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Scientific Reports Jun 2024We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl... (Randomized Controlled Trial)
Randomized Controlled Trial
We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl estradiol (EE) and 0.075 mg of gestodene (GS) in ovulation inhibition and inducing unfavorable cervical mucus changes using a delayed-starting approach. This randomized controlled trial involved 36 participants aged 18-45 years. The major outcomes included ovulation inhibition assessed using the Hoogland and Skouby score, and cervical mucus permeability, assessed using the modified World Health Organization score. The results demonstrated ovulation inhibition rates of 77.8% for the EE/GS group and 88.9% for the DRSP group. The risk ratio and absolute risk reduction were 0.50 (95% confidence interval [CI]: 0.10, 2.40) and - 0.11 (95% CI: - 0.35, 0.13), respectively, satisfying the 20% non-inferiority margin threshold. The median time to achieve unfavorable cervical mucus changes was comparable between the DRSP (3 days, interquartile range [IQR]: 6 days) and EE/GS (3.5 days, IQR: 4 days) groups. However, the DRSP group had a higher incidence of unscheduled vaginal bleeding (55.56% vs. 11.11%; p = 0.005). DRSP-only pills, initiated on days 7-9 of the menstrual cycle, were non-inferior to EE/GS pills in ovulation inhibition. However, they exhibited delayed unfavorable cervical mucus changes compared to the standard two-day backup recommendation.Clinical trial registration: Thai Clinical Trials Registry (TCTR20220819001) https://www.thaiclinicaltrials.org/show/TCTR20220819001 .
Topics: Humans; Female; Adult; Ethinyl Estradiol; Androstenes; Young Adult; Adolescent; Contraceptives, Oral, Combined; Ovulation Inhibition; Single-Blind Method; Middle Aged; Norpregnenes; Ovulation; Cervix Mucus
PubMed: 38898193
DOI: 10.1038/s41598-024-64753-7 -
Biomaterials Jun 2024Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric...
Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric cancer patients with Helicobacter pylori (H. pylori) infection have higher overall survival, whether H. pylori can be used as therapeutics agent and oral drug delivery system for gastric cancer. Hence, we constructed engineered H. pylori for gastric cancer treatment. A type Ⅱ H. pylori with low pathogenicity, were conjugated with photosensitizer to develop the engineered living bacteria NIR-triggered system (Hp-Ce6). Hp-Ce6 could maintain activity in stomach acid, quickly infiltrate through mucus layer and finally migrate to tumor region owing to the cell morphology and urease of H. pylori. H. pylori, accumulated in the tumor site, severed as vaccine to activate cGAS-STING pathway, and synergistically remodel the macrophages phenotype. Upon irradiation within stomach, Hp-Ce6 directly destroyed tumor cells via photodynamic effect inherited by Ce6, companied by inducing immunogenic tumor cell death. Additionally, Hp-Ce6 exhibited excellent biosafety with fecal elimination and minimal blood absorption. This work explores the feasibility and availability of H. pylori-based oral delivery platforms for gastric tumor and further provides enlightening strategy to utilize H. pylori invariably presented in the stomach as in-situ immunomodulator to enhance antitumor efficacy.
PubMed: 38897029
DOI: 10.1016/j.biomaterials.2024.122672 -
Veterinary Microbiology Jun 2024The intestinal barrier of newborn piglets is vulnerable and underdeveloped, making them susceptible to enteric virus infections. Benzoic acid (BA), employed as a growth...
The intestinal barrier of newborn piglets is vulnerable and underdeveloped, making them susceptible to enteric virus infections. Benzoic acid (BA), employed as a growth promoter, exhibits the potential to enhance the gut health of piglets by modulating intestinal morphometry and tight junction dynamics. However, the extent to which BA regulates the intestinal mucus barrier through its impact on stem cells remains inadequately elucidated. Therefore, this study was conducted to investigate the effects of BA on the intestinal barrier and the differentiation of intestinal stem cells, employing in vivo piglet and in vitro intestinal organoid models. Our investigation revealed a significant increase in the number of goblet cells within the small intestine, as well as the strengthening of the mucus barrier in vivo following oral treatment with BA, providing partial protection against PEDV infection in piglets. Additionally, in vitro cultivation of enteroids with BA led to a notable increase in the number of MUC2 GCs, indicating the promotion of GC differentiation by BA. Furthermore, transcriptome analysis revealed an upregulation of the number of GCs and the expression of cell vesicle transport-related genes during BA stimulation, accompanied by the downregulation of the Wnt and Notch signaling pathways. Mechanistically, MCT1 facilitated the transport of BA, subsequently activating the MAPK pathway to mediate GC differentiation. Overall, this study highlights a novel function for BA as a feed additive in enhancing the intestinal mucus barrier by promoting intestinal GC differentiation, and further prevents viral infection in piglets.
PubMed: 38896938
DOI: 10.1016/j.vetmic.2024.110152 -
Diagnostics (Basel, Switzerland) May 2024These images involved the case of a 51-year-old woman who had a history of chronic abdominal pain, iron deficiency, and diarrhoea but no blood or mucus in her stool. She...
These images involved the case of a 51-year-old woman who had a history of chronic abdominal pain, iron deficiency, and diarrhoea but no blood or mucus in her stool. She had never undergone major abdominal surgery, and her past medical evaluation diagnosed her with celiac disease, leading to the adoption of a gluten-free diet alleviating most of her gastrointestinal symptoms. However, years later, her abdominal pain returned, so she underwent an abdominal ultrasound, revealing non-specific bowel loop dilation, and a weakly positive faecal occult blood test led to a colonoscopy. Despite many efforts to advance the scope beyond the transverse colon, colonoscopy was arduous and not complete, even after several changes in decubitus and abdominal compressions. Therefore, a virtual colonoscopy was conducted, revealing no intraluminal masses, but the entire colon was located on the left side of the abdomen. Indeed, the results showed sigma and that most of the colon was curled up in the small pelvis. This rare anatomical variant, known as "Mesenterium commune" (MC), is a type of gut malrotation that develops in childhood due to a lack of omphalomesenteric loop rotation during the embryonic period. This condition can lead to episodes of intestinal obstruction, potentially resulting in an acute abdomen and leading to surgical correction. Symptoms include chronic recurring abdominal pain, nausea, vomiting, and occasionally bloody stools. Few cases of this extremely rare condition have been reported in the literature so far.
PubMed: 38893599
DOI: 10.3390/diagnostics14111072 -
International Journal of Molecular... Jun 2024Eosinophils are myeloid effector cells whose main homing is the gastrointestinal tract. There, they take part in type I and type II immune responses. They also... (Review)
Review
Eosinophils are myeloid effector cells whose main homing is the gastrointestinal tract. There, they take part in type I and type II immune responses. They also contribute to other non-immunological homeostatic functions like mucus production, tissue regeneration, and angiogenesis. In colorectal cancer (CRC), eosinophils locate in the center of the tumor and in the front of invasion and play an anti-tumoral role. They directly kill tumor cells by releasing cytotoxic compounds and eosinophil extracellular traps or indirectly by activating other immune cells via cytokines. As CRC progresses, the number of infiltrating eosinophils decreases. Although this phenomenon is not fully understood, it is known that some changes in the microenvironmental milieu and microbiome can affect eosinophil infiltration. Importantly, a high number of intratumoral eosinophils is a favorable prognostic factor independent from the tumor stage. Moreover, after immunotherapy, responding patients usually display eosinophilia, so eosinophils could be a good biomarker candidate to monitor treatment outcomes. Finally, even though eosinophils seem to play an interesting anti-tumoral role in CRC, much more research is needed to fully understand their interactions in the CRC microenvironment. This review explores the multifaceted roles of eosinophils in colorectal cancer, highlighting their anti-tumoral effects, prognostic significance, and potential as a biomarker for treatment outcomes.
Topics: Humans; Colorectal Neoplasms; Eosinophils; Tumor Microenvironment; Prognosis; Animals; Immunotherapy; Biomarkers, Tumor
PubMed: 38892286
DOI: 10.3390/ijms25116098 -
International Journal of Molecular... May 2024N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important... (Review)
Review
N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important etiological factors of lower respiratory tract infections, and exposure to air pollution appears to be additionally associated with higher RSV incidence and disease severity. We aimed to systematically review the existing literature to determine which molecular mechanisms mediate the effects of NAC in an RSV infection and air pollution, and to identify the knowledge gaps in this field. A search for original studies was carried out in three databases and a calibrated extraction grid was used to extract data on the NAC treatment (dose, timing), the air pollutant type, and the most significant mechanisms. We identified only 28 studies conducted in human cellular models ( = 18), animal models ( = 7), and mixed models ( = 3). NAC treatment improves the barrier function of the epithelium damaged by RSV and air pollution, and reduces the epithelial permeability, protecting against viral entry. NAC may also block RSV-activated phosphorylation of the epidermal growth factor receptor (EGFR), which promotes endocytosis and facilitates cell entry. EGFR also enhances the release of a mucin gene, MUC5AC, which increases mucus viscosity and causes goblet cell metaplasia; the effects are abrogated by NAC. NAC blocks virus release from the infected cells, attenuates the cigarette smoke-induced shift from necrosis to apoptosis, and reverses the block in IFN-γ-induced antiviral gene expression caused by the inhibited Stat1 phosphorylation. Increased synthesis of pro-inflammatory cytokines and chemokines is induced by both RSV and air pollutants and is mediated by the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that are activated in response to oxidative stress. MCP-1 (monocyte chemoattractant protein-1) and RANTES (regulated upon activation, expressed and secreted by normal T cells) partially mediate airway hyperresponsiveness (AHR), and therapeutic (but not preventive) NAC administration reduces the inflammatory response and has been shown to reduce ozone-induced AHR. Oxidative stress-induced DNA damage and cellular senescence, observed during RSV infection and exposure to air pollution, can be partially reversed by NAC administration, while data on the emphysema formation are disputed. The review identified potential common molecular mechanisms of interest that are affected by NAC and may alleviate both the RSV infection and the effects of air pollution. Data are limited and gaps in knowledge include the optimal timing or dosage of NAC administration, therefore future studies should clarify these uncertainties and verify its practical use.
Topics: Humans; Acetylcysteine; Respiratory Syncytial Virus Infections; Animals; Air Pollution; ErbB Receptors
PubMed: 38892239
DOI: 10.3390/ijms25116051 -
International Journal of Molecular... May 2024Inflammatory bowel disease (IBD) is a nonspecific chronic inflammatory disease resulting from an immune disorder in the intestine that is prone to relapse and incurable....
Inflammatory bowel disease (IBD) is a nonspecific chronic inflammatory disease resulting from an immune disorder in the intestine that is prone to relapse and incurable. The understanding of the pathogenesis of IBD remains unclear. In this study, we found that (angiotensin-converting enzyme), expressed abundantly in the intestine, plays an important role in IBD. The deletion of in zebrafish caused intestinal inflammation with increased expression of the inflammatory marker genes interleukin 1 beta (), matrix metallopeptidase 9 (), myeloid-specific peroxidase (), leukocyte cell-derived chemotaxin-2-like (), and chemokine (C-X-C motif) ligand 8b (). Moreover, the secretion of mucus in the mutants was significantly higher than that in the wild-type zebrafish, validating the phenotype of intestinal inflammation. This was further confirmed by the IBD model constructed using dextran sodium sulfate (DSS), in which the mutant zebrafish had a higher susceptibility to enteritis. Our study reveals the role of in intestinal homeostasis, providing a new target for potential therapeutic interventions.
Topics: Animals; Zebrafish; Peptidyl-Dipeptidase A; Disease Models, Animal; Dextran Sulfate; Inflammation; Zebrafish Proteins; Intestines; Inflammatory Bowel Diseases; Interleukin-1beta; Intestinal Mucosa
PubMed: 38891786
DOI: 10.3390/ijms25115598 -
Healthcare (Basel, Switzerland) May 2024(1) Background: FABMs (fertility awareness-based methods) are methods that rely on the observation of clinical signs related to fertility found in women, the so-called...
Usefulness of the Sympto-Thermal Method with Standardized Cervical Mucus Assessment (InVivo Method) for Evaluating the Monthly Cycle in Women with Polycystic Ovary Syndrome (PCOS).
(1) Background: FABMs (fertility awareness-based methods) are methods that rely on the observation of clinical signs related to fertility found in women, the so-called fertility bioindicators. They can be a valuable tool for diagnosing monthly cycle disorders and infertility, for example, among patients with PCOS (polycystic ovary syndrome). Until now, it has been difficult for women with PCOS to use FABM, due to the difficulty of describing fertility bioindicators and their disorders due to the biology of the syndrome. The new InVivo sympto-thermal method with standardized cervical mucus assessment may provide a valuable diagnostic and therapeutic tool for observing the monthly cycle in this group of women. (2) Methods: The monthly cycle was evaluated in a group of 32 women of reproductive age. A total of 108 monthly cycle observation cards were analyzed: 35 monthly cycle cards were collected from 18 women with PCOS, and 73 monthly cycle cards collected from 14 healthy women. In addition, 32 pairs of macroscopic and microscopic images were evaluated: 17 pairs from the study group (four subjects) and 15 pairs from women in the control group (six subjects). (3) Results: We showed that in the group of patients with PCOS, menstruation was longer ( = 0.000814), the number of mucus peaks was statistically higher ( = 0.040747), and the interquartile range (IQR) of the duration of the follicular phase (calculated according to the BBT) was significantly higher (8 days) compared to women in the control group. We also observed that among all the women studied, the microscopic image of cervical mucus correlated with the cycle phase described in the observation card, as determined by reference to the BBT chart, provided that it showed the correct features. (4) Conclusions: Systematic maintenance of monthly cycle observation charts using the InVivo method can be an important supplement to the medical history, as it allows for a thorough assessment of, among others, the timing of monthly bleeding, cervical mucus symptoms, BBT changes, and the duration of the follicular and luteal phases among both healthy and PCOS women.
PubMed: 38891183
DOI: 10.3390/healthcare12111108 -
Scientific Reports Jun 2024The mucus surface layer serves vital functions for scleractinian corals and consists mainly of carbohydrates. Its carbohydrate composition has been suggested to be...
The mucus surface layer serves vital functions for scleractinian corals and consists mainly of carbohydrates. Its carbohydrate composition has been suggested to be influenced by environmental conditions (e.g., temperature, nutrients) and microbial pressures (e.g., microbial degradation, microbial coral symbionts), yet to what extend the coral mucus composition is determined by phylogeny remains to be tested. To investigate the variation of mucus carbohydrate compositions among coral species, we analyzed the composition of mucosal carbohydrate building blocks (i.e., monosaccharides) for five species of scleractinian corals, supplemented with previously reported data, to discern overall patterns using cluster analysis. Monosaccharide composition from a total of 23 species (belonging to 14 genera and 11 families) revealed significant differences between two phylogenetic clades that diverged early in the evolutionary history of scleractinian corals (i.e., complex and robust; p = 0.001, R = 0.20), mainly driven by the absence of arabinose in the robust clade. Despite considerable differences in environmental conditions and sample analysis protocols applied, coral phylogeny significantly correlated with monosaccharide composition (Mantel test: p < 0.001, R = 0.70). These results suggest that coral mucus carbohydrates display phylogenetic dependence and support their essential role in the functioning of corals.
Topics: Anthozoa; Animals; Phylogeny; Mucus; Carbohydrates; Monosaccharides
PubMed: 38890484
DOI: 10.1038/s41598-024-64828-5 -
JCI Insight Jun 2024Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and...
Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and studies in human airway epithelial cells (HAECs) show that interleukin 13 (IL-13) activated cells generate pathologic mucus independently of immune cells. To determine how HAECs autonomously generate pathologic mucus, we used a magnetic microwire rheometer to characterize the viscoelastic properties of mucus secreted under varying conditions. We found that normal HAEC mucus exhibits viscoelastic liquid behavior and that mucus secreted by IL-13 activated HAECs exhibits solid-like behavior caused by mucin cross-linking. In addition, IL-13 activated HAECs show increased peroxidase activity in apical secretions, and an overlaid thiolated polymer (thiomer) solution shows an increase in solid behavior that is prevented by peroxidase inhibition. Furthermore, gene expression for thyroid peroxidase (TPO), but not lactoperoxidase (LPO), is increased in IL-13 activated HAECs and both TPO and LPO catalyze the formation of oxidant acids that cross-link thiomer solutions. Finally, gene expression for TPO in airway epithelial brushings is increased in asthma patients with high airway mucus plug scores. Together, our results show that IL-13 activated HAECs autonomously generate pathologic mucus via peroxidase-mediated cross-linking of mucin polymers.
PubMed: 38889046
DOI: 10.1172/jci.insight.181024