The microbial composition of pancreatic ductal adenocarcinoma: A systematic review of 16S rRNA gene sequencing.

BACKGROUND: Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), continues to pose a significant clinical and scientific challenge. The most significant finding of recent years is that PDAC tumours harbour their specific microbiome, which differs amongst tumour entities and is distinct from healthy tissue. This review aims to evaluate and summarise all PDAC studies that have used the next-generation technique, 16S rRNA gene amplicon sequencing within each bodily compartment. As well as establishing a causal relationship between PDAC and the microbiome. MATERIALS AND METHODS: This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive search strategy was designed, and 1727 studies were analysed. RESULTS: In total, 38 studies were selected for qualitative analysis and summarised significant PDAC bacterial signatures. Despite the growing amount of data provided, we are not able to state a universal 16S rRNA gene microbial signature that can be used for PDAC screening. This is most certainly due to the heterogeneity of the presentation of results, lack of available datasets and the intrinsic selection bias between studies. CONCLUSION: Several key studies have begun to shed light on causality and the influence the microbiome constituents and their produced metabolites could play in tumorigenesis and influencing outcomes. The challenge in this field is to shape the available microbial data into targetable signatures. Making sequenced data readily available is critical, coupled with the coordinated standardisation of data and the need for consensus guidelines in studies investigating the microbiome in PDAC.

Catalytic hairpin assembly-based AIEgen/graphene oxide nanocomposite for fluorescence-enhanced and high-precision spatiotemporal imaging of microRNA in living cells.

The low abundance, heterogeneous expression, and temporal changes of miRNA in different cellular locations pose significant challenges for both the detection sensitivity of miRNA liquid biopsy and intracellular imaging. In this work, we report an intelligently assembled biosensor based on catalytic hairpin assembly (CHA) and aggregation-induced emission (AIE), named as catalytic hairpin aggregation-induced emission (CHAIE), for the ultrasensitive detection and intracellular imaging of miRNA-155. To achieve such goal, tetraphenylethylene-N3 (TPE-N3) is used as AIE luminogen (AIEgen), while graphene oxide is introduced to quench the fluorescence. When the target miRNA is present, CHA reaction is triggered, causing the AIEgen to self-assemble with the hairpin DNA. This will restrict the intramolecular rotation of the AIEgen and produce a strong AIE fluorescence. Interestingly, CHAIE does not require any enzyme or expensive thermal cycling equipment, and therefore provides a rapid detection. Under optimal conditions, the proposed biosensor can determine miRNA in the concentration range from 2 pM to 200 nM within 30 min, with the detection limit of 0.42 pM. The proposed CHAIE biosensor in this work offers a low background signal and high sensitivity, making it applicable for highly precise spatiotemporal imaging of target miRNA in living cells.

The Roles and Interactions of Porphyromonas gingivalis and Fusobacterium nucleatum in Oral and Gastrointestinal Carcinogenesis: A Narrative Review.

Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. Porphyromonas gingivalis and Fusobacteria nucleatum, which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of P. gingivalis and F. nucleatum in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between P. gingivalis and F. nucleatum in affecting oral and gastrointestinal carcinogenesis. P. gingivalis and F. nucleatum, which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field.

Effects of meiotic stage-specific oocyte vitrification on mouse oocyte quality and developmental competence.

Introduction: Acquisition of germinal vesicle (GV) stage oocytes for fertility preservation (FP) offers several benefits over in vivo matured oocyte cryopreservation following ovarian stimulation, particularly for cancer patients necessitating immediate treatment. Two FP approaches for GV oocytes are available: vitrification before in vitro maturation (IVM) at the GV stage (GV-VI) or post-IVM at the metaphase II (MII) stage (MII-VI). The optimal method remains to be determined. Methods: In this study, mouse oocytes were collected without hormonal stimulation and vitrified either at the GV stage or the MII stage following IVM; non-vitrified in vitro matured MII oocytes served as the control (CON). The oocyte quality and developmental competence were assessed to obtain a better method for immediate FP. Results: No significant differences in IVM and survival rates were observed among the three groups. Nevertheless, GV-VI oocytes exhibited inferior quality, including abnormal spindle arrangement, mitochondrial dysfunction, and early apoptosis, compared to MII-VI and CON oocytes. Oocyte vitrification at the GV stage impacted maternal mRNA degradation during IVM. In addition, the GV-VI group demonstrated significantly lower embryonic developmental competence relative to the MII-VI group. RNA sequencing of 2-cell stage embryos revealed abnormal minor zygotic genome activation in the GV-VI group. Conclusion: Vitrification at the GV stage compromised oocyte quality and reduced developmental competence. Consequently, compared to the GV stage, oocyte vitrification at the MII stage after IVM is more suitable for patients who require immediate FP.

The Applications of Electrochemical Immunosensors in the Detection of Disease Biomarkers: A Review.

Disease-related biomarkers may serve as indicators of human disease. The clinical diagnosis of diseases may largely benefit from timely and accurate detection of biomarkers, which has been the subject of extensive investigations. Due to the specificity of antibody and antigen recognition, electrochemical immunosensors can accurately detect multiple disease biomarkers, including proteins, antigens, and enzymes. This review deals with the fundamentals and types of electrochemical immunosensors. The electrochemical immunosensors are developed using three different catalysts: redox couples, typical biological enzymes, and nanomimetic enzymes. This review also focuses on the applications of those immunosensors in the detection of cancer, Alzheimer's disease, novel coronavirus pneumonia and other diseases. Finally, the future trends in electrochemical immunosensors are addressed in terms of achieving lower detection limits, improving electrode modification capabilities and developing composite functional materials.

A sandwich-type electrochemical immunosensor based on spherical nucleic acids-templated Ag nanoclusters for ultrasensitive detection of tumor biomarker.

The accurate determination of tumor biomarkers in blood is of vital significance in the diagnosis and therapy of tumor disease. In this research, an innovative sandwich-type electrochemical immunosensor is designed for the ultrasensitive determination of tumor biomarker AFP using spherical nucleic acids-templated silver nanoclusters (AgNCs) sensing platform. For this purpose, on one hand, DNA functionalized gold nanoparticles (AuNPs@DNA) is selected not only as the cross-linker to immobilize the primary antibody (anti-AFP antibody 1, Ab1) to obtain AuNPs@DNA-Ab1, but also as the template for synthesizing AgNCs on AuNPs to form AuNPs@DNA-AgNCs. On the other hand, p-sulfonated calix[4]arene (pSC4) modified Au is chosen to immobilize the secondary antibody (anti-AFP antibody 2, Ab2) through host-guest recognition between Ab2 and pSC4. When AFP is encountered, the immunoreaction signal can be significantly amplified by the electrochemical reduction of AgNCs. Under optimal circumstances, the sandwich-type electrochemical immunosensor exhibits broad limit of linearity from 0.001 to 100 ng mL-1 (R2 = 0.997) and low detection limit of 7.74 fg mL-1 (S/N = 3). The immunosensor possesses excellent repeatability and selectivity, offering a novel method for sensitive clinical diagnosis of tumor markers in human hepatocellular carcinoma.

Simple Lymphangioma of the Scrotum: A Case Report.

As scrotal simple lymphangioma is a rare benign proliferation of lymphatic vessels in the scrotum, a few reports were documented. A 68-year-old man gradually developed vesicles on the scrotum for ten years and easily ruptured due to friction. Physical examination showed diffuse millet-sized vesicles on the scrotum with milky white fluids and chyle-like exudates. Histopathological examination revealed proliferating and dilated lymphatic vessels with various sizes of lumens in the dermis. An immunohistochemical study showed positive staining for D2-40 and CD31. Therefore, the patient was diagnosed with scrotal lymphangioma and received carbon dioxide laser therapy. After the treatment, the vesicles markedly decreased, and no apparent exudates were observed. During one year of the follow-up, no relapse, scars, or other complications occurred.

A Novel Variant and a Missense Variant Identified in the DKC1 Gene in Three Chinese Familieswith Dyskeratosis Congenita.

Purpose: Dyskeratosis congenita (DC) is an inherited telomere biology disorder characterized clinically by mucocutaneous triad of reticulate hyperpigmentation, nail changes and oral leukoplakia. Bone marrow failure, pulmonary fibrosis and malignancies are the mainly life-threatening causes. There are X-linked recessive, autosomal dominant and autosomal recessive patterns of DC. DKC1 is the most common pathogenic mutation gene responsible for X-linked DC, and it encodes a protein, dyskerin, which is a component of telomerase holoenzyme complex essential for telomere maintenance. Patients with DC have very short telomeres, but the precise pathogenic mechanism remains unclear. This study aimed to identify the causative mutations in the DKC1 gene in three Chinese families with the X-linked form of DC. Patients and Methods: Three Chinese families with DC were included in this study. Whole exome sequencing and Sanger sequencing were performed to clarify the mutation of DKC1 gene. Measurement of relative telomere length through qPCR. Predictions of protein structure and function were performed using bioinformatics tools, including I-TASSER, Polyphen-2 and SIFT. Results: There were four males with DC and a female carrier in three Chinese pedigrees. The novel mutation c.92A>C (p. Q31P) and the missense mutation c.1058C>T (p. A353V) in DKC1 were identified. Both mutations locally changed the structure of dyskerin. Variant Q31P and A353V were predicted to have "deleterious" and "natural" effects on the function of dyskerin, respectively. Conclusion: The novel variant and missense variant detected in the DKC1 gene improve our understanding of DC and broaden the mutation spectrum of the DKC1 gene.

Role of drug catabolism, modulation of oncogenic signaling and tumor microenvironment in microbe-mediated pancreatic cancer chemoresistance.

Pancreatic ductal adenocarcinoma (PDAC) has one of the highest incidence/death ratios among all neoplasms due to its late diagnosis and dominant chemoresistance. Most PDAC patients present with an advanced disease characterized by a multifactorial, inherent and acquired resistance to current anticancer treatments. This remarkable chemoresistance has been ascribed to several PDAC features including the genetic landscape, metabolic alterations, and a heterogeneous tumor microenvironment that is characterized by dense fibrosis, and a cellular contexture including functionally distinct subclasses of cancer-associated fibroblasts, immune suppressive cells, but also a number of bacteria, shaping a specific tumor microbiome microenvironment. Thus, recent studies prompted the emergence of a new research avenue, by describing the role of the microbiome in gemcitabine resistance, while next-generation-sequencing analyses identified a specific microbiome in different tumors, including PDAC. Functionally, the contribution of these microbes to PDAC chemoresistance is only beginning to be explored. Here we provide an overview of the studies demonstrating that bacteria have the capacity to metabolically transform and hence inactivate anticancer drugs, as exemplified by the inhibition of the efficacy of 10 out of 30 chemotherapeutics by Escherichia coli. Moreover, a number of bacteria modulate specific oncogenic pathways, such as Fusobacterium nucleatum, affecting autophagy and apoptosis induction by 5-fluorouracil and oxaliplatin. We hypothesize that improved understanding of how chemoresistance is driven by bacteria could enhance the efficacy of current treatments, and discuss the potential of microbiome modulation and targeted therapeutic approaches as well as the need for more reliable models and biomarkers to translate the findings of preclinical/translational research to the clinical setting, and ultimately overcome PDAC chemoresistance, hence improving clinical outcome.

An ultrasensitive immunosensor based on cellulose nanofibrils/polydopamine/Cu-Ag nanocomposite for the detection of AFP.

In this work, an ultrasensitive immunosensor for amperometric determination of alpha-fetoprotein (AFP) was developed utilizing Ag and Cu nanoparticles on polydopamine (PDA) functionalized cellulose nanofibrils (CNFs) composite (CNFs/PDA/Cu-Ag) as signal amplifier. PDA was first prepared by self-polymerizing of dopamine, and then was adsorbed on CNFs. The obtained CNFs/PDA was applied as substrate to electrolessly deposit Cu-Ag nanoparticles, using NaBH4 as reducing agent. The structure and morphology of the synthesized CNFs/PDA/Cu-Ag nanocomposite were analyzed through Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray powder diffraction, scanning electron microscopy, particle size analyzer and transmission electron microscopy. The CNFs/PDA/Cu-Ag modified glassy carbon electrode can fix AFP antibody (Ab), and further capture AFP specifically. Electrochemical impedance spectroscopy and cyclic voltammetry were used to characterize the assembly process of immunosensor. The immunoreaction was amplified by electrocatalytical reduction of H2O2 on Cu-Ag nanoparticles, through which AFP was quantitatively detected. The developed sensor exhibits wide linear range of 0.01-100 ng mL-1 (R2 = 0.9963) with low detection limit of 4.27 pg mL-1 (S/N = 3). In addition, it has been used for the detection of AFP in human serum, manifesting its preeminent application prospect in early liver cancer diagnosis.

Clinical characteristics, pregnancy outcomes and ovarian function of pregnancy-associated breast cancer patients: a retrospective age-matched study.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is a rare disease with increasing incidence. The prognosis, pregnancy outcomes and subsequent ovarian function of PABC patients are attracting attention. METHODS: Sixty-three PABC patients and 126 age-matched non-PABC patients were obtained in Tongji Hospital from January 2011 to September 2019. The clinical characteristics and ovarian function of PABC patients were compared with those of non-PABC patients. The pregnancy outcomes and neonatal outcomes of patients with breast cancer diagnosed during pregnancy (BCP) were described. Nonparametric tests, the χ2-test Kaplan-Meier, Cox regression and binomial logistic regression were used for analysis. RESULTS: PABC patients were diagnosed with a more advanced tumour stage (II: 47.6% vs. 45.2%, III: 33.3% vs. 19.8%, IV 3.2% vs. 0%, p = 0.003), which caused worse progression-free survival (PFS) (log-rank p = 0.0138) and breast cancer-specific survival (CSS) (log-rank p = 0.0076) than non-PABC patients. Tumour stage (III/IV vs. 0/I/II) (HR 16.017, 95% CI 5.830 ~ 44.006, p < 0.001) and endocrine therapy (HR 0.254, 95% CI 0.099 ~ 0.653, p = 0.004) were predictors of PFS. Tumour stage (III/IV vs. 0/I/II) (HR 30.875, 95% CI 7.232 ~ 131.820, p < 0.001), endocrine therapy (HR 0.200, 95% CI 0.049 ~ 0.818, p = 0.025) and targeted therapy (HR 0.143, 95% CI 0.028 ~ 0.743, p = 0.021) were predictors for breast CSS. Among the 15 BCP patients, 11 patients voluntarily continued their pregnancy, and the newborns had no obvious birth defects, either in 5 patients who received chemotherapy or in 6 patients who did not receive chemotherapy during pregnancy. Among the patients who received chemotherapy and did not receive endocrine therapy, 24 PABC patients and 48 non-PABC patients experienced chemotherapy-induced amenorrhea. There was no significant difference in resumption of menstruation between the two groups at 6 months and 12 months after the end of chemotherapy. No potential factors affecting resumption of menstruation were found. CONCLUSION: Pregnancy at diagnosis or within 1 year after delivery was not a risk factor for a worse prognosis in PABC patients. Compared with non-PABC patients, patients with PABC presented more aggressive tumour characteristics, which could mostly explain the worse prognosis observed in PABC patients. Receiving the appropriate regimen of chemotherapy in the second and third trimesters did not affect the maternal outcomes or neonatal outcomes of BCP patients. The special physiological state during pregnancy and lactation did not interfere with the damage of chemotherapy to ovarian function.

Adjuvant Chemotherapy May Not Be Necessary for Women with Stage IC1 Epithelial Ovarian Cancer.

OBJECTIVE: To determine whether adjuvant chemotherapy improves the prognoses in women with stage IC1 epithelial ovarian cancer (EOC). METHODS: All eligible women diagnosed with stage IC1 EOC from 2003 to 2019 in Tongji Hospital were included. Patient characteristics, tumor features, surgical types, and chemotherapeutic treatments were collected. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate progression-free survival (PFS) and overall survival (OS). RESULTS: Of the 140 patients (median age: 47 years old), 13 patients did not receive chemotherapy, and 127 received adjuvant chemotherapy. Kaplan-Meier analysis indicated that adjuvant chemotherapy offered no obvious improvements in PFS or OS. Subgroup analysis was conducted to adjust for the significant difference in incomplete staging surgery between the two groups, and chemotherapy still showed no benefit for survival. Cox regression analysis indicated that incomplete staging surgery was a risk factor for a worse PFS and that adjuvant chemotherapy remained unrelated to the prognosis. The patients were further divided based on the National Comprehensive Cancer Network recommendations: patients for whom observation is optional and chemotherapy would not improve the prognosis; and patients for whom chemotherapy is recommended. The results showed that postoperative chemotherapy had little correlation with survival. CONCLUSION: Our study suggests that postoperative chemotherapy may be unnecessary for patients with stage IC1 EOC. According to our results, incomplete staging surgery is a significant risk factor for PFS.

Propagation dynamics and radiation forces of autofocusing circle Bessel Gaussian vortex beams in a harmonic potential.

In this paper, the circle Bessel Gaussian vortex beams (CBGVBs) are introduced in a harmonic potential for the first time, whose autofocusing properties are explored by theoretical analysis as well as numerical simulation. According to the dimensionless linear (2+1)D Schrödinger equation, we numerically simulate the transmission trajectories of different topological charges of the off-axis vortices and the positions, the intensity and the phase distributions, the maximum transmission intensity, the center of mass, the energy flow, and the angular momentum. The simulation results show that the periodically autofocusing CBGVBs can flexibly adjust the position, the intensity, and the focus points by controlling the parameters. By increasing the number of off-axis vortices and adjusting the position of off-axis vortices, the transmission trajectory and the intensity of the CBGVBs can be controlled. Furthermore, we notice that the larger the slope of the curve where the combined force of the scattering force and the gradient force is 0, the particles are more likely to be trapped.

Anchoring zinc-doped carbon dots on a paper-based chip for highly sensitive fluorescence detection of copper ions.

In this work, zinc-doped carbon dots (Zn-CDs) were anchored on a three-dimensional wheel type paper-based microfluidic chip, and were decorated with 6-mercaptonicotinic acid (MNA) and L-cysteine (L-Cys) for highly sensitive and rapid fluorescence detection of Cu2+. Zn-CDs were first anchored on paper through the amide bonds between the carboxyl groups of the Zn-CDs and the amino groups of the paper. Afterwards, Zn-CDs were decorated with MNA and L-Cys, effectively preventing the Zn-CDs from aggregation. The nitrogen atom on the pyridine ring and the carboxylic acid groups in MNA and L-Cys coordinated with Cu2+ to form a nonfluorescent ground-state complex, causing the fluorescence quenching of the Zn-CDs. The three-dimensional rotary design could simplify the operation process and achieve simultaneous analysis of multiple samples with different concentrations. Under optimal conditions, the fluorescent sensor exhibits linear response for the determination of Cu2+ in the range from 0.1 to 60 µg L-1 with the detection limit (LOD) of 0.018 µg L-1. The proposed strategy provides a novel way for the highly sensitive detection of Cu2+ in a complex water environment.

Successful Treatment With Intrathecal and Intravenous Polymyxin B-Based Combination Against MDR Acinetobacter baumannii Meningitis in Pediatric Patient: A Case Report.

Background: Nosocomial meningitis with multidrug-resistant (MDR) or extensively drug-resistant (XDR) Acinetobacter baumannii is a life-threatening complication in neurosurgery. Treatment of these infections is challenging because of poor penetration of the available antibiotics into the cerebrospinal fluid (CSF). Intrathecal (ITH) or intraventricular (IVT) administration of antibiotics is increasingly used as the last treatment option against MDR/XDR Gram-negative bacteria meningitis not responding to intravenous (IV) regimens. However, pertinent data in pediatric patients is scarce. Case Presentation: A 14-year-old male patient developed meningitis from an MDR strain of A. baumannii following endoscopic endonasal resection of craniopharyngioma. Despite a combination therapy involving IV tigecycline, we observed clinical and bacteriologic failure. The patient was then successfully treated with an ITH and IV polymyxin B-based combination. Quantification of tigecycline and polymyxin B in CSF was performed with two-dimensional high-performance liquid chromatography (2D-HPLC) and HDLC coupled with tandem mass spectrometry (HPLC-MS/MS), respectively. Adverse drug reactions (neurotoxicity and skin hyperpigmentation), probably induced by polymyxin B, were acceptable and reversible. Conclusions: The case illustrates ITH and IV Polymyxin B-based combination is an optimal therapeutic option against MDR A. baumannii meningitis in this pediatric patient. In the future, real-time PK/PD data obtained from patients during ITH/IVT polymyxin B therapy should be required to optimize polymyxin use with maximal efficacy and minimal adverse effects.

Patch test-relevant concentrations of metal salts cause localized cytotoxicity, including apoptosis, in skin ex vivo.

BACKGROUND: Metal alloys containing contact sensitizers (nickel, palladium, titanium) are extensively used in medical devices, in particular dentistry and orthopaedic surgery. The skin patch test is used to test for metal allergy. OBJECTIVE: To determine whether metal salts, when applied to freshly excised skin at patch test-relevant concentrations and using a method which mimics skin patch testing, cause in changes in the epidermis and dermis. METHODS: Tissue histology, apoptosis, metabolic activity, and inflammatory cytokine release were determined for two nickel salts, two palladium salts, and four titanium salts. RESULTS: Patch test-relevant concentrations of all metal salts caused localized cytotoxicity. This was observed as epidermis separation at the basement membrane zone, formation of vacuoles, apoptotic nuclei, decreased metabolic activity, and (pro)inflammatory cytokine release. Nickel(II) sulfate hexahydrate, nickel(II) chloride hexahydrate, titanium(IV) bis(ammonium lactato)dihydroxide, and calcium titanate were highly cytotoxic. Palladium(II) chloride, sodium tetrachloropalladate(II), titanium(IV) isopropoxide, and titanium(IV) dioxide showed mild cytotoxicity. CONCLUSION: The patch test in itself may be damaging to the skin of the patient being tested. These results need further verification with biopsies obtained during clinical patch testing. The future challenge is to remain above the elicitation threshold at noncytotoxic metal concentrations.

Novel dental implant modifications with two-staged double benefits for preventing infection and promoting osseointegration in vivo and in vitro.

Peri-implantitis are a major problem causing implant failure these days. Accordingly, anti-infection during the early stage and subsequent promotion of osseointegration are two main key factors to solve this issue. Micro-arc oxidation (MAO) treatment is a way to form an oxidation film on the surface of metallic materials. The method shows good osteogenic properties but weak antibacterial effect. Therefore, we developed combined strategies to combat severe peri-implantitis, which included the use of a novel compound, PD, comprising dendrimers poly(amidoamine) (PAMAM) loading dimethylaminododecyl methacrylate (DMADDM) as well as MAO treatment. Here, we explored the chemical properties of the novel compound PD, and proved that this compound was successfully synthesized, with the loading efficiency and encapsulation efficiency of 23.91% and 31.42%, respectively. We further report the two-stage double benefits capability of PD + MAO: (1) in the first stage, PD + MAO could decrease the adherence and development of biofilms by releasing DMADDM in the highly infected first stage after implant surgery both in vitro and in vivo; (2) in the second stage, PD + MAO indicated mighty anti-infection and osteoconductive characteristics in a rat model of peri-implantitis in vivo. This study first reports the two-staged, double benefits of PD + MAO, and demonstrates its potential in clinical applications for inhibiting peri-implantitis, especially in patients with severe infection risk.

Effects of Antibiotics Versus Repeated Applications of Photodynamic Therapy as an Adjunctive Treatment for Periodontitis: A Systematic Review and Meta-Analysis.

Objective: Although multiple applications of antimicrobial photodynamic therapy (aPDT) and antibiotics (AB) have been proved to have a biomodulatory effect, no systematic review has exclusively compared the effectiveness as an adjunct to scaling and root planning (SRP). This study sought to systematically compare the clinical efficacy of repeated antimicrobial photodynamic therapy (RaPDT) with that of the systemic administered AB as an alternative approach to SRP in treating periodontitis. Methods: In this systematic review, two independent reviewers searched PubMed, Embase, and CENTRAL databases. The primary outcomes assessed were bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL). Results: Five randomized clinical trials were included after screening 457 records. Results revealed that when patients from all studies were categorized based on their baseline CAL, AB demonstrated significant benefits over RaPDT in the improvement of PPD [weighted mean differences (WMD) = -0.36, 95% confidence interval (CI) = -0.71 to -0.02, p < 0.05] in the patients with severe periodontitis (CAL baseline ≥5 mm) 3-month postoperatively, and CAL (WMD = -0.57, 95% CI = -1.11 to -0.04, p < 0.05) at 6-month observation. Nevertheless, AB failed to show significant benefits over RaPDT, when CAL baseline <5 mm in terms of clinical parameters. Conclusions: RaPDT may represent an alternative approach to SRP in treating slight-to-moderate periodontitis cases (CAL <5 mm), whereas AB remain a main therapy for treating severe periodontitis (CAL ≥5 mm).

Smoking reduces cathelicidin LL-37 and human neutrophil peptide 1-3 levels in the gingival crevicular fluid of patients with periodontitis.

BACKGROUND: Antimicrobial peptides are components of innate immune response that have a key role on susceptibility and resistance of the oral cavity to diseases. This study aimed to investigate the influence of smoking on cathelicidin LL-37 and human neutrophil peptides 1 through 3 (HNP 1-3) levels in the gingival crevicular fluid (GCF) of patients with periodontitis. The relationship between levels of these peptides with the periodontal status and selected inflammatory mediators levels in smokers and non-smokers was also evaluated. METHODS: Forty patients with periodontitis, 20 smokers and 20 non-smokers were recruited. After a full periodontal clinical assessment, GCF samples were collected from healthy (n = 5) and diseased (n = 5) sites of each patient. Peptides and inflammatory mediators in the GCF were quantitated by sandwich ELISAs and Multiplex assay, respectively. RESULTS: Diseased sites had significantly (P <0.05) higher levels of LL-37 and lower levels of HNP 1-3 than healthy sites in both smokers and non-smokers. Diseased sites of smokers presented significantly lower levels of LL-37 and HNP 1-3 when compared with diseased sites of non-smokers. Concentration of LL-37 was directly correlated with the presence of proinflammatory mediators matrix metalloproteinase (MMP)-8 and interleukin (IL)-1ß and inversely correlated with concentration of IL-10. HNP 1-3 concentration was positively correlated with IL-10 and negatively correlated with concentrations of MMP-8 and IL-1ß. CONCLUSIONS: Smoking was associated with reduced levels of LL-37 and HNP 1-3 in GCF of patients with periodontitis. LL-37 had a distinct expression pattern from HNP 1-3: LL-37 was upregulated in diseased sites, and HNP 1-3 was increased in periodontally healthy sites.1.