Molecular and thermodynamic insights into interfacial interactions between collagen and cellulose investigated by molecular dynamics simulation and umbrella sampling.

Cellulose/collagen composites have been widely used in biomedicine and tissue engineering. Interfacial interactions are crucial in determining the final properties of cellulose/collagen composite. Molecular dynamics simulations were carried out to gain insights into the interactions between cellulose and collagen. It has been found that the structure of collagen remained intact during adsorption. The results derived from umbrella sampling showed that (110) and ([Formula: see text]) faces exhibited the strongest affinity with collagen (100) face came the second and (010) the last, which could be attributed to the surface roughness and hydrogen-bonding linkers involved water molecules. Cellulose planes with flat surfaces and the capability to form hydrogen-bonding linkers produce stronger affinity with collagen. The occupancy of hydrogen bonds formed between cellulose and collagen was low and not significantly contributive to the binding affinity. These findings provided insights into the interactions between cellulose and collagen at the molecular level, which may guide the design and fabrication of cellulose/collagen composites.

Molecular Mechanism of the Asarum-Angelica Drug Pair in the Treatment of Periodontitis Based on Network Pharmacology and Experimental Verification.

(1) To examine the potential mechanism of the Asarum-Angelica drug pair against periodontitis and provide an experimental basis for the treatment of periodontitis with herbal medicine. (2) The core components and core targets of the Asarum-Angelica drug pair in the treatment of periodontitis were detected according to network pharmacology methods. Finally, the effect of the Asarum-Angelica drug pair on osteogenic differentiation was observed in mouse embryonic osteoblast precursor cells. (3) According to the results of network pharmacology, there are 10 potential active ingredients in the Asarum-Angelica drug pair, and 44 potential targets were obtained by mapping the targets with periodontitis treatment. Ten potential active ingredients, such as kaempferol and ß-sitosterol, may play a role in treating periodontitis. Cell experiments showed that the Asarum-Angelica drug pair can effectively promote the expression of osteoblast markers alkaline phosphatase (ALP), Runt-related Transcription Factor 2 (RUNX2), and BCL2 mRNA and protein in an inflammatory environment (p < 0.05). (4) Network pharmacology effectively analyzed the molecular mechanism of Asarum-Angelica in the treatment of periodontitis, and the Asarum-Angelica drug pair can promote the differentiation of osteoblasts.

Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers.

In the present study, novel gastroretentive bilayer tablets were developed that are promising for the once-a-day oral delivery of the drug candidate MT-1207. The gastroretentive layer consisted of a combination of hydrophilic and hydrophobic polymers, namely polyethylene oxide and Kollidon® SR. A factorial experiment was conducted, and the results revealed a non-effervescent gastroretentive layer that, unlike most gastroretentive layers reported in the literature, was easy to prepare, and provided immediate tablet buoyancy (mean floating lag time of 1.5 s) that lasted over 24 h in fasted state simulated gastric fluid (FaSSGF) pH 1.6, irrespective of the drug layer, thereby allowing a 24-hour sustained release of MT-1207 from the drug layer of the tablets. Furthermore, during in vitro buoyancy testing of the optimised bilayer tablets in media of different pH values (1.0, 3.0, 6.0), the significant difference (one-way ANOVA, p < 0.001) between the respective total floating times indicated that stomach pH effects on tablet buoyancy are important to be considered during the development of non-effervescent gastroretentive formulations and the choice of dosing regimen. To the best of our knowledge, this has not been reported before, and it should probably be factored in when designing dosing regimens. Finally, a pharmacokinetic study in Beagle dogs indicated a successful in vivo 24-hour sustained release of MT-1207 from the optimised gastroretentive bilayer tablet formulations with the drug plasma concentration remaining above the estimated minimum effective concentration of 1 ng/mL at the 24-hour timepoint and also demonstrated the gastroretentive capabilities of the hydrophilic and hydrophobic polymer combination. The optimised formulations will be forwarded to clinical development.

Biomimetic Chiral Photonic Materials with Tunable Metallic Colorations Prepared from Chiral Melanin-like Nanorods for UV Shielding, Humidity Sensing, and Cosmetics.

Many biological species combine the helical organization of cellulose or chitin microfibrils with broadband light absorption of black melanin to produce brilliant structural colors with metallic and glossy effects and other diverse functions. In this work, based on core-shell CNC@PDA chiral nanorods consisting of cellulose nanocrystals (CNCs) as the core and melanin-like polydopamine (PDA) as the shell that can form well-defined chiral liquid crystal phases, we report chiral photonic materials that closely mimic the unique coloration mechanisms and functionalities mastered by several biological species. The photonic films formed by such single CNC@PDA nanorods have brilliant iridescent structural colors originating from selective reflection of circularly polarized lights by the helical organization of CNC@PDAs across the films. Furthermore, the colors of such films have background-independent brightness, high visibility, and metallic effects that arise from the light absorption of the PDA component. Especially, the color ranges and metallic effects of the films can be conveniently tuned by varying the thickness of the PDA shell. In addition, the UV absorption and hygroscopic properties of PDA endow these CNC@PDA films with efficient broadband UV shielding and sensitive humidity-induced dynamic color changes. Due to the mussel-like superior adhesion of PDA, CNC@PDA-based photonic coatings can be formed conformably onto diverse kinds of substrates. A shiny eye shadow with viewing angle-dependent colorful patterns was used to demonstrate the potential applications. With combinations of multiple unique properties in one photonic material fabricated from a single building block, these CNC@PDA-based films are expected to have potential applications in cosmetics, UV protection, anticounterfeiting, chiral reflectors, etc.

Environmentally benign cinchonain IIa from Uncaria laevigata for corrosion inhibition of Q235 steel in HCl corrosive medium: Experimental and theoretical investigation.

Traditional corrosion inhibitors make great contribution to metal protection, but also cause environmental pollution. To solve the problem, plant extracts as green corrosion inhibitors have attracted much attention in recent years. Plants are good raw materials for corrosion inhibitors and also meet the requirements of industry. However, they have not been successfully applied in industry due to the unknown composition of the effective corrosion inhibitors and large dosage thereof. Therefore, cinchonain IIa was separated from Uncaria laevigata with abundant sources and low cost from nature in this work. Here we hypothesized that cinchonain IIa could show good corrosion inhibition performance for Q235 steel in the acidic medium. Through experiments and theoretical calculation, we studied the corrosion inhibition effect of cinchonain IIa on Q235 in 1 M HCl solution at 298 K for 48 h. Electrochemical experiments revealed that the inhibition efficiency of 200 mg/L cinchonain IIa in 1 M HCl for Q235 steel was 94.08% for 48 h. It even showed over 93% corrosion inhibition efficiency and durable protection performance to 28 d. Surface observations indicated that cinchonain IIa were firmly attached to the steel surface by forming a protective film. Moreover, quantum chemical calculation and molecular dynamics simulation revealed the inhibition mechanism at molecular and atomic level. Compared with some plant extracts, here we demonstrate that the outstanding advantages of cinchonain IIa include sustained protective effect, small dosage, and low toxicity. Accordingly, it may be used as a green industrial corrosion inhibitor with great potential in oilfield acidification and acid pickling.

Development, In Vitro and In Vivo Evaluation of Racecadotril Orodispersible Films for Pediatric Use.

The present study endeavored to develop orodispersible films (ODFs) containing 30 mg racecadotril for pediatric use, which focuses on improving the compliance of pediatric patients and reducing risk of choking. The challenge of this study is to prepare high drug loading ODFs with successful mechanical and physicochemical properties. Compatibilities between drug and different polymers (hydroxypropyl methylcellulose, HPMC; polyvinyl alcohol, PVA; low-substituted hydroxypropyl cellulose, L-HPC; pullulan, PU) were investigated to select stable and safe film-forming polymers. Afterwards, the study explored the maximum amount of racecadotril incorporated into PVA films and PU films. Subsequently, disintegrant (Lycoat RS720, 4-10%, w/w) and plasticizers (glycerol, 2-6%, w/w) were investigated to reduce disintegration time of PVA films and enhance the flexibility of PU films, respectively. Formulation characteristics (appearance, tensile strength, percent elongation, disintegration time, drug content, weight, thickness, pH value, moisture content, moisture uptake, and Q5min) of prepared ODFs were examined to obtain the optimal compositions of racecadotril ODFs. Differential scanning calorimetry (DSC) study, powder X-ray diffraction (XRD) study, Fourier transform infrared (FTIR) study, comparative in vitro dissolution study, and pharmacokinetic study in Beagle dogs of optimized racecadotril ODFs were then conducted. Eventually, ODFs containing 50% racecadotril, 38% PVA, 7% Lycoat RS720, 2% sucralose, 2% apricot, and 1% titanium dioxide could achieve desirable mechanical properties, disintegrating within a few seconds and releasing more than 85% drug within 5 min in four dissolution media. An in vivo study showed optimized racecadotril ODF and Hidrasec were bioequivalent in Beagle dogs. In summary, ODFs containing 30 mg racecadotril were successfully prepared by solvent casting method, and it was suitable for the administration to the pediatric patients.

Polymeric "Clickase" Accelerates the Copper Click Reaction of Small Molecules, Proteins, and Cells.

Recent work has shown that polymeric catalysts can mimic some of the remarkable features of metalloenzymes by binding substrates in proximity to a bound metal center. We report here an unexpected role for the polymer: multivalent, reversible, and adaptive binding to protein surfaces allowing for accelerated catalytic modification of proteins. The catalysts studied are a group of copper-containing single-chain polymeric nanoparticles (CuI-SCNP) that exhibit enzyme-like catalysis of the copper-mediated azide-alkyne cycloaddition reaction. The CuI-SCNP use a previously observed "uptake mode", binding small-molecule alkynes and azides inside a water-soluble amphiphilic polymer and proximal to copper catalytic sites, but with unprecedented rates. Remarkably, a combined experimental and computational study shows that the same CuI-SCNP perform a more efficient click reaction on modified protein surfaces and cell surface glycans than do small-molecule catalysts. The catalysis occurs through an "attach mode" where the SCNPs reversibly bind protein surfaces through multiple hydrophobic and electrostatic contacts. The results more broadly point to a wider capability for polymeric catalysts as artificial metalloenzymes, especially as it relates to bioapplications.

Design and synthesis of novel PEG-conjugated 20(S)-camptothecin sulfonylamidine derivatives with potent in vitro antitumor activity via Cu-catalyzed three-component reaction.

In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel structurally diverse PEG-based 20(S)-CPT sulfonylamidine derivatives were designed, synthesized via a Cu-multicomponent reaction (MCR), and evaluated for cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and KBvin). All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, and were more potent than irinotecan. Significantly, these derivatives exhibited comparable cytotoxicity against KBvin, while irinotecan was less active against this cell line. With a concise efficient synthesis and potent cytotoxic profiles, especially significant activity towards KBvin, these compounds merit further development as a new generation of CPT-derived PEG-conjugated drug candidates.

3D embedded bioprinting of large-scale intestine with complex structural organization and blood capillaries.

Accurate reproduction of human intestinal structure and functionin vitrois of great significance for understanding the development and disease occurrence of the gut. However, mostin vitrostudies are often confined to 2D models, 2.5D organ chips or 3D organoids, which cannot fully recapitulate the tissue architecture, microenvironment and cell compartmentalization foundin vivo. Herein, a centimeter-scale intestine tissue that contains intestinal features, such as hollow tubular structure, capillaries and tightly connected epithelium with invivo-likering folds, crypt-villi, and microvilli is constructed by 3D embedding bioprinting. In our strategy, a novel photocurable bioink composed of methacrylated gelatin, methacrylated sodium alginate and poly (ethylene glycol) diacrylate is developed for the fabrication of intestinal model. The Caco-2 cells implanted in the lumen are induced by the topological structures of the model to derive microvilli, crypt-villi, and tight junctions, simulating the intestinal epithelial barrier. The human umbilical vein endothelial cells encapsulated within the model gradually form microvessels, mimicking the dense capillary network in the intestine. This intestine-like tissue, which closely resembles the structure and cell arrangement of the human gut, can act as a platform to predict the therapeutic and toxic side effects of new drugs on the intestine.

Lipid Nanoparticles-Based Therapy in Liver Metastasis Management: From Tumor Cell-Directed Strategy to Liver Microenvironment-Directed Strategy.

Metastasis to the liver, as one of the most frequent metastatic patterns, was associated with poor prognosis. Major drawbacks of conventional therapies in liver metastasis were the lack of metastatic-targeting ability, predominant systemic toxicities and incapability of tumor microenvironment modulations. Lipid nanoparticles-based strategies like galactosylated, lyso-thermosensitive or active-targeting chemotherapeutics liposomes have been explored in liver metastasis management. This review aimed to summarize the state-of-art lipid nanoparticles-based therapies in liver metastasis management. Clinical and translational studies on the lipid nanoparticles in treating liver metastasis were searched up to April, 2023 from online databases. This review focused not only on the updates in drug-encapsulated lipid nanoparticles directly targeting metastatic cancer cells in treating liver metastasis, but more importantly on research frontiers in drug-loading lipid nanoparticles targeting nonparenchymal liver tumor microenvironment components in treating liver metastasis, which showed promise for future clinical oncological practice.

Injectable Double-Network Hydrogel-Based Three-Dimensional Cell Culture Systems for Regenerating Dental Pulp.

The regeneration of dental pulp tissue is very important, but difficult, in dentistry. The biocompatibility, water content, and viscoelastic properties of pulp-like tissue must be optimized to achieve the efficient transfer of metabolites and nutrients, a suitable degradation rate, distribution of encapsulated cells, injectability, and gelation in situ under physiological conditions. As promising materials for pulp regeneration, hydrogel scaffolds have been produced to simulate the extracellular matrix and transmit signaling molecules. It is imperative to develop hydrogels to effectively regenerate pulp tissue for clinical application. Here, two injectable double-network (DN) hydrogel-based three-dimensional (3D) cell culture systems were developed for regenerating dental pulp. The microstructure, mechanical property, rheology property, and degradation behavior of the injectable DN glycol chitosan-based hydrogels in a simulated root canal model were characterized and compared to a single-network (SN) glycol chitosan-based hydrogel. Human dental pulp stem cells (hDPSCs) were then encapsulated into the GC-based hydrogels for the regeneration of pulp tissue, and the biological performance was investigated both in vitro and in vivo. The results showed that the DN hydrogels had ideal injectability under physiological conditions due to the dynamic nature of the crosslinks. Besides, the DN hydrogels exhibited better mechanical properties and longer degradation duration than the corresponding SN hydrogel. As a 3D cell culture system, the characteristics of the DN hydrogel facilitated odontogenic differentiation and mineralization of hDPSCs in vitro. Further in vivo analysis confirmed that the chemical composition, matrix stiffness, and degradation rate of the DN hydrogel matched those of pulp-like fibrous connective tissue, which might be related to Smad3 activation. These findings demonstrate that DN glycol chitosan-based hydrogels are suitable for the regeneration of pulp tissue.

Evaluation of a dynamic navigation system for endodontic microsurgery: study protocol for a randomised controlled trial.

INTRODUCTION: Endodontic microsurgery is a very important technique for preserving the natural teeth. The outcomes of endodontic microsurgery largely depend on the skill and experience of the operators, especially for cases in which the apices are located far away from the labial/buccal cortical bone. A dynamic navigation system (DNS) could provide a more accurate and efficient way to carry out endodontic microsurgery. This study is devoted to comparing the clinical outcomes of the DNS technique with those of the freehand technique. METHODS AND ANALYSIS: Sixteen patients will be randomly assigned to one of two groups. For the experimental group, the osteotomy and root-end resection will be performed under the guidance of dynamic navigation. For the control group, these procedures will be performed freehand by an endodontist. The required time to perform these procedures will be used to evaluate the efficiency of the DNS technique. A Visual Analogue Scale will be used to evaluate pain at 1, 3 and 7 days after endodontic microsurgery. Preoperative and postoperative cone beam CT scans will be obtained to evaluate the accuracy of the DNS technique. The global coronal deviations, the apical deviations and the angular deflection will be measured. The root-end resection length deviation, the root-end resection angle deviations, the extent of the osteotomy and the volume change of the buccal cortical bone will also be measured. Periapical radiographs will be obtained to evaluate the outcome at 1 year after microsurgery. The time to execute the study, including follow-ups, will last from 1 June 2022 to 31 December 2025. ETHICS AND DISSEMINATION: The present study has received approval from the Ethics Committee of Peking University School and Hospital of Stomatology. The results will be disseminated through scientific journals. TRIAL REGISTRATION NUMBER: ChiCTR2200059389.

Emulsifying properties of naturally acetylated xylans and their application in lutein delivery emulsion.

Xylans play an important role in dispersing and lubricating cellulose fibrils in lignocellulosic plant cell walls. However, the effect of acetylation on the dispersing and emulsifying properties of xylan is still unclear. In this study, we show that the natural degree of acetylation is vital to ensure xylan an excellent water solubility and emulsifying ability. Alkali extracted xylans were artificially acetylated to degree of substitution (DSAc) between 0.12 and 2.00, while the DMSO extracted originally acetylated xylan (OAX) shows a DSAc of 0.18. Artificially acetylated xylans (AX) with DSAc value similar to OAX shows water solubility and emulsifying ability similar to those of OAX and the best among all the AX samples with different DSAc. They demonstrate excellent emulsifying properties with an emulsifying activity of ~1.3 and an emulsion cream index of ~5 %. AX with the natural DSAc value also demonstrates strong barrier effects in preparing lutein delivery emulsions.

Platelet-rich fibrin/anorganic bovine bone mineral complex as grafting materials in endodontic microsurgery with a large lesion size: study protocol for a randomised controlled trial.

INTRODUCTION: Endodontic microsurgery is a treatment of last resort for preserving natural teeth. According to radiographic evaluation, the percentage of complete healing after endodontic microsurgery is only 74.3%. The use of regenerative techniques in endodontic microsurgery for large lesions (>10 mm diameter) is therefore recommended. The most frequently used bone graft in endodontic microsurgery is anorganic bovine bone mineral (ABBM) but this only has an osteoconductive effect. Thus, when platelet-rich fibrin (PRF), a reservoir of growth factors, is used together with ABBM, it increases the regenerative effect. This study is devoted to comparing the clinical outcomes of PRF with/without ABBM as grafting biomaterials in endodontic microsurgery cases with large lesion size to provide some valuable reference data for dentists. METHODS AND ANALYSIS: Sixteen patients who are in need of endodontic microsurgery will be recruited. The patients will be randomly assigned to one of two groups: an experimental group, treated with PRF/ABBM complex and collagen membrane, and a control group, treated with ABBM and collagen membrane. Clinical examination including percussion, mobility testing and presence/absence of sinus will be recorded at 7 days, and at 3, 6 and 12 months after endodontic microsurgery. A Visual Analogue Scale will be used by the patients to evaluate pain at 1, 3 and 7 days after endodontic microsurgery. Routine paralleling radiographs will be obtained before and at 3, 6 and 12 months follow-up after endodontic microsurgery. Cone-beam CT (CBCT) scans will be obtained at the 12-month follow-up. Bone formation will be evaluated according to CBCT and paralleling radiographs. The study execute time including follow-ups last from 1 June 2021 to 31 December 2024. ETHICS AND DISSEMINATION: This study received approval from the Ethics Committee of Peking University School and Hospital of Stomatology. The results will be disseminated through scientific journals. TRIAL REGISTRATION NUMBER: Research data will be registered with the International Clinical Trials Registry Platform (ICTRP), ID: ChiCTR2100046684.

Micro- and nanofibrillated cellulose from virgin and recycled fibers: A comparative study of its effects on the properties of hygiene tissue paper.

This study aims to understand the effect of micro- and nanofibrillated cellulose (MNFC) on the tensile index, softness, and water absorbency of tissue paper. MNFC was produced from four different fiber sources. The results show that MNFC acts as an effective strength enhancer at the expense of a reduced water absorbency and softness. The impact of the fiber source on MNFC manufacturing cost and the trade-off with performance was also investigated. MNFCs produced from southern bleached hardwood kraft, northern bleached softwood kraft, and deinked pulp exhibited similar performance trends with the MNFC from the deinked pulp having a significantly lower cost. This suggests that MNFCs with similar degrees of fibrillation may be used interchangeably regardless of the fiber source, revealing the possibility to minimize MNFC manufacturing costs based on fiber selection. MNFC produced from bleached Eucalyptus kraft showed the lowest degree of fibrillation and the lowest strength improvements among the MNFCs evaluated.

Optimized Neural Network Based on Genetic Algorithm to Construct Hand-Foot-and-Mouth Disease Prediction and Early-Warning Model.

Accompanied by the rapid economic and social development, there is a phenomenon of the crazy spread of many infectious diseases. It has brought the rapid growth of the number of people infected with hand-foot-and-mouth disease (HFMD), and children, especially infants and young children's health is at great risk. So it is very important to predict the number of HFMD infections and realize the regional early-warning of HFMD based on big data. However, in the current field of infectious diseases, the research on the prevalence of HFMD mainly predicts the number of future cases based on the number of historical cases in various places, and the influence of many related factors that affect the prevalence of HFMD is ignored. The current early-warning research of HFMD mainly uses direct case report, which uses statistical methods in time and space to have early-warnings of outbreaks separately. It leads to a high error rate and low confidence in the early-warning results. This paper uses machine learning methods to establish a HFMD epidemic prediction model and explore constructing a variety of early-warning models. By comparison of experimental results, we finally verify that the HFMD prediction algorithm proposed in this paper has higher accuracy. At the same time, the early-warning algorithm based on the comparison of threshold has good results.

A circRNA-miRNA-mRNA network plays a role in the protective effect of diosgenin on alveolar bone loss in ovariectomized rats.

BACKGROUND: The present study aimed to assess the perturbation in circular RNA (circRNA)/mRNA expression profiles and a circRNA-miRNA-mRNA coexpression network involved in the potential protective effect of diosgenin (DIO) on alveolar bone loss in rats subjected to ovariectomy (OVX). METHODS: The Wistar rats (female) manipulated with sham operation were classified as the SHAM group and the grouping of OVX rats administered with DIO, estradiol valerate or vehicle for 12 weeks was DIO group, EV group and OVX group respectively. Following treatments, the plasmatic levels of osteocalcin and tumor necrosis factor-alpha and the microstructure of alveolar bone were assayed. Based on microarray analyses, we identified differentially expressed (DE) circRNAs and mRNAs in alveolar bone of rats in both OVX and DIO group. The DE circRNAs and DE mRNAs involved in the bone metabolism pathway validated by RT-qPCR were considered key circRNAs/mRNAs. On the basis of these key circRNAs/mRNAs, we predicted the overlapping relative miRNAs of key circRNAs/mRNAs, and a circRNA-miRNA-mRNA network was built. RESULTS: DIO showed an anti-osteopenic effect on the rat alveolar bone loss induced by OVX. In total, we found 10 DE circRNAs (6 downregulated and 4 upregulated) and 614 DE mRNAs (314 downregulated and 300 upregulated) in samples of the DIO group compared with those of the OVX group. However, only one circRNA (rno_circRNA_016717) and seven mRNAs (Sfrp1, Csf1, Il1rl1, Nfatc4, Tnfrsf1a, Pik3c2g, and Wnt9b) were validated by qRT-PCR and therefore considered key circRNA/mRNAs. According to these key circRNA/mRNAs and overlapping predicted miRNAs, a coexpression network was constructed. After network analysis, one circRNA-miRNA-mRNA axis (circRNA_016717/miR-501-5p/Sfrp1) was identified. CONCLUSION: The mechanism of DIO inhibiting alveolar bone loss after OVX is possibly relevant to the simultaneous inhibition of osteogenesis and osteoclastogenesis by mediating the expression of important molecules in the Wnt, PI3K, RANK/RANKL or osteoclastogenic cytokine pathways. The circRNA_016717/miR-501-5p/Sfrp1 axis may play important roles in these processes.

MicroRNAs as new biomarkers for human papilloma virus related head and neck cancers.

Head and neck cancers are the sixth most common cancer in the world and the predominant type of which consist of squamous cell carcinomas (head and neck squamous cell carcinoma, HNSCC). Besides tobacco smoking and alcohol consumption, human papilloma virus (HPV) infection is the third leading cause of the occurrence of HNSCC. The presence of HPV is a distinct group of head and neck cancers exhibiting epidemiological, histopathological, clinical and prognostic differences opposed to the typical HNSCC. HPV positive HNSCC normally have a favorable prognosis compared with HPV negative HNSCC, so biomarkers suitable for the early detection of HPV positive HNSCC should be developed urgently to improve patient outcomes. HPV DNA screening is sensitive, but probably not useful because of the high prevalence of oral HPV and low risk of HNSCC. MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that act as post-transcriptional regulators of gene expression. Since miRNAs have a role in the cancer development and HPV status may affect the miRNAs expression pattern in HNSCC, the specific of miRNAs' expression in HPV positive HNSCC may expound the role of HPV in HNSCC and be new biomarkers for the early detection of HNSCC. More excitingly, saliva as proximal biofluid in the context of HNSCC contains a good deal of miRNAs. These miRNAs are stabile and may be suitable for noninvasive biomarkers of HNSCC.