An observational study of the pH value during the healing process of diabetic foot ulcer.

OBJECTIVE: In this study, we evaluated the pH (potential of hydrogen) value of diabetic foot ulcers and explored the relationship between the pH value and infection, sinus formation, stasis dermatitis, and the process of healing. METHODS: From October 2022 to June 2023, 99 patients with 106 diabetic foot ulcers were selected. Diabetic foot ulcers were treated in a standardized manner by a professional team. The pH value, area, PUSH (Pressure Ulcer Scale for Healing) score, and the degree of infection of the wounds were compared before and after the treatment. RESULTS: The baseline wound pH value in 76.4% of the patients was in the alkaline range and was closely related to the degree of infection (P < 0.05). As the ulcers healed, the pH decreased. For moderately and severely infected diabetic foot ulcers, each unit decrease in pH was associated with a decrease in the PUSH score of approximately 4.6 points (P < 0.05). The pH values of wounds with surrounding ecchymosis dermatitis were significantly higher than those of wounds without ecchymosis dermatitis (P < 0.05). The pH value of the wound with a sinus tract was higher. After treatment, there was no significant difference in pH value between the patients with and without sinus tracts (P < 0.05). CONCLUSIONS: The measurement of pH value is efficient and simple, and the patient suffers no discomfort in the process. The change in pH helps predict the healing process of diabetic foot ulcers and quickly identify whether there are key factors such as infection and ischemia in the wound. It is suggested that dynamic pH monitoring be included in the whole course evaluation and intervention strategy development of diabetic foot.

Nucleic Acid Plate Culture: Label-Free and Naked-Eye-Based Digital Loop-Mediated Isothermal Amplification in Hydrogel with Machine Learning.

Digital nucleic acid amplification enables the absolute quantification of single molecules. However, due to the ultrasmall reaction volume in the digital system (i.e., short light path), most digital systems are limited to fluorescence signals, while label-free and naked-eye readout remain challenging. In this work, we report a digital nucleic acid plate culture method for label-free, ultrasimple, and naked-eye nucleic acid analysis. As simple as the bacteria culture, the nanoconfined digital loop-mediated isothermal amplification was performed by using polyacrylamide (PAM) hydrogel as the amplification matrix. The nanoconfinement of PAM hydrogel with an ionic polymer chain can remarkably accelerate the amplification of target nucleic acids and the growth of inorganic byproducts, namely, magnesium pyrophosphate particles (MPPs). Compared to that in aqueous solutions, MPPs trapped in the hydrogel with enhanced light scattering characteristics are clearly visible to the naked eye, forming white "colony" spots that can be simply counted in a label-free and instrument-free manner. The MPPs can also be photographed by a smartphone and automatically counted by a machine-learning algorithm to realize the absolute quantification of antibiotic-resistant pathogens in diverse real samples.

Integrated anti-vascular and immune-chemotherapy for colorectal carcinoma using a pH-responsive polymeric delivery system.

Colorectal carcinoma (CRC) has become one of the most prevalent malignant tumors and exploring a potential therapeutic strategy with diminished drug-associated adverse effects to combat CRC is urgent. Herein, we designed a pH-responsive polymer to efficiently encapsulate a stimulator of interferon genes (STING) agonist (5,6- dimethylxanthenone-4-acetic acid, termed ASA404) and a common clinically used chemotherapeutic agent (1-hexylcarbamoyl-5-fluorouracil, termed HCFU). Investigations in vitro demonstrated that polymer encapsulation endowed the system with a pH-dependent disassembly behavior (pHt 6.37), which preferentially selected cancerous cells with a favorable dose reduction (dose reduction index (DRI) of HCFU was 4.09). Moreover, the growth of CRC in tumor-bearing mice was effectively suppressed, with tumor suppression rates up to 94.74%, and a combination index (CI) value of less than one (CI = 0.41 for CT26 cell lines), indicating a significant synergistic therapeutic effect. Histological analysis of the tumor micro-vessel density and enzyme-linked immunosorbent assay (ELISA) tests indicated that the system increased TNF-α and IFN-ß levels in serum. Therefore, this research introduces a pH-responsive polymer-based theranostic platform with great potential for immune-chemotherapeutic and anti-vascular combination therapy of CRC.

Biexcitons-plasmon coupling of Ag@Au hollow nanocube/MoS2 heterostructures based on scattering spectra.

The strong interaction between light and matter is one of the current research hotspots in the field of nanophotonics, and provides a suitable platform for fundamental physics research such as on nanolasers, high-precision sensing in biology, quantum communication and quantum computing. In this study, double Rabi splitting was achieved in a composite structure monolayer MoS2 and a single Ag@Au hollow nanocube (HNC) in room temperature mainly due to the two excitons in monolayer MoS2. Moreover, the tuning of the plasmon resonance peak was realized in the scattering spectrum by adjusting the thickness of the shell to ensure it matches the energy of the two excitons. Two distinct anticrossings are observed at both excitons resonances, and large double Rabi splittings (90 meV and 120 meV) are obtained successfully. The finite-difference time domain (FDTD) method was also used to simulate the scattering spectra of the nanostructures, and the simulation results were in good agreement with the experimental results. Additionally, the local electromagnetic field ability of the Ag@Au hollow HNC was proved to be stronger by calculating and comparing the mode volume of different nanoparticles. Our findings provides a good platform for the realization of strong multi-mode coupling and open up a new way to construct nanoscale photonic devices.

STMP and PVPA as Templating Analogues of Noncollagenous Proteins Induce Intrafibrillar Mineralization of type I Collagen via PCCP Process.

The phosphorylated noncollagenous proteins (NCPs) play a vital role in manipulating biomineralization, while the mechanism of phosphorylation of NCPs in intrafibrillar mineralization of collagen fibril has not been completely deciphered. Poly(vinylphosphonic acid) (PVPA) and sodium trimetaphosphate (STMP) as templating analogues of NCPs induce hierarchical mineralization in cooperation with indispensable sequestration analogues such as polyacrylic acid (PAA) via polymer-induced liquid-like precursor (PILP) process. Herein, we propose STMP-Ca and PVPA-Ca complexes to achieve rapid intrafibrillar mineralization through polyelectrolyte-Ca complexes pre-precursor (PCCP) process. This strategy is further verified effectively for remineralization of demineralized dentin matrix both in vitro and vivo. Although STMP micromolecule fails to stabilize amorphous calcium phosphate (ACP) precursor, STMP-Ca complexes facilely permeate into intrafibrillar interstices and trigger phase transition of ACP to hydroxyapatite within collagen. In contrast, PVPA-stabilized ACP precursors lack liquid-like characteristic and crystallize outside collagen due to rigid conformation of PVPA macromolecule, while PVPA-Ca complexes infiltrate into partial intrafibrillar intervals under electrostatic attraction and osmotic pressure as evidenced by intuitionistic three-dimensional stochastic optical reconstruction microscopy (3D-STORM). The study not only extends the variety and size range of polyelectrolyte for PCCP process but also sheds light on the role of phosphorylation for NCPs in biomineralization. This article is protected by copyright. All rights reserved.

LncTCONS_00058568 is involved in the pathophysiologic processes mediated by P2X7R in the lower thoracic spinal cord after acute kidney injury.

Acute kidney injury (AKI), a prevalent clinical syndrome, involves the participation of the nervous system in neuroimmune regulation. However, the intricate molecular mechanism that governs renal function regulation by the central nervous system (CNS) is complex and remains incompletely understood. In the present study, we found that the upregulated expression of lncTCONS_00058568 in lower thoracic spinal cord significantly ameliorated AKI-induced renal tissue injury, kidney morphology, inflammation and apoptosis, and suppressed renal sympathetic nerve activity. Mechanistically, the purinergic ionotropic P2X7 receptor (P2X7R) was overexpressed in AKI rats, whereas lncTCONS_00058568 was able to suppress the upregulation of P2X7R. In addition, RNA sequencing data revealed differentially expressed genes associated with nervous system inflammatory responses after lncTCONS_00058568 was overexpressed in AKI rats. Finally, the overexpression of lncTCONS_00058568 inhibited the activation of PI3K/Akt and NF-κB signaling pathways in spinal cord. Taken together, the results from the present study show that lncTCONS_00058568 overexpression prevented renal injury probably by inhibiting sympathetic nerve activity mediated by P2X7R in the lower spinal cord subsequent to I/R-AKI.

Multifunctional fluorescence probe for simultaneous detection of viscosity, polarity, and ONOO- and its bioimaging in vitro and vivo.

Intracellular microenvironment (viscosity and polarity) and peroxynitrite ions (ONOO-) are involved in maintaining cell morphology, cell function, and signaling so that it is crucial to explore their level changes in vitro and vivo. In this work, we designed and synthesized a mitochondria-targeted fluorescence probe XBL for monitoring the dynamic changes of viscosity, polarity, and ONOO- based on TICT and ICT mechanism. The fluorescence spectra showed obvious changes for polarity at 500 nm as well as ONOO- and viscosity at 660 nm, respectively. The XBL can image simultaneously viscosity, polarity, and ONOO- in cells, and the results showed excess ONOO- leaded to the increase of viscosity in mitochondrial. The ferroptosis process was accompanied by increase of intracellular viscosity and ONOO- levels (or decrease of polarity), which allowed us to better understand the relevant physiological and pathological processes. The XBL can distinguish normal cells and cancerous cells by the fluorescence intensity changes in green and red channels, and image viscosity in inflamed mice. Thus, XBL can provided the chemical tool to understand the physiological and pathological mechanisms of disease by simultaneous detection of viscosity, polarity and ONOO-.

TRIM27 elicits protective immunity against tuberculosis by activating TFEB-mediated autophagy flux.

Infectious diseases, such as Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), remain a global threat exacerbated by increasing drug resistance. Host-directed therapy (HDT) is a promising strategy for infection treatment through targeting host immunity. However, the limited understanding of the function and regulatory mechanism of host factors involved in immune defense against infections has impeded HDT development. Here, we identify the ubiquitin ligase (E3) TRIM27 (tripartite motif-containing 27) as a host protective factor against Mtb by enhancing host macroautophagy/autophagy flux in an E3 ligase activity-independent manner. Mechanistically, upon Mtb infection, nuclear-localized TRIM27 increases and functions as a transcription activator of TFEB (transcription factor EB). Specifically, TRIM27 binds to the TFEB promoter and the TFEB transcription factor CREB1 (cAMP responsive element binding protein 1), thus enhancing CREB1-TFEB promoter binding affinity and promoting CREB1 transcription activity toward TFEB, eventually inducing autophagy-related gene expression as well as autophagy flux activation to clear the pathogen. Furthermore, TFEB activator 1 can rescue TRIM27 deficiency-caused decreased autophagy-related gene transcription and attenuated autophagy flux, and accordingly suppressed the intracellular survival of Mtb in cell and mouse models. Taken together, our data reveal that TRIM27 is a host defense factor against Mtb, and the TRIM27-CREB1-TFEB axis is a potential HDT-based TB target that can enhance host autophagy flux.

A genome-wide association study identifies genes associated with cuticular wax metabolism in maize.

The plant cuticle is essential in plant defense against biotic and abiotic stresses. To systematically elucidate the genetic architecture of maize (Zea mays L.) cuticular wax metabolism, 2 cuticular wax-related traits, the chlorophyll extraction rate (CER) and water loss rate (WLR) of 389 maize inbred lines, were investigated and a genome-wide association study (GWAS) was performed using 1.25 million single nucleotide polymorphisms (SNPs). In total, 57 nonredundant quantitative trait loci (QTL) explaining 5.57% to 15.07% of the phenotypic variation for each QTL were identified. These QTLs contained 183 genes, among which 21 strong candidates were identified based on functional annotations and previous publications. Remarkably, 3 candidate genes that express differentially during cuticle development encode ß-ketoacyl-CoA synthase (KCS). While ZmKCS19 was known to be involved in cuticle wax metabolism, ZmKCS12 and ZmKCS3 functions were not reported. The association between ZmKCS12 and WLR was confirmed by resequencing 106 inbred lines, and the variation of WLR was significant between different haplotypes of ZmKCS12. In this study, the loss-of-function mutant of ZmKCS12 exhibited wrinkled leaf morphology, altered wax crystal morphology, and decreased C32 wax monomer levels, causing an increased WLR and sensitivity to drought. These results confirm that ZmKCS12 plays a vital role in maize C32 wax monomer synthesis and is critical for drought tolerance. In sum, through GWAS of 2 cuticular wax-associated traits, this study reveals comprehensively the genetic architecture in maize cuticular wax metabolism and provides a valuable reference for the genetic improvement of stress tolerance in maize.

Intrafibrillar mineralization of type I collagen with calcium carbonate and strontium carbonate induced by polyelectrolyte-cation complexes.

Calcium carbonate (CaCO3), possessing excellent biocompatibility, bioactivity, osteoconductivity and superior biodegradability, may serve as an alternative to hydroxyapatite (HAp), the natural inorganic component of bone and dentin. Intrafibrillar mineralization of collagen with CaCO3 was achieved through the polymer-induced liquid precursor (PILP) process for at least 2 days. This study aims to propose a novel pathway for rapid intrafibrillar mineralization with CaCO3 by sequential application of the carbonate-bicarbonate buffer and polyaspartic acid (pAsp)-Ca suspension. Fourier transform infrared (FTIR) spectroscopy, zeta potential measurements, atomic force microscopy/Kelvin probe force microscopy (AFM/KPFM), and three-dimensional stochastic optical reconstruction microscopy (3D STORM) demonstrated that the carbonate-bicarbonate buffer significantly decreased the surface potential of collagen and CO32-/HCO3- ions could attach to collagen fibrils via hydrogen bonds. The electropositive pAsp-Ca complexes and free Ca2+ ions are attracted to and interact with CO32-/HCO3- ions through electrostatic attractions to form amorphous calcium carbonate that crystallizes gradually. Moreover, like CaCO3, strontium carbonate (SrCO3) can deposit inside the collagen fibrils through this pathway. The CaCO3-mineralized collagen gels exhibited better biocompatibility and cell proliferation ability than SrCO3. This study provides a feasible strategy for rapid collagen mineralization with CaCO3 and SrCO3, as well as elucidating the tissue engineering of CaCO3-based biomineralized materials.

MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation.

BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.

Effect of Predamage on the Fracture Energy of Double-Network Hydrogels.

Double-network (DN) hydrogels are tough soft materials, and the high fracture resistance can be attributed to the formation of a large damage zone (internal fracture of the brittle first network) around the crack tip. In this work, we studied the effect of predamage in the brittle network on the fracture energy Γc of DN hydrogels. The prestretch of the first network was induced by prestretching the DN gels to prestretch ratio λpre. Depending on the λpre in relative to the yielding stretch ratio λy, above which the brittle first network starts to break into discontinuous fragments inside DN gels, two regimes were observed: Γc decreases monotonically with λpre in the regime of λpre < λy, mainly due to the decreasing contribution from the bulk internal damage, while Γc increases with λpre in the regime of λpre > λy. The latter can be understood by the release of the hidden length of the stretchable network strands by the rupture of the brittle network, whereby the broken fragments of the brittle network could serve as sliding cross-links to further delocalize the stress-concentration near the crack tip and prevent chain scissions.

Ectopic Expression of a Truncated Isoform of Hair Keratin 81 in Breast Cancer Alters Biophysical Characteristics to Promote Metastatic Propensity.

Keratins are an integral part of cell structure and function. Here, it is shown that ectopic expression of a truncated isoform of keratin 81 (tKRT81) in breast cancer is upregulated in metastatic lesions compared to primary tumors and patient-derived circulating tumor cells, and is associated with more aggressive subtypes. tKRT81 physically interacts with keratin 18 (KRT18) and leads to changes in the cytosolic keratin intermediate filament network and desmosomal plaque formation. These structural changes are associated with a softer, more elastically deformable cancer cell with enhanced adhesion and clustering ability leading to greater in vivo lung metastatic burden. This work describes a novel biomechanical mechanism by which tKRT81 promotes metastasis, highlighting the importance of the biophysical characteristics of tumor cells.

MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation

Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.

Value of Contrast-Enhanced Microflow Imaging in Diagnosis of Breast Masses in Comparison with Contrast-Enhanced Ultrasound.

RATIONALE AND OBJECTIVES: To investigate the value of contrast-enhanced microflow imaging (CEUS-MFI) in distinguishing benign and malignant breast masses. METHODS: A total of 116 breast masses classified as Breast Imaging Reporting and Data System (BI-RADS) category 3-5 by ultrasound (US) were included. Both contrast-enhanced ultrasound (CEUS) and CEUS-MFI were performed before excision or biopsy, with features and diagnostic efficiency analyzed. The US and CEUS BI-RADS 4A masses were also re-assessed by CEUS-MFI. RESULTS: The features of CEUS-MFI including both interior and peripheral enlarged, twisted vessels (both P < 0.05), penetrating vessels (P = 0.007), and radial/spiculated vessels (P < 0.001) were more frequently detected in malignant masses, while peripheral annular vessels were mostly observed in benign masses (P < 0.001). Interestingly, a significant difference in the orientation of penetrating vessels between benign and malignant masses was found (P < 0.001), with parallel orientation mostly displayed in benign masses, while vertical or multiple-direction orientation mostly displayed in malignant masses. The microvascular architecture of breast masses was categorized into five patterns: avascular, line-like, tree-like, root hair-like, and crab claw-like pattern. Benign masses mainly displayed tree-like pattern (77.1% vs 10.9%, P < 0.05); malignant masses mainly displayed root hair-like (34.8% vs 5.7%, P < 0.05) and crab claw-like patterns (50.0% vs 1.4%, P < 0.05). The diagnostic efficiency of CEUS-MFI was higher relative to CEUS and US. In addition, CEUS-MFI decreased the biopsy rates of US and CEUS BI-RADS 4A masses without missing malignancies. CONCLUSION: CEUS-MFI could be a valuable and promising technique in diagnosis of breast masses, and could provide more diagnostic information for radiologists.

Perceptions of protective shoes and recommendations from patients with diabetic foot ulcers.

Development of diabetic foot can cause serious harm to a patient's body and pose a heavy burden on family members and society. Protective shoes are of great significance to preventing diabetic foot. The aim of the current study was to understand patients' views and suggestions concerning the selection and promotion of protective shoes for diabetics in order to explore existing obstacles and to provide a reference for improving relevant public health care policies and clinical decision-making for patients with diabetic foot ulcers (DFUs). A total of 10 patients with DFUs were recruited. All participants completed a one-hour semi-structured interview, and results reflected the participants' choice of footwear, the patients' perceptions and acceptance of protective footwear, and factors influencing those processes. The use and promotion of protective shoes in China requires greater support, including improved medical insurance policies, promotion of multidisciplinary cooperation between medicine and industry in clinical practice, and better health education.

Identification of potential biomarkers and therapeutic targets for antineutrophil cytoplasmic antibody-associated glomerulonephritis.

Exploring key genes for antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) is of great significance. Through bioinformatics analysis, 79 immune protein-differentially expressed genes (IP-DEGs) were obtained. Six hub genes (PTPRC, CD86, TLR2, IL1B, CSF-1R, and CCL2) were identified and verified to be increased in ANCA-GN patients. Random forest algorithm and ROC analysis showed that CSF-1R was a potential biomarker. Plasma CSF-1R levels increased significantly in ANCA-GN-active patients compared with remission stage and control. Correlation analysis revealed that CSF-1R levels had positive relationship with serum creatinine and Birmingham scoring, while inversely correlated with eGFR. Multivariate analysis revealed that plasma CSF-1R were an independent poor prognostic variable for end-stage renal disease or death, after adjusting for age and gender (HR = 3.05, 95% CI = 1.45-6.43, p = 0.003). Overall, we revealed that the CSF-1R is related to disease activity and might be a vital gene associated with the pathogenesis of ANCA-GN.

Hydrogel Digital LAMP with Suppressed Nonspecific Amplification for Rapid Diagnostics of Fungal Disease in Fresh Fruits.

Fungal disease, mainly caused by Alternaria alternata infection, can generate severe economic losses and health hazards. However, rapid nucleic acid test without nonspecific reaction still remains challenging. Here, we reported the hydrogel digital loop-mediated isothermal amplification (HdLAMP) with suppressed nonspecific amplification for rapid diagnosis of fungi in fresh fruits. The introduction of hydrogel offered a simple platform to achieve absolute quantification. By breaking the 3'end G-C anchor, the nonspecific amplification of primers could be suppressed, while the specific positive reaction in HdLAMP was not affected. This method could be applied for A. alternata detection in 9 min with excellent performances in speed, specificity, reproducibility, sensitivity, and detection limit down to a single copy. Finally, the real diseased jujubes during postharvest storage were successfully diagnosed as an A. alternata infection. HdLAMP promotes the molecular diagnosis of fungal diseases and broadens the application of hydrogels in the agricultural and food industry.

PRMT3-Mediated Arginine Methylation of METTL14 Promotes Malignant Progression and Treatment Resistance in Endometrial Carcinoma.

Protein arginine methyltransferase (PRMT) plays essential roles in tumor initiation and progression, but its underlying mechanisms in the treatment sensitivity of endometrial cancer (EC) remain unclear and warrant further investigation. Here, a comprehensive analysis of the Cancer Genome Atlas database and Clinical Proteomic Tumor Analysis Consortium database identifies that PRMT3 plays an important role in EC. Specifically, further experiments show that PRMT3 inhibition enhances the susceptibility of EC cells to ferroptosis. Mechanistically, PRMT3 interacts with Methyltransferase 14 (METTL14) and is involved in its arginine methylation. In addition, PRMT3 inhibition-mediated METTL14 overexpression promotes methylation modification via an m6 A-YTHDF2-dependent mechanism, reducing Glutathione peroxidase 4 (GPX4) mRNA stability, increasing lipid peroxidation levels, and accelerating ferroptosis. Notably, combined PRMT3 blockade and anti-PD-1 therapy display more potent antitumor effects by accelerating ferroptosis in cell-derived xenograft models. The specific PRMT3 inhibitor SGC707 exerts the same immunotherapeutic sensitizing effect in a patient-derived xenograft model. Notably, blocking PRMT3 improves tumor suppression in response to cisplatin and radiation therapy. Altogether, this work demonstrates that PRMT3 depletion is a promising target for EC.

METTL3-mediated HPV vaccine enhances the effect of anti PD-1 immunotherapy to alleviate the development of cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) develops from epithelial keratinocytes by dysregulation of self-renewal and differentiation. Recent studies have found that the size and number of cSCC tumors gradually decrease or even disappear after HPV vaccination. However, the role of the HPV vaccine in the cSCC mechanism is poorly understood. OBJECTIVE: The aim of this study is to investigate the effect and mechanism of the HPV vaccine in cSCC. METHODS: Immunofluorescence was used to study the immune infiltrating cells in the tumor tissues of patients with cSCC. The effects of the HPV vaccine on cSCC cells and tissues were studied by Cell Culture, Real-time PCR, Western Blot, Cytotoxicity Assay, Enzyme-linked Immunosorbent Assay, m6A Blotting, CCK-8 Assay, m6A Ribonucleic acid Methylation Quantification and tumor transplantation. RESULTS: The HPV vaccine enhanced the toxic effect of CD8+T cells on cSCC cells and promoted the secretion of multiple cytokines by CD8+T cells. In addition, HPV vaccines can increase tumor sensitivity to anti-PD-1 therapy by downregulating METTL3 in tumor tissue, with the combination of HPV vaccine and PD-1 monoclonal antibodies producing enhanced immune cell infiltration compared to PD-1 blockade alone. STUDY LIMITATIONS: It is important to note the limitations of this study, including the small sample size, the construction of the mouse model, and the choice of HPV vaccine and PD-1 monoclonal antibody, which may limit the generalization of our findings to a wider population. CONCLUSIONS: It is hoped that this research will contribute to a deeper understanding of the role of the HPV vaccine in the treatment of cSCC. HPV vaccine is expected to become an important approach to alleviate the development of cSCC.