Engineered Biomaterials Trigger Remineralization and Antimicrobial Effects for Dental Caries Restoration.

Dental caries is the most prevalent chronic disease globally, significantly impacting individuals' quality of life. A key reason behind the failure of implanted restorations is their biological inactivity, meaning they are unable to form crosslinks with the surrounding tooth structures, thus making patients susceptible to implant loss and recurrent tooth decay. For the treatment of caries, antibacterial medicine and remineralization are effective means of treating the recurrence of caries. Owing to the rapid progression in the biomaterials field, several biomaterials have been reported to display antimicrobial properties and aid in dentin remineralization. Bioactive materials hold considerable potential in diminishing biofilm accumulation, inhibiting the process of demineralization, enabling dentin remineralization, and combating bacteria related to caries. Bioactive materials, such as fluoride, amorphous calcium phosphate, bioactive glass, collagen, and resin-based materials, have demonstrated their effectiveness in promoting dentin remineralization and exerting antibacterial effects on dental caries. However, the concentration of fluoride needs to be strictly controlled. Although amorphous calcium phosphate can provide the necessary calcium and phosphorus ions for remineralization, it falls short in delivering the mechanical strength required for oral mastication. Resin-based materials also offer different advantages due to the complexity of their design. In this review, we delve into the application of advanced bioactive materials for enhancing dentin remineralization and antibacterial properties. We eagerly anticipate future developments in bioactive materials for the treatment of dental caries.

Radial and ulnar forearm free flaps: A critical comparison of donor site morbidity and its impact on quality of life.

BACKGROUND: A poor evidence basis exists regarding direct comparing objective and subjective donor site morbidity associated with forearm flap. The authors evaluated the postoperative donor-site complications and quality of life outcomes between radial forearm free flap (RFFF) and ulnar forearm free flap (UFFF). METHODS: All patients undergoing RFFF or UFFF harvest were included. Grip strength, pinch strength, wrist range of movement, and testing skin sensitivity were assessed with the appropriate scales at different time intervals. In addition, cosmetic and quality of life were assessed using the Patient and Observer Scar Assessment Scale (POSAS) and Disability of Arm, Shoulder, and Hand (DASH) score. RESULTS: Eighty patients were enrolled (40 RFFF and 40 UFFF). The results showed a short-term reduction in grip strength, fine motor skills (tip pinch, key pinch, palmar pinch), and range of motion was observed for RFFF and improved over time. None of the patients in either group experienced functional disturbance in grip strength, wrist motion, fine motor skills, or sensation to light touch at 1 year. Nine patients experienced partial skin graft loss (RFFF = 6; UFFF = 3). There was a significantly higher incidence of temporary numbness in the RFFF group (p=0.040). Persistent numbness occurred in 3 cases in RFFF. Cold intolerance was significantly lower in UFFF (2.5 %) than in RFFF (22.5%). Moreover, the mean POSAS and DASH score reduced at 12 months compared to 6 months, significantly superior for UFFF. CONCLUSION: Objective function limitations are reversible short-term effects after forearm flap and do not affect daily routines in the long term. Additionally, UFFF appears to be preferred over RFFF for subjective outcomes, which emphasizes the UFFF should be considered an alternative to RFFF for reconstructing soft-tissue defects.

Reconstruction of large defects of anterior floor of mouth with free flaps using a novel individualized flap design method.

The purpose of this study was to introduce a novel individualized flap design method for large anterior floor of the mouth (AFOM) defect reconstruction, review experience with the use of this flap design method for large AFOM defect reconstruction, and assess its functional results. A retrospective study of patients who received large AFOM defect reconstruction with free flaps was conducted. There was a cohort of patients who were treated using the novel individualized flap design method and a cohort without flap design. Functional outcomes were evaluated with appropriate scales. Outcomes were analyzed, and a p-value <0.05 was considered significant. 22 patients received the individualized flap design, while 21 patients were treated without a special flap design. All flaps survived. All free flaps harvested with the novel individualized flap design method better matched AFOM defects. Relative to patients without flap design, patients in the novel individualized flap design group showed significant improvement in speech intelligibility (p = 0.036) and swallowing function (p = 0.019). Within the limitation of the study it seems that large AFOM defect reconstruction with the novel individualized flap design method can not only cover and close the wound to avoid oral-neck fistulae, but also maintains tongue mobility to achieve better functional outcomes than in patients without flap design.

A novel flap design technique for subtotal tongue reconstruction with an "Individualized and Convenient Tongue Model".

BACKGROUND: To achieve improved functional outcomes in subtotal tongue reconstruction, a flap design with sufficient volume and appropriate shape is necessary. In this study, we introduce an "Individualized and Convenient Tongue Model" (ICTM) for flap design in subtotal tongue reconstruction. METHODS: By studying the anatomical morphology of the tongue, we found a similar geometry within the dorsum and body of the tongue as well as the mouth floor. This can be used to create an ICTM through folding and splicing. We can simulate tongue defects in the ICTM and transform defect shapes into guide plates for flap design. In this study, fifty-eight patients requiring subtotal tongue reconstruction were randomly divided into two groups: an ICTM group (35 patients) and a conventional group (31 patients). In the ICTM group, we individually designed profunda artery perforator flaps (PAPFs) or anterolateral thigh flaps (ALTFs) using the ICTM method. In the conventional group, the flap was designed according to the surgeon's clinical experience. Patient demographics, operative and follow-up data were recorded. Swallowing, speech intelligibility, and cosmetic results were assessed using appropriate scales. RESULTS: All flaps survived, although there were no significant differences in tumor size, operation time, flap size, and complication rate compared to the conventional group. Patients in the ICTM group had significantly improved speech intelligibility (p = 0.019), cosmetic appearance (p = 0.009), and swallowing ability (p = 0.003). CONCLUSIONS: The ICTM technique is an effective and convenient solution for subtotal tongue reconstruction that provides an individualized flap design and improves functional outcomes compared to the conventional design.

Isoflavone glucoside genistin, an inhibitor targeting Sortase A and Listeriolysin O, attenuates the virulence of Listeria monocytogenes in vivo and in vitro.

As a common intracellular facultative anaerobic Gram-positive bacterium, Listeria monocytogenes (L. monocytogenes) exhibits strong resistance to extreme environments, such as low temperature and a wide range of pH values, causing contamination in food production and processing. Sortase A (SrtA) and listeriolysin O (LLO), two crucial virulence factors of L. monocytogenes, are widely recognized as potential targets for the development of anti-L. monocytogenes infection drugs. In this study, we found that genistin simultaneously inhibits the peptidase activity of SrtA and the hemolytic activity of LLO without affecting the growth of L. monocytogenes, alleviating concerns about developing resistance. Furthermore, we demonstrated that genistin reduces L. monocytogenes biofilm formation and invasion of human colorectal cancer (Caco-2) cells. Subsequent mechanistic studies revealed that genistin inhibited LLO-mediated Caco-2 cell damage by blocking LLO oligomerization. Fluorescence quenching assay revealed the potential binding mode of SrtA and LLO to genistin. Genistin might bind to the active pocket of SrtA through residues Leu33, Asn29, and Met40, interacting with D1 domain of LLO involved in oligomerization and pore formation through residues Asn259. Studies in infection models revealed that genistin reduces mortality and pathological damage in mice infected with L. monocytogenes. These results indicate that genistin is a promising anti-virulence agent that could be considered an alternative candidate for the treatment of L. monocytogenes infection.

Smart nanogels for cancer treatment from the perspective of functional groups.

Introduction: Cancer remains a significant health challenge, with chemotherapy being a critical treatment modality. However, traditional chemotherapy faces limitations due to non-specificity and toxicity. Nanogels, as advanced drug carriers, offer potential for targeted and controlled drug release, improving therapeutic efficacy and reducing side effects. Methods: This review summarizes the latest developments in nanogel-based chemotherapy drug delivery systems, focusing on the role of functional groups in drug loading and the design of smart hydrogels with controlled release mechanisms. We discuss the preparation methods of various nanogels based on different functional groups and their application in cancer treatment. Results: Nanogels composed of natural and synthetic polymers, such as chitosan, alginate, and polyacrylic acid, have been developed for chemotherapy drug delivery. Functional groups like carboxyl, disulfide, and hydroxyl groups play crucial roles in drug encapsulation and release. Smart hydrogels have been engineered to respond to tumor microenvironmental cues, such as pH, redox potential, temperature, and external stimuli like light and ultrasound, enabling targeted drug release. Discussion: The use of functional groups in nanogel preparation allows for the creation of multifunctional nanogels with high drug loading capacity, controllable release, and good targeting. These nanogels have shown promising results in preclinical studies, with enhanced antitumor effects and reduced systemic toxicity compared to traditional chemotherapy. Conclusion: The development of smart nanogels with functional group-mediated drug delivery and controlled release strategies represents a promising direction in cancer therapy. These systems offer the potential for improved patient outcomes by enhancing drug targeting and minimizing adverse effects. Further research is needed to optimize nanogel design, evaluate their safety and efficacy in clinical trials, and explore their potential for personalized medicine.

Corilagin: A Novel Antivirulence Strategy to Alleviate Streptococcus pneumoniae Infection by Diminishing Pneumolysin Oligomers.

Pneumolysin (PLY) is a significant virulence factor of Streptococcus pneumoniae (S. pneumoniae), able to break through the defense system of a host and mediate the occurrence of a series of infections. Therefore, PLY as the most ideal target to prevent S. pneumoniae infection has received more and more attention and research. Corilagin is a tannic acid that exhibits excellent inhibition of PLY oligomers without bacteriostatic activity to S. pneumoniae. Herein, hemolytic activity assays, cell viability tests and western blot experiments are executed to evaluate the antivirulence efficacy of corilagin against PLY in vitro. Colony observation, hematoxylin and eosin (H&E) staining and cytokines of bronchoalveolar lavage fluid (BALF) are applied to assess the therapeutic effect of corilagin in mice infected by S. pneumoniae. The results indicate the related genes of corilagin act mainly via enrichment in pathways associated with pneumonia disease. Furthermore, molecular docking and molecular dynamics simulations show that corilagin might bind with domains 3 and 4 of PLY and interfere with its hemolytic activity, which is further confirmed by the site-directed mutagenesis of PLY. Additionally, corilagin limits PLY oligomer production without impacting PLY expression in S. pneumoniae cultures. Moreover, corilagin effectively relieves PLY-mediated cell injury without any cytotoxicity, even then reducing the colony count in the lung and the levels of pro-inflammatory factors in BALF and remarkably improving lung lesions. All the results demonstrate that corilagin may be a novel strategy to cope with S. pneumoniae infection by inhibiting PLY oligomerization.

Insecure Birth: A Qualitative Study of Everyday Violence During Pregnancy in Port au Prince, Haiti.

INTRODUCTION: While the city offers economic opportunities for women in many countries, their safety and security remain vulnerable to urban violence, especially in poor areas. In Haiti, poor urban women may be subjected to multiple forms of physical, sexual, and structural violence leading to adverse birth outcomes. We explored some of the complexities of how pregnancy is experienced under the reality and threat of urban violence in Haiti. METHODS: We examined data from focus group discussions with fourteen women who lived in severely disenfranchised neighborhoods in Port au Prince and who were pregnant or had recently delivered at the time of the study. RESULTS: We report on three recurring themes that emerged from the discussion: (a) ways in which the threat or experience of violence affected women's ability to access maternal healthcare, (b) ways in which women altered their behavior to accommodate everyday violence, and (c) the extent to which violence was embedded in women's consensual and non-consensual sexual encounters with perpetrators. We found that Haitian women considered violence, labeled ensekirite (insecurity), to be an everyday threat in their lives and that they strategized ways to access maternal health care and other services while navigating ensekirite. DISCUSSION: Pregnancy adds another layer of vulnerability that may necessitate further negotiations with the threat and presence of violence. The pervasiveness and impact of urban violence in women's daily lives needs to be better evaluated in maternal and newborn health research and programs.

Specificity protein 1/microRNA-92b forms a feedback loop promoting the migration and invasion of head and neck squamous cell carcinoma.

In this study we report a novel specificity protein 1 (SP1)/microRNA-92b (miR-92b) feedback loop regulating the migration and invasion of head and neck squamous cell carcinoma (HNSCC). Microarray and real-time Polymerase Chain Reaction (PCR) were used to detect gene expression in HNSCC tissues and cell lines. Transwell migration, invasion, wound healing and cell counting kit - 8 (CCK-8) cell assays were used to compare cell migration, invasion and proliferation abilities. Chromatin Immunoprecipitation (ChIP) assays were used to detect SP1 binding to the miR-92b promoter. Western blot was used to detect protein levels. An in vivo tumorigenesis experiment was used to evaluate the effect of SP1 knockdown on tumor growth and protein levels were evaluated by immunohistochemistry. We found that the miR-92b expression level was elevated in HNSCC primary focus tissue compared with adjacent normal tissue, and a higher level of miR-92b was related to a higher clinical stage and worse prognosis of HNSCC patients. MiR-92b and SP1 mutually promoted each expression and cooperatively facilitated the migration, invasion and proliferation of HNSCC cells. A decreased level of SP1/miR-92b resulted in a restraint of in vivo tumor growth. In conclusion, our results suggest that the SP1/miR-92b feedback loop generally promotes HNSCC invasion and metastasis, thus presenting a possible therapeutic target in the treatment of HNSCC patients.

Hsa-let-7e-5p Inhibits the Proliferation and Metastasis of Head and Neck Squamous Cell Carcinoma Cells by Targeting Chemokine Receptor 7.

This study aimed at determining the role of hsa-let-7e-5p in the progression of head and neck squamous cell carcinoma (HNSCC). The relative levels of hsa-let-7e-5p transcripts in 15 paired of HNSCC and adjacent non-tumor tissues and cells were examined by quantitative real-time PCR (qRT-PCR). The potential targets of hsa-let-7e-5p were predicted and validated by luciferase assay. The impact of altered hsa-let-7e-5p expression on HNSCC cell proliferation and metastasis was determined by CCK-8, wound healing, transwell migration and invasion assays. The effect of hsa-let-7e-5p over-expression on the growth of HNSCC was examined in vivo. Hsa-let-7e-5p expression was significantly down-regulated in HNSCC tissues and highly metastatic PCI-37B cells. Bioinformatic analysis predicted that hsa-let-7e-5p bound to the 3'untranslated region (3'UTR) of chemokine receptor 7(CCR7), which was validated by luciferase assay. While transfection with hsa-let-7e-5p mimic significantly decreased CCR7 protein expression, transfection with hsa-let-7e-5p inhibitor increased CCR7 protein expression in HNSCC cells. Similarly, hsa-let-7e-5p over-expression inhibited PCI-37B cell proliferation, wound healing, migration and invasion, while inhibition of endogenous hsa-let-7e-5p had opposite effects in PCI-37A cells. Hsa-let-7e-5p over-expression inhibited PCI-37B tumor growth in vivo. Therefore, hsa-let-7e-5p acts as a tumor suppressor to inhibit the progression of HNSCC by targeting CCR7 expression. Hsa-let-7e-5p and CCR7 may be therapeutic targets of HNSCC.

Upregulated miR­20a­5p expression promotes proliferation and invasion of head and neck squamous cell carcinoma cells by targeting of TNFRSF21.

MicroRNAs (miRNAs) play important roles in regulation of proliferation, migration, and invasion of head and neck squamous cell carcinoma (HNSCC). The present study assessed expression, functions and mechanisms of miR­20a­5p in the regulation of HNSCC cell proliferation, migration and invasion. miR­20a­5p expression in HNSCC cell lines and tissues was detected using qRT­PCR, while miR­20a­5p mimics and inhibitor were transfected into HNSCC cells for assessment of the effects using different assays (CCK­8, wound healing and Transwell assays) and expression of miR­20a­5p­targeting genes (using western blot and luciferase reporter assays). The data revealed that miR­20a­5p was upregulated in both HNSCC tissues and metastatic HNSCC cells. Upregulated miR­20a­5p expression in HNSCC cells promoted tumor cell proliferation, migration and invasion capacities, but resulted in downregulation of TNFRSF21 expression and in turn upregulation of C­C motif chemokine receptor 7 (CCR7) in HNSCC cells. Concordantly, knockdown of miR­20a­5p in HNSCC had the opposite results. In conclusion, miR­20a­5p functioned as an oncogene in HNSCC by downregulating TNFRSF21 and subsequently, upregulating CCR7 expression.

Overexpression of hsa-miR-125a-5p enhances proliferation, migration and invasion of head and neck squamous cell carcinoma cell lines by upregulating C-C chemokine receptor type 7.

Head and neck squamous cell carcinoma (HNSCC) is usually diagnosed accompanied by lymph node metastasis. C-C chemokine receptor type 7 (CCR7) is associated with the invasion and metastasis of tumors in HNSCC through various signaling pathways. The role of hsa-miR-125a-5p in HNSCC remains unclear. The present study was performed to investigate the association between hsa-miR-125a-5p and CCR7 in HNSCC. Reverse transcription-quantitative polymerase chain reaction was applied to analyze the expression of hsa-miR-125a-5p in clinical samples. Cell Counting Kit-8, Transwell and wound healing assays were used to detect cell proliferation, invasion, and metastasis, respectively, following overexpression of hsa-miR-125a-5p. Changes in protein expression of CCR7 were observed using western blotting. In the survival analysis, Student's t-tests and log rank tests were performed to analyze the association between the expression of hsa-miR-125a-5p, and HNSCC according to the Cancer Genome Atlas database. The expression of hsa-miR-125a-5p was identified to be significantly lower in cancer tissue compared with the corresponding adjacent normal tissues in clinical samples (P=0.038). The results of western blotting indicated that there was a positive regulatory association between hsa-miR-125a-5p and CCR7. Furthermore, overexpression of hsa-miR-125a-5p significantly enhanced the ability of cell proliferation, migration and invasion in HNSCC, with upregulation of CCR7. The results of survival analysis revealed that patients in the low expression group of hsa-miR-125a-5p tended to have longer survival times compared with the high expression group (P=0.045). Altogether, the data raised the possibility that hsa-miR-125a-5p has a significant role in promoting cancer in HNSCC, which may provide a basis for the treatment of HNSCC in molecular targeted therapy. Further studies are required to ascertain the role of hsa-miR-125a-5p in other HNSCC cell lines and in vivo.

MiR-1275 promotes cell migration, invasion and proliferation in squamous cell carcinoma of head and neck via up-regulating IGF-1R and CCR7.

PURPOSE: miRNAs can play vital role in migration, invasion and proliferation in Squamous cell carcinoma of head and neck (SCCHN). In our study, we attempted to validate the expression and function of miR-1275 in SCCHN, and we also identified the mechanism by which miR-1275 affects migration, invasion and proliferation of SCCHN. METHODS: Real-time polymerase chain reaction (RT-PCR) was employed to evaluate the expression of miR-1275 in both SCCHN tissues and cell lines. The role of miR-1275 in SCCHN cells was verified by cell function experiments upon transfection with miR-1275 mimics and inhibitor. Western blot analysis was employed to test the target gene expression of miR-1275. Survival analysis was made with the information of SCCHN patients expressed miR-1275 from The Cancer Genome Atlas (TCGA) database. RESULTS: miR-1275 expression was up-regulated in SCCHN tissues and advanced metastatic SCCHN cells. Increasing miR-1275 expression in SCCHN could promote cell migration, invasion and proliferation probably by upregulating Insulin-like growth factor 1 receptor (IGF-1R) and C-C chemokine receptor type 7(CCR7) protein levels, whereas inhibition of miR-1275 could lead the opposite effects, although others have already demonstrated that IGF-1R is a direct target of miR-1275. Survival analysis suggested that patients with lower miR-1275 expression may have a better outcome. CONCLUSIONS: Herein we report for the first time that miR-1275 could act as a tumor-promoter in SCCHN possibly by regulating its target gene via novel miRNA mechanisms. MiR-1275 plays an important role in promoting SCCHN progression. The miR-1275 may be a potential therapeutic target for SCCHN treatment in the future.

Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF-1/IGF-1R signaling.

Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF-1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF-1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF-1/IGF-1R-induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF-1/IGF-1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies.

Primary neuroendocrine small cell carcinoma of the parotid gland: A case report and review of the literature.

Small cell carcinoma (SCC) is a malignant epithelial tumor that predominantly arises in the lungs. Primary SCC of the parotid gland is rare and difficult to diagnose by analysis of frozen sections obtained during surgery. Due to the aggressive nature of SCC and the frequent occurrence of distant metastases, identification of the disease is important. The current study reports the case of a male patient who presented with a right parotid gland mass. The tumor was resected and evaluated by light microscopy and immunohistochemical analysis. Immunohistochemically, the tumor was positive for cytokeratin, epithelial membrane antigen, cluster of differentiation 117, synaptophysin and thyroid transcription factor-1, which indicated that the tumor was a SCC of the parotid gland. An extended resection of the right parotid gland mass and dissection of the facial nerve were performed. Following discharge from the hospital, the patient received radiation therapy postoperatively. The patient has remained disease free during five months of follow-up.

Experimental observation of nanojets formed by heating PbO-coated Pb clusters.

We are reporting the first experimental observation of nanojets formed by heating PbO-coated Pb clusters, which has been predicted theoretically by Moseler and Landman. During heating, the hot liquid is ejected through the broken orifice into a vacuum and forms a condensed trail in the shape of a tadpole, as shown in the transmission electron micrographs. The temperature-variable Raman spectra indicate that nanojet formation is closely related to the heating temperature and thus essentially to the pressure in the coated clusters. The pressure inside the shell rises from the inner core's melting and its confined volume expansion. It then drops after the final explosion, dominating the whole nanojetting process.