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Pharmacological Research Jun 2024Accumulating evidence has proved the close association between alterations in gut microbiota and resistance to chemotherapeutic drugs. However, the potential roles of...
Accumulating evidence has proved the close association between alterations in gut microbiota and resistance to chemotherapeutic drugs. However, the potential roles of gut microbiota in regulating oxaliplatin sensitivity in gastric cancer (GC) have not been investigated before. We first found that antibiotic treatment diminished the therapeutic efficacy of oxaliplatin in a GC mouse model. Importantly, this effect could be transmitted to germ-free mice via fecal microbiota transplantation, indicating a potential role of gut microbiota modulation in oxaliplatin efficacy. Further, metagenomics data showed that Akkermansia muciniphila (A. muciniphila) ranked first among the bacterial species with decreased relative abundances after antibiotic treatment. Metabolically active A. muciniphila promotes oxaliplatin efficacy. As shown by metabolomics analysis, the metabolic pattern of gut microbiota was disrupted with significantly downregulated levels of pentadecanoic acid (PEA), and the use of PEA significantly promoted oxaliplatin efficacy. Mechanistically, FUBP1 positively regulated aerobic glycolysis of GC cells to hinder the therapeutic efficacy of oxaliplatin. A. muciniphila-derived PEA functioned as an inhibitory factor of glycolysis by directly antagonizing the activity of FUBP1, which potentiated GC responses to oxaliplatin. Our research suggested a key role for intestinal A. muciniphila and its metabolite PEA in promoting oxaliplatin efficacy, thus providing a new perspective for probiotic and prebiotic intervention in GC patients during chemotherapy.
PubMed: 38908613
DOI: 10.1016/j.phrs.2024.107278 -
Pharmaceutics May 2024infection is an infectious disease that must be controlled because it becomes chronic and difficult to treat, owing to its unique system of toxin production/injection...
infection is an infectious disease that must be controlled because it becomes chronic and difficult to treat, owing to its unique system of toxin production/injection and elimination of other bacteria. Here, we noninvasively monitored using single-photon emission computed tomography (SPECT) imaging. Determining the amount and localization of the will enable making faster clinical diagnoses and selecting the most appropriate therapeutic agents and methods. Nonclinically, this information can be used for imaging in combination with biofilms and toxin probes and will be useful for discovering drugs targeting . To study accumulation, we conducted in vitro and in vivo studies using iodine-123 β-methyl--iodophenyl-pentadecanoic acid (I-BMIPP), which we previously reported using for . In vitro, I-BMIPP accumulated in by being taken up into the bacteria and adsorbing to the bacterial surface. In vivo, I-BMIPP accumulated significantly more in infected sites than in noninfected sites and could be quantified by SPECT. These results suggest that I-BMIPP can be used as a probe for for SPECT. Establishing a noninvasive monitoring method using SPECT will allow further progress in studying .
PubMed: 38794318
DOI: 10.3390/pharmaceutics16050656 -
Microbial Pathogenesis Jul 2024Bacterial wilt of tomato caused by Ralstonia solanacearum is a critical soilborne disease that drastically reduces yield. In the current study, an endophytic strain...
Bacterial wilt of tomato caused by Ralstonia solanacearum is a critical soilborne disease that drastically reduces yield. In the current study, an endophytic strain NEAU-CP5 with strong antagonistic activity against R. solanacearum was isolated from tomato seeds and characterized. The strain was identified as Bacillus velezensis based on 16S rRNA gene and whole genome sequence analysis. NEAU-CP5 can secrete amylase, protease, and cellulase, and also produce known antibacterial metabolites, including cyclo (leucylprolyl), cyclo (phenylalanyl-prolyl), cyclo (Pro-Gly), 3-benzyl-2,5-piperazinedione, pentadecanoic acid, eicosane, 2-methyoic acid, isovaleric acid, dibuty phthalate, and esters of fatty acids (HFDU), which may be responsible for its strong antibacterial activity. Fourteen gene clusters associated with antibacterial properties were also identified in the whole genome sequence of NEAU-CP5. Pot experiment demonstrated that the application of 10 CFU/mL NEAU-CP5 on tomato plants significantly reduced the incidence of tomato bacterial wilt by 68.36 ± 1.67 %. NEAU-CP5 also increased the activity of defense-related enzymes (CAT, POD, PPO, SOD, and PAL) in tomato plants. This is the first report of an effective control of bacterial wilt on tomato plants by B. velezensis and highlights the potential of NEAU-CP5 as a potential biocontrol agent for the management of tomato bacterial wilt.
Topics: Solanum lycopersicum; Plant Diseases; Ralstonia solanacearum; Bacillus; Seeds; RNA, Ribosomal, 16S; Phylogeny; Anti-Bacterial Agents; Endophytes; Genome, Bacterial; Whole Genome Sequencing; Antibiosis; Multigene Family; Amylases; DNA, Bacterial
PubMed: 38777241
DOI: 10.1016/j.micpath.2024.106707 -
International Heart Journal May 2024The effectiveness of ischemic postconditioning (iPoC) in patients with ST-elevation myocardial infarction (STEMI) without ischemic preconditioning has not been...
The effectiveness of ischemic postconditioning (iPoC) in patients with ST-elevation myocardial infarction (STEMI) without ischemic preconditioning has not been determined. Therefore, we investigated the impact of iPoC and its potential mechanism related to heat shock protein 72 (HSP72) induction on myocardial salvage in patients with STEMI without prodromal angina (PA).We retrospectively analyzed data from 102 patients with STEMI with successful reperfusion among 323 consecutive patients with acute coronary syndrome. Among these, 55 patients with iPoC (iPoC (+) ) underwent 4 cycles of 60-second inflation and 30-second deflation of the angioplasty balloon. Both the iPoC (+) and iPoC (-) groups were divided into 2 further subgroups: patients with PA (PA (+) ) and those without (PA (-) ). We analyzed HSP72 levels in neutrophils, which were measured until 48 hours after reperfusion. I-123 β-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) scintigraphy was performed within a week of reperfusion therapy. In 64% of patients, thallium-201 (TL) scintigraphy was performed 6-8 months after STEMI onset.Using BMIPP and TL, in the PA (-) subgroups, the iPoC (+) group had a significantly greater myocardial salvage ratio than the iPoC (-) group. iPoC was identified as an independent predictor of the myocardial salvage ratio. The HSP72 increase ratio was significantly elevated in the iPoC (+) PA (-) group. Importantly, the myocardial salvage effect in patients without PA was significantly correlated with the HSP72 increase ratio, which was greater in patients with iPoC.These results suggest the potential impact of iPoC via HSP72 induction on myocardial salvage; however, the effects may be limited to patients with STEMI without PA.
Topics: Humans; Male; Female; HSP72 Heat-Shock Proteins; Retrospective Studies; Aged; Middle Aged; ST Elevation Myocardial Infarction; Ischemic Postconditioning; Angina Pectoris; Prodromal Symptoms; Percutaneous Coronary Intervention; Neutrophils
PubMed: 38749746
DOI: 10.1536/ihj.23-651 -
Foods (Basel, Switzerland) Apr 2024Strong-flavor Daqu, as a fermentation agent, plays a significant role in shaping the quality of strong-flavor baijius, and fungal species in Daqu are important factors...
Strong-flavor Daqu, as a fermentation agent, plays a significant role in shaping the quality of strong-flavor baijius, and fungal species in Daqu are important factors affecting the quality of Daqu. Therefore, we selected strong-flavor Daqu from seven different origins to study the fungal composition and the effects of the fungal composition on the physicochemical properties and volatile organic compounds (VOCs). It was found that the fungal composition influences the physicochemical properties of Daqu. Specifically, there was a positive link between , , , and liquefying activity and a positive correlation between and fermenting activity. Furthermore, the relationships between esterifying activity and , , , , and were found to be positive. The VOCs in Daqu were affected by , , , and . was significantly positively correlated with benzeneethanol as well as and pentadecanoic acid ethyl ester, ethyl myristate. and were significantly negatively correlated with benzaldehyde and 2-furaldehyde. This study deepens our understanding of the relationship between VOCs, the physicochemical properties with microbial communities, and reference significance for the production of better-quality strong-flavor Daqu.
PubMed: 38672935
DOI: 10.3390/foods13081263 -
Frontiers in Medicine 2024Hypoxic conditions and () infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the...
BACKGROUND
Hypoxic conditions and () infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC).
METHODS
EBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and isolation was analyzed, which may relate to the severity of bronchiectasis disease.
RESULTS
Levels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in (+) group compared to the (-) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with isolation.
CONCLUSION
The study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.
PubMed: 38633315
DOI: 10.3389/fmed.2024.1345165 -
Journal of Imaging Feb 2024The mortality rate of cancer patients has been decreasing; however, patients often suffer from cardiac disorders due to chemotherapy or other cancer therapies (e.g.,...
The mortality rate of cancer patients has been decreasing; however, patients often suffer from cardiac disorders due to chemotherapy or other cancer therapies (e.g., cancer-therapy-related cardiovascular toxicity (CVR-CVT)). Therefore, the field of cardio-oncology has drawn more attention in recent years. The first European Society of Cardiology (ESC) guidelines on cardio-oncology was established last year. Echocardiography is the gold standard for the diagnosis of CVR-CVT, but many breast cancer patients are unable to undergo echocardiography due to their surgery wounds or anatomical reasons. We performed a study to evaluate the usefulness of myocardial scintigraphy using Iodine-123 β-methyl-P-iodophenyl-pentadecanoic acid (I-BMIPP) in comparison with echocardiography and published the results in the Journal of Imaging last year. This is the secondary analysis following our previous study. A total of 114 breast cancer patients who received chemotherapy within 3 years underwent echocardiography, as well as Thallium (Tl) and I-BMIPP myocardial perfusion and metabolism scintigraphy. The ratio of isotope uptake reduction was scored by Heart Risk View-S software (Nihon Medi-Physics). The scores were then compared with the echocardiography parameters. All the patients' charts and data from January 2022 to November 2023 were reviewed for the secondary analysis. Echocardiogram parameters were obtained from 99 patients (87% of total patients). No correlations were found between the echocardiography parameters and Heart Risk View-S scores of Tl myocardial perfusion scintigraphy, nor those of the BMIPP myocardial metabolism scintigraphy. In total, 8 patients out of 114 (7.0%) died within 22 months, while 3 patients out of 26 CVR-CVT patients (11.5%) died within 22 months. Evaluation by echocardiography was sometimes difficult to perform on breast cancer patients. However, other imaging modalities, including myocardial scintigraphy, cannot serve as alternatives to echocardiography. Cardiac scintigraphy detects circulation disorder or metabolism disorder in the myocardium; therefore, it should be able to reveal myocardial damage to some extent. The mortality rate of breast cancer patients was higher with CVR-CVT. A new modality to detect CVR-CVT besides echocardiography can possibly be anticipated for patients who cannot undergo echocardiography.
PubMed: 38535135
DOI: 10.3390/jimaging10030054 -
PloS One 2024Despite growing evidence supporting the importance of the quality of attachment during adolescence, no studies have been conducted to date in the Arab world due to an...
Despite growing evidence supporting the importance of the quality of attachment during adolescence, no studies have been conducted to date in the Arab world due to an absence of valid and reliable tools to measure this construct in Arabic. The Inventory of Parent and Peer Attachment-Revised (IPPA-R) was devised as a self-report questionnaire in English to assess the quality of adolescent attachment to mother, father, and peers, each scale consisting of 25 items. The current study sets out to determine the psychometric properties of the Arabic IPPA-R and to explore attachment styles in Lebanon in a sample of 765 Lebanese adolescents. Results suggested a modified three-factor structure to reach satisfactory reliability of the Arabic IPPA-R, resulting in a modified questionnaire consisting of 19 items for each of mother (α = .82) and father (α = .85), and 21 items for peers (α = .89). Strict measurement invariance across gender was achieved for the IPPA-R parental forms, while only scalar invariance was achieved for the IPPA-R peers form. Overall, there were significant differences in attachment scores to mother and father, with adolescents scoring higher on attachment to mother, with both scores being significantly lower than attachment to peers. Gender differences were found on the peer scale with girls scoring significantly higher than boys. Results are interpreted from a cultural lens, emphasizing the importance of accounting for cultural, religious, and socio-economic factors in understanding adolescent attachment. This study is the first conducted in the Arab region and provides a road map to understanding gender-roles, parental expectations and adolescent perceived parenting, and their impact on adolescent attachment scores.
Topics: Male; Female; Humans; Adolescent; Reproducibility of Results; Parents; Mothers; Peer Group; Psychometrics; Iodobenzenes
PubMed: 38507401
DOI: 10.1371/journal.pone.0298084 -
Journal of Cardiology Cases Mar 2024The patient was a 68-year-old woman who experienced loss of consciousness owing to a seizure while walking and bruised her face. Twelve‑lead electrocardiography...
UNLABELLED
The patient was a 68-year-old woman who experienced loss of consciousness owing to a seizure while walking and bruised her face. Twelve‑lead electrocardiography displayed a complete atrioventricular block. Transthoracic echocardiography displayed hypokinesis from the middle to apex of the myocardium. Emergency coronary angiography displayed no clear stenosis of the coronary arteries, and left ventriculography displayed takotsubo-like abnormal left ventricular wall motion. Tc-sestamibi/I-beta-methyl iodophenyl pentadecanoic acid dual single-photon emission computed tomography displayed a perfusion/metabolism mismatch in the left apex, anterior segment, and inferior segment of the myocardium in the acute phase, which improved in the chronic phase. Similar mismatch findings were observed in the ventricular septum, which persisted in the chronic phase. Blood biomarkers of sarcoidosis were positive. Myocardial delayed enhancement was observed in the mid layer of the basal septum and inferior wall on cardiac magnetic resonance imaging. Fluorodeoxyglucose-positron emission tomography displayed signal accumulation in the basal septum. The clinical course of the patient suggested the possibility of cardiac sarcoidosis combined with takotsubo cardiomyopathy. This is a valuable case in which changes over time were detected by multimodality cardiac imaging.
LEARNING OBJECTIVE
Cardiac manifestations of both takotsubo cardiomyopathy and sarcoidosis are similar, with both causing abnormal left ventricular wall motion. The co-occurrence of these conditions has been seldomly reported to date. The similarity of the characteristics of each condition poses a challenge in the diagnostic process. The utilization of multimodality cardiac imaging techniques, as demonstrated in the present case, is an effective means of establishing a diagnosis.
PubMed: 38481645
DOI: 10.1016/j.jccase.2023.11.013 -
Journal of Ethnopharmacology Jun 2024The Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits...
ETHNOPHARMACOLOGICAL RELEVANCE
The Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits of Ganoderma sinense particularly in addressing pulmonary-related ailments. Ganoderma formosanum, an indigenous subspecies of G. sinense from Taiwan, has demonstrated the same therapeutic properties.
AIM OF THE STUDY
The aim of this study is to identify bioactive compounds and evaluate the potential of G. formosanum extracts as a novel treatment to alleviate pulmonary fibrosis (PF). Using an in-house drug screening platform, two-stage screening was performed to determine their anti-fibrotic efficacy.
METHODS AND MATERIALS
G. formosanum was fractionated into four partitions by solvents of different polarities. To determine their antifibrotic and pro-apoptotic properties, the fractions were analyzed using two TGF-β1-induced pulmonary fibrosis cell models (NIH-3T3) and human pulmonary fibroblast cell lines, immunoblot, qRT-PCR, and annexin V assays. Subsequently, transcriptomic analysis was conducted to validate the findings and explore possible molecular pathways. The identification of potential bioactive compounds was achieved through UHPLC-MS/MS analysis, while molecular interaction study was investigated by multiple ligands docking and molecular dynamic simulations.
RESULTS
The ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-β1-induced fibrotic models. Moreover, the EAF exhibited no discernible cytotoxicity. Untargeted UHPLC-MS/MS analysis identified potential bioactive compounds in EAF, including stearic acid, palmitic acid, and pentadecanoic acid. Multiple ligands docking and molecular dynamic simulations further confirmed that those bioactive compounds possess the ability to inhibit TGF-β receptor 1.
CONCLUSION
Potential bioactive compounds in G. formosanum were successfully extracted and identified in the EAF, whose anti-fibrotic and pro-apoptotic properties could potentially modulate pulmonary fibrosis. This finding not only highlights the EAF's potential as a promising therapeutic candidate to treat pulmonary fibrosis, but it also elucidates how Ganoderma confers pulmonary health benefits as described in the ancient texts.
Topics: Humans; Pulmonary Fibrosis; Transforming Growth Factor beta1; Materia Medica; Tandem Mass Spectrometry; Fibrosis; Ganoderma; Lung
PubMed: 38458343
DOI: 10.1016/j.jep.2024.118008