Front Microbiol. 2023 Jun 14;14:1216811. doi: 10.3389/fmicb.2023.1216811. eCollection 2023.

ABSTRACT

Studies have shown that microbes are closely related to human health. Clarifying the relationship between microbes and diseases that cause health problems can provide new solutions for the treatment, diagnosis, and prevention of diseases, and provide strong protection for human health. Currently, more and more similarity fusion methods are available to predict potential microbe-disease associations. However, existing methods have noise problems in the process of similarity fusion. To address this issue, we propose a method called MSIF-LNP that can efficiently and accurately identify potential connections between microbes and diseases, and thus clarify the relationship between microbes and human health. This method is based on matrix factorization denoising similarity fusion (MSIF) and bidirectional linear neighborhood propagation (LNP) techniques. First, we use non-linear iterative fusion to obtain a similarity network for microbes and diseases by fusing the initial microbe and disease similarities, and then reduce noise by using matrix factorization. Next, we use the initial microbe-disease association pairs as label information to perform linear neighborhood label propagation on the denoised similarity network of microbes and diseases. This enables us to obtain a score matrix for predicting microbe-disease relationships. We evaluate the predictive performance of MSIF-LNP and seven other advanced methods through 10-fold cross-validation, and the experimental results show that MSIF-LNP outperformed the other seven methods in terms of AUC. In addition, the analysis of Cystic fibrosis and Obesity cases further demonstrate the predictive ability of this method in practical applications.

PMID:37389340 | PMC:PMC10303805 | DOI:10.3389/fmicb.2023.1216811

World J Gastroenterol. 2023 Jun 14;29(22):3400-3421. doi: 10.3748/wjg.v29.i22.3400.

ABSTRACT

Small intestinal bacterial overgrowth (SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The presence of SIBO is detected in 33.8% of patients with gastroenterological complaints who underwent a breath test, and is significantly associated with smoking, bloating, abdominal pain, and anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicates the course of a number of diseases and may be of pathogenetic significance in the development of their symptoms. SIBO is significantly associated with functional dyspepsia, irritable bowel syndrome, functional abdominal bloating, functional constipation, functional diarrhea, short bowel syndrome, chronic intestinal pseudo-obstruction, lactase deficiency, diverticular and celiac diseases, ulcerative colitis, Crohn's disease, cirrhosis, metabolic-associated fatty liver disease (MAFLD), primary biliary cholangitis, gastroparesis, pancreatitis, cystic fibrosis, gallstone disease, diabetes, hypothyroidism, hyperlipidemia, acromegaly, multiple sclerosis, autism, Parkinson's disease, systemic sclerosis, spondylarthropathy, fibromyalgia, asthma, heart failure, and other diseases. The development of SIBO is often associated with a slowdown in orocecal transit time that decreases the normal clearance of bacteria from the small intestine. The slowdown of this transit may be due to motor dysfunction of the intestine in diseases of the gut, autonomic diabetic polyneuropathy, and portal hypertension, or a decrease in the motor-stimulating influence of thyroid hormones. In a number of diseases, including cirrhosis, MAFLD, diabetes, and pancreatitis, an association was found between disease severity and the presence of SIBO. Further work on the effect of SIBO eradication on the condition and prognosis of patients with various diseases is required.

PMID:37389240 | PMC:PMC10303511 | DOI:10.3748/wjg.v29.i22.3400

Oncoimmunology. 2023 Jun 27;12(1):2227510. doi: 10.1080/2162402X.2023.2227510. eCollection 2023.

ABSTRACT

Toll-like receptor 3 (TLR3) agonists such as polyinosinic:polycytidylic acid (poly(I:C)) have immunostimulatory effects that can be taken advantage of to induce anticancer immune responses in preclinical models. In addition, poly(I:C) has been introduced into clinical trials to demonstrate its efficacy as an adjuvant and to enhance the immunogenicity of locally injected tumors, thus reverting resistance to PD-L1 blockade in melanoma patients. Here, we report the pharmacokinetic, pharmacodynamic, mechanistic and toxicological profile of a novel TLR3 agonist, TL-532, a chemically synthesized double-stranded RNA that is composed by blocks of poly(I:C) and poly(A:U) (polyadenylic - polyuridylic acid). In preclinical models, we show that TL-532 is bioavailable after parenteral injection, has an acceptable toxicological profile, and stimulates the production of multiple chemokines and interleukins that constitute pharmacodynamic markers of its immunostimulatory action. When given at a high dose, TL-532 monotherapy reduced the growth of bladder cancers growing on mice. In addition, in immunodeficient mice lacking formylpeptide receptor-1 (FPR1), TL-532 was able to restore the response of orthotopic subcutaneous fibrosarcoma to immunogenic chemotherapy. Altogether, these findings may encourage further development of TL-532 as an immunotherapeutic anticancer agent.

PMID:37389102 | PMC:PMC10305499 | DOI:10.1080/2162402X.2023.2227510

World J Transplant. 2023 Jun 18;13(4):138-146. doi: 10.5500/wjt.v13.i4.138.

ABSTRACT

BACKGROUND: Gastroesophageal reflux (GER) has been associated with poor outcomes after lung transplantation for chronic lung disease, including increased risk of chronic rejection. GER is common in cystic fibrosis (CF), but factors influencing the likelihood of pre-transplant pH testing, and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.

AIM: To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.

METHODS: This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant. Patients with pre-transplant anti-reflux surgery were excluded. Baseline characteristics (age at transplantation, gender, race, body mass index), self-reported GER symptoms prior to transplantation, and pre-transplant cardiopulmonary testing results, were recorded. Reflux testing consisted of either 24-h pH- or combined multichannel intraluminal impedance and pH monitoring. Post-transplant care included a standard immunosuppressive regimen, and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients. The primary outcome of chronic lung allograft dysfunction (CLAD) was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria. Statistical analysis was performed with Fisher's exact test to assess differences between cohorts, and time-to-event Cox proportional hazards modeling.

RESULTS: After applying inclusion and exclusion criteria, a total of 60 patients were included in the study. Among all CF patients, 41 (68.3%) completed reflux monitoring as part of pre-lung transplant evaluation. Objective evidence of pathologic reflux, defined as acid exposure time > 4%, was found in 24 subjects, representing 58% of the tested group. CF patients with pre-transplant reflux testing were older (35.8 vs 30.1 years, P = 0.01) and more commonly reported typical esophageal reflux symptoms (53.7% vs 26.3%, P = 0.06) compared to those without reflux testing. Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing. Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses (68% vs 85%, P = 0.003). There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not, after controlling for confounders (Cox Hazard Ratio 0.26; 95%CI: 0.08-0.92).

CONCLUSION: Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD. Systematic reflux testing may enhance outcomes in this patient population.

PMID:37388387 | PMC:PMC10303416 | DOI:10.5500/wjt.v13.i4.138

Front Pediatr. 2023 Jun 14;11:1211547. doi: 10.3389/fped.2023.1211547. eCollection 2023.

ABSTRACT

BACKGROUND: Increased maximal oxygen uptake (V̇O2max) is beneficial in children with cystic fibrosis (CF) but remains lower compared to healthy peers. Intrinsic metabolic deficiencies within skeletal muscle (muscle "quality") and skeletal muscle size (muscle "quantity") are both proposed as potential causes for the lower V̇O2max, although exact mechanisms remain unknown. This study utilises gold-standard methodologies to control for the residual effects of muscle size from V̇O2max to address this "quality" vs. "quantity" debate.

METHODS: Fourteen children (7 CF vs. 7 age- and sex-matched controls) were recruited. Parameters of muscle size - muscle cross-sectional area (mCSA) and thigh muscle volume (TMV) were derived from magnetic resonance imaging, and V̇O2max obtained via cardiopulmonary exercise testing. Allometric scaling removed residual effects of muscle size, and independent samples t-tests and effect sizes (ES) identified differences between groups in V̇O2max, once mCSA and TMV were controlled for.

RESULTS: V̇O2max was shown to be lower in the CF group, relative to controls, with large ES being identified when allometrically scaled to mCSA (ES = 1.76) and TMV (ES = 0.92). Reduced peak work rate was also identified in the CF group when allometrically controlled for mCSA (ES = 1.18) and TMV (ES = 0.45).

CONCLUSIONS: A lower V̇O2max was still observed in children with CF after allometrically scaling for muscle size, suggesting reduced muscle "quality" in CF (as muscle "quantity" is fully controlled for). This observation likely reflects intrinsic metabolic defects within CF skeletal muscle.

PMID:37388288 | PMC:PMC10300555 | DOI:10.3389/fped.2023.1211547

Evid Based Complement Alternat Med. 2023 Jun 21;2023:9758012. doi: 10.1155/2023/9758012. eCollection 2023.

ABSTRACT

[This retracts the article DOI: 10.1155/2021/7254391.].

PMID:37387828 | PMC:PMC10307377 | DOI:10.1155/2023/9758012

Eur Respir J. 2023 Jun 29:2300286. doi: 10.1183/13993003.00286-2023. Online ahead of print.

NO ABSTRACT

PMID:37385656 | DOI:10.1183/13993003.00286-2023

Eur Respir J. 2023 Jun 29;61(6):2300769. doi: 10.1183/13993003.00769-2023. Print 2023 Jun.

NO ABSTRACT

PMID:37385653 | DOI:10.1183/13993003.00769-2023

Zhonghua Er Ke Za Zhi. 2023 Jul 2;61(7):626-630. doi: 10.3760/cma.j.cn112140-20230216-00106.

ABSTRACT

Objective: To evaluate the value of nasal nitric oxide (nNO) measurement as a diagnostic tool for Chinese patients with primary ciliary dyskinesia (PCD). Methods: This study is a retrospective study. The patients were recruited from those who were admitted to the respiratory Department of Respiratory Medicine, Children's Hospital of Fudan University from March 2018 to September 2022. Children with PCD were included as the PCD group, and children with situs inversus or ambiguus, cystic fibrosis (CF), bronchiectasis, chronic suppurative lung disease and asthma were included as the PCD symptom-similar group. Children who visited the Department of Child health Care and urology in the same hospital from December 2022 to January 2023 were selected as nNO normal control group. nNO was measured during plateau exhalation against resistance in three groups. Mann-Whitney U test was used to analyze the nNO data. The receiver operating characteristic of nNO value for the diagnosis of PCD was plotted and, the area under the curve and Youden index was calculated to find the best cut-off value. Results: nNO was measured in 40 patients with PCD group, 75 PCD symptom-similar group (including 23 cases of situs inversus or ambiguus, 8 cases of CF, 26 cases of bronchiectasis or chronic suppurative lung disease, 18 cases of asthma), and 55 nNO normal controls group. The age of the three groups was respectively 9.7 (6.7,13.4), 9.3 (7.0,13.0) and 9.9 (7.3,13.0) years old. nNO values were significantly lower in children with PCD than in PCD symptom-similar group and nNO normal controls (12 (9,19) vs. 182 (121,222), 209 (165,261) nl/min, U=143.00, 2.00, both P<0.001). In the PCD symptom-similar group, situs inversus or ambiguus, CF, bronchiectasis or chronic suppurative lung disease and asthma were significantly higher than children with PCD (185 (123,218), 97 (52, 132), 154 (31, 202), 266 (202,414) vs. 12 (9,19) nl/min,U=1.00, 9.00, 133.00, 0, all P<0.001). A cut-off value of 84 nl/min could provide the best sensitivity (0.98) and specificity (0.92) with an area under the curve of 0.97 (95%CI 0.95-1.00, P<0.001). Conclusions: nNO value can draw a distinction between patients with PCD and others. A cut-off value of 84 nl/min is recommended for children with PCD.

PMID:37385806 | DOI:10.3760/cma.j.cn112140-20230216-00106

Front Physiol. 2023 Jun 13;14:1233276. doi: 10.3389/fphys.2023.1233276. eCollection 2023.

NO ABSTRACT

PMID:37383143 | PMC:PMC10295136 | DOI:10.3389/fphys.2023.1233276

Cells. 2023 Jun 16;12(12):1642. doi: 10.3390/cells12121642.

ABSTRACT

Unlocking cell secretion capacity is of paramount interest for the pharmaceutical industry focused on biologics. Here, we leveraged retention using a selective hook (RUSH) system for the identification of human osteosarcoma U2OS cell secretion modulators, through automated, high-throughput screening of small compound libraries. We created a U2OS cell line which co-expresses a variant of streptavidin addressed to the lumen-facing membrane of the endoplasmic reticulum (ER) and a recombinant anti-PD-L1 antibody. The heavy chain of the antibody was modified at its C-terminus, to which a furin cleavage site, a green fluorescent protein (GFP), and a streptavidin binding peptide (SBP) were added. We show that the U2OS cell line stably expresses the streptavidin hook and the recombinant antibody bait, which is retained in the ER through the streptavidin-SBP interaction. We further document that the addition of biotin to the culture medium triggers the antibody release from the ER, its trafficking through the Golgi where the GFP-SBP moiety is clipped off, and eventually its release in the extra cellular space, with specific antigen-binding properties. The use of this clone in screening campaigns led to the identification of lycorine as a secretion enhancer, and nigericin and tyrphostin AG-879 as secretion inhibitors. Altogether, our data support the utility of this approach for the identification of agents that could be used to improve recombinant production yields and also for a better understanding of the regulatory mechanism at work in the conventional secretion pathway.

PMID:37371112 | PMC:PMC10297138 | DOI:10.3390/cells12121642

Urology. 2023 Jun 26:S0090-4295(23)00529-0. doi: 10.1016/j.urology.2023.06.017. Online ahead of print.

ABSTRACT

Cystic Fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Due to the distribution of the CFTR protein, CF presents with a heterogeneous phenotype. Men with CF may present with infertility due to congenital abnormalities of the vas deferens. In addition, they may experience testosterone deficiency. Today, they can father biological children with assisted reproductive technologies. We reviewed the current literature on the pathophysiology of these conditions, describe interventions that allow men with CF to conceive biological children, and provide recommendations for management of CF patients with reproductive health concerns.

PMID:37380131 | DOI:10.1016/j.urology.2023.06.017

Nat Protoc. 2023 Jun 28. doi: 10.1038/s41596-023-00850-7. Online ahead of print.

NO ABSTRACT

PMID:37380826 | DOI:10.1038/s41596-023-00850-7

Expert Opin Pharmacother. 2023 Jun 28. doi: 10.1080/14656566.2023.2230129. Online ahead of print.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF), a potentially fatal genetic disease, is caused by loss-of-function variants in the gene encoding for the CFTR chloride/bicarbonate channel. Modulator drugs rescuing mutant CFTR traffic and function are now in the clinic, providing unprecedented breakthrough therapies for people with CF (PwCF) carrying specific genotypes. However, several CFTR variants are unresponsive to these therapies.

AREA COVERED: We discussed several therapeutic approaches that are under development to tackle the fundamental cause of CF, including strategies targeting defective CFTR mRNA and/or protein expression and function. Alternatively, defective chloride secretion and dehydration in CF epithelia could be restored by exploiting pharmacological modulation of alternative targets, i.e. alternative ion channels/transporters that concur with the maintenance of airway surface liquid homeostasis (e.g. ENaC, TMEM16A, SLC26A4, SLC26A9, and ATP12A). Finally, we assessed progress and challenges in the development of gene-based therapies to replace or correct the mutant CFTR gene.

EXPERT OPINION: CFTR modulators are benefiting many PwCF responsive to these drugs, yielding substantial improvements in various clinical outcomes. Meanwhile, the CF therapy development pipeline continues to expand with the development of novel CFTR modulators and alternative therapeutic strategies with the ultimate goal to provide effective therapies for all PwCF in the foreseeable future.

PMID:37379072 | DOI:10.1080/14656566.2023.2230129

Expert Rev Clin Immunol. 2023 Jun 28. doi: 10.1080/1744666X.2023.2231153. Online ahead of print.

ABSTRACT

INTRODUCTION: Chronic rhinosinusitis (CRS) is characterized by inflammation of the paranasal sinus mucosa persisting for more than twelve weeks. This condition is associated with reduced quality-of-life and causes a high direct and indirect economic burden. Several pathogenic factors have been attributed to CRS, including bacterial and fungal biofilms on the sinonasal mucosa. Biofilms are well-established contributors to recalcitrance to treatment in other chronic inflammatory mucosal conditions such as cystic fibrosis and otitis media.

AREAS COVERED: This review will present an overview of the role of biofilms in CRS, including the evidence for biofilms being present on the sinonasal mucosa and their implications for disease severity. Furthermore, the interactions between biofilms and host-mediated immune factors are explored.

EXPERT OPINION: The eradication of biofilms has been a focus of research shortly after their recognition as a cause of disease. The currently available methodologies for identifying biofilms on mucosal surfaces are not sufficiently well-developed to be used in a clinical setting. A more accurate, cheaper, faster approach for biofilm detection is necessary, and molecular techniques may provide the possibility for this.

PMID:37378564 | DOI:10.1080/1744666X.2023.2231153

Pediatr Pulmonol. 2023 Jun 28. doi: 10.1002/ppul.26570. Online ahead of print.

ABSTRACT

Postinfectious bronchiolitis obliterans (PiBO) is a rare and severe form of chronic obstructive lung disease caused by an infectious injury to the lower respiratory tract. The most commonly recognized inciting stimuli leading to PiBO are airway pathogens, such as adenovirus and Mycoplasma. PiBO is characterized by persistent and nonreversible airway obstruction, with functional and radiological evidence of small airway involvement. The literature has limited information on the aetiology, clinical profile, treatment, and outcome of PiBO.

PMID:37378463 | DOI:10.1002/ppul.26570

ERJ Open Res. 2023 Jun 26;9(3):00055-2023. doi: 10.1183/23120541.00055-2023. eCollection 2023 May.

ABSTRACT

This case series suggests that successful eradication therapy of BCC in cystic fibrosis can be done with a combination of inhaled and oral medication, which in many cases may eliminate the need for intensive treatment with intravenous antibiotics https://bit.ly/40oOMIn.

PMID:37377654 | PMC:PMC10291312 | DOI:10.1183/23120541.00055-2023

ERJ Open Res. 2023 Jun 26;9(3):00156-2023. doi: 10.1183/23120541.00156-2023. eCollection 2023 May.

ABSTRACT

Genome sequencing of 130 Pseudomonas aeruginosa isolates from 110 bronchiectasis patients identified a few dominant clones common in the global bacterial population and numerous rare clones infrequently seen in the environment or other human infections https://bit.ly/3lIfD2X.

PMID:37377651 | PMC:PMC10291309 | DOI:10.1183/23120541.00156-2023

J Paediatr Child Health. 2023 Jun 28. doi: 10.1111/jpc.16463. Online ahead of print.

NO ABSTRACT

PMID:37377373 | DOI:10.1111/jpc.16463

Vaccines (Basel). 2023 May 30;11(6):1039. doi: 10.3390/vaccines11061039.

ABSTRACT

The Burkholderia cepacia complex comprises environmental and clinical Gram-negative bacteria that infect particularly debilitated people, such as those with cystic fibrosis. Their high level of antibiotic resistance makes empirical treatments often ineffective, increasing the risk of worst outcomes and the diffusion of multi-drug resistance. However, the discovery of new antibiotics is not trivial, so an alternative can be the use of vaccination. Here, the reverse vaccinology approach has been used to identify antigen candidates, obtaining a short-list of 24 proteins. The localization and different aspects of virulence were investigated for three of them-BCAL1524, BCAM0949, and BCAS0335. The three antigens were localized in the outer membrane vesicles confirming that they are surface exposed. We showed that BCAL1524, a collagen-like protein, promotes bacteria auto-aggregation and plays an important role in virulence, in the Galleria mellonella model. BCAM0949, an extracellular lipase, mediates piperacillin resistance, biofilm formation in Luria Bertani and artificial sputum medium, rhamnolipid production, and swimming motility; its predicted lipolytic activity was also experimentally confirmed. BCAS0335, a trimeric adhesin, promotes minocycline resistance, biofilm organization in LB, and virulence in G. mellonella. Their important role in virulence necessitates further investigations to shed light on the usefulness of these proteins as antigen candidates.

PMID:37376428 | DOI:10.3390/vaccines11061039