The effect of subjective understanding on patients' trust in AI pharmacy intravenous admixture services.

Introduction: Medical services are getting automated and intelligent. An emerging medical service is the AI pharmacy intravenous admixture service (PIVAS) that prepares infusions through robots. However, patients may distrust these robots. Therefore, this study aims to investigate the psychological mechanism of patients' trust in AI PIVAS. Methods: We conducted one field study and four experimental studies to test our hypotheses. Study 1 and 2 investigated patients' trust of AI PIVAS. Study 3 and 4 examined the effect of subjective understanding on trust in AI PIVAS. Study 5 examined the moderating effect of informed consent. Results: The results indicated that patients' reluctance to trust AI PIVAS (Studies 1-2) stems from their lack of subjective understanding (Study 3). Particularly, patients have an illusion of understanding humans and difficulty in understanding AI (Study 4). In addition, informed consent emerges as a moderating factor, which improves patients' subjective understanding of AI PIVAS, thereby increasing their trust (Study 5). Discussion: The study contributes to the literature on algorithm aversion and cognitive psychology by providing insights into the mechanisms and boundary conditions of trust in the context of AI PIVAS. Findings suggest that medical service providers should explain the criteria or process to improve patients' subjective understanding of medical AI, thus increasing the trust in algorithm-based services.

Antibiotic prophylaxis for surgical wound infections in clean and clean-contaminated surgery: an updated systematic review and meta-analysis.

BACKGROUND: The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial. METHODS: The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery. RESULTS: A total of 16 189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability. CONCLUSION: Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization.

Prx1/PHB2 axis mediates mitophagy in oral leukoplakia cellular senescence.

BACKGROUND: Oral leukoplakia (OLK) is the most common oral potentially malignant disorder (OPMD), which can be malignantly transformed into oral squamous cell carcinoma (OSCC). Peroxiredoxin1(Prx1) has been predicted to bind to Prohibitin2 (PHB2), which confers to affect OLK progression; however, the mechanism of Prx1/PHB2 mediated mitophagy involved in OLK remains unclear. METHODS: This study aimed to explore the mechanism of the Prx1/PHB2 axis on senescence in OLK through mediating mitophagy. The positive rate of Ki67 and the expression of p21, p16, PHB2, and LC3 in human normal, OLK, and OSCC tissues were detected by immunohistochemical staining. The mitophagy and mitochondrial function changes were then analyzed in Prx1 knockdown and Prx1C52S mutations in dysplastic oral keratinocyte (DOK) cells treated with H2O2. In situ Proximity Ligation Assay combined with co-immunoprecipitation was used to detect the interaction between Prx1 and PHB2. RESULTS: Clinically, the positive rate of Ki67 progressively increased from normal to OLK, OLK with dysplasia, and OSCC. Higher p21, p16, PHB2, and LC3 expression levels were observed in OLK with dysplasia than in normal and OSCC tissues. In vitro, PHB2 and LC3II expression gradually increased with the degree of DOK cell senescence. Prx1/PHB2 regulated mitophagy and affected senescence in H2O2-induced DOK cells. Furthermore, Prx1C52S mutation specifically reduced interaction between Prx1 and PHB2. Prx1Cys52 is associated with mitochondrial reactive oxygen species (ROS) accumulated and cell cycle arrest. CONCLUSION: Prx1Cys52 functions as a redox sensor that binds to PHB2 and regulates mitophagy in the senescence of OLK, suggesting its potential as a clinical target.

Conditional knockout mouse model reveals a critical role of peroxiredoxin 1 in oral leukoplakia carcinogenesis.

Peroxiredoxin 1 (Prx1) is an antioxidant protein that may promote the carcinogenesis in oral leukoplakia (OLK). To investigate the effect of Prx1 on the oral mucosal epithelium of OLK, we generated a Prx1 conditional knockout (cKO) mouse model. The mRNA and gRNA were generated using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technique. An infusion cloning method was used to construct a homologous recombination vector. To obtain the F0 generation mice, fertilized eggs of C57BL/6J mice were microinjected with Cas9 mRNA, gRNA, and a donor vector. Polymerase chain reaction (PCR) amplification and sequencing were used to identify F1 generation mice. Using the cyclization recombination-enzyme-locus of the X-overP1 (Cre-loxP) system, we created a Prx1 cKO mouse model, and the effectiveness of the knockout was confirmed through immunohistochemistry. We examined the influence of Prx1 knockout on the occurrence of OLK in mice by constructing a model of tongue mucosa carcinogenesis induced by 4-nitroquinoline-1-oxide (4NQO). Prx1 modification was present in the F1 generation, as evidenced by PCR amplification and sequencing. Prx1flox/flox: Cre + mice exhibited normal growth and fertility. Immunohistochemical analysis revealed that tongue epithelial cells in Prx1flox/flox: Cre + mice displayed a distinct deletion of Prx1. An examination of the heart, liver, spleen, lung, and kidney tissues revealed no visible histological changes. Histological analysis showed a reduction in the occurrence of the malignant transformation of OLK in the tongue tissues of Prx1flox/flox: Cre + mice. Ki67 immunostaining showed that Prx1 knockout significantly inhibited cell proliferation in the tongue epithelial. Our research developed a conditional knockout mouse model for Prx1. The obtained results provide insights into the function of Prx1 in the development of oral cancer and emphasize its potential as a therapeutic target for precancerous oral lesions.

The interaction of PRDX1 with Cofilin promotes oral squamous cell carcinoma metastasis.

Peroxiredoxin 1 (PRDX1) is an important member of the peroxiredoxin family (PRDX) and is upregulated in a variety of tumors. Previous studies have found that high PRDX1 expression is closely related to the metastasis of oral squamous cell carcinoma (OSCC), but the specific molecular mechanism is elusive. To elucidate the role of PRDX1 in the metastasis process of OSCC, we evaluated the expression of PRDX1 in OSCC clinical specimens and its impact on the prognosis of OSCC patients. Then, the effect of PRDX1 on OSCC metastasis and cytoskeletal reconstruction was explored in vitro and in nude mouse tongue cancer models, and the molecular mechanisms were also investigated. PRDX1 can directly interact with the actin-binding protein Cofilin, inhibiting the phosphorylation of its Ser3 site, accelerating the depolymerization and turnover of actin, promoting OSCC cell movement, and aggravating the invasion and metastasis of OSCC. In clinical samples and mouse tongue cancer models, PRDX1 also increased lymph node metastasis of OSCC and was negatively correlated with the phosphorylation of Cofilin; PRDX1 also reduced the overall survival rate of OSCC patients. In summary, our study identified that PRDX1 may be a potential therapeutic target to inhibit OSCC metastasis.

Induction of Peroxiredoxin 1 by Hypoxia Promotes Cellular Autophagy and Cell Proliferation in Oral Leukoplakia via HIF-1α/BNIP3 Pathway.

Hypoxia is a key trigger in the transformation of oral leukoplakia into oral cancer. However, it is still too early to determine the role of hypoxia in the development of oral leukoplakia. Prx1, an antioxidant protein, upregulated by hypoxia, regulates cellular autophagy in leukoplakia. This study aimed to understand the mechanisms by which hypoxia induces Prx1 expression during autophagy in oral leukoplakia. We used an experimental model of tongue epithelial hyperplasia induced by 4-nitroquinoline-1-oxide (4NQO) and dysplastic oral keratinocytes. Prx1 knockdown DOK cells, Leuk-1 cells and control cells were harvested, and cell proliferation was assayed using the Cell Counting Kit-8. Several hypoxia and autophagy-related proteins were examined using quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and western blotting in cells and mouse tongue tissues. In addition, the ultrastructure of the cells was observed by transmission electron microscopy. Hypoxia induces cell proliferation, autophagic vesicles and the expression of Prx1, BNIP3, LC3II/I and Beclin-1 in DOK and Leuk-1 cells. However, these effects were all attenuated by Prx1 knockdown. Histologically, 4NQO induced epithelial hyperplasia in the tongue mucosa. The expression of proliferation marker PCNA, autophagy-related proteins LC3B and Beclin-1, as well as HIF-1α/BNIP3 was significantly lower in the tongue tissues of Prx1flox/flox:Cre+ mice compared with Prx1flox/flox mice. In Prx1flox/flox:Cre+ mice, an increased expression of HIF-1α/BNIP3, LC3B and Beclin-1 was detected in epithelial hyperplasia tongue tissues compared to normal tissues. The current study suggests that Prx1 may promotes cell proliferation and autophagy in oral leukoplakia cells via the HIF-1α/BNIP3 pathway.

[Incidence and risk factors of deep vein thrombosis in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the incidence and risk factors of deep vein thrombosis (DVT) in patients with rheumatoid arthritis (RA). METHODS: The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed, including demographic characteristics, concomitant diseases, laboratory examinations (blood routine, biochemistry, coagulation, inflammatory markers, rheumatoid factor, antiphospholipid antibodies and lupus anticoagulant, etc.) and treatment regimens. The patients were compared according to the presence or absence of DVT, and the t test, Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT, followed by Logistic regression analysis to determine risk factors for DVT in patients with RA. RESULTS: The incidence of DVT in the RA patients was 9.6% (31/322); the median age of RA in DVT group was significantly older than that in non-DVT group [64 (54, 71) years vs. 50 (25, 75) years, P < 0.001]; the level of disease activity score using 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) in DVT group was higher than that in non-DVT group [5.2 (4.5, 6.7) vs. 4.5(4.5, 5.0), P < 0.001]; the incidence of hypertension, chronic kidney disease, fracture or surgery history within 3 months, and varicose veins of the lower extremities in DVT group was higher than that in non-DVT group (P < 0.001). The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group (P=0.009, P=0.004), while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group (P < 0.001). The use rate of glucocorticoid in DVT group was higher than that in non-DVT group (P=0.009). Logistic regression analysis showed that the age (OR=1.093, P < 0.001), chronic kidney disease (OR=7.955, P=0.005), fracture or surgery history within 3 months (OR=34.658, P=0.002), DAS28-ESR (OR=1.475, P=0.009), and the use of glucocorticoid (OR=5.916, P=0.003) were independent risk factors for DVT in RA patients. CONCLUSION: The incidence of DVT in hospitalized RA patients was significantly increased, in addition to traditional factors, such as age and chronic kidney disease, increased DAS28-ESR level and the use of glucocorticoid were also independent risk factors for DVT.

Boosted dipper throated optimization algorithm-based Xception neural network for skin cancer diagnosis: An optimal approach.

Skin cancer is a prevalent form of cancer that necessitates prompt and precise detection. However, current diagnostic methods for skin cancer are either invasive, time-consuming, or unreliable. Consequently, there is a demand for an innovative and efficient approach to diagnose skin cancer that utilizes non-invasive and automated techniques. In this study, a unique method has been proposed for diagnosing skin cancer by employing an Xception neural network that has been optimized using Boosted Dipper Throated Optimization (BDTO) algorithm. The Xception neural network is a deep learning model capable of extracting high-level features from skin dermoscopy images, while the BDTO algorithm is a bio-inspired optimization technique that can determine the optimal parameters and weights for the Xception neural network. To enhance the quality and diversity of the images, the ISIC dataset is utilized, a widely accepted benchmark system for skin cancer diagnosis, and various image preprocessing and data augmentation techniques were implemented. By comparing the method with several contemporary approaches, it has been demonstrated that the method outperforms others in detecting skin cancer. The method achieves an average precision of 94.936%, an average accuracy of 94.206%, and an average recall of 97.092% for skin cancer diagnosis, surpassing the performance of alternative methods. Additionally, the 5-fold ROC curve and error curve have been presented for the data validation to showcase the superiority and robustness of the method.

Design, optimization, and evaluation for a long-time-released transdermal microneedle delivery system containing estradiol.

Transdermal drug delivery systems (TDDS) have drawbacks such as poor absorption, low blood concentration, and delayed effects. Dissolving microneedle has sharp tips and short length, which overcome patients' pain and improve transdermal efficiency but has low mechanical strength and drug loading capacity. This study thereby proposes a microemulsion-encapsulated and long-time-released transdermal microneedle (MN) delivery system with estradiol (Es) as the model drug. The microemulsion (ME) was optimized by utilizing the pseudo-ternary phase diagram and D-optimal mixture design. The estradiol microemulsion-encapsulated microneedle (Es-ME-MN) was optimized by Box-Behnken design and prepared by freeze-thaw method. The Es-ME-MN obtained was characterized and evaluated through a large variety of studies. Es-ME-MN had sufficient mechanical strength to pierce skin and was safe enough, the length of which was 600 µm, and the Es content was 177.12 ± 0.72 µg/patch without drug-excipient chemical interaction. In vitro permeation study showed that Es-ME-MN has a higher transdermal efficiency and lower retention capacity than commercial estradiol patch and conventional MN. Es plasma concentration began to increase at 3 h and remained at 12.98-23.52 ng/mL until 72 h by pharmacokinetic experiments in the Es-ME-MN group. Es-ME-MN rapidly achieves effective blood concentrations through needle puncture and microemulsion delivery and maintains blood concentrations through the baseplate long-time release. Microemulsion-encapsulated, organic solvent-free, and long-time-released transdermal microneedle will make progress and provide a new idea for transdermal delivery of lipophilic drugs.

WITHDRAWN: Long-time-released Transdermal Microneedle Delivery System.

The article has been withdrawn at the request of the authors of the journal "Current Drug Delivery", Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Identification of an important QTL for seed oil content in soybean.

Seed oil content is one of the most important quantitative traits in soybean (Glycine max) breeding. Here, we constructed a high-density single nucleotide polymorphism linkage map using two genetically similar parents, Heinong 84 and Kenfeng 17, that differ dramatically in their seed oil contents, and performed quantitative trait loci (QTL) mapping of seed oil content in a recombinant inbred line (RIL) population derived from their cross. We detected five QTL related to seed oil content distributed on five chromosomes. The QTL for seed oil content explained over 10% of the phenotypic variation over two years. This QTL was mapped to an interval containing 20 candidate genes, including a previously reported gene, soybean RING Finger 1a (RNF1a) encoding an E3 ubiquitin ligase. Notably, two short sequences were inserted in the GmRNF1a coding region of KF 17 compared to that of HN 84, resulting in a longer protein variant in KF 17. Our results thus provide information for uncovering the genetic mechanisms determining seed oil content in soybean, as well as identifying an additional QTL and highlighting GmRNF1a as candidate gene for modulating seed oil content in soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01384-2.

Role of gut microbiota and bacterial metabolites in mucins of colorectal cancer.

Colorectal cancer (CRC) is a major health burden, accounting for approximately 10% of all new cancer cases worldwide. Accumulating evidence suggests that the crosstalk between the host mucins and gut microbiota is associated with the occurrence and development of CRC. Mucins secreted by goblet cells not only protect the intestinal epithelium from microorganisms and invading pathogens but also provide a habitat for commensal bacteria. Conversely, gut dysbiosis results in the dysfunction of mucins, allowing other commensals and their metabolites to pass through the intestinal epithelium, potentially triggering host responses and the subsequent progression of CRC. In this review, we summarize how gut microbiota and bacterial metabolites regulate the function and expression of mucin in CRC and novel treatment strategies for CRC.

Transdermal Delivery of Estradiol Simultaneously Possessing Rapid Release and Sustained Release Effect.

Dissolving microneedle (DMN) has been researched as a drug delivery technology that improves drug molecule transportation through the skin with little discomfort. However, the sluggish drug absorption, poor skin dissolution, and lengthy time lags of DMN have limited its potential uses. The aim of this study was to design a novel DMN system for the administration of the poorly water-soluble drug, estradiol (E2), with fast skin penetration and a stable release rate for a long time. DMN containing E2 emulsion (E2-EM-DMN) and traditional DMN (T-DMN) were prepared. Rat skin was used for penetration test and guinea pig skin was used for skin irritation experiment. The drug release profiles and stability properties of these two kinds of DMNs were also investigated. High performance liquid chromatography was employed to determine the E2 content in DMN. The E2 concentration in rat plasma was achieved by a newly developed liquid chromatography-mass spectrometry method that was fast, reproducible, and specific. The height of E2-EM-DMN and T-DMN was 600 µm. The drug loading of the E2-EM-DMN and T-DMN was 667.30 ± 7.21 µg/patch and 672.56 ± 6.98 µg/patch. E2-EM-DMN possessed enough mechanical strength to penetrate the skin and caused no irritation to the skin. E2-EM-DMN could release the drug more rapidly and more continuously than T-DMN. E2-EM-DMN had good pharmaceutical stability. In summary, the E2-EM-DMN showed reliable quality and superior release performance. Emulsion-embedded DMN is an ideal transdermal delivery system for drugs.

Corrigendum: Molar loss further exacerbates 2-VO-induced cognitive impairment associated with the activation of p38MAPK/NFκB pathway.

[This corrects the article DOI: 10.3389/fnagi.2022.930016.].

Fine Mapping the Soybean Mosaic Virus Resistance Gene in Soybean Cultivar Heinong 84 and Development of CAPS Markers for Rapid Identification.

Heinong 84 is one of the major soybean varieties growing in Northeast China, and is resistant to the infection of all strains of soybean mosaic virus (SMV) in the region including the most prevalent strain, N3. However, the resistance gene(s) in Heinong 84 and the resistant mechanism are still elusive. In this study, genetic and next-generation sequencing (NGS)-based bulk segregation analysis (BSA) were performed to map the resistance gene using a segregation population from the cross of Heinong 84 and a susceptible cultivar to strain N3, Zhonghuang 13. Results show that the resistance of Heinong 84 is controlled by a dominant gene on chromosome 13. Further analyses suggest that the resistance gene in Heinong 84 is probably an allele of Rsv1. Finally, two pairs of single-nucleotide-polymorphism (SNP)-based primers that are tightly cosegregated with the resistance gene were designed for rapidly identifying resistant progenies in breeding via the cleaved amplified polymorphic sequence (CAPS) assay.

Molar loss further exacerbates 2-VO-induced cognitive impairment associated with the activation of p38MAPK/NFκB pathway.

Background: Vascular dementia is characterized by reduced cognitive function due to chronic cerebral hypoperfusion and has become a significant public health challenge as the global population ages. Recent studies suggested that molar loss, a common problem among the elderly, may trigger the development of cognitive decline. Our previous study found that the molar loss affected cognitive dysfunction, and the astrocytes in the hippocampus of chronic cerebral ischemia rats were affected, but the underlying mechanism is unclear. Methods: In this study, we established the animal model of molar loss with 2-VO rats and the Morris water maze was used to test the cognitive ability of rats in each group. The damage to neurons was observed via Nissl staining, and neuronal apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in the hippocampus of the rats. Quantitative Real-Time PCR and immunohistochemistry and histology (IHC) were used to detect the expression of p38MAPK, NFκB, caspase 3, and iNOS in the hippocampus. The astrocytes were detected by IHC and Immunofluorescence analysis for GFAP. After 2-VO MO surgery, rats were administered DMSO or p38MAPK inhibitor (SB203580) by intrathecal injection. Results: The Morris water maze test showed that the molar loss aggravated spatial memory learning ability with chronic cerebral ischemia decreased in the rats. The neuronal damage and more apoptotic cells were observed in the hippocampus of 2-VO rats. After the molar loss, the mRNA and protein expression of iNOS, p38MAPK, NFκB, and caspase 3 were further upregulated in 2-VO rats. Molar loss upregulated GFAP expression, and the p38MAPK-positive cells were labeled with the astrocyte marker GFAP. SB203580 reduced cognitive impairment and apoptosis of hippocampal neurons in 2-VO rats following the molar loss. Conclusion: Molar loss can aggravate cognitive impairment in 2-VO rats to a certain extent. The mechanism of molar loss exacerbating the cognitive decline in 2-VO rats may be associated with the activation of the p38MAPK-NFκB-caspase 3 signaling pathway, which induces neuronal apoptosis.

QTL Mapping of Palmitic Acid Content Using Specific-Locus Amplified Fragment Sequencing (SLAF-Seq) Genotyping in Soybeans (Glycine max L.).

Soybeans are essential crops that supply protein and oil. The composition and contents of soybean fatty acids are relevant to human health and have a significant relationship with soybean oil processing and applications. Identifying quantitative trait locus (QTL) genes related to palmitic acid could facilitate the development of a range of nutritive soybean cultivars using molecular marker-assisted selection. In this study, we used a cultivar with higher palmitic acid content, 'Dongnong42', and a lower palmitic acid content cultivar, 'Hobbit', to establish F2:6 recombinant inbred lines. A high-density genetic map containing 9980 SLAF markers was constructed and distributed across 20 soybean chromosomes. The genetic map contained a total genetic distance of 2602.58 cM and an average genetic distance of 0.39 cM between adjacent markers. Two QTLs related to palmitic acid content were mapped using inclusive composite interval mapping, explaining 4.2-10.1% of the phenotypic variance in three different years and environments, including the QTL included in seed palmitic 7-3, which was validated by developing SSR markers. Based on the SNP/Indel and significant differential expression analyses of Dongnong42 and Hobbit, two genes, Glyma.15g119700 and Glyma.15g119800, were selected as candidate genes. The high-density genetic map, QTLs, and molecular markers will be helpful for the map-based cloning of palmitic acid content genes. These could be used to accelerate breeding for high nutritive value cultivars via molecular marker-assisted breeding.

Azoxystrobin induces apoptosis via PI3K/AKT and MAPK signal pathways in oral leukoplakia progression.

Background: Oral leukoplakia (OLK) is one of the oral potentially malignant disorders (OPMDs) with an increased risk of developing oral squamous cell carcinoma (OSCC). There is no ideal therapeutic drug yet. Our previous study showed azoxystrobin (AZOX) inhibited the viability of OLK cells and the incidence of mouse tongue cancer. However, its specific mechanism has not been clarified. Here, we used network pharmacology with experimental validation to investigate the roles and mechanisms of AZOX in OLK. Methods: The targets of AZOX and OLK were obtained from online databases. The overlapping genes were identified by the Jvenn database. STRING and Cytoscape software were used to construct the PPI network. GO and KEGG enrichment analyses were used to analyze the biological function. Molecular docking and CETSA were used to verify the direct binding between AZOX and its key targets. 4NQO induced mouse tongue carcinogenesis model was constructed to clarify the treatment response of AZOX in vivo. TUNEL staining was performed to detect the effect of AZOX on apoptosis in mouse OLK tissues. CCK8 assay, flow cytometry, and western blot were used to detect the effect of AZOX on cell proliferation and apoptosis in DOK cells. The expression of PI3K/AKT and MAPK markers were analyzed by immunohistochemistry in vivo or by western blot in vitro. Results: Venn diagram showed 457 overlapping targets, which were involved in the PI3K/AKT, MAPK, and apoptosis pathways, and the top 5 hub modules were TP53, STAT3, AKT1, MAPK1, and PIK3R1. AZOX was bound with the highest force to AKT and PI3K by AutoDock Vina. PyMOL software visualized that AZOX could fit in the binding pocket of the AKT and PI3K. The carcinogenesis rate of the mouse OLK in the high-dose AZOX group was significantly reduced. AZOX induced apoptosis in the OLK tissues and DOK cells, and the expression of PI3K, AKT, p-ERK was decreased, and the expression of p-p38 and p-JNK was increased. CETSA indicated that AZOX might have a direct binding with AKT and PI3K. Conclusion: AZOX may induce apoptosis via PI3K/AKT and MAPK pathways in OLK. This study reveals the potential therapeutic targets of AZOX in OLK.

Synthesis and Biological Evaluation of Novel Phthalide Analogs-1,2,4-Oxadiazole Hybrids as Potential Anti-Inflammatory Agents.

A series of novel pathalide-1,2,4-oxadiazole analogs were synthesized for discovering novel anti-inflammatory agents. After the assessment of their cytotoxicity in vitro, all compounds had been screened for their anti-inflammatory activity by evaluating their inhibitory effect on LPS-induced NO production in RAW 264.7 macrophages. SARs had been concluded, and finally compound E13 was found to be the most potent compound. This compound could also significantly decrease the production of iNOS and COX-2. Preliminary mechanism studies indicated that compound E13 could inhibit the TLR4/NF-κB and ERK/p38 signaling pathways. These findings indicate that E13 holds great potential to be a lead compound for discovering novel anti-inflammatory drugs.

Peroxiredoxin 1 inhibits autophagy through interacting with Rab7 in human dysplastic oral keratinocyte cells.

OBJECTIVE: As a major risk factor for oral leukoplakia (OLK), oxidative stress can induce intracellular reactive oxygen species (ROS), which is closely related to autophagy. Ras-related protein 7 (Rab7) is an important molecule involved in autophagy. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, overexpressed in a variety of malignant tumors. We found that the expression of Prx1 in OLK was up-regulated, and Prx1 is associated with autophagy. This study aims to identify mechanisms of Prx1 in oxidative stress associated autophagy in human dysplastic oral keratinocyte (DOK) cells. DESIGN: Hydrogen peroxide (H2O2) was used to induce autophagy in DOK cells. CCK8 assay and flow cytometry were conducted to examine cell viability, cell apoptosis and intracellular ROS level. Autophagy-associated proteins were detected by western blot and immunofluorescence. MHY1485 was applied to investigate the role of Prx1 in autophagy. On the basis of online docking tool Zdock, Prx1 interacting with Rab7 was verified by immunofluorescence double-staining, Duolink PLA, and Co-immunoprecipitation (Co-IP). RESULTS: H2O2 induced autophagy and ROS increase in DOK cells, and the expression of Prx1 increased gradually according to H2O2 concentration. Prx1 knockdown attenuated the inhibition of MHY1485 on the expressions of autophagy-related proteins and the ratio of LC3 II/LC3 I induced by H2O2. Moreover, Prx1 interacted with Rab7 in DOK cells. CONCLUSIONS: Prx1 was involved in the regulation of H2O2-induced autophagy in DOK cells partly by physically interacting with Rab7. Prx1 knockdown promoted autophagy maybe by releasing more Rab7 into the autophagy process.