FDA-approved small molecule kinase inhibitors for cancer treatment (2001-2015): Medical indication, structural optimization, and binding mode Part I.

The dysregulation of kinases has emerged as a major class of targets for anticancer drug discovery given its node roles in the etiology of tumorigenesis, progression, invasion, and metastasis of malignancies, which is validated by the FDA approval of 28 small molecule kinase inhibitor (SMKI) drugs for cancer treatment at the end of 2015. While the preclinical and clinical data of these drugs are widely presented, it is highly essential to give an updated review on the medical indications, design principles and binding modes of these anti-tumor SMKIs approved by the FDA to offer insights for the future development of SMKIs with specific efficacy and safety.

Design, synthesis and biological evaluation of sulfonylamidines as potent c-Met inhibitors by enhancing hydrophobic interaction.

The dysregulation of c-Met kinase has emerged as a significant contributing factor for the occurrence, progression, poor clinical outcomes and drug resistance of various human cancers. In our ongoing pursuit to identify promising c-Met inhibitors as potential antitumor agents, a docking study of the previously reported c-Met inhibitor 7 revealed a large unoccupied hydrophobic pocket, which could present an opportunity for further exploration of structure-activity relationships to improve the binding affinity with the allosteric hydrophobic back pocket of c-Met. Herein we performed structure-activity relationship and molecular modeling studies based on lead compound 7.

Design, synthesis, and biological evaluation of thiazole/thiadiazole carboxamide scaffold-based derivatives as potential c-Met kinase inhibitors for cancer treatment.

As part of our continuous efforts to discover novel c-Met inhibitors as antitumor agents, four series of thiazole/thiadiazole carboxamide-derived analogues were designed, synthesised, and evaluated for the activity against c-Met and four human cancer cell lines. After five cycles of optimisation on structure-activity relationship, compound was found to be the most promising inhibitor in both biochemical and cellular assays. Moreover, exhibited potency against several c-Met mutants.

Efficacy and risk factors of traditional denture restoration versus biofunctional complete denture restoration system.

Objective: This study was designed to determine the efficacy of a traditional complete denture and a biofunctional prosthetic system of a complete denture, and risk factors affecting their efficacy.

Methods: A retrospective analysis was performed on 95 patients with total dentition loss admitted to our hospital from January 2015 to June 2022. Among them, 45 patients who received traditional dentures were assigned to a control group, and the other 50 who received a biofunctional prosthetic system with complete dentures were assigned to an observation group.

[Determination of bisphenols in sediment by accelerated solvent extraction and solid-phase extraction purification coupled with ultra performance liquid chromatography-tandem mass spectrometry].

Bisphenols are endocrine disruptors that are characterized with bioaccumulation, persistence, and estrogenic activity. Even low contents of bisphenols can exert adverse effects on human health and the ecological environment. Herein, a method combining accelerated solvent extraction and solid-phase extraction purification with ultra performance liquid chromatography-tandem mass spectrometry was developed for the accurate detection of bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), bisphenol Z (BPZ), bisphenol AF (BPAF), and bisphenol AP (BPAP) in sediments.

Effects of G-CSF on hPDLSC proliferation and osteogenic differentiation in the LPS-induced inflammatory microenvironment.

Background: Periodontitis is a chronic infectious disease of periodontal support tissue caused by microorganisms in dental plaque, which causes alveolar bone resorption and tooth loss. Periodontitis treatment goals include prevention of alveolar bone resorption and promotion of periodontal regeneration. We previously found that granulocyte colony-stimulating factor (G-CSF) was involved in periodontitis-related alveolar bone resorption through induction of an immune response and subsequent destruction of periodontal tissue.

Polydopamine surface-modified hyperbranched polymeric nanoparticles for synergistic chemo/photothermal therapy of oral cancer.

A novel drug delivery system for the treatment of oral cancer was developed using a facile polydopamine (PDA)-based surface modification and a binding mechanism linking folic acid-targeting ligands. The system was able to achieve the following objectives: loading of chemotherapeutic agents, active targeting, pH responsiveness, and prolonged blood circulation. DOX-loaded polymeric nanoparticles (DOX/H20-PLA@PDA NPs) were functionalized with amino-poly (ethylene glycol)-folic acid (HN-PEG-FA) after coating them with PDA to form the targeting combination, DOX/H20-PLA@PDA-PEG-FA NPs.

AMPK inhibitor BML-275 induces neuroprotection through decreasing cyt c and AIF expression after transient brain ischemia.

Stroke is a major public health problem with an imperative need for a more effective and tolerated therapy. Neuroprotective therapy may be an effective therapeutic intervention for stroke. The morbidity and mortality of stroke-induced secondary brain injury is mainly caused by neuronal apoptosis, which can be executed in a caspase-dependent or apoptosis inducing factor (AIF)-dependent manner.

Study on the application of oral digital design in aesthetic restoration of anterior teeth of cleft lip/palate patients.

Objectives: A study was conducted to investigate the clinical effects of oral digital design on the aesthetic restoration of anterior teeth of cleft lip/palate patients.

Methods: Nine adult cleft lip/palate patients who need aesthetic restoration of anterior teeth were recruited. Digital information of patients' dental arches, the surrounding soft tissue and face were captured by digital camera and scanner.

Occurrence, distribution, and risk assessment of bisphenol analogues in Luoma Lake and its inflow rivers in Jiangsu Province, China.

Bisphenol analogs (BPs) are widely used in industrial and commercial products and have been detected in surface water, sediment, sewage, and sludge. The presence of BPs in the natural environment poses threats to the aquatic ecosystem and human health. The concentration, distribution, seasonal variation, and risk assessment of BPA and BPA structural analogs including BPB, BPF, BPS, BPZ, BPAF, and BPAP in surface water and sediment during dry season and flood season in Luoma Lake and its inflow rivers in Jiangsu Province, China, were investigated in this study.

Double-edged effects of interferons on the regulation of cancer-immunity cycle.

Interferons (IFNs) are a large family of pleiotropic cytokines that regulate both innate and adaptive immunity and show anti-cancer effects in various cancer types. Moreover, it was revealed that IFN signaling plays critical roles in the success of cancer therapy strategies, thereby enhancing their therapeutic effects. However, IFNs have minimal or even adverse effects on cancer eradication, and mediate cancer immune escape in some instances.

Integrative Analysis of DNA Methylation Data and Transcriptome Data Identified a DNA Methylation-Dysregulated Four-LncRNA Signature for Predicting Prognosis in Head and Neck Squamous Cell Carcinoma.

Increasing evidence has demonstrated the crosstalk between DNA epigenetic alterations and aberrant expression of long non-coding RNAs (lncRNAs) during carcinogenesis. However, epigenetically dysregulated lncRNAs and their functional and clinical roles in Head and Neck Squamous Cell Carcinoma (HNSCC) are still not explored. In this study, we performed an integrative analysis of DNA methylation data and transcriptome data and identified a DNA methylation-dysregulated four-lncRNA signature (DNAMeFourLncSig) from 596 DNA methylation-dysregulated lncRNAs using a machine-learning-based feature selection method, which classified the patients of the discovery cohort into two risk groups with significantly different survival including overall survival, disease-specific survival, and progression-free survival.

Charge-reversal nanomedicine based on black phosphorus for the development of A Novel photothermal therapy of oral cancer.

Driven by the lifestyle habits of modern people, such as excessive smoking, drinking, and chewing betel nut and other cancer-causing foods, the incidence of oral cancer has increased sharply and has a trend of becoming younger. Given the current mainstream treatment means of surgical resection will cause serious damage to many oral organs, so that patients lose the ability to chew, speak, and so on, it is urgent to develop new oral cancer treatment methods. Based on the strong killing effect of photothermal therapy on exposed superficial tumors, we developed a pH-responsive charge reversal nanomedicine system for oral cancer which is a kind of classic superficial tumor.

Mussel-Inspired Polydopamine: The Bridge for Targeting Drug Delivery System and Synergistic Cancer Treatment.

Polydopamine (PDA), a mussel-inspired molecule, has been recognized as attractive in cancer therapy due to a number of inherent advantages, such as good biocompatibility, outstanding drug-loading capacity, degradability, superior photothermal conversion efficiency, and low tissue toxicity. Furthermore, due to its strong adhesive property, PDA is able to functionalize various nanomaterials, facilitating the construction of a PDA-based multifunctional platform for targeted or synergistic therapy. Herein, recent PDA research, including targeted drug delivery, single-mode therapy, and diverse synergistic therapies against cancer, are summarized and discussed.

Epidemiological pattern of maxillofacial fractures in northern China: A retrospective study of 829 cases.

This study was performed to examine the epidemiological features of maxillofacial fracture, including the incidence, causes, age and sex distribution, methods of treatment, and prognosis, in a local area.A retrospective study was performed to investigate the epidemiological characteristics of 829 patients with maxillofacial fractures treated in a hospital in northern China from August 2011 to July 2019. Sex, age, etiology, fracture site, and treatment method were obtained from the medical records.

Castleman Disease of the Parotid Gland: A Case Report.

Castleman disease is a rare lymphoproliferative disorder characterized by the formation of painless hyperplastic lymph nodes. It can affect any lymph nodes of the body but rarely affects the salivary gland. We describe a patient with unicentric Castleman disease presenting as a parotid tumor and discuss the diagnosis and treatment of Castleman disease.

[Impact assessment on enamel remineralization after orthodontic treatment with casein phosphopeptide calcium phosphate complex].

Purpose: To compare the effect on enamel demineralization following fluoride rinse or casein phosphopeptide calcium phosphate complex (CPP-ACP) after fixed appliance orthodontic treatment.

Methods: The study population consisted of 21 post-orthodontic patients (13 females, 8 males, 84 affected teeth) with white spot lesions (WSL). They were divided into 3 groups with 28 affected teeth in each group.

[Effect of HBXIP on biological function and PI3K/Akt signaling pathway of adenoid cystic carcinoma cell line ACC-M].

Purpose: To study the effect of hepatitis B virus X protein binding protein (HBXIP) on proliferation, migration and invasion of adenoid cystic carcinoma cell line ACC-M, and the possible mechanism of PI3K/Akt signaling pathway.

Methods: HBXIP plasmid was transfected into ACC-M. The cells were divided into experimental group (transfected with plasmid pEGFP-N1-HBXIP) control group (non-transfected group) and blank control group (vector group, pEGFP-N1).

Influence of microbial community structure of seed sludge on the properties of aerobic nitrifying granules.

In order to evaluate the influence of microbial community structure of seed sludge on the properties of aerobic nitrifying granules, these granules were cultivated with different seed sludge, and the variation of microbial community and dominant bacterial groups that impact the nitrogen removal efficiency of the aerobic nitrifying granules were analyzed and identified using 16s rDNA sequence and denaturing gradient gel electrophoresis (DGGE) profiles. The results presented here demonstrated that the influence of the community structure of seed sludge on the properties of aerobic nitrifying granules was remarkable, and the granules cultivated by activated sludge from a beer wastewater treatment plant showed better performance, with a stable sludge volume index (SVI) value of 20mL/g, high extracellular polymeric substance (EPS) content of 183.3mg/L, high NH4(+)-N removal rate of 89.

An inverse association of Helicobacter pylori infection with oral squamous cell carcinoma.

Background: Few studies have focused on the relationship between Helicobacter pylori (H. pylori) infection and oral diseases. In this study, we explored the correlation between H.

[DNA repair gene polymorphisms in ERCC4 rs6498486 and ERCC5 rs751402 and risk of salivary gland tumors].

Purpose: To investigate the association between ERCC4 and ERCC5 polymorphisms and risk of salivary gland tumors.

Methods: Case-control study was carried out in 133 cases of histologically confirmed salivary gland tumors and 142 age and gender matched healthy control cases. Polymorphisms of ERCC4 rs6498486 and ERCC5 rs751402 were detected by PCR-RFLP.

[Expression and significance of pericytes and TGF-β in infantile parotid hemangioma].

Purpose: To study the expression and significance of pericytes and TGF-β in infantile parotid hemangioma.

Methods: The expressions of pericytes and TGF-β at protein level were examined in 76 cases of infant parotid hemangioma by strep avidin-biotin complex (SABC) immunohistochemical technique. All statistical analysis were performed using SPSS 13.

[Expression of ERK and nm23-H1 in tongue squamous cell carcinoma and its relation with invasion and metastasis].

Purpose: To reveal the relations between expression of extracellular signal-regulated kinase (ERK) and nm23-H1 and tumor invasion and metastasis in tongue squamous cell carcinoma (TSCC).

Methods: The expression of ERK and nm23-H1 at protein level was examined in 74 cases of TSCC by strep avidin-biotin complex (SABC) immunohistochemical technique. SPSS10.