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To accurately measure the vaginal mucosa thickness across different age groups using histopathologic techniques and investigate the factors that may influence the thickness changes. This study aims to provide clinicians with objective evidence of variations in vaginal mucosal thickness, facilitating personalized medical decisions for patients. A retrospective analysis was conducted on clinical data from 348 patients who underwent local vaginal wall resection at the West China Second University Hospital, Sichuan University, from January 2021 and May 2022. The thickness of vaginal mucosa, epithelium and lamina propria was measured precisely under the microscope. And the 10th, 25th, 50th, 75th, and 90th percentile values of vaginal mucosa thickness across different age groups were counted and charted a dot-line plot. The percentile values for vaginal mucosa thickness exhibited a decreasing trend with increasing age; vaginal mucosa thickness showed significant correlations with times of delivery ( P  = 0.031) and age ( P  < 0.001), both of which were negatively associated. And vaginal mucosa thickness demonstrated no significant correlation with body mass index (BMI) ( P  = 0.325), times of abortions ( P  = 0.511), times of gestation ( P  = 0.101), menstrual cycle ( P  = 0.533), or types of delivery ( P  = 0.056); epithelial thickness showed significant associations with age ( P  < 0.001) and types of delivery ( P  = 0.017), both of which were negative correlations. Moreover, BMI ( P  = 0.429), times of abortions ( P  = 0.764), delivery ( P  = 0.079), gestation ( P  = 0.475), and menstrual cycle ( P  = 0.950) were nonassociated with epithelial thickness; lamina propria thickness displayed a significant correlation only with age ( P  = 0.002), and there were no obvious correlations observed between lamina propria thickness and BMI ( P  = 0.374), times of abortion ( P  = 0.417), delivery ( P  = 0.053), gestation ( P  = 0.101), types of delivery ( P  = 0.132) and menstrual cycle ( P  = 0.495). Moreover, when the age segmentation was thresholded at 35 and 50 years, both epithelial thickness and vaginal mucosa thickness were significantly correlated with age ( P  < 0.05). Lamina propria thickness was associated with age when the age threshold was set at 35 years ( P  = 0.007), whereas it showed no strong link with age when the age threshold was 50 years ( P  = 0.072). This study has innovatively established percentile reference values for vaginal mucosa thickness based on histopathology, furnishing clinicians with objective evidence of variations in vaginal mucosal thickness to facilitate personalized medical decisions for patients. The findings demonstrated a strong link between vaginal mucosa thickness and age, with epithelium likely playing a predominant role, while the association with lamina propria appeared to be less significant. Further research involving a larger sample size is warranted to elucidate the potential relationship with the lamina propria.

The mucosal surfaces of our body are the main contact site where the immune system encounters non-self molecules from food-derived antigens, pathogens, and symbiotic bacteria. γδ T cells are one of the most abundant populations in the gut. Firstly, they include intestinal intraepithelial lymphocytes, which screen and maintain the intestinal barrier integrity in close contact with the epithelium. A second layer of intestinal γδ T cells is found among lamina propria lymphocytes (LPL)s. These γδ LPLs are able to produce IL-17 and likely have functional overlap with local Th17 cells and innate lymphoid cells. In addition, a third population of γδ T cells resides within the Peyer´s patches, where it is probably involved in antigen presentation and supports the mucosal humoral immunity. Current obstacles in understanding γδ T cells in the gut include the lack of information on cognate ligands of the γδ TCR and an incomplete understanding of their physiological role. In this review, we summarize and discuss what is known about different subpopulations of γδ T cells in the murine and human gut and we discuss their interactions with the gut microbiota in the context of homeostasis and pathogenic infections.

The gram-negative facultative intracellular bacteria Salmonella Typhimurium (STM) often leads to subclinical infections in pigs, but can also cause severe enterocolitis in this species. Due to its high zoonotic potential, the pathogen is likewise dangerous for humans. Vaccination with a live attenuated STM strain (Salmoporc) is regarded as an effective method to control STM infections in affected pig herds. However, information on the cellular immune response of swine against STM is still scarce. In this study, we investigated the T-cell immune response in pigs that were vaccinated twice with Salmoporc followed by a challenge infection with a virulent STM strain. Blood- and organ-derived lymphocytes (spleen, tonsils, jejunal and ileocolic lymph nodes, jejunum, ileum) were stimulated in vitro with heat-inactivated STM. Subsequently, CD4 + T cells present in these cell preparations were analyzed for the production of IFN-γ, TNF-α, and IL-17A by flow cytometry and Boolean gating. Highest frequencies of STM-specific cytokine-producing CD4 + T cells were found in lamina propria lymphocytes of jejunum and ileum. Significant differences of the relative abundance of cytokine-producing phenotypes between control group and vaccinated + infected animals were detected in most organs, but dominated in gut and lymph node-residing CD4 + T cells. IL-17A producing CD4 + T cells dominated in gut and gut-draining lymph nodes, whereas IFN-γ/TNF-α co-producing CD4 + T cells were present in all locations. Additionally, the majority of cytokine-producing CD4 + T cells had a CD8α + CD27 - phenotype, indicative of a late effector or effector memory stage of differentiation. In summary, we show that Salmonella -specific multifunctional CD4 + T cells exist in vaccinated and infected pigs, dominate in the gut and most likely contribute to protective immunity against STM in the pig.

Cytosolic Malic Enzyme (ME1) provides reduced NADP for anabolism and maintenance of redox status. To examine the role of ME1 in tumor genesis of the gastrointestinal tract, we crossed mice having augmented intestinal epithelial expression of ME1 (ME1-Tg mice) with Apc Min/+ mice to obtain male Apc Min/+ /ME1-Tg mice. ME1 protein levels were significantly greater within gut epithelium and adenomas of male Apc Min/+ /ME1-Tg than Apc Min/+ mice. Male Apc Min/+ /ME1-Tg mice had larger and greater numbers of adenomas in the small intestine (jejunum and ileum) than male Apc Min/+ mice. Male Apc Min/+ /ME1-Tg mice exhibited greater small intestine crypt depth and villus length in non-adenoma regions, correspondent with increased KLF9 protein abundance in crypts and lamina propria . Small intestines of male Apc Min/+ /ME1-Tg mice also had enhanced levels of Sp5 mRNA, suggesting Wnt/β-catenin pathway activation. A small molecule inhibitor of ME1 suppressed growth of human CRC cells in vitro , but had little effect on normal rat intestinal epithelial cells. Targeting of ME1 may add to the armentarium of therapies for cancers of the gastrointestinal tract.

Since their discovery, innate lymphoid cells (ILCs) have gradually been gaining greater relevance in the field of immunology due to their multiple functions in the innate immune response. They can mainly be found in mucosal and barrier organs like skin, gut, and lungs, and have been classified into five main types (NKs, ILC1s, ILC2s, ILC3s, and Lti cells) according to their function and development. They all play major roles in functions such as tissue homeostasis, early pathogen defense, regulation of inflammation, or tissue remodeling. ILCs are mostly tissue-resident cells tightly bound to the tissue structure, a fact that requires long and complex protocols that do not always provide sufficient yield for analysis. This suggests the need for optimized approaches aimed at ensuring that enriched and viable ILC samples are obtained, in order to furnish quality results. Herein a detailed protocol is established for obtaining a single-cell suspension highly enriched in lymphoid cells from mouse gut in order to identify the different subsets of ILCs by means of flow cytometry. The cell marker panel and flow cytometry gating strategies for identification and quantification of all the different ILC populations are provided for simultaneous analysis. Moreover, the protocol described includes a procedure for studying the different cytokines produced by ILC3s involved in maintaining the integrity of the gut barrier and defending against extracellular pathogens. As a result, herein an efficient method is presented for studying mouse ILCs within the lamina propria of the small intestine and colon; this can constitute a useful tool for future investigations in the field.

Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to suprasacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor), three types of telocytes (TC) are present and form a 3D‐network. TC are stromal cells able to form the scaffold that contains and organizes the connective components, to serve as guide for tissue (re)‐modelling, to produce trophic and/or regulatory molecules, to share privileged contacts with the immune cells. Specimens of full thickness bladder wall from NDO patients were collected with the aim to investigate possible changes of the three TC types using histology, immunohistochemistry and transmission electron microscopy. The results show that NDO causes several morphological TC changes without cell loss or network interruption. With the exception of those underlying the urothelium, all the TC display signs of activation (increase in Caveolin1 and caveolae, αSMA and thin filaments, Calreticulin and amount of cisternae of the rough endoplasmic reticulum, CD34, euchromatic nuclei and large nucleoli). In all the specimens, a cell infiltrate, mainly consisting in plasma cells located in the vicinity or taking contacts with the TC, is present. In conclusion, our findings show that NDO causes significant changes of all the TC. Notably, these changes can be interpreted as TC adaptability to the pathological condition likely preserving each of their peculiar functions.

Adenosine 5′-triphosphate (ATP) is released in the bladder lumen during filling. Urothelial ATP is presumed to regulate bladder excitability. Urinary ATP is suggested as a urinary biomarker of bladder dysfunctions since ATP is increased in the urine of patients with overactive bladder, interstitial cystitis or bladder pain syndrome. Altered urinary ATP might also be associated with voiding dysfunctions linked to disease states associated with metabolic syndrome. Extracellular ATP levels are determined by ATP release and ATP hydrolysis by membrane-bound and soluble nucleotidases (s-NTDs). It is currently unknown whether s-NTDs regulate urinary ATP. Using etheno-ATP substrate and HPLC-FLD detection techniques, we found that s-NTDs are released in the lumen of ex vivo mouse detrusor-free bladders. Capillary immunoelectrophoresis by ProteinSimple Wes determined that intraluminal solutions (ILS) collected at the end of filling contain ENTPD3 > ENPP1 > ENPP3 ≥ ENTPD2 = NT5E = ALPL/TNAP. Activation of adenylyl cyclase with forskolin increased luminal s-NTDs release whereas the AC inhibitor SQ22536 had no effect. In contrast, forskolin reduced and SQ22536 increased s-NTDs release in the lamina propria. Adenosine enhanced s-NTDs release and accelerated ATP hydrolysis in ILS and lamina propria. Therefore, there is a regulated release of s-NTDs in the bladder lumen during filling. Aberrant release or functions of urothelial s-NTDs might cause elevated urinary ATP in conditions with abnormal bladder excitability.

Infectious bursal disease virus (IBDV) is one of the most important infectious diseases of poultry around the world. Gut-associated lymphoid tissues (GALT) are the first line of defense of the host against the infection. The purpose of this study was to investigate the role of innate immune antiviral signaling triggered by Toll-like receptor 3 (TLR3), as well as macrophage activation and cytokine response in the intestinal lamina propria (ILP) cells after the oral challenge of IBDV in relation to IBDV virulence and disease pathogenesis. The results showed that the expression levels of TLR3, IRF7, IFN-α/β and the corresponding downstream antiviral factors OAS, PKR and Mx were all upregulated in the SPF chicken ILP cells at 8 h post-infection (hpi) and 12 hpi. Similarly, macrophages were activated, with the initial macrophage M1 activation observed at 8 hpi, but then it rapidly shifted to a non-protective M2-type. Both Th1 (IFN-γ, TNF-α, IL-12) and Th2 (IL-4 and IL-10) types of cytokines were differentially upregulated during the early stage of infection; however, the Th1 cytokines exhibited stronger activation before 8 hpi compared to those of the Th2 cytokines. Interestingly, differential regulations of gene expression induced by different IBDV strains with different virulence were detected. The HLJ0504-like very virulent (vv) IBDV strain NN1172 induced stronger activation of TLR3-IFN-α/β pathway, macrophages and the Th1/2 cytokines’ expression, compared to those induced by the attenuated strain B87 at 8 hpi and 12 hpi in the ILP cells. In conclusion, the innate antiviral response mediated by the TLR3-IRF7 pathway, macrophage activation and cytokine expression in the GALT cells at the early stage of IBDV infection was differentially modulated, and the HLJ0504-like vvIBDV strain triggered stronger activation than the attenuated vaccine strain, and that may play an important role in the progression of disease.

Sulcus vocalis is a frequent cause of glottic insufficiency that leads to incomplete vocal fold closure during phonation. Type II sulcus vocalis is defined as a partial defect of the lamina propria (LP). Treatment with fillers, such as fat or hyaluronic acid (HA), in the vocal folds is widely used, but the duration of effect is variable. Platelet-rich plasma (PRP) can enhance the survival of autologous fat in fat grafting, and also is used to treat sulcus vocalis. This study aimed to compare the effectiveness of autologous fat graft versus fat graft plus PRP to treat type II sulcus vocalis. Thirty-four patients with a voice handicap index (VHI) ≥ 11 were randomized to two groups, which received LP injections of fat graft (n = 17) or fat graft plus PRP (n = 17). At 1 month and 6 months after injection, the VHI decreased significantly in both groups. The fat plus PRP group had better Jitter, Shimmer, and noise to harmonic ratio (NHR) in 1 month and 6 months after surgery. The fat plus PRP group resulted in lower VHI scores one month after surgery, and stroboscopy revealed sustained smaller gaps after six months. These results indicate that a combination of fat graft plus PRP is safe and effective for treating sulcus vocalis type II and associated vocal atrophy.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are involved in anti-bacterial immunity. MAIT cells are found in the intestines, but their role and distribution within the large intestine have not been fully elucidated. Therefore, we investigated the distribution of MAIT cells within the cecum and colon. Surgically resected tissues of the cecum and colon were obtained from 4 patients with cecal appendix cancer and 8 patients with colorectal cancer, respectively. Lymphocytes were isolated from the intestinal epithelium (intraepithelial lymphocytes - IELs) and the underlying lamina propria (lamina propria lymphocytes - LPLs), and then, MAIT cells were analyzed by flow cytometry. Compared with the colon, the cecum showed a significantly increased frequency of MAIT cells among IELs (p < 0.01). CD69 expression on MAIT cells was significantly increased in the cecum and colon compared with that in the blood, and the frequency of natural killer group 2, member A cells among MAIT cells was significantly increased in the cecum. These results suggest that the distribution of MAIT cells was different between the cecum and colon and that MAIT cells were more likely to be activated, especially in the intestinal epithelium of the cecum than in the colon and blood.