Mucosal Surfaces Research Articles

C3d Immunohistochemical Staining on Paraffin-Embedded Tissue for Diagnosis of Pemphigus.

Pemphigus is an autoimmune blister disease that causes blisters on the skin and mucosal surfaces. Direct immunofluorescence (DIF) testing is critical for the clinical diagnosis of pemphigus. However, it is limited to fresh tissue specimens and fluorescence microscopy. To assess the value of C3d immunohistochemistry (IHC) on paraffin-embedded skin tissue for the diagnosis of pemphigus by comparing C3d-IHC results to DIF and enzyme-linked immunosorbent assay testing in pemphigus and other blister-related skin diseases. C3d-IHC assays were retrospectively performed on paraffin-embedded skin tissue sections from 115 patients (63 with pemphigus and 52 controls). Both the case group and the control group underwent the same protocol, and cases with C3d position in the peripheral spinous layer were considered as positive samples. C3d-IHC and DIF testing had similar performance for pemphigus diagnosis, with a sensitivity of 71.0% (95% CI, 51.8%-85.1%) and 77.4% (95% CI, 58.5%-89.7%), specificity of 96.4% (95% CI, 79.8%-99.8%) and 100% (95% CI, 85.0%-100%), positive predictive value of 95.7% (95% CI, 76.0%-99.8%) and 100% (95% CI, 82.8%-100%), and a negative predictive value of 75.0% (95% CI, 57.5%-87.3%) and 80.0% (95% CI, 62.5%-90.9%), respectively. Our study indicated that C3d-IHC results for paraffin-fixed tissues were not significantly different from DIF results for the diagnosis of pemphigus. The C3d-IHC assay has the potential for routine diagnosis of pemphigus, especially in the absence of fresh-frozen tissue.

Crosstalk Between Microbiota, Microbial Metabolites, and Interferons in the Inflammatory Bowel Disease Gut.

With the prevalence of inflammatory bowel diseases (IBD) continuing to rise in Canada and globally, developing improved therapeutics that successfully treat greater percentages of patients with reduced complications is paramount. A better understanding of pertinent immune pathways in IBD will improve our ability to both successfully dampen inflammation and promote gut healing, beyond just inhibiting specific immune proteins; success of combination therapies supports this approach. Interferons (IFNs) are key cytokines that protect mucosal barrier surfaces, and their roles in regulating gut homeostasis and inflammation differ between the three IFN families (type I, II, and III). Interestingly, the gut microbiota and microbial metabolites impact IFN-signaling, yet how this system is impacted in IBD remains unclear. In this review, we discuss the current knowledge of how gut microbiota directly or indirectly impact IFN levels/responses, and what is known about IFNs differentially regulating gut homeostasis and inflammation in animal models or patients with IBD.

Differentiation of Pig Gastric Primary Cells into Mucus Producing Epithelial Cells.

There is a growing interest in the development of in vitro models that mimic the intrinsic characteristics of cells in vivo to replace and/or reduce the use of experimental animals. The stomach is lined with mucus secreting epithelial cells, creating a thick mucus layer that protects the underlying epithelial cells from acid, pathogens, and other harmful agents. Mucins are a main component of the mucus layer, and their secretion is an important protective feature of epithelial cells in vivo. Here, we present a method that differentiates pig gastric primary cells into mucin secreting epithelial cells by culturing the cells on polyester membranes under semi-wet interface for 14days, using differentiation medium containing the N-[(3,5-difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester (DAPT) in the basolateral compartment for the first 7days and subsequent 7-day culture in non-differentiation medium. The in vitro mucosal surfaces created by these cells are harvested 2weeks post confluence, and two preservation methods are described to fix the monolayers for further analysis.

Mucosal SARS-CoV-2 vaccination of rodents elicits superior systemic T central memory function and cross-neutralising antibodies against variants of concern

COVID-19 vaccines used in humans are highly effective in limiting disease and death caused by the SARS-CoV-2 virus, yet improved vaccines that provide greater protection at mucosal surfaces, which could reduce break-through infections and subsequent transmission, are still needed. Here we tested an intranasal (I.N.) vaccination with the receptor binding domain of Spike antigen of SARS-CoV-2 (S-RBD) in combination with the mucosal adjuvant mastoparan-7 compared with the sub-cutaneous (S.C.) route, adjuvanted by either M7 or the gold-standard adjuvant, alum, in mice, for immunological read-outs. The same formulation delivered I.N. or S.C. was tested in hamsters to assess efficacy. I.N. vaccination improved systemic T cell responses compared to an equivalent dose of antigen delivered S.C. and T cell phenotypes induced by I.N. vaccine administration included enhanced polyfunctionality (combined IFN-γ and TNF expression) and greater numbers of T central memory (TCM) cells. These phenotypes were T cell-intrinsic and could be recalled in the lungs and/or brachial LNs upon antigen challenge after adoptive T cell transfer to naïve recipients. Furthermore, mucosal vaccination induced antibody responses that were similarly effective in neutralising the binding of the parental strain of S-RBD to its ACE2 receptor, but showed greater cross-neutralising capacity against multiple variants of concern (VOC), compared to S.C. vaccination. I.N. vaccination provided significant protection from lung pathology compared to unvaccinated animals upon challenge with homologous and heterologous SARS-CoV-2 strains in a hamster model. These results highlight the role of nasal vaccine administration in imprinting an immune profile associated with long-term T cell retention and diversified neutralising antibody responses, which could be applied to improve vaccines for COVID-19 and other infectious diseases. This study was funded by Duke-NUS Medical School, the Singapore Ministry of Education, the National Medical Research Council of Singapore and a DBT-BIRAC Grant.

Thiolated chitosan encapsulation constituted mucoadhesive nanovaccine confers broad protection against divergent influenza A viruses

Influenza A virus (IAV) poses a significant threat to human and animal health, necessitating the development of universal influenza vaccines that can effectively activate mucosal immunity. Intranasal immunization has attracted significant attention due to its capacity to induce triple immune responses, including mucosal secretory IgA. However, inducing mucosal immunity through vaccination is challenging due to the self-cleansing nature of the mucosal surface. Thiolated chitosan (TCS) were explored for mucosal vaccine delivery, capitalizing on biocompatibility and bioadhesive properties of chitosan, with thiol modification enhancing mucoadhesive capability. The focus was on developing a universal nanovaccine by utilizing TCS-encapsulated virus-like particles displaying conserved B-cell and T-cell epitopes from M2e and NP proteins of IAV. The optimal conditions for nanoparticle formation were investigated by adjusting the thiol groups content of TCS and the amount of sodium tripolyphosphate. The nanovaccine induced robust immune responses and provided complete protection against IAVs from different species following intranasal immunization. The broad protective effect of nanovaccines can be attributed to the synergistic effect of antibodies and T cells. This study developed a universal intranasal nanovaccine and demonstrated the potential of TCS in the development of mucosal vaccines for respiratory infectious diseases.

Causes of digestive symptoms in patients with COVID-19

This literature review discusses the problem of the causes of digestive symptoms in COVID-19 patients, examining papers in which SARS-CoV-2 gastrointestinal infection was the underlying cause of symptoms and papers in which the occurrence of such symptoms was associated with exacerbation of pre-existing, including previously undiagnosed GI diseases.
 Objective: to identify the most likely underlying cause of digestive symptoms in COVID-19 patients. Materials and Methods. We searched 59 literature sources from eLibrary, PubMed, Scopus, and Google scholar databases. All papers were published in the last 4 years.
 Results. The resulting digestive symptoms in coronavirus lesions are caused by direct disruption of the intestinal barrier; also, these symptoms may be a manifestation of exacerbation or debut of chronic digestive diseases on the background of COVID-19, and exacerbate the course of infection; or a result of COVID-19 therapy. A differential diagnosis of COVID-19 with inflammatory bowel diseases, chronic liver diseases, chronic and acute biliary pancreatitis is required in patients with diarrhea, abdominal pain, elevated blood liver and pancreatic enzymes. The correlation of gastroenterological symptoms with the direct COVID-19 lesion can be established by comparing the clinical picture with the detection of RNA virus in stool, histologic specimens, but sometimes there may be no unambiguous answer. Specific changes on computed tomography with angiography of the abdominal cavity organs (peri-intestinal fatty tissue strands against the background of intestinal wall thickening) are described only in the initial stage of COVID-19, at later stages the changes are nonspecific. Data from endoscopic studies in patients with COVID-19 are limited to single clinical cases or case series describing nonspecific findings and suggesting that the virus directly damages GI mucosal surfaces. This calls into question the results of the studies that have been conducted, most of which were retrospective and did not evaluate the baseline presence of gastrointestinal symptoms prior to COVID-19. Due to the peculiarities of the virus interaction with body cells and the diversity of clinical manifestations of the disease, a combined approach in the diagnosis of GI diseases in COVID-19 is necessary.

Nasal polyps show decreased mucociliary transport despite vigorous ciliary beating

ObjectiveMucociliary transport function in the airway mucosa is essential for maintaining a clean mucosal surface. This function is impaired in upper and lower airway diseases. Nasal polyps are a noticeable pathological feature that develop in some of the patients with chronic rhinosinusitis. Like ordinary nasal mucosae, nasal polyps have a ciliated pseudostratified epithelium with vigorous ciliary beating. We measured ex vivo Mucociliary Transport Velocity (MCTV) and Ciliary Beat Frequency (CBF) and explored the expressions of Planar Cell Polarity (PCP) proteins in nasal polyps in comparison with turbinate mucosae. MethodsInferior turbinates and nasal polyps were surgically collected from patients with chronic rhinosinusitis. Ex vivo MCTV and CBF were measured using a high-speed digital imaging system. Expressions of PCP proteins were explored by fluorescence immunohistochemistry and quantitative RT-PCR. ResultsThe MCTV of nasal polyps was significantly lower than that of the turbinates (7.43 ± 2.01 vs. 14.56 ± 2.09 μm/s; p = 0.0361), whereas CBF did not differ between the two tissues. The MCTV vector was pointed to the posteroinferior direction in all turbinates with an average inclination angle of 41.0 degrees. Immunohistochemical expressions of Dishevelled-1, Dishevelled-3, Frizzled3, Frizzled6, Prickle2 and Vangl2 were lower in the nasal polyps than in the turbinates. Confocal laser scanning microscopy showed that Frizzled3 was localized along the cell junction on the apical surface. The expression levels of mRNAs for Dishevelled-1, Dishevelled-3 and Frizzled3 in the nasal polyps were also decreased in comparison with the turbinates. ConclusionThese results indicate that muco ciliary transport in nasal polyps is impaired although vigorous ciliary beating is maintained, and that the impairment may be caused by a decrease in Dishevelled/Frizzled proteins and resultant PCP disarrangement. Level of evidenceLevel 3.

Knowledge of head and neck cancer among medical students in the UK

Head and neck cancer (HNC) refers to malignancies found in mucosal surfaces anywhere from the paranasal sinuses to the larynx, including the various glands and cavities. Between the years 2016 and 2018, there were about 3900 new cases every year in women and 8600 in men, making it the thirteenth most common cancer in women and fourth most common in men. The aim of our study was to evaluate the amount and type of teaching United Kingdom (UK) medical students receive on HNC, and to assess their current knowledge of these cancers. An online survey distributed via university representatives was responded to by 311 final year medical students from 25 medical schools across the UK. Regarding HNC teaching, 72 students (23.2%) reported receiving no teaching at their medical school. Of the 239 who reported receiving teaching, 169 (54.3%) received it in the format of a non-interactive, large group lecture. A total of 271 respondents (87.1%) believed that medical students at their university would benefit from more teaching on HNC. Based on our sample, there appears to be an overall dissatisfaction and lack of confidence surrounding HNC in the undergraduate curriculum. With its increasing prevalence in the UK, it is vital that red-flag symptoms and referral criteria are understood by the future medical workforce.

Ovarian sex steroid and epithelial control of immune responses in the uterus and oviduct: human and animal models†.

The female reproductive tract (FRT), including the uterus and oviduct (Fallopian tube), is responsible for maintaining an optimal microenvironment for reproductive processes, such as gamete activation and transportation, sperm capacitation, fertilization, and early embryonic and fetal development. The mucosal surface of the FRT may be exposed to pathogens and sexually transmitted microorganisms due to the opening of the cervix during mating. Pathogens and endotoxins may also reach the oviduct through the peritoneal fluid. To maintain an optimum reproductive environment while recognizing and killing pathogenic bacterial and viral agents, the oviduct and uterus should be equipped with an efficient and rigorously controlled immune system. Ovarian sex steroids can affect epithelial cells and underlying stromal cells, which have been shown to mediate innate and adaptive immune responses. This, in turn, protects against potential infections while maintaining an optimal milieu for reproductive events, highlighting the homeostatic involvement of ovarian sex steroids and reproductive epithelial cells. This article will discuss how ovarian sex steroids affect the immune reactions elicited by the epithelial cells of the non-pregnant uterus and oviduct in the bovine, murine, and human species. Finally, we propose that there are regional and species-specific differences in the immune responses in FRT.

Mucosal antibody responses to SARS-CoV-2 booster vaccination and breakthrough infection.

Antibodies on mucosal surfaces of the upper respiratory tract have been shown to be important for protection from infection with SARS-CoV-2. Here we investigate the induction of serum IgG, saliva IgG, and saliva sIgA after COVID-19 mRNA booster vaccination or breakthrough infections.

Whole genome sequence and comparative genomics analysis of multidrug-resistant Staphylococcus xylosus NM36 isolated from a cow with mastitis in Basrah city

BackgroundStaphylococcus xylosus is a coagulase-negative, gram-positive coccus that is found in the environment and as a commensal organism on the skin and mucosal surfaces of animals. Despite the fact that S. xylosus is considered a nonpathogenic bacterium, several studies have linked S. xylosus to opportunistic infections in both animals and humans. During an investigation of mastitis-causing agents in the governorate of Basrah, Iraq, we identified an antibiotic-resistant strain of S. xylosus NM36 from a milk sample from a cow with chronic mastitis. In addition to robust biofilm formation, multiple antibiotic resistance phenotypes were found. To further understand the genetic background for these phenotypes, the full genome of S. xylosus NM36 was analyzed. ResultsThe genome consisted of a single circular 2,668,086 base pairs chromosome containing 32.8% G + C. There were 2454 protein-coding sequences, 4 ribosomal RNA (rRNA) genes, and 50 transfer RNA (tRNA) genes in the genome. In addition, genetic variation was studied by searching sequence data against a representative reference genome. Consequently, single-nucleotide polymorphism analysis was conducted and showed that there were 46,610 single-nucleotide polymorphisms (SNPs), 523 insertions, and 551 deletions. In order to overcome antibiotics, S. xylosus NM36 had been armed with several antibiotic resistance genes from several groups and families. The genome annotation service in PathoSystems Resource Integration Center (PATRIC) and Rapid Annotation using Subsystem Technology (RAST) annotation servers showed that there are multiple antimicrobial resistance elements, including antibiotic inactivation enzymes (BlaZ family, FosB), antibiotic resistance gene clusters (TcaB, TcaB2, TcaR), proteins involved in methicillin resistance (LytH, FmtA, FemC, HmrB, HmrA), TetR family transcriptional regulators, and efflux pumps conferring antibiotic resistance (NorA). In addition, we investigated and categorized the biofilm and quorum-sensing elements of the NM36 strain and found that it has multiple subsets of biofilm regulators, confirming its pathogenic nature. ConclusionsThese findings necessitate a reevaluation of microbial and clinical interventions when dealing with coagulase-negative staphylococci, particularly in the context of studies pertaining to public health. This is the first time, to our knowledge, that the entire genome of S. xylosus has been sequenced in Iraq.

Application of narrow band imaging and Lugol's iodine staining in screening for nasopharyngeal carcinoma

BackgroundTo investigate the diagnostic value of conventional white light endoscopy (WLE), narrow band imaging (NBI) endoscopy, and Lugol's iodine staining under WLE (endoscopic iodine staining) in the screening and early diagnosis of nasopharyngeal carcinoma.MethodsPatients with nasopharyngeal lesions requiring biopsy attending the Department of Otolaryngology Head and Neck Surgery in our hospital between January 2021 and April 2023 were included in this study. Before biopsy, all subjects underwent conventional WLE, NBI endoscopy, and endoscopic iodine staining. On WLE, according to nasopharyngeal lesion morphology and color, patients were diagnosed with nasopharyngeal carcinoma ( +) or chronic hyperplastic nasopharyngitis (-). On NBI endoscopy, according to nasopharyngeal lesion vascular morphology, patients with type V manifestations (nasopharyngeal carcinoma) were categorized as NBI ( +) and patients with type I-IV manifestations (chronic hyperplastic nasopharyngitis) were categorized as NBI (-). Endoscopic iodine staining (1.6% Lugol's iodine solution) was positive ( +) if the mucosal surface was brown with no white patches, or negative (-) if there was no or light brown staining of the mucosal surface. Patients were divided into 2 groups based on histopathological diagnosis: nasopharyngeal carcinoma or chronic hyperplastic nasopharyngitis. Endoscopic diagnoses were compared with histopathological findings. The diagnostic performance of WLE, NBI endoscopy and endoscopic iodine staining for nasopharyngeal carcinoma were determined.ResultsThis study included 159 patients. On histopathology, 29 patients were diagnosed with nasopharyngeal carcinoma, and 130 patients were diagnosed with chronic hyperplastic nasopharyngitis. There were no significant differences in the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic (ROC) curve (AUC) of conventional WLE, NBI endoscopy or endoscopic iodine staining for differentiating nasopharyngeal carcinoma and chronic hyperplastic nasopharyngitis. The diagnostic performance of the combination of conventional WLE, NBI endoscopy and endoscopic iodine staining was significantly improved compared to any procedure alone.ConclusionsConventional WLE, NBI endoscopy or endoscopic iodine staining had good diagnostic performance for differentiating nasopharyngeal carcinoma and chronic hyperplastic nasopharyngitis. In particular, NBI endoscopy and endoscopic iodine staining alone or combined had clinical utility for identifying patients with nasopharyngeal lesions that are eligible for a watch-and-wait strategy.

Mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via mTORC2/HK1-mediated metabolic rewiring

Bacillus Calmette–Guérin (BCG) vaccination induces a type of immune memory known as “trained immunity”, characterized by the immunometabolic and epigenetic changes in innate immune cells. However, the molecular mechanism underlying the strategies for inducing and/or boosting trained immunity in alveolar macrophages remains unknown. Here, we found that mucosal vaccination with the recombinant strain rBCGPPE27 significantly augmented the trained immune response in mice, facilitating a superior protective response against Mycobacterium tuberculosis and non-related bacterial reinfection in mice when compared to BCG. Mucosal immunization with rBCGPPE27 enhanced innate cytokine production by alveolar macrophages associated with promoted glycolytic metabolism, typical of trained immunity. Deficiency of the mammalian target of rapamycin complex 2 and hexokinase 1 abolished the immunometabolic and epigenetic rewiring in mouse alveolar macrophages after mucosal rBCGPPE27 vaccination. Most noteworthy, utilizing rBCGPPE27’s higher-up trained effects: The single mucosal immunization with rBCGPPE27-adjuvanted coronavirus disease (CoV-2) vaccine raised the rapid development of virus-specific immunoglobulin G antibodies, boosted pseudovirus neutralizing antibodies, and augmented T helper type 1-biased cytokine release by vaccine-specific T cells, compared to BCG/CoV-2 vaccine. These findings revealed that mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via reprogramming mTORC2- and HK-1-mediated aerobic glycolysis, providing new vaccine strategies for improving tuberculosis (TB) or coronavirus variant vaccinations, and targeting innate immunity via mucosal surfaces.

SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses

Mucosal antibodies play a key role in the protection against SARS-CoV-2 infection in the upper respiratory tract, and potentially in limiting virus replication and therefore onward transmission. While systemic immunity to SARS-CoV-2 is well understood, we have a limited understanding about the antibodies present on the nasal mucosal surfaces. In this study, we evaluated SARS-CoV-2 mucosal antibodies following previous infection, vaccination, or a combination of both. Paired nasal fluid and serum samples were collected from 143 individuals, which include convalescent, vaccinated, or breakthrough infections. We detected a high correlation between IgG responses in serum and nasal fluids, which were higher in both compartments in vaccinated compared to convalescent participants. Contrary, nasal and systemic SARS-CoV-2 IgA responses were weakly correlated, indicating a compartmentalization between the local and systemic IgA responses. SARS-CoV-2 secretory component IgA (s-IgA) antibodies, present exclusively on mucosal surfaces, were detected in the nasal fluid only in a minority of vaccinated subjects and were significantly higher in previously infected individuals. Depletion of IgA antibodies in nasal fluids resulted in a tremendous reduction of neutralization activity against SARS-CoV-2, indicating that IgA is the crucial contributor to neutralization in the nasal mucosa. Neutralization against SARS-CoV-2 was higher in the mucosa of subjects with previous SARS-CoV-2 infections compared to vaccinated participants. In summary, we demonstrate that currently available vaccines elicit strong systemic antibody responses, but SARS-CoV-2 infection generates higher titers of binding and neutralizing mucosal antibodies. Our results support the importance to develop SARS-CoV-2 vaccines that elicit mucosal antibodies. The work was funded by the COVID-19 National Research Program 78 (grant number 198412) of the Swiss National Science Foundation.

Single-cell landscape reveals the epithelial cell-centric pro-inflammatory immune microenvironment in dry eye development

Dry eye disease (DED) is a prevalent chronic eye disease characterized by an aberrant inflammatory response in ocular surface mucosa. The immunological alterations underlying DED remain largely unknown. In this study, we employed single-cell transcriptome sequencing of conjunctival tissue from environment-induced DED mice to investigate multicellular ecosystem and functional changes at different DED stages. Our results revealed an epithelial subtype with fibroblastic characteristics and pro-inflammatory effects emerging in the acute phase of DED. We also found that T helper (Th)1, Th17, and regulatory T cells (Treg) were the dominant clusters of differentiation (CD)4+ T-cell types involved in regulating immune responses and identified three distinct macrophage subtypes, with the CD72+CD11c+ subtype enhancing chronic inflammation. Furthermore, bulk transcriptome analysis of video display terminal-induced DED consistently suggested the presence of the pro-inflammatory epithelial subtype in human conjunctiva. Our findings have uncovered a DED-associated pro-inflammatory microenvironment in the conjunctiva, centered around epithelial cells, involving interactions with macrophages and CD4+ T cells, which deepens our understanding of ocular surface mucosal immune responses during DED progression.

Trueperella pyogenes endocarditis in a Swiss farmer: a case report and review of the literature

BackgroundTrueperella pyogenes (T. pyogenes) is a bacterium that colonizes the skin and mucosal surfaces of various domestic and wild animals. It rarely leads to infections in humans, with only a few descriptions available in the literature.Case presentationA 71-year-old Swiss farmer with a history of recurring basal cell carcinoma and metastasized pancreatic neuroendocrine tumor presented with signs of sepsis after a three-day history of general weakness, malaise and fever. Clinical and echocardiographic findings, as well as persistent bacteremia were consistent with mitral valve endocarditis caused by T. pyogenes. The patient’s condition gradually improved under antibiotic treatment with piperacillin/tazobactam (empiric therapy of sepsis), and later penicillin G based on resistance testing. He was discharged after 13 days and continued outpatient antibiotic therapy with ceftriaxone, resulting in a total antibiotic treatment duration of six weeks. This is the first literature review of T. pyogenes endocarditis in humans. Among nine cases of T. pyogenes endocarditis, three patients had documented contact with farm animals and five had an underlying condition that compromised the immune system. While antibiotic resistance of T. pyogenes is an emerging concern, susceptibility to beta-lactam antibiotics seems to persist. The mortality of T. pyogenes endocarditis described in the literature was high, with 66% of patients not surviving the disease.ConclusionsT. pyogenes is a rare causative organism of infectious endocarditis in humans and descriptions are mainly restricted to case reports. In our review of the literature, we found that both an impaired immune system and contact with farm animals might be risk factors. Growth of T. pyogenes in blood cultures is unlikely to be missed during routine analysis, as it shows marked beta-hemolysis on blood agar culture plates, which generally leads to further characterization of the bacteria. Susceptibility to penicillin, ceftriaxone, and macrolides seems to be retained and the reported mortality in the few patients with T. pyogenes endocarditis is high.

Effects of Nicotine on the Central Nervous System and Sleep Quality in Relation to Other Stimulants: A Narrative Review.

Nicotine is used extensively across the globe despite the common awareness of the fact that it might stimulate the neurological system in those who indulge in its consumption. Nicotine can be consumed in a wide number of various forms and can also be delivered in a wide variety of different ways. After it has been heated, it can be smoked, consumed sublingually, or brought into touch with mucosal surfaces, with the buccal mucosa being the most popular one. These three methods of consumption account for the vast majority of its use. It has been demonstrated without a reasonable doubt that people who partake in nicotine do, in fact, experience an increase in their levels of alertness, wakefulness, attention, and focus. The half-life of the substance, in addition to its effects, is highly variable depending on the forms in which it is consumed, viz. cigarettes, tobacco, gums, lozenges, and the manner in which it is administered. This is the case regardless of whether the chemical is administered orally or intravenously. It is common for a person to require multiple "hits" of the chemical throughout the course of the day, though the frequency of these needs and the intervals between them can vary greatly. The time interval between each of these "hits" can range anywhere from a few hours to a few minutes. The user has the potential to develop a tolerance to the neurostimulatory and systemic effects of nicotine, as well as a heightened sensitivity to those effects, and even hereditary predispositions to specific adverse consequences. There is also a possibility that the user will develop an addiction to nicotine. This literature review aims to explore the relationship between nicotine consumption and its effects on the central nervous system, especially on sleep.

Sinomenine improves resistance to foodborne enteritis and Anti-bacteria mucosal immunity in grass carp

Based on our previous study in zebrafish, sinomenine was found to relieve foodborne enteritis through immunomodulation. To examine the protective effects of sinomenine on mucosal immunity in farmed fish species, a dietary inclusion study was conducted in grass carp juveniles by adding sinomenine to soybean meal feed. After a 5-week feeding trial to model foodborne enteritis, the gut and liver tissues were examined for histopathology, enteritis-related gene expression, transcriptome, and 16 s rRNA gene sequencing. The results demonstrated that including sinomenine in the diet at the concentration of 2 g/kg could prevent intestinal pathological changes, such as a decrease in the number of goblet cells and increased glycogen, induced by 40% soybean meal substitution. At the molecular level, the downregulated proinflammatory genes, together with upregulated anti-inflammatory genes (such as il10, il13, and tgfβ) were observed. At the omics level, for the DEGs, the downregulated intestinal pathway “phagosome” and term “platelet activation” indicated control of inflammation, while the upregulation of the “PPAR signaling pathway” in both the gut and liver, suggests enhanced immune homeostasis. For the mucosal surface in the sinomenine-supplemented group, we observed not only control of pathogenic Camparilobacterota and Aeromonas but also an increase in Actinobacteria, which may enhance mucosal immunity. Due to the influence of the gut-liver axis, hepatic metabolism was altered, particularly with an upregulation of “fatty acid degradation” and “tryptophan metabolism”. Subsequently, the fish in the sinomenine group exhibited a significantly higher survival rate after a 7-day immersion challenge with Aeromonas hydrophila, with less inflammatory CD4 signals in the gills. Hepatic hypoxia and low respiratory efficiency in the gill may be a side effect. In summary, sinomenine demonstrated a protective effect on the mucosal immunity of the gut and gill, thereby preventing enteritis and subsequent bacteria challenges. Therefore, sinomenine could be employed in aquaculture as phytotherapy, at the very least through dietary supplementation in fish.

Pressure-controlled ventilation-volume guaranteed mode improves bronchial mucus transport velocity in patients during laparoscopic surgery for gynecological oncology: a randomized controlled study

BackgroundMechanical ventilation during general anesthesia may impair airway mucosal function. This study aimed to investigate the effect of pressure-controlled ventilation-volume guaranteed (PCV-VG) on bronchial mucus transport velocity (BTV) in patients during laparoscopic surgery for gynecological oncology compared with volume controlled ventilation (VCV).Methods66 patients undergoing elective a laparoscopic surgery for gynecological oncology. The patients were randomized into two group receiving either PCV-VG or VCV. a drop of methylene blue was placed on the surface of the airway mucosa under the bronchoscopeand, then the distance the dye movement was measured after 2, 4, and 6 min. Outcomes were assessed at T0 (5 min after endotracheal intubation and before initiation of pneumoperitoneum), T1 and T2 (1 and 2 h after stabilization of pneumoperitoneum respectively). BTV at T0, T1 and T2 was the primary outcome. Secondary outcomes included heart rate (HR), mean arterial pressure (MAP), body temperature, end-tidal CO2 pressure (PETCO2), tidal volume(VT), peak inspiratory pressure (PIP), mean inspiratory pressure (Pmean), respiratory rate (RR), and dynamic compliance (CDyn) at T0, T1, and T2.Results64 patients were included in the analysis. The median [interquartile range] BTV was significantly lower in VCV group at T1 and T2 that at T0 (P < 0.05). Furthermore, BTV was slightly reduced in PCV-VG compared with VCV. BTV in PCV-VG was significantly decreased at T2 compared with BTV at T0 (P < 0.05) and slightly decreased at T1 compared with T0(P > 0.05). Compared with the PCV-VG group, BTV in VCV group significantly decreased at T2 (P < 0.05). No participants experienced respiratory complications.ConclusionsPCV-VG is more suitable for patients undergoing laparoscopic surgery for gynecological oncology than VCV since it can protect mucociliary clearance function.Trial registrationThis trial is registered on https://www.chictr.org.cn/ in Chinese Clinical Trial Registry (ChiCTR.2200064564: Date of registration 11/10/2022).

Impact of COVID-19 vaccination on saliva immune barriers: IgA, lysozyme, and lactoferrin.

Understanding the role of salivary constituents, such as lactoferrin, lysozyme, and secretory immunoglobulin A (sIgA), in immune protection and defense mechanisms against microbial invasion and colonization of the airways is important in light of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The salivary immune barrier in individuals affected by COVID-19 may contribute to disease prognosis. Thus, the aim of the present review is to evaluate the effect of COVID-19 vaccines on the immunological composition of saliva. IgA antibodies generated by vaccination can neutralize the virus at mucosal surfaces, whereas antimicrobial peptides, such as lysozyme and lactoferrin, have broad-spectrum antimicrobial activity. Collectively, these components contribute to the protective immune response of the oral cavity and may help minimize viral transmission as well as the severity of COVID-19. Measuring the levels of these components in the saliva of COVID-19-vaccinated individuals can help in evaluating the vaccine's ability to induce mucosal immunity, and it might also provide insights into whether saliva can be used in diagnostics or surveillance for monitoring immune responses following vaccination. This also has implications for viral transmission.