With the advancement of medical and digital technologies, smart skin adhesive patches have emerged as a key player for complex medical purposes. In particular, skin adhesive patches with integrated ...electronics have created an excellent platform for monitoring health conditions and intelligent medication. However, the efficient design of the adhesive patches is still challenging as it requires a strong combination of network structure, adhesion, physical properties, and biocompatibility. To design an assimilated device, one must have a deep knowledge of various skin adhesive patches. This article provides a comprehensive review of the recent advances in skin‐adhesive patches, including hydrogel‐based adhesive patches, transdermal patches, and electronic skin (E‐skin) patches, for various biomedical applications such as wound healing, drug delivery, biosensing, and health monitoring. Furthermore, the key challenges, implementable strategies, and future designs that can potentially provide researchers in designing innovative multipurpose smart skin patches are discussed. These advanced approaches are promising for managing the health and fitness of patients who require regular medical care.
While skin adhesive patches have emerged as a promising solution for transdermal theragnostic; the cutting‐edge design of skin patches is still challenging for translational applications. This review recapitulates the latest advances in skin‐adhesive patches, including hydrogel‐based adhesive patches, transdermal patches, and E‐skin patches that can help researchers to design innovative multipurpose skin patches.
Skin infections caused by bacteria, viruses and fungi are difficult to treat by conventional topical administration because of poor drug penetration across the stratum corneum. This results in low ...bioavailability of drugs to the infection site, as well as the lack of prolonged release. Emerging antimicrobial transdermal and ocular microneedle patches have become promising medical devices for the delivery of various antibacterial, antifungal, and antiviral therapeutics. In the present review, skin anatomy and its barriers along with skin infection are discussed. Potential strategies for designing antimicrobial microneedles and their targeted therapy are outlined. Finally, biosensing microneedle patches associated with personalized drug therapy and selective toxicity toward specific microbial species are discussed.
Antimicrobial microneedle (MN) patches are portable medical devices for combating skin infections. Contrary to conventional topical administration, MNs enhance the bioavailability of antibacterial, antifungal, and antiviral therapeutics to the skin and eyes. These promising armaments release their cargo in controlled release. They can respond to biosignals such as changes in pH and microbial enzyme load at the infection site.
Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide. Because the production of T cells ...declines with age, naive T cells must be long-lived. However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens. The concentration of S1P is higher in circulatory fluids than in lymphoid organs, and the S1P
receptor (S1P
R) directs the exit of T cells from the spleen into blood, and from lymph nodes and Peyer's patches into lymph. Here we show that S1P is essential not only for the circulation of naive T cells, but also for their survival. Using transgenic mouse models, we demonstrate that lymphatic endothelial cells support the survival of T cells by secreting S1P via the transporter SPNS2, that this S1P signals through S1P
R on T cells, and that the requirement for S1P
R is independent of the established role of the receptor in guiding exit from lymph nodes. S1P signalling maintains the mitochondrial content of naive T cells, providing cells with the energy to continue their constant migration. The S1P signalling pathway is being targeted therapeutically to inhibit autoreactive T cell trafficking, and these findings suggest that it may be possible simultaneously to target autoreactive or malignant cell survival.
Coptis chinensis Franch is one of the most widely used traditional Chinese herbs in China and was firstly recorded in "Shennong's Classic of Materia Medica” in the Han Dynasty. The medical records in ...past thousands years have fully confirmed the clinical efficacies of Coptis chinensis Franch against intestinal diseases. The polysaccharides in herbal medicines can be digested by the flora and uptaken by the Peyer's patches (PPs) in intestine. It can be reasonably presumed that the polysaccharides in Coptis chinensis Franch (CCP) should be one of the critical element in the regulation of intestinal microenvironment.
This study intended to explore the dynamic regulation of CCP on intestinal microenvironment from the perspective of the intestinal mucosal immunity and the intestinal flora, in order to provide a new research perspective for the pharmacological mechanism of Coptis chinensis Franch.
The absorption and distribution of CCP in intestinal tissues were observed after the perfusion of FITC labeled CCP. The influences of CCP on intestinal flora were evaluated by the 16sRNA gene illumina-miseq sequencing after gavage. The regulations of CCP on intestinal mucosal immunity were evaluated by the immunohistochemical analysis of the interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) secretion in PPs and intestinal epithelial tissue.
With the self-aggregation into particles morphology, CCP can be up-taken by PPs and promote the IFN-γ, IL-4, IL-17 and TGF-β secretion in PPs in a dose-dependent manner. The CCP can also be utilized by the intestinal flora and dynamically regulate the diversity, composition and distribution of the intestinal flora. The temporal regulations of CCP on IFN-γ, IL-4, IL-17 and TGF-β secretions in intestinal epithelial tissues are consistent with the variation tendency of intestinal flora.
CCP can provide effective, dynamical and dose-dependent regulations on intestinal microenvironment, not only the intestinal flora but also the PPs and intestinal epithelium related immune response. These may be involved in the multiple biological activities of Coptis chinensis Franch.
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•Coptis chinensis Franch Polysaccharides (CCP) enters PPs in the form of particle.•CCP can dynamically regulate intestinal flora diversity；.•CCP can dynamically regulate the intestinal immune microenvironment.
In this study, an acidic polysaccharide from
Nannf. var.
(Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to ...consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-β-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of β-d-(1→4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4
/CD8
T lymphocyte ratio. These results suggest that β-d-(1→4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.
Despite our knowledge of the protective role of antibodies passed to infants through breast milk, our understanding of immunity transfer via maternal leukocytes is still limited. To emulate the ...immunological interface between the mother and her infant while breast-feeding, we used murine pups fostered after birth onto MHC-matched and MHC-mismatched dams. Overall, data revealed that: 1) Survival of breast milk leukocytes in suckling infants is possible, but not significant after the foster-nursing ceases; 2) Most breast milk lymphocytes establish themselves in specific areas of the intestine termed Peyer's patches (PPs); 3) While most leukocytes in the milk bolus were myeloid cells, the majority of breast milk leukocytes localized to PPs were T lymphocytes, and cytotoxic T cells (CTLs) in particular; 4) These CTLs exhibit high levels of the gut-homing molecules α4β7 and CCR9, but a reduced expression of the systemic homing marker CD62L; 5) Under the same activation conditions, transferred CD8 T cells through breast milk have a superior capacity to produce potent cytolytic and inflammatory mediators when compared to those generated by the breastfed infant. It is therefore possible that maternal CTLs found in breast milk are directed to the PPs to compensate for the immature adaptive immune system of the infant in order to protect it against constant oral infectious risks during the postnatal phase.
Fibroblastic reticular cells (FRCs) determine the organization of lymphoid organs and control immune cell interactions. While the cellular and molecular mechanisms underlying FRC differentiation in ...lymph nodes and the splenic white pulp have been elaborated to some extent, in Peyer's patches (PPs) they remain elusive. Using a combination of single-cell transcriptomics and cell fate mapping in advanced mouse models, we found that PP formation in the mouse embryo is initiated by an expansion of perivascular FRC precursors, followed by FRC differentiation from subepithelial progenitors. Single-cell transcriptomics and cell fate mapping confirmed the convergence of perivascular and subepithelial FRC lineages. Furthermore, lineage-specific loss- and gain-of-function approaches revealed that the two FRC lineages synergistically direct PP organization, maintain intestinal microbiome homeostasis and control anticoronavirus immune responses in the gut. Collectively, this study reveals a distinct mosaic patterning program that generates key stromal cell infrastructures for the control of intestinal immunity.
Microbiota-induced cytokine responses participate in gut homeostasis, but the cytokine balance at steady-state and the role of individual bacterial species in setting the balance remain elusive. ...Herein, systematic analysis of gnotobiotic mice indicated that colonization by a whole mouse microbiota orchestrated a broad spectrum of proinflammatory T helper 1 (Th1), Th17, and regulatory T cell responses whereas most tested complex microbiota and individual bacteria failed to efficiently stimulate intestinal T cell responses. This function appeared the prerogative of a restricted number of bacteria, the prototype of which is the segmented filamentous bacterium, a nonculturable Clostridia-related species, which could largely recapitulate the coordinated maturation of T cell responses induced by the whole mouse microbiota. This bacterium, already known as a potent inducer of mucosal IgA, likely plays a unique role in the postnatal maturation of gut immune functions. Changes in the infant flora may thus influence the development of host immune responses.
The interrelationship between IgAs and microbiota diversity is still unclear. Here we show that BALB/c mice had higher abundance and diversity of IgAs than C57BL/6 mice and that this correlated with ...increased microbiota diversity. We show that polyreactive IgAs mediated the entrance of non-invasive bacteria to Peyer’s patches, independently of CX3CR1+ phagocytes. This allowed the induction of bacteria-specific IgA and the establishment of a positive feedback loop of IgA production. Cohousing of mice or fecal transplantation had little or no influence on IgA production and had only partial impact on microbiota composition. Germ-free BALB/c, but not C57BL/6, mice already had polyreactive IgAs that influenced microbiota diversity and selection after colonization. Together, these data suggest that genetic predisposition to produce polyreactive IgAs has a strong impact on the generation of antigen-specific IgAs and the selection and maintenance of microbiota diversity.
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•Different mouse strains have diverse predisposition to produce innate IgAs•Innate IgAs allow a controlled bacterial entrance•IgA-coated bacteria initiate a positive feedback loop of IgA production•IgA diversity results in microbiota diversification
Reduced microbiota diversity has been associated with several pathologic conditions. Rescigno et al. show that the capacity to produce innate IgAs has an impact on microbiota diversity. IgAs can mediate the internalization of non-invasive bacteria and the initiation of a positive feedback loop of IgA production. IgA diversity might be a marker of a healthy condition.
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