Antimicrobial peptides (AMPs), such as cathelicidins, show dual functionality by directly combating pathogens and indirectly eliminating them through stimulation of the immune system, generating interest in their therapeutic potential. Pigs have a large set of 11 cathelicidins, of which PMAP-37 is relatively understudied compared to some of the better-known cathelicidins. This study describes the effectiveness of PMAP-37 against both bacteria and viruses. PMAP-37 exhibited potent in vitro antimicrobial activity against both Gram-positive (Bacillus globigii) and Gram-negative bacteria (Escherichia coli) with minimum bactericidal concentrations (MBCs) of 2.5 and 5 μM, respectively. PMAP-37 caused a rapid permeabilization of E. coli's outer and inner membranes within 5 min, indicating its efficacy in disrupting bacterial cell membranes. Furthermore, PMAP-37 neutralized nitric oxide production in a macrophage cell line stimulated with various forms of LPS, Lipid A, or LTA in a dose-dependent manner. Flow cytometric analysis confirmed PMAP-37's capacity to inhibit LPS binding to macrophages, while zeta potential analysis showed the peptide's capacity to neutralize the negative charge of both the E. coli membrane and LPS micellular surfaces. Interestingly, PMAP-37 also exhibited antiviral activity against an important porcine pathogen, the porcine epidemic diarrhea virus (PEDV). These findings underscore the multifunctional properties of PMAP-37, and provide potential leads for future therapeutic use within the pig industry.

The human defensins are a group of cationic antimicrobial peptides that range in size from 2 to 5 kDa and share a common structural motif of six disulphide-linked cysteines. Several naturally occurring human α- and β-defensins have been identified over the past two decades. They have a wide variety of antimicrobial effects, and their potential to avoid the development of resistance to antimicrobial treatment makes them attractive as therapeutic agents. Human defensins have recently been the focus of medical and molecular biology studies due to their promising application in medicine and the pharmaceutical industry. This work aims to provide a comprehensive summary of the current developments of human defensins, including their identification, categorization, molecular features, expression, modes of action, and potential application in medical settings. Current obstacles and future opportunities for using human defensins are also covered. Furthermore, we shed light on the potential of this class as an antiviral agent, particularly against SARS CoV-2, by providing an in silico-based investigation of their plausible mechanisms of action.

Defensins are a type of host defense peptides (HDPs), belonging to a family of cationic antimicrobial peptides (AMPs) that exhibit activity against various infectious microorganisms including bacteria, viruses, and fungi. Due to the uniqueness of the ocean's ecological environment, defensins from marine animals have a rich biodiversity and some special molecular features so as to possess significant potential. They exert antibacterial activity by binding to cell membranes, forming specific channels, or interacting with lipid II. These peptides can be utilized through various nanotechnologies, such as antimicrobial peptide-antibiotic conjugates, nanonets, and nanoparticle-based drug delivery systems, to enhance their antibacterial activities and broaden their spectra. This review summarizes the structural characteristics and classification of defensins from marine animals (mainly fish and shellfish), outlines their evolutionary trajectory, and discusses their antibacterial, antiviral, immune-regulation, and reproductive functions. Finally, the future therapeutic potential of defensins from marine animals is highlighted for fighting antibiotic resistance and treating other diseases. This review provides new insights into the future development of marine resources and natural peptides.

Biosimilars represent medicinal products that exhibit a high degree of similarity to an already sanctioned reference biologic agent, with negligible clinically significant disparities concerning safety, purity, or potency. These therapeutic modalities are formulated as economically viable substitutes for established biologics, thereby facilitating increased accessibility to sophisticated treatments for a range of medical conditions, including infectious diseases caused by bacterial, fungal, and viral pathogens. The current landscape of biosimilars includes therapeutic proteins, such as monoclonal antibodies, antimicrobial peptides, antiviral peptides, and antifungal peptides. Here, we discuss the obstacles inherent in the development of biosimilars, including the rapid mutation rates of pathogens. Furthermore, we discuss innovative technologies within the domain, including antibody engineering, synthetic biology, and cell-free protein synthesis, which exhibit potential for improving the potency and production efficiency of biosimilars. We end with a prospective outlook to highlight the importance and capacity of biosimilars to tackle emerging infectious diseases, highlighting the imperative need for ongoing research and financial commitment.

Bacterial keratitis is a prevalent, and severe corneal illness resulting from bacterial pathogens. Failure to administer a timely and suitable therapy may lead to corneal opacity, ulceration, significant vision impairment, or potential blindness. Current clinical interventions for bacterial keratitis involve the administration of topical antimicrobial agents and systemic antibiotics. However, the misuse and overuse of antibiotics have led to the rapid emergence of antibiotic-resistant bacteria. Additionally, the restricted antibacterial spectrum and possible adverse effects of antibiotics have provided considerable obstacles to traditional therapies. This highlights the urgent need for novel and highly effective antimicrobial agents. Antimicrobial peptides (AMPs) are a class of naturally occurring or synthetically designed small molecules that have gained significant attention due to their unique antimicrobial mechanisms and low risk of resistance development. AMPs exhibit promising potential in treating bacterial keratitis through direct antibacterial mechanisms, such as inhibiting cell wall synthesis, disrupting cell membranes, and interfering with nucleic acid metabolism, as well as indirect mechanisms, including modulation of the host immune response. This review provides a comprehensive overview of the antibacterial mechanisms of AMPs and their advancements in the treatment of bacterial keratitis. It emphasizes the role of various modification strategies and artificial-intelligence-assisted design in enhancing the antibacterial efficacy, stability, and biocompatibility of AMPs. Furthermore, this review discusses the latest progress in combining AMPs with delivery systems for improved therapeutic outcomes. Finally, the review highlights the current challenges and future perspectives of AMPs in bacterial keratitis treatment, providing valuable insights for developing novel AMPs with high antibacterial efficacy, stability, and safety for bacterial keratitis therapies.

Among all malignancies, colorectal cancer ranks third in incidence rate and second in mortality rate. Human beta-defensin-1 (hBD-1) has broad-spectrum antimicrobial properties, and it plays an important role in the tumor microenvironment. Circular ribonucleic acids (circRNAs) regulate the proliferation and progression of colorectal cancer cells via cancer-related signaling pathways.

Cell proliferation was assessed using the Cell Counting Kit-8 assay to determine the optimal hBD-1 concentration. Intracellular autophagic vesicles were visualized via monodansylcadaverine staining. In addition, the levels of AKT and mammalian target of rapamycin (mTOR)-associated signaling proteins were analyzed via Western blot analysis. CircRNA microarrays and quantitative real-time polymerase chain reaction were used to identify differentially expressed circRNAs in colon cancer cell lines. The functional role of HAS-CIRCpedia-5280 in vitro was demonstrated by overexpressing HAS-CIRCpedia-5280 and inhibiting miR-4712-5p. HAS-CIRCpedia-5280 could be a sponge of miR-4712-5p, mimicking the effect induced by HAS-CIRCpedia-5280 overexpression in colon cancer cells.

hBD-1 inhibited the proliferation of colon cancer cells and increased the number of intracellular autophagic vesicles. In addition, hBD-1 inhibited the AKT/mTOR signaling pathway, thereby enhancing cellular autophagy. Further, the interaction of HAS-CIRCpedia-5280 and miR-4712-5p was investigated. hBD-1 upregulated the expression level of HAS-CIRCpedia-5280 and downregulated the expression level of miR-4712-5p in colon cancer cells. Subsequently, the overexpression of HAS-CIRCpedia-5280 or the inhibition of miR-4712-5p activated the AKT/mTOR signaling pathway, leading to cellular autophagy inhibition. Conversely, the mimicry of miR-4712-p counteracted the effect of HAS-CIRCpedia 5280 overexpression in colon cancer cells by inhibiting the activation of the AKT/mTOR signaling pathway and, thereby, enhancing cellular autophagy.

hBD-1 can have an inhibitory effect against cell proliferation in colon cancer SW-620/HCT-116 cells via the HAS-CIRCpedia-5280/miR-4712-5p-mediated activation of autophagy.

The global health crisis triggered by the SARS-CoV-2 virus has highlighted the urgent need for effective treatments. As existing drugs are not specifically targeted at this virus, there is a growing interest in exploring natural antimicrobial peptides such as defensin as potential therapeutic options. Human β defensin type 2 (hBD-2), which is a cationic cysteine-rich peptide, serves as the initial barrier against bacterial and fungal invaders in mammals. It can bind with Spike-RBD and occupy the same site as the ACE2 receptor, thereby hindering viral entry into cells expressing ACE2. To explore the effect of different point mutations on the binding of hBD-2 with RBD, the binding dynamics and interactions between hBD-2 point mutants with RBD were studied and compared with that of RBD&hBD-2 wild-type complex. In total, 247 hBD-2 point mutants were built with the mutation sites at the binding region of hBD-2 (RES18-30) with the RBD of CoV-2. All-atom molecular dynamics simulations were carried out on RBD binding with hBD-2 point mutants. Analysis based on root-mean-square deviation (RMSD), hydrogen bonds analysis, and binding free energy using the MM/PBSA method revealed that many point mutants of hBD-2 exhibit weaker binding with RBD compared to the wild type; however, a subset of mutants, including C20I, C20K, R22W, R23H, R23L, Y24L, K25F, K25H, G28Y, T29R, and C30K, displayed enhanced binding with RBD. The findings can offer insights designing hBD-2-based novel drugs to combat SARS-CoV-2 in the long term.

Neutrophilic inflammation and a high level of free α-defensins are main features of chronic airway inflammation in alpha-1 antitrypsin-deficient (AATD) individuals. Despite the antimicrobial activities of α-defensins by direct bacterial killing and by modulation of immune responses, AATD individuals are paradoxically burdened by recurrent exacerbation triggered by bacterial infections, frequently with nontypeable Haemophilus influenzae (NTHi). Previous studies demonstrated that high, rather than low α-defensin level could modulate the local pro-inflammatory milieu of bronchial epithelial cells and macrophages promoting chronic inflammation and lower pathogen phagocytosis. IgG-mediated phagocytosis and NTHi adherence, engulfment and phagocytosis were measured in human alveolar macrophages and monocyte-derived macrophages (MDM) isolated from patients with AATD and from healthy individuals. A high concentration of free α-defensins induced NTHi adherence to MDMs but decreased IgG-mediated phagocytosis by MDMs. The decreased phagocytosis was associated with TLR4 activation, downstream signaling via NF-κB p65 and marked increased secretion of inflammatory cytokines, CXCL8, IL-1b, and TNFα by the α-defensin-treated and NTHi-infected MDMs. Exogenous AAT treatment and TLR4 inhibitor decreased TNFα expression in α-defensin-treated cells. Dampening the downstream effects of a high concentration of α-defensins may render AAT and TLR4 inhibitors as potential therapies to decrease NTHi colonization and increase its clearance by phagocytosis in AATD individuals.

Infertility is associated with the alteration of the seminal microbiome. However, the onset of dysbiosis remains controversial and the involvement of host factors remains elusive. This study investigates the alterations of the seminal microbiome in male infertility and examines the association and function of DEFB119, a reproductive-tract-specific host antimicrobial peptide, on the seminal microbiome and male fertility. While we observed comparable genera, diversity and evenness of bacterial communities, a marked decrease in the modularity of the metacommunities was observed in patients with abnormal spermiogram (n = 57) as compared to the control (n = 30). A marked elevation of DEFB119 was observed in a subpopulation of male infertile patients (n = 5). Elevated seminal DEFB119 was associated with a decrease in the observed genera, diversity and evenness of bacterial communities, and further distortion of the metacommunities. Mediation analysis suggests the involvement of elevated DEFB119 and dysbiosis of the seminal microbiome in mediating the abnormalities in the spermiogram. Functional experiments showed that recombinant DEFB119 significantly decrease the progressive motility of sperm in patients with abnormal spermiogram. Moreover, DEFB119 demonstrated species-specific antimicrobial activity against common seminal and nonseminal species. Our work identifies an important host factor that mediates the host-microbiome interaction and stratifies the seminal microbiome associated with male infertility. These results may lead to a new diagnostic method for male infertility and regimens for formulating the microbiome in the reproductive tract and other organ systems.

In this narrative review, we assess the pathophysiology of severe adverse events that presented after vaccination with DNA and mRNA vaccines against COVID-19. The focus is on the perspective of an undersulfated and degraded glycocalyx, considering its impact on immunomodulation, inflammatory responses, coagulation and oxidative stress. The paper explores various factors that lead to glutathione and inorganic sulfate depletion and their subsequent effect on glycocalyx sulfation and other metabolites, including hormones. Components of COVID-19 vaccines, such as DNA and mRNA material, spike protein antigen and lipid nanoparticles, are involved in possible cytotoxic effects. The common thread connecting these adverse events is endotheliopathy or glycocalyx degradation, caused by depleted glutathione and inorganic sulfate levels, shear stress from circulating nanoparticles, aggregation and formation of protein coronas; leading to imbalanced immune responses and chronic release of pro-inflammatory cytokines, ultimately resulting in oxidative stress and systemic inflammatory response syndrome. By understanding the underlying pathophysiology of severe adverse events, better treatment options can be explored.

Invasion and adhesion of neutrophils into tissues and their concomitant secretion play an important role in the development of vascular pathologies, including abdominal aortic aneurysm (AAA). Chronic administration of angiotensin II is used to initiate AAA formation in mice. The role of aldosterone in this process is being studied. We conducted for the first time a complex comparative study of the effects of angiotensin II and aldosterone on the adhesion of human neutrophils to fibronectin and the concomitant secretion of proteins, free amino acids as well as reactive oxygen (ROS) and nitrogen (NO) species. Neither angiotensin II nor aldosterone affected the attachment of neutrophils to fibronectin and the concomitant production of ROS. We showed for the first time that aldosterone stimulated the release of amino acid hydroxylysine, a product of lysyl hydroxylase, the activity of which is positively correlated with cell invasiveness. Aldosterone also initiates the secretion of matrix metalloproteinase 9 (MMP-9) and cathepsin G, which may reorganize the extracellular matrix and stimulate the recruitment and adhesion of neutrophils to the aortic walls. Angiotensin II did not affect protein secretion. It may contribute to neutrophil-induced vascular injury by inhibiting the production of NO or by increasing the secretion of isoleucine. Our results suggest that it is aldosterone-induced neutrophil secretion that may play a significant role in neutrophil-induced vascular wall destruction in angiotensin II-induced AAA or other vascular complications.

Disulfide-rich peptides such as defensins play diverse roles in immunity and ion channel modulation, as well as constituting the bioactive components of many animal venoms. We investigated the structure and bioactivity of U-RDTX-Pp19, a peptide previously discovered in venom of the assassin bug Pristhesancus plagipennis. Recombinant Pp19 (rPp19) was found to possess insecticidal activity when injected into Drosophila melanogaster. A bioinformatic search revealed that domains homologous to Pp19 are produced by assassin bugs and diverse other arthropods. rPp19 co-eluted with native Pp19 isolated from P. plagipennis, which we found is more abundant in hemolymph than venom. We solved the three-dimensional structure of rPp19 using 2D 1H NMR spectroscopy, finding that it adopts a disulfide-stabilized structure highly similar to known trans-defensins, with the same cystine connectivity as human α-defensin (I-VI, II-IV, and III-V). The structure of Pp19 is unique among reported structures of arthropod peptides.

The increasing threat of antibiotic resistance among pathogenic microorganisms and the urgent demand for new antibiotics require immediate attention. Antimicrobial peptides exhibit effectiveness against microorganisms, fungi, viruses, and protozoa. The discovery of human β-defensins represents a major milestone in biomedical research, opening new avenues for scientific investigation into the innate immune system and its resistance mechanisms against pathogenic microorganisms. Multiple defensins present a promising alternative in the context of antibiotic abuse. However, obstacles to the practical application of defensins as anti-infective therapies persist due to the unique properties of human β-defensins themselves and serious pharmacological and technical challenges. To overcome these challenges, diverse delivery vehicles have been developed and progressively improved for the conjugation or encapsulation of human β-defensins. This review briefly introduces the biology of human β-defensins, focusing on their multistage structure and diverse functions. It also discusses several heterologous systems for producing human β-defensins, various delivery systems created for these peptides, and patent applications related to their utilization, concluding with a summary of current challenges and potential solutions.

Colorectal cancer (CRC) represents a significant global healthcare burden, with a particularly concerning rising incidence among younger adults. This trend may highlight potential links between diet, gut microbiome, and CRC risk. Novel therapeutic options have been increasingly based on the understanding of molecular mechanisms and pathways. The PI3K/AKT/mTOR pathway, a crucial cell growth regulator, offers a promising target for CRC therapy. mTOR, a key component within this pathway, controls cell growth, survival, and metabolism. Understanding the specific roles of defensins, particularly human β-Defensin 1 (HBD-1), in CRC is crucial. HBD-1 exhibits potent antimicrobial activity and may influence CRC development. Deciphering defensin expression patterns in CRC holds the promise of improved understanding of tumorigenesis, which may pave the way for improved diagnostics and therapies. This article reviews recent advances in understanding regarding how HBD-1 influences CRC initiation and progression, highlighting the molecular mechanisms by which it impacts CRC. Further, we describe the interaction between defensins and mTOR pathway in CRC.

Immunopeptides have low toxicity, low immunogenicity and targeting, and broad application prospects in drug delivery and assembly, which are diverse in application strategies and drug combinations. Immunopeptides are particularly important for regulating ocular immune homeostasis, as the eye is an immune-privileged organ. Immunopeptides have advantages in adaptive immunity and innate immunity, treating eye immune-related diseases by regulating T cells, B cells, immune checkpoints, and cytokines. This article summarizes the application strategies of immunopeptides in innate immunity and adaptive immunity, including autoimmunity, infection, vaccine strategies, and tumors. Furthermore, it focuses on the mechanisms of immunopeptides in mediating ocular immunity (autoimmune diseases, inflammatory storms, and tumors). Moreover, it reviews immunopeptides' application strategies and the therapeutic potential of immunopeptides in the eye. We expect the immune peptide to get attention in treating eye diseases and to provide a direction for eye disease immune peptide research.

Human defensins are cysteine-rich peptides (Cys-rich peptides) of the innate immune system. Defensins contain an ancestral structural motif (i.e., γ-core motif) associated with the antimicrobial activity of natural Cys-rich peptides. In this study, low concentrations of human α- and β-defensins showed microbicidal activity that was not associated with cell membrane permeabilization. The cell death pathway was similar to that previously described for human lactoferrin, also an immunoprotein containing a γ-core motif. The common features were (1) cell death not related to plasma membrane (PM) disruption, (2) the inhibition of microbicidal activity via extracellular potassium, (3) the influence of cellular respiration on microbicidal activity, and (4) the influence of intracellular pH on bactericidal activity. In addition, in yeast, we also observed (1) partial K+-efflux mediated via Tok1p K+-channels, (2) the essential role of mitochondrial ATP synthase in cell death, (3) the increment of intracellular ATP, (4) plasma membrane depolarization, and (5) the inhibition of external acidification mediated via PM Pma1p H+-ATPase. Similar features were also observed with BM2, an antifungal peptide that inhibits Pma1p H+-ATPase, showing that the above coincident characteristics were a consequence of PM H+-ATPase inhibition. These findings suggest, for the first time, that human defensins inhibit PM H+-ATPases at physiological concentrations, and that the subsequent cytosolic acidification is responsible for the in vitro microbicidal activity. This mechanism of action is shared with human lactoferrin and probably other antimicrobial peptides containing γ-core motifs.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN.

The gene chip data were retrieved from the GEO database using the search term ' diabetic nephropathy '. The ' limma ' software package was used to identify differentially expressed genes (DEGs) between DN and control samples. Gene set enrichment analysis (GSEA) was performed on genes obtained from the molecular characteristic database (MSigDB. The R package 'WGCNA' was used to identify gene modules associated with tubulointerstitial injury in DN, and it was crossed with immune-related DEGs to identify target genes. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on differentially expressed genes using the 'ClusterProfiler' software package in R. Three methods, least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE) and random forest (RF), were used to select immune-related biomarkers for diagnosis. We retrieved the tubulointerstitial dataset from the Nephroseq database to construct an external validation dataset. Unsupervised clustering analysis of the expression levels of immune-related biomarkers was performed using the 'ConsensusClusterPlus 'R software package. The urine of patients who visited Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2021 to March 2023 was collected, and Elisa was used to detect the mRNA expression level of immune-related biomarkers in urine. Pearson correlation analysis was used to detect the effect of immune-related biomarker expression on renal function in DN patients.

Four microarray datasets from the GEO database are included in the analysis : GSE30122, GSE47185, GSE99340 and GSE104954. These datasets included 63 DN patients and 55 healthy controls. A total of 9415 genes were detected in the data set. We found 153 differentially expressed immune-related genes, of which 112 genes were up-regulated, 41 genes were down-regulated, and 119 overlapping genes were identified. GO analysis showed that they were involved in various biological processes including leukocyte-mediated immunity. KEGG analysis showed that these target genes were mainly involved in the formation of phagosomes in Staphylococcus aureus infection. Among these 119 overlapping genes, machine learning results identified AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1 and FSTL1 as potential tubulointerstitial immune-related biomarkers. External validation suggested that the above markers showed diagnostic efficacy in distinguishing DN patients from healthy controls. Clinical studies have shown that the expression of AGR2, CX3CR1 and FSTL1 in urine samples of DN patients is negatively correlated with GFR, the expression of CX3CR1 and FSTL1 in urine samples of DN is positively correlated with serum creatinine, while the expression of DEFB1 in urine samples of DN is negatively correlated with serum creatinine. In addition, the expression of CX3CR1 in DN urine samples was positively correlated with proteinuria, while the expression of DEFB1 in DN urine samples was negatively correlated with proteinuria. Finally, according to the level of proteinuria, DN patients were divided into nephrotic proteinuria group (n = 24) and subrenal proteinuria group. There were significant differences in urinary AGR2, CCR2 and DEFB1 between the two groups by unpaired t test (P < 0.05).

Our study provides new insights into the role of immune-related biomarkers in DN tubulointerstitial injury and provides potential targets for early diagnosis and treatment of DN patients. Seven different genes ( AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1, FSTL1 ), as promising sensitive biomarkers, may affect the progression of DN by regulating immune inflammatory response. However, further comprehensive studies are needed to fully understand their exact molecular mechanisms and functional pathways in DN.

As a family of cationic host defense peptides, human β-defensins (HBDs) are ubiquitous in the oral cavity and are mainly synthesized primarily by epithelial cells, serving as the primary barrier and aiming to prevent microbial invasion, inflammation, and disease while maintaining physiological homeostasis. In recent decades, there has been great interest in their biological functions, structure-activity relationships, mechanisms of action, and therapeutic potential in oral diseases. Meanwhile, researchers are dedicated to improving the properties of HBDs for clinical application. In this review, we first describe the classification, structural characteristics, functions, and mechanisms of HBDs. Next, we cover the role of HBDs and their synthetic analogs in oral diseases, including dental caries and pulp infections, periodontitis, peri-implantitis, fungal/viral infections and oral mucosal diseases, and oral squamous cell carcinoma. Finally, we discuss the limitations and challenges of clinical translation of HBDs and their synthetic analogs, including, but not limited to, stability, bioavailability, antimicrobial activity, resistance, and toxicity. Above all, this review summarizes the biological functions, mechanisms of action, and therapeutic potential of both natural HBDs and their synthetic analogs in oral diseases, as well as the challenges associated with clinical translation, thus providing substantial insights into the laboratory development and clinical application of HBDs in oral diseases.

Currently, the spread of fungal infections is becoming an urgent problem. Fungi of the Candida genus are opportunistic microorganisms that cause superficial and life-threatening systemic candidiasis in immunocompromised patients. The list of antifungal drugs for the treatment of candidiasis is very limited, while the prevalence of resistant strains is growing rapidly. Therefore, the search for new antimycotics, including those exhibiting immunomodulatory properties, is of great importance. Plenty of natural compounds with antifungal activities may be extremely useful in solving this problem. This review evaluates the features of natural antimicrobial peptides, namely plant defensins as possible prototypes of new anticandidal agents. Plant defensins are important components of the innate immune system, which provides the first line of defense against pathogens. The introduction presents a brief summary regarding pathogenic Candida species, the pathogenesis of candidiasis, and the mechanisms of antimycotic resistance. Then, the structural features of plant defensins, their anticandidal activities, their mechanisms of action on yeast-like fungi, their ability to prevent adhesion and biofilm formation, and their combined action with conventional antimycotics are described. The possible mechanisms of fungal resistance to plant defensins, their cytotoxic activity, and their effectiveness in in vivo experiments are also discussed. In addition, for the first time for plant defensins, knowledge about their immunomodulatory effects is also presented.

Epithelial cells form a resilient barrier and orchestrate defensive and reparative mechanisms to maintain tissue stability. This review focuses on gut and airway epithelia, which are positioned where the body interfaces with the outside world. We review the many signaling pathways and mechanisms by which epithelial cells at the interface respond to invading pathogens to mount an innate immune response and initiate adaptive immunity and communicate with other cells, including resident microbiota, to heal damaged tissue and maintain homeostasis. We compare and contrast how airway and gut epithelial cells detect pathogens, release antimicrobial effectors, collaborate with macrophages, Tregs and epithelial stem cells to mount an immune response and orchestrate tissue repair. We also describe advanced research models for studying epithelial communication and behaviors during inflammation, tissue injury and disease.

Colorectal cancer has a low 5-year survival rate and high mortality. Human β-defensin-1 (hBD-1) may play an integral function in the innate immune system, contributing to the recognition and destruction of cancer cells. Long non-coding RNAs (lncRNAs) are involved in the process of cell differentiation and growth.

To investigate the effect of hBD-1 on the mammalian target of rapamycin (mTOR) pathway and autophagy in human colon cancer SW620 cells.

CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration. Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation. Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway. Additionally, p-mTOR (Ser2448), Beclin1, and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.

hBD-1 inhibited the proliferative ability of SW620 cells, as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1. hBD-1 decreased the expression of p-mTOR (Ser2448) protein and increased the expression of Beclin1 and LC3II/I protein. Furthermore, bioinformatics analysis identified seven lncRNAs (2 upregulated and 5 downregulated) related to the mTOR pathway. The lncRNA TCONS_00014506 was ultimately selected. Following the inhibition of the lncRNA TCONS_00014506, exposure to hBD-1 inhibited p-mTOR (Ser2448) and promoted Beclin1 and LC3II/I protein expression.

hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

Intercalated cells (ICs) in the kidney collecting duct have a versatile role in acid-base and electrolyte regulation along with the host immune defense. Located in the terminal kidney tubule segment, ICs are among the first kidney cells to encounter bacteria when bacteria ascend from the bladder into the kidney. ICs have developed several mechanisms to combat bacterial infections of the kidneys. For example, ICs produce antimicrobial peptides (AMPs), which have direct bactericidal activity, and in many cases are upregulated in response to infections. Some AMP genes with IC-specific kidney expression are multiallelic, and having more copies of the gene confers increased resistance to bacterial infections of the kidney and urinary tract. Similarly, studies in human children demonstrate that those with history of UTIs are more likely to have single-nucleotide polymorphisms in IC-expressed AMP genes that impair the AMP's bactericidal activity. In murine models, depleted or impaired ICs result in decreased clearance of bacterial load following transurethral challenge with uropathogenic E. coli. A 2021 study demonstrated that ICs even act as phagocytes and acidify bacteria within phagolysosomes. Several immune signaling pathways have been identified in ICs which may represent future therapeutic targets in managing kidney infections or inflammation. This review's objective is to highlight IC structure and function with an emphasis on current knowledge of IC's diverse innate immune capabilities.

Background: Neutrophils are thought to play a pivotal role in the pathogenesis of many inflammatory diseases, such as hepatitis, liver cirrhosis, etc. Activated human neutrophils release human neutrophil peptides (HNP1-3) or alpha-defensins that are antimicrobial peptides in azurophil granules. Furthermore, HNP1-3 build a scaffold of neutrophil extracellular traps (NETs) and promote the process of programmed cell death called NETosis. Our study aimed to investigate the role of alpha-defensins in the pathogenesis of alcohol-related liver cirrhosis (ALC). Methods: The concentrations of alpha-defensins in the plasma of 62 patients with ALC and 24 healthy subjects were measured by ELISA. The patients with ALC were prospectively recruited based on the severity of liver dysfunction according to the Child-Pugh and Model of End-Stage Liver Disease-Natrium (MELD-Na) scores, modified Maddrey's Discriminant Function (mDF), and the presence of ALC complications. Results: The concentrations of alpha-defensins in plasma were significantly higher in the ALC patients than in the controls. The plasma levels of HNP1-3 correlated with the MELD and mDF scores. ALC subgroups with MELD > 20 and mDF > 32 displayed significantly higher HNP1-3 concentrations. The plasma levels of HNP1-3 revealed a good predictive AUC for hepatic encephalopathy and ascites development (0.81 and 0.74, respectively) and for patient survival (0.87) in those over 40 years of age. Conclusion: These findings suggest that alpha-defensins play an important role in the assessment of ALC.

Antimicrobial peptides (AMPs) constitute a complex network of 10-100 amino acid sequence molecules widely distributed in nature. While over 300 AMPs have been described in mammals, cathelicidins and defensins remain the most extensively studied. Some publications have explored the role of AMPs in COVID-19, but these findings are preliminary, and in vivo studies are still lacking. In this study, we report the plasma levels of five AMPs (LL-37, α-defensin 1, α-defensin 3, β-defensin 1, and β-defensin 3), using the ELISA technique (MyBioSource, San Diego, CA, United States, kits MBS2601339 (beta-defensin 1), MBS2602513 (beta-defensin 3), MBS703879 (alpha-defensin 1), MBS706289 (alpha-defensin 3), MBS7234921 (LL37)), and the measurement of six cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, interferon-γ, and monocyte chemoattractant protein-1), through the magnetic bead immunoassay Milliplex® and the MAGPIX® System (MilliporeSigma, Darmstadt, Germany, kit HCYTOMAG-60 K (cytokines)), in 15 healthy volunteers, 36 COVID-19 patients without Acute Kidney Injury (AKI) and 17 COVID-19 patients with AKI. We found increased levels of α-defensin 1, α-defensin 3 and β-defensin 3, in our COVID-19 population, when compared to healthy controls, along with higher levels of interleukin-6, interleukin-10, interferon-γ, and monocyte chemoattractant protein-1. These findings suggest that these AMPs and cytokines may play a crucial role in the systemic inflammatory response and tissue damage characterizing severe COVID-19. The levels of α-defensin 1 and α-defensin 3 were significantly higher in COVID-19 AKI group in comparison to the non-AKI group. Furthermore, IL-10 and the product IL-10 × IL-1B showed excellent performance in discriminating AKI, with AUCs of 0.86 and 0.88, respectively. Among patients with COVID-19, AMPs may play a key role in the inflammation process and disease progression. Additionally, α-defensin 1 and α-defensin 3 may mediate the AKI process in these patients, representing an opportunity for further research and potential therapeutic alternatives in the future.

The increasing prevalence of multidrug-resistant bacterial infections necessitates the exploration of novel paradigms for anti-infective therapy. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), have garnered extensive recognition as immunomodulatory molecules that leverage natural host mechanisms to enhance therapeutic benefits. The unique immune mechanism exhibited by certain HDPs that involves self-assembly into supramolecular nanonets capable of inducing bacterial agglutination and entrapping is significantly important. This process effectively prevents microbial invasion and subsequent dissemination and significantly mitigates selective pressure for the evolution of microbial resistance, highlighting the potential of HDP-based antimicrobial therapy. Recent advancements in this field have focused on developing bio-responsive materials in the form of supramolecular nanonets. A comprehensive overview of the immunomodulatory and bacteria-agglutinating activities of HDPs, along with a discussion on optimization strategies for synthetic derivatives, is presented in this article. These optimized derivatives exhibit improved biological properties and therapeutic potential, making them suitable for future clinical applications as effective anti-infective therapeutics.

Short sequences of amino acids called peptides have a wide range of biological functions and the potential to treat a number of diseases. Bioactive peptides can be derived from different sources, including marine organisms, and synthetic design, making them versatile candidates for production of therapeutic agents. Their therapeutic effects span across areas such as antimicrobial activity, cells proliferation and migration, synthesis of collagen, and more. This current review explores the fascinating realm of bioactive peptides as promising therapeutic agents for skin wound healing. This review focuses on the multifaceted biological effects of specific peptides, shedding light on their potential to revolutionize the field of dermatology and regenerative medicine. It delves into how these peptides stimulate collagen synthesis, inhibit inflammation, and accelerate tissue regeneration, ultimately contributing to the effective repair of skin wounds. The findings underscore the significant role several types of bioactive peptides can play in enhancing wound healing processes and offer promising insights for improving the quality of life for individuals with skin injuries and dermatological conditions. The versatility of peptides allows for the development of tailored treatments catering to specific wound types and patient needs. As continuing to delve deeper into the realm of bioactive peptides, there is immense potential for further exploration and innovation. Future endeavors may involve the optimization of peptide formulations, elucidation of underlying molecular and cellular mechanisms.

Defensins and inflammation are innate immune barriers of the body against infectious pathogens. Searching for a compound that can inhibit infectious diseases by affecting human β-defensin (HBD) and proinflammatory cytokines is the new trend in research to control bacterial infection. The aim of this study is to provide a natural compound, Filipendula glaberrima Nakai extract (FGE), which is able to induce the expression of an antimicrobial defensin as well as reduce inflammation. FGE induced the expression of HBD2 and HBD3 through activating both p38 and NF-κB signaling pathways. Furthermore, FGE inhibited the expression of TNF-α and IL-6 via p38 and NF-κB pathways in Staphylococcus aureus-stimulated THP1 cells. Injection of FGE alleviated cutaneous erythema and swelling caused by S. aureus injection in mice ears. Taken together, FGE could reduce bacterial infection by inducing the expression of defensin and anti-inflammatory activity.

Porphyromonas gingivalis is a keystone pathogen associated with periodontitis development, a chronic inflammatory pathology characterized by the destruction of the supporting teeth structure. Macrophages are recruited cells in the inflammatory infiltrate from patients with periodontitis. They are activated by the P. gingivalis virulence factors arsenal, promoting an inflammatory microenvironment characterized by cytokine production (TNF-α, IL-1β, IL-6), prostaglandins, and metalloproteinases (MMPs) that foster the tissular destruction characteristic of periodontitis. Furthermore, P. gingivalis suppresses the generation of nitric oxide, a potent antimicrobial molecule, through its degradation, and incorporating its byproducts as a source of energy. Oral antimicrobial peptides can contribute to controlling the disease due to their antimicrobial and immunoregulatory activity, which allows them to maintain homeostasis in the oral cavity. This study aimed to analyze the immunopathological role of macrophages activated by P. gingivalis in periodontitis and suggested using antimicrobial peptides as therapeutic agents to treat the disease.

As a family of cationic host defense peptides, defensins are mainly synthesized by Paneth cells, neutrophils, and epithelial cells, contributing to host defense. Their biological functions in innate immunity, as well as their structure and activity relationships, along with their mechanisms of action and therapeutic potential, have been of great interest in recent years. To highlight the key research into the role of defensins in human and animal health, we first describe their research history, structural features, evolution, and antimicrobial mechanisms. Next, we cover the role of defensins in immune homeostasis, chemotaxis, mucosal barrier function, gut microbiota regulation, intestinal development and regulation of cell death. Further, we discuss their clinical relevance and therapeutic potential in various diseases, including infectious disease, inflammatory bowel disease, diabetes and obesity, chronic inflammatory lung disease, periodontitis and cancer. Finally, we summarize the current knowledge regarding the nutrient-dependent regulation of defensins, including fatty acids, amino acids, microelements, plant extracts, and probiotics, while considering the clinical application of such regulation. Together, the review summarizes the various biological functions, mechanism of actions and potential clinical significance of defensins, along with the challenges in developing defensins-based therapy, thus providing crucial insights into their biology and potential clinical utility.

Human skin microbiome is the first barrier against exogenous attack and is associated with various skin disease pathogenesis and progression. Advancements in high-throughput sequencing technologies have paved the way for a deeper understanding of this field. Based on the bibliometric analysis, this investigation aimed to identify the hotspots and future research trends associated with human skin microbiomes studied over the past decade.

The published research on skin microbiome from January 2013 to January 2023 was retrieved from the Web of Science Core Collection. Data cleaning processes to ensure robust data and the bibliometrix packages R, CiteSpace, VOSviewer, Origin, and Scimago Graphica for bibliometric and visual analyses were utilized.

A total of 1629 published documents were analyzed. The overall publication trend steadily increased, with relatively fast growth in 2017 and 2020. The United States of America has the highest number of publications and citations and shows close collaborations with China and Germany. The University of California, San Diego, indicated a higher number of publications than other institutions and the fastest growth rate. The top three most publishing journals on this topic are Microorganisms, Frontiers in Microbiology, and Experimental dermatology. Gallo RL is the most influential author with the highest h- and g-index and most publications in skin microecology, followed by Grice EA and Kong HH. The top 10 most frequently used keywords in recent years included skin microbiome, microbiome, staphylococcus aureus, diversity, atopic dermatitis, skin, bacteria, infections, gut microbiota, and disease.

The skin microbiome is an area of research that requires continuous analysis, and even with much-achieved progress, future research will further be aided as technology develops.

Respiratory Syncytial Virus (RSV) is a non-segmented negative-sense RNA virus belonging to the paramyxovirus family. RSV infects the respiratory tract to cause pneumonia and bronchiolitis in infants, elderly, and immunocompromised patients. Effective clinical therapeutic options and vaccines to combat RSV infection are still lacking. Therefore, to develop effective therapeutic interventions, it is imperative to understand virus-host interactions during RSV infection. Cytoplasmic stabilization of β-catenin protein results in activation of canonical Wingless (Wnt)/β-catenin signaling pathway that culminates in transcriptional activation of various genes regulated by T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors. This pathway is involved in various biological and physiological functions. Our study shows RSV infection of human lung epithelial A549 cells triggering β-catenin protein stabilization and induction of β-catenin mediated transcriptional activity. Functionally, the activated β-catenin pathway promoted a pro-inflammatory response during RSV infection of lung epithelial cells. Studies with β-catenin inhibitors and A549 cells lacking optimal β-catenin activity demonstrated a significant loss of pro-inflammatory chemokine interleukin-8 (IL-8) release from RSV-infected cells. Mechanistically, our studies revealed a role of extracellular human beta defensin-3 (HBD3) in interacting with cell surface Wnt receptor LDL receptor-related protein-5 (LRP5) to activate the non-canonical Wnt independent β-catenin pathway during RSV infection. We showed gene expression and release of HBD3 from RSV-infected cells and silencing of HBD3 expression resulted in reduced stabilization of β-catenin protein during RSV infection. Furthermore, we observed the binding of extracellular HBD3 with cell surface localized LRP5 protein, and our in silico and protein-protein interaction studies have highlighted a direct interaction of HBD3 with LRP5. Thus, our studies have identified the β-catenin pathway as a key regulator of pro-inflammatory response during RSV infection of human lung epithelial cells. This pathway was induced during RSV infection via a non-canonical Wnt-independent mechanism involving paracrine/autocrine action of extracellular HBD3 activating cell surface Wnt receptor complex by directly interacting with the LRP5 receptor.

Candidiasis is one of the most common fungal diseases that can pose a threat to life in immunodeficient individuals, particularly in its disseminated form. Not only fungal invasion but also fatal infection-related inflammation are common causes of systemic candidiasis. In this study, we investigated in vitro immunomodulatory properties of the antifungal pea defensin Psd1 upon Candida albicans infection. Using the real-time PCR, we showed that Psd1 inhibited the antimicrobial peptide HBD-2 and pro-inflammatory cytokines IL-1 and IL-8 downregulation at mRNA level in epithelium cells caused by C. albicans infection. By using the Caco-2/immune cells co-culture upon C. albicans infection and the multiplex xMAP assay, we demonstrated that this pathogenic fungus induced a pronounced host defense response; however, the cytokine responses were different in the presence of dendritic cells or monocytes. We revealed that Psd1 at a low concentration (2 µM) had a pronounced immunomodulatory effect on the Caco-2/immune cells co-culture upon fungal infection. Thus, we hypothesized that the pea defensin Psd1 might be an effective agent in the treatment of candidiasis not only due to its antifungal activity, but also owing to its ability to modulate a protective immune response upon infection.

Vesicoureteral reflux represents one of the most concerning topics in pediatric nephrology due to its frequency, clinical expression with the potential to evolve into chronic kidney disease, and last but not least, its socio-economic implications. The presence of vesicoureteral reflux, the occurrence of urinary tract infections, and the development of reflux nephropathy, hypertension, chronic kidney disease, and finally, end-stage renal disease represent a progressive spectrum of a single physiopathological condition. For the proper management of these patients with the best clinical outcomes, and in an attempt to prevent the spread of uropathogens' resistance to antibacterial therapy, we must better understand the physiopathology of urinary tract infections in patients with vesicoureteral reflux, and at the same time, we should acknowledge the implication and response of the innate immune system in this progressive pathological condition. The present paper focuses on theoretical aspects regarding the physiopathology of vesicoureteral reflux and the interconditionality between urinary tract infections and the innate immune system. In addition, we detailed aspects regarding cytokines, interleukins, antimicrobial peptides, and proteins involved in the innate immune response as well as their implications in the physiopathology of reflux nephropathy. New directions of study should focus on using these innate immune system effectors as diagnostic and therapeutic tools in renal pathology.

Both defensin and inflammation are part of the human innate immune system that responds rapidly to pathogens. The combination of defensins with pro- or anti-inflammatory effects can be a potential research direction for the treatment of infection by pathogens. This study aimed to identify whether MSF (Miracle Synergy material made using Filipendula glaberrima), a probiotic lysate of Filipendula glaberrima extracts fermented with Lactiplantibacillus plantarum K8, activates the expression of human β-defensin (HBD2 and HBD3) to protect the host against pathogens and inhibit inflammation caused by S. aureus, in vitro with Western blot analysis, qRT-PCR and in vivo studies with a mouse model were used to evaluate the effects of MSF. The MSF treatment induced HBD2 and HBD3 expression via the p38 and NF-κB pathways. Furthermore, MSF treatment significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), also through p38 and NF-κB in S. aureus-induced inflammatory condition. MSF treatment remarkably reduced erythema in mice ears caused by the injection of S. aureus, while K8 lysate treatment did not initiate a strong recovery. Taken together, MSF induced the expression of HBD2 and HDB3 and activated anti-inflammatory activity more than the probiotic lysates of L. plantarum K8. These findings show that MSF is a potential defensin inducer and anti-inflammatory agent.

Antimicrobial peptides (AMP) are essential components of innate immunity with a broad range of antimicrobial activities against bacteria, viruses, and fungi. The aim of this study was to investigate AMP expression in the upper gastrointestinal tract in normal and pathological metabolic states in humans. Furthermore, we examined the correlation between vitamin D levels and AMP expression in the same cohort. Serum concentrations of 25-hydroxyvitamin D3 were measured, and mRNA expression of β-defensins HBD-1, -2, -3, -4, α-defensins HD-5 and -6 and cathelicidin in the upper gastrointestinal tract epithelia were determined by quantitative RT-PCR in 31 individuals (10 with type 2 diabetes, 10 with insulin resistance, and 11 healthy controls). The majority of the cohort showed low vitamin D concentrations, which were negatively correlated with mRNA expression levels of HBD-3 in corpus mucosa. HBD-1 and HBD-3 mRNA were expressed in corpus mucosa, with the former significantly decreased in patients with diabetes. Hence, we conclude that type 2 diabetes is associated with reduced AMP expression in the upper gastrointestinal tract, which might contribute towards epithelial barrier dysfunction and increased bacterial translocation in these patients.

The dramatic rise in cancer incidence, alongside treatment deficiencies, has elevated cancer to the second-leading cause of death globally. The increasing morbidity and mortality of this disease can be traced back to a number of causes, including treatment-related side effects, drug resistance, inadequate curative treatment and tumor relapse. Recently, anti-cancer bioactive peptides (ACPs) have emerged as a potential therapeutic choice within the pharmaceutical arsenal due to their high penetration, specificity and fewer side effects. In this contribution, we present a general overview of the literature concerning the conformational structures, modes of action and membrane interaction mechanisms of ACPs, as well as provide recent examples of their successful employment as targeting ligands in cancer treatment. The use of ACPs as a diagnostic tool is summarized, and their advantages in these applications are highlighted. This review expounds on the main approaches for peptide synthesis along with their reconstruction and modification needed to enhance their therapeutic effect. Computational approaches that could predict therapeutic efficacy and suggest ACP candidates for experimental studies are discussed. Future research prospects in this rapidly expanding area are also offered.

Vitiligo is an acquired depigmented skin disorder. It has a genetic and autoimmune background. Human beta defensin-1(HBD-1) plus its gene polymorphism were linked to some autoimmune disorders.

To elucidate the possible role of HBD-1 in the pathogenesis of non-segmental vitiligo (NSV) through evaluation of HBD-1 serum levels and its single nucleotide polymorphism (SNP) in patients having NSV, in addition, to correlating the results with the extent of vitiligo in those patients.

A current case-control study included 50 patients having NSV and 50 controls. The authors used Vitiligo Area Scoring Index (VASI) score to assess vitiligo severity and laboratory investigations to assess serum HBD-1 level using ELISA and defensin-beta1 (DEFB1) SNP using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

There were significantly lower HBD-1 serum levels in NSV cases than in controls (p < 0.001). There was a significant predominance of GG DEFB1 genotype and G allele in NSV patients in comparison to controls (p < 0.001). The levels of serum HBD-1 and DEFB1 genotypes were not associated or correlated significantly with any of the personal and clinical parameters of vitiligo patients.

The small sample size.

DEFB1 gene polymorphism (GG genotype and G allele) may modulate vitiligo risk and contribute to vitiligo development in Egyptian populations. Decreased circulating HBD-1 levels might have an active role in vitiligo etiopathogenesis that could be mediated through its possible anti-inflammatory effects.

Cancer is a serious concern in public health worldwide. Numerous modalities including surgery, radiotherapy, and chemotherapy, have been used for cancer therapies in clinic. Despite progress in anticancer therapies, the usage of these methods for cancer treatment is often related to deleterious side effects and multidrug resistance of conventional anticancer drugs, which have prompted the development of novel therapeutic methods. Anticancer peptides (ACPs), derived from naturally occurring and modified peptides, have received great attention in these years and emerge as novel therapeutic and diagnostic candidates for cancer therapies, because of several advantages over the current treatment modalities. In this review, the classification and properties of ACPs, the mode of action and mechanism of membrane disruption, as well as the natural sources of bioactive peptides with anticancer activities were summarised. Because of their high efficacy for inducing cancer cell death, certain ACPs have been developed to work as drugs and vaccines, evaluated in varied phases of clinical trials. We expect that this summary could facilitate the understanding and design of ACPs with increased specificity and toxicity towards malignant cells and with reduced side effects to normal cells.

The percutaneous device dilemma describes etiological factors, centered around the disrupted epithelial tissue surrounding non-remodelable devices, that contribute to rampant percutaneous device infection. Natural percutaneous organs, in particular their extracellular matrix mediating the "device"/epithelium interface, serve as exquisite examples to inspire longer lasting long-term percutaneous device design. For example, the tooth's imperviousness to infection is mediated by the epithelium directly surrounding it, the junctional epithelium (JE). The hallmark feature of JE is formation of hemidesmosomes, cell/matrix adhesive structures that attach surrounding oral gingiva to the tooth's enamel through a basement membrane. Here, the authors survey the multifaceted functions of the JE, emphasizing the role of the matrix, with a particular focus on hemidesmosomes and their five main components. The authors highlight the known (and unknown) effects dental implant - as a model percutaneous device - placement has on JE regeneration and synthesize this information for application to other percutaneous devices. The authors conclude with a summary of bioengineering strategies aimed at solving the percutaneous device dilemma and invigorating greater collaboration between clinicians, bioengineers, and matrix biologists.

Human β-defensins (HBDs) are an important class of antimicrobial peptides that have immunomodulatory functions; however, the role of HBDs have not been well explored in the pathogenesis of meningitis. A cross-sectional study was performed to explore the levels of HBD1, HBD2, HBD3, and HBD4 in the cerebrospinal fluid (CSF) of 176 suspected meningitis cases. CSF samples were first subjected to PCR analysis using a set of universal primers targeting a portion of the eubacteria 16S rRNA gene. The analysis demonstrated that 66 samples (37.5%) were PCR-positive, whilst 110 samples (62.5%) were PCR-negative. DNA sequence analysis of the PCR-positive products identified two broad categories of bacteria, Gram-negative (68.2%) and Gram-positive (31.8%). A total of 88 PCR-negative CSF samples showed abnormal leukocyte counts, glucose concentrations, and/or protein concentrations, and were considered abnormal (ABN). The remaining 22 CSF samples were considered normal (NOR). HBD1, HBD2, and HBD4 levels did not exhibit significant differences between PCR-positive, ABN, and NOR CSF samples. However, HBD3 levels were significantly higher in the ABN CSF samples than in the NOR CSF samples (P=0.005). HBD3 levels were also elevated in the PCR-positive CSF samples compared with the NOR CSF samples, but the difference was not significant (P=0.151). HBD2, HBD3, and HBD4 were correlated with leukocyte counts, glucose concentration, and protein concentration. In conclusion, HBD3 levels were significantly elevated in the CSF of suspected meningitis cases regardless of the cause of meningitis. The CSF levels of certain HBDs were affected by specific diagnostic laboratory parameters for meningitis, including leukocyte counts, glucose concentration, and protein concentration.

Pathway analysis is a key analytical stage in the interpretation of omics data, providing a powerful method for detecting alterations in cellular processes. We recently developed a sensitive and distribution-free statistical framework for multisample distribution testing, which we implement here in the open-source R package single-cell pathway analysis (SCPA). We demonstrate the effectiveness of SCPA over commonly used methods, generate a scRNA-seq T cell dataset, and characterize pathway activity over early cellular activation. This reveals regulatory pathways in T cells, including an intrinsic type I interferon system regulating T cell survival and a reliance on arachidonic acid metabolism throughout T cell activation. A systems-level characterization of pathway activity in T cells across multiple tissues also identifies alpha-defensin expression as a hallmark of bone-marrow-derived T cells. Overall, this work provides a widely applicable tool for single-cell pathway analysis and highlights regulatory mechanisms of T cells.

The adverse consequences resulting from diabetes are often presented as severe complications. Diabetic wounds are one of the most commonly occurring complications in diabetes, and the control and treatment of this is costly. Due to a series of pathophysiological mechanisms, diabetic wounds remain in the inflammatory phase for a prolonged period of time, and face difficulty in entering the proliferative phase, thus leading to chronic non-healing wounds. The current consensus on the treatment of diabetic wounds is through multidisciplinary comprehensive management, however, standard wound treatment methods are still limited and therefore, more effective methods are required. In recent years, defensins have been found to play diverse roles in a variety of diseases; however, the molecular mechanisms underlying these activities are still largely unknown. Defensins can be constitutively or inductively produced in the skin, therefore, their local distribution is affected by the microenvironment of these diabetic wounds. Current evidence suggests that defensins are involved in the diabetic wound pathogenesis, and can potentially promote the early completion of each stage, thus making research on defensins a promising area for developing novel treatments for diabetic wounds. In this review, we describe the complex function of human defensins in the development of diabetic wounds, and suggest potential thera-peutic benefits.