Nat Cancer. 2024 Feb 14. doi: 10.1038/s43018-024-00731-2. Online ahead of print.

ABSTRACT

Pancreatic ductal adenocarcinoma is a highly metastatic disease and macrophages support liver metastases. Efferocytosis, or engulfment of apoptotic cells by macrophages, is an essential process in tissue homeostasis and wound healing, but its role in metastasis is less well understood. Here, we found that the colonization of the hepatic metastatic site is accompanied by low-grade tissue injury and that efferocytosis-mediated clearance of parenchymal dead cells promotes macrophage reprogramming and liver metastasis. Mechanistically, progranulin expression in macrophages is necessary for efficient efferocytosis by controlling lysosomal acidification via cystic fibrosis transmembrane conductance regulator and the degradation of lysosomal cargo, resulting in LXRα/RXRα-mediated macrophage conversion and upregulation of arginase 1. Pharmacological blockade of efferocytosis or macrophage-specific genetic depletion of progranulin impairs macrophage conversion, improves CD8+ T cell functions, and reduces liver metastasis. Our findings reveal how hard-wired functions of macrophages in tissue repair contribute to liver metastasis and identify potential targets for prevention of pancreatic ductal adenocarcinoma liver metastasis.

PMID:38355776 | DOI:10.1038/s43018-024-00731-2

J Cyst Fibros. 2024 Feb 13:S1569-1993(24)00016-X. doi: 10.1016/j.jcf.2024.02.002. Online ahead of print.

NO ABSTRACT

PMID:38355351 | DOI:10.1016/j.jcf.2024.02.002

J Cyst Fibros. 2024 Feb 13:S1569-1993(24)00018-3. doi: 10.1016/j.jcf.2024.02.003. Online ahead of print.

ABSTRACT

Many people with CF (pwCF) desire a reduction in inhaled treatment burden after initiation of elexacaftor/tezacaftor/ivacaftor. The randomized, open-label SIMPLIFY study showed that discontinuing hypertonic saline (HS) or dornase alfa (DA) was non-inferior to continuation of each treatment with respect to change in lung function over a 6-week period. In this SIMPLIFY substudy, we used gamma scintigraphy to determine whether discontinuation of either HS or DA was associated with deterioration in the rate of in vivo mucociliary clearance (MCC) in participants ≥12 years of age. While no significant differences in MCC endpoints were associated with HS discontinuation, significant improvement in whole and peripheral lung MCC was observed after discontinuing DA. These results suggest that pwCF on ETI with mild lung disease do not experience a subclinical deterioration in MCC that could later impact health outcomes after discontinuing HS, and in fact may benefit from improved MCC after stopping DA treatment.

PMID:38355350 | DOI:10.1016/j.jcf.2024.02.003

Am J Respir Crit Care Med. 2024 Feb 14. doi: 10.1164/rccm.202311-2199LE. Online ahead of print.

NO ABSTRACT

PMID:38354409 | DOI:10.1164/rccm.202311-2199LE

Am J Respir Crit Care Med. 2024 Feb 14. doi: 10.1164/rccm.202311-2124LE. Online ahead of print.

NO ABSTRACT

PMID:38354402 | DOI:10.1164/rccm.202311-2124LE

PLoS One. 2024 Feb 14;19(2):e0299166. doi: 10.1371/journal.pone.0299166. eCollection 2024.

ABSTRACT

[This corrects the article DOI: 10.1371/journal.pone.0272091.].

PMID:38354208 | DOI:10.1371/journal.pone.0299166

Arch Microbiol. 2024 Feb 14;206(3):101. doi: 10.1007/s00203-023-03826-z.

ABSTRACT

A biofilm is a collection of microorganisms organized in a matrix of extracellular polymeric material. Biofilms consist of microbial cells that attach to both surfaces and each other, whether they are living or non-living. These microbial biofilms can lead to hospital-acquired infections and are generally detrimental. They possess the ability to resist the human immune system and antibiotics. The National Institute of Health (NIH) states that biofilm formation is associated with 65% of all microbial illnesses and 80% of chronic illnesses. Additionally, non-device-related microbial biofilm infections include conditions like cystic fibrosis, otitis media, infective endocarditis, and chronic inflammatory disorders. This review aims to provide an overview of research on chronic infections caused by microbial biofilms, methods used for biofilm detection, recent approaches to combat biofilms, and future perspectives, including the development of innovative antimicrobial strategies such as antimicrobial peptides, bacteriophages, and agents that disrupt biofilms.

PMID:38353831 | DOI:10.1007/s00203-023-03826-z

Microbiol Spectr. 2024 Feb 14:e0352823. doi: 10.1128/spectrum.03528-23. Online ahead of print.

ABSTRACT

Mycobacterium abscessus is a non-tuberculous mycobacterium, causing lung infections in cystic fibrosis patients. During pulmonary infection, M. abscessus switches from smooth (Mabs-S) to rough (Mabs-R) morphotypes, the latter being hyper-virulent. Previously, we isolated the lsr2 gene as differentially expressed during S-to-R transition. lsr2 encodes a pleiotropic transcription factor that falls under the superfamily of nucleoid-associated proteins. Here, we used two functional genomic methods, RNA-seq and chromatin immunoprecipitation-sequencing (ChIP-seq), to elucidate the molecular role of Lsr2 in the pathobiology of M. abscessus. Transcriptomic analysis shows that Lsr2 differentially regulates gene expression across both morphotypes, most of which are involved in several key cellular processes of M. abscessus, including host adaptation and antibiotic resistance. These results were confirmed through quantitative real-time PCR, as well as by minimum inhibitory concentration tests and infection tests on macrophages in the presence of antibiotics. ChIP-seq analysis revealed that Lsr2 extensively binds the M. abscessus genome at AT-rich sequences and appears to form long domains that participate in the repression of its target genes. Unexpectedly, the genomic distribution of Lsr2 revealed no distinctions between Mabs-S and Mabs-R, implying more intricate mechanisms at play for achieving target selectivity.IMPORTANCELsr2 is a crucial transcription factor and chromosome organizer involved in intracellular growth and virulence in the smooth and rough morphotypes of Mycobacterium abscessus. Using RNA-seq and chromatin immunoprecipitation-sequencing (ChIP-seq), we investigated the molecular role of Lsr2 in gene expression regulation along with its distribution on M. abscessus genome. Our study demonstrates the pleiotropic regulatory role of Lsr2, regulating the expression of many genes coordinating essential cellular and molecular processes in both morphotypes. In addition, we have elucidated the role of Lsr2 in antibiotic resistance both in vitro and in vivo, where lsr2 mutant strains display heightened sensitivity to antibiotics. Through ChIP-seq, we reported the widespread distribution of Lsr2 on M. abscessus genome, revealing a direct repressive effect due to its extensive binding on promoters or coding sequences of its targets. This study unveils the significant regulatory role of Lsr2, intricately intertwined with its function in shaping the organization of the M. abscessus genome.

PMID:38353553 | DOI:10.1128/spectrum.03528-23