Precision Drug Repurposing: A Deep Learning Toolkit for Identifying 34 Hyperpigmentation-Associated Genes and Optimizing Treatment Selection.

BACKGROUND: Hyperpigmentation is a skin disorder characterized by a localized darkening of the skin due to increased melanin production. When patients fail first line topical treatments, secondary treatments such as chemical peels and lasers are offered. However, these interventions are not devoid of risks and are associated with postinflammatory hyperpigmentation. In the quest for novel therapeutic potentials, this study aims to investigate computational methods in the identification of new targeted therapies in the treatment of hyperpigmentation. METHODS: We used a comprehensive approach, which integrated text mining, interpreting gene lists through enrichment analysis and integration of diverse biological information (GeneCodis), protein-protein association networks and functional enrichment analyses (STRING), and plug-in network centrality parameters (Cytoscape) to pinpoint genes closely associated with hyperpigmentation. Subsequently, analysis of drug-gene interactions to identify potential drugs (Cortellis) was utilized to select drugs targeting these identified genes. Lastly, we used Deep Learning Based Drug Repurposing Toolkit (DeepPurpose) to conduct drug-target interaction predictions to ultimately identify candidate drugs with the most promising binding affinities. RESULTS: Thirty-four hyperpigmentation-related genes were identified by text mining. Eight key genes were highlighted by utilizing GeneCodis, STRING, Cytoscape, gene enrichment, and protein-protein interaction analysis. Thirty-five drugs targeting hyperpigmentation-associated genes were identified by Cortellis, and 29 drugs, including 16 M2PK1 inhibitors, 11 KRAS inhibitors, and 2 BRAF inhibitors were recommended by DeepPurpose. CONCLUSIONS: The study highlights the promise of advanced computational methodology for identifying potential treatments for hyperpigmentation.

The Impact of Socioeconomic Status on the Incidence and Stage of Melanoma in China: A Single-Center Observational Study.

BACKGROUND: The role of high socioeconomic status (SES) as an established risk factor for melanoma has been well documented in Western countries and regions. However, research on the association between melanoma and SES in China remains limited. This study aimed to investigate the association between SES and melanoma incidence and stage in China. METHODS: Five measures of SES were accessed, including education level, ethnic background, per capita household income, occupation, and medical insurance coverage. A scoring system based on the Kuppuswamy Socio-Economic Scale was used to create a quantitative assessment of SES. To improve clarity and precision, we refined the language in the original text. Clinical stage at diagnosis was classified according to the Chinese Society Oncology Melanoma Guidelines. RESULTS: A total of 122 patients with pathologic melanoma were enrolled in this study from January 2013 to December 2017. Of these patients, 58 (48%) were male and 64 (52%) were female, with a mean age of 59.23 ± 9.91 years. Patients in the age groups of 45-59 and 60-73 had a higher incidence of melanoma compared to other age groups. Acral lentiginous melanoma was the most commonly observed subtype, accounting for 48% of cases. Patients with a low level of education (middle school and below) and a low level of monthly household income (<3000 CNY) had a higher risk of developing melanoma, as did those who were unemployed. Interestingly, a higher proportion of melanoma diagnoses were made in patients with medical insurance than those without. However, no significant differences in melanoma staging were found based on education level (P = 0.153), monthly household income (P = 0.507), occupation (P = 0.687), or insurance status (P = 0.537). According to the Kuppuswamy Socio-Economic Scale, there were 0 in upper class, 50 in upper middle class, 44 in lower middle class, 28 in upper lower class, 0 in lower class. The mean K-score was 13.85. No statistically significant interaction was observed between K-score and tumor stage. CONCLUSIONS: Patients with lower SES have a higher risk of developing melanoma. However, no significant differences were found in melanoma staging based on SES.

miRSNP rs188493331: A key player in genetic control of microRNA-induced pathway activation in hypertrophic scars and keloids.

BACKGROUND: Our study aims to delineate the miRSNP-microRNA-gene-pathway interactions in the context of hypertrophic scars (HS) and keloids. MATERIALS AND METHODS: We performed a computational biology study involving differential expression analysis to identify genes and their mRNAs in HS and keloid tissues compared to normal skin, identifying key hub genes and enriching their functional roles, comprehensively analyzing microRNA-target genes and related signaling pathways through bioinformatics, identifying MiRSNPs, and constructing a pathway-based network to illustrate miRSNP-miRNA-gene-signaling pathway interactions. RESULTS: Our results revealed a total of 429 hub genes, with a strong enrichment in signaling pathways related to proteoglycans in cancer, focal adhesion, TGF-ß, PI3K/Akt, and EGFR tyrosine kinase inhibitor resistance. Particularly noteworthy was the substantial crosstalk between the focal adhesion and PI3K/Akt signaling pathways, making them more susceptible to regulation by microRNAs. We also identified specific miRNAs, including miRNA-1279, miRNA-429, and miRNA-302e, which harbored multiple SNP loci, with miRSNPs rs188493331 and rs78979933 exerting control over a significant number of miRNA target genes. Furthermore, we observed that miRSNP rs188493331 shared a location with microRNA302e, microRNA202a-3p, and microRNA20b-5p, and these three microRNAs collectively targeted the gene LAMA3, which is integral to the focal adhesion signaling pathway. CONCLUSIONS: The study successfully unveils the complex interactions between miRSNPs, miRNAs, genes, and signaling pathways, shedding light on the genetic factors contributing to HS and keloid formation.

Fudan Zhongshan Plastic Surgery Forum.

ABSTRACT: The Fudan Zhongshan Plastic Surgery Forum along with the National Continuing Education Course is authorized and supported by the Shanghai Medical Association for Plastic and Reconstructive Surgery and the Fudan University. The annual conference this year along with the course focusing on the "Advances and New Techniques in Plastic Surgery" is successfully held at Zhongshan Hospital affiliated with Fudan University, on August 26-27, 2023 in Shanghai, China.

Preservation of Eschar Prevents Excessive Wound Healing by Reducing M2 Macrophages Polarization.

Background: Removal of the eschar has gradually become a consensus on treatments of deep dermal necrosis after skin trauma in recent years, whereas exaggerated scar contracture and tissue proliferation developed during healing have received little attention. Here, the authors investigated the effects of eschar on excessive wound healing of small dermal damage and focused on the role M2 macrophages played, hoping to offer a theoretical basis to improve patients' cosmetic satisfaction. Methods: A mouse dorsal wound model (n = 12) was established by electric heating pads heating for 20 seconds on each side of the spine, and the left side was the preserved group. Macrophage numbers, expression of wound-healing-associated proteins, and inflammatory cytokine levels were assessed at different time points by immunohistochemistry and quantitative real-time polymerase chain reaction. A co-culture system of M2 macrophages and myofibroblasts was created in vitro. Immunohistochemistry, real-time polymerase chain reaction, and Western blot were performed to evaluate the proliferation, migration, and protein expression of myofibroblasts. Results: Preserving eschar inhibited contraction-associated proteins (α-smooth muscle actin and vimentin) and collagen expression, inflammatory cytokine (IL-1ß, IL-10, TFN-α, and IL-4) expression, and M2 macrophage infiltration. Mechanistically, M2 macrophages potentially contributed to excessive wound healing by promoting myofibroblasts proliferation, migration, and production of contraction-associated proteins. Conclusion: Eschar preservation in wounds could reduce inflammation and negatively modulate myofibroblasts by inhibiting M2 macrophage polarization and infiltration, preventing excessive wound contraction and collagen deposition.

SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathway.

Macrophages preferentially polarize to the anti-inflammatory M2 subtype in response to alterations in the wound microenvironment. SUMO-specific protease 3 (SENP3), a SUMO-specific protease, has been proven to regulate inflammation in macrophages by deSUMOylating substrate proteins, but its contribution to wound healing is poorly defined. Here, we report that SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing in macrophage-specific SENP3 knockout mice. Notably, it affects wound healing through the suppression of inflammation and promotion of angiogenesis and collagen remodeling. Mechanistically, we identified that SENP3 knockout facilitates M2 polarization through the Smad6/IκB/p65 signaling pathway. SENP3 knockout elevated the expression of Smad6 and IκB. Moreover, Smad6 silencing enhanced the expression of p-p65 and proinflammatory cytokines while inhibiting the level of IκB. Our study revealed the essential role of SENP3 in M2 polarization and wound healing, which offers a theoretical basis for further research and a therapeutic strategy for wound healing.

Identification of Drug Compounds for Capsular Contracture Based on Text Mining and Deep Learning.

BACKGROUND: Capsular contracture is a common and unpredictable complication after breast implant placement. Currently, the pathogenesis of capsular contracture is unclear, and the effectiveness of nonsurgical treatment is still doubtful. The authors' study aimed to investigate new drug therapies for capsular contracture by using computational methods. METHODS: Genes related to capsular contracture were identified by text mining and GeneCodis. Then, the candidate key genes were selected through protein-protein interaction analysis in Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. Drugs targeting the candidate genes with relation to capsular contracture were screened out in Pharmaprojects. Based on the drug-target interaction analysis by DeepPurpose, candidate drugs with highest predicted binding affinity were obtained eventually. RESULTS: The authors' study identified 55 genes related to capsular contracture. Gene set enrichment analysis and protein-protein interaction analysis generated eight candidate genes. One hundred drugs targeting the candidate genes were selected. The seven candidate drugs with the highest predicted binding affinity were determined by DeepPurpose, including tumor necrosis factor alpha antagonist, estrogen receptor agonist, insulin-like growth factor 1 receptor, tyrosine kinase inhibitor, and matrix metallopeptidase 1 inhibitor. CONCLUSION: Text mining and DeepPurpose can be used as a promising tool for drug discovery in exploring nonsurgical treatment to capsular contracture. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Aura Intervention for Temporal Lobe Epilepsy: A Prospective, Randomized, Controlled Clinical Trial Protocol.

AIM: To determine the feasibility and efficacy of aura intervention in preventing the recurrence of temporal lobe epilepsy (TLE) by observing the changes in the seizure frequency and quality of life (QOL) scale score. MATERIAL AND METHODS: A total of 160 patients will be selected from a pre-established database and randomly divided into the experimental group and the control group. The proposed study is divided into four stages and requires approximately one and a half years for completion. The primary outcome measure is the change in seizure frequency, and the secondary one is the quality of life. RESULTS: We expect that our subjects show a lasting, stable, and clinically relevant reduction in seizure frequency and improvement in the quality of life, suggesting that aura intervention may be one more feasible way to treat patients with auras, specifically those who experience refractory epilepsy. CONCLUSION: The ability to perceive auras is the premise of our trial. We mainly study TLE as it relatively has more incidence of auras and a higher cure possibility compared to other types of epilepsy. Although we currently address our problems in a small group of subjects, we believe that the studied aura intervention can easily be applied to millions of patients with epilepsy worldwide if this intervention is considered effective.

Waterjet in Bacterial Clearance of Diabetic Lower Extremity Contaminated Wounds: A Retrospective Cohort Study.

The waterjet debridement is now a standard practice in contaminated or infected diabetic lower extremity wounds. The bacterial clearance of the waterjet debridement remains an important parameter that should be predicted in this application. This study aimed to investigate the waterjet in reducing the diabetic lower extremity wound contaminants. A retrospective cohort study was conducted. Patients' etiology and pathogen diagnosis were established as diabetic lower extremity contaminated wound. The high-power waterjet (Versajet™, Smith-Nephew) was used in the treatment group and conventional surgical methods were used in the control group. The bacteriological swab samples were collected before and after the debridement. The results of bacterial culture were analyzed. A total of 74 patients were included in our study, 40 patients in the treatment group and 34 in the control group. Patient characteristics were well matched. The preoperative bacteriological swab samples of the 2 groups showed no significant difference between each other with a P value of .1022. The culture result of postoperative bacteriological swab samples in the treatment group was significantly lower than control with a P value of .0099. The odds of bacterial clearance were greater in the treatment group than in the control group (odds ratio, 5.139; 95% confidence interval, 1.386-18.41). As demonstrated by this retrospective research, waterjet debridement reduced the bacterial load in the diabetic lower extremity contaminated wounds.

Is It a "Colon Perforation"? A Case Report and Review of the Literature.

Background: Intrauterine devices (IUDs) are commonly used as a contraceptive method. IUD migration and colon perforation are rare but serious complications occurring sometimes years after insertion. Case: A 42-year-old woman with complaints of slight abdominal pain underwent a colonoscopy. Colonoscopy showed that a "nail" had penetrated the ascending colon wall and that an arm of the "nail" was embedded in the colon wall. We did not remove the "nail" rashly under colonoscopy. Considering the safety and effectiveness of the patient's operation, we were able to remove the "nail" easily by performing laparoscopic-endoscopic cooperative surgery (LECS) combined with hysteroscopy at the same time. Conclusion: We report a case of successful removal of a colonic perforation device by colonoscopy, laparoscopy, and hysteroscopy, which is the first method used.

Trends of Antibiotic Use and Expenditure After an Intensified Antimicrobial Stewardship Policy at a 2,200-Bed Teaching Hospital in China.

Objective: This study aimed to evaluate the effects of intensified Chinese special rectification activity on clinical antibiotic use (CSRA) policy on a tertiary-care teaching hospital. Methods: A 48-month longitudinal dataset involving inpatients, outpatients, and emergency patients were collected. Study period included pre-intervention stage (adopting soft measures like systemic training) and post-intervention stage (applying antibiotic control system to intensify CSRA policy). Antibiotic use was evaluated by antibiotic use rate (AUR) or antibiotic use density (AUD). Economic indicator was evaluated by antibiotic cost in prescription or antibiotic expenditure in hospitalization. Data was analyzed by interrupted time series (ITS) analysis. Results: The medical quality indicators remained stable or improved during the study period. AUR of inpatients (AURI) declined 0.553% per month (P = 0.025) before the intervention and declined 0.354% per month (P = 0.471) after the intensified CSRA policy was implemented. AUD, expressed as defined daily doses per 100 patients per day (DDDs/100PD), decreased by 1.102 DDDs/100PD per month (P = 0.021) before and decreased by 0.597 DDDs/100PD per month (P = 0.323) thereafter. The ratio of antibiotic expenditure to medication expenditure (AE/ME) decreased by 0.510% per month (P = 0.000) before and fell by 0.096% (P = 0.000) per month thereafter. AE per patient decreased by 25.309 yuan per month (P = 0.002) before and decreased by 7.987 yuan per month (P = 0.053) thereafter. AUR of outpatient (AURO) decreased by 0.065% per month before (P = 0.550) and decreased by 0.066% per month (P = 0.994) thereafter. The ratio of antibiotic cost to prescription cost in outpatient (ACO/PCO) decreased by 0.182% per month (P = 0.506) before and decreased by 0.216% per month (P = 0.906) thereafter. AUR of emergency patient (AURE) decreased by 0.400% per month (P = 0.044) before and decreased by 0.092% per month (P = 0.164) thereafter. The ratio of antibiotic cost to prescription cost in emergency patient (ACE/PCE) decreased by 0.616% per month (P < 0.001) before and decreased by 0.151% per month (P < 0.001) thereafter. Conclusions: Implementation of CSRA policy was associated with declining antibiotic use and antibiotic expenditure in inpatients, outpatients, and emergency patients. However, it is also important to note that the declining trend of antibiotic consumption slowed due to the limited capacity for decline in the later stages of CSRA intervention.

Protein tyrosine phosphatase 1B(PTP1B) promotes melanoma cells progression through Src activation.

Previous studies have demonstrated that protein tyrosine phosphatase 1B (PTP1B) can promote tumor progression in breast cancer, colon cancer and prostate cancer. Additionally, PTP1B also acts as a tumor suppressor in esophageal cancer and lymphoma. These findings suggest that PTP1B functions as a double-faceted molecule in tumors. However, the role of PTP1B in malignant melanoma (MM) is still unknown. PTP1B expression in normal and melanoma tissues was evaluated by GEO analysis and immunohistochemistry. The effects of PTP1B on cell migration and invasion were evaluated in melanoma cells with up - and downregulated PTP1B expression. In this study, we initially demonstrated that the expression of PTP1B in malignant melanoma tissue is significantly higher than its expression in benign nevus tissue and indicated poor survival of malignant melanoma patients. In vitro studies have demonstrated that inhibition of PTP1B suppresses and overexpression of PTP1B promotes migration and invasion of melanoma cells. Moreover, we found that PTP1B could interact with Src via coimmunoprecipitation and dephosphorylation of the Src at Tyr530 site. Collectively, our study revealed that PTP1B can promote melanoma cell metastasis by interacting with Src and provides a theoretical basis for future applications of PTP1B inhibitors in the treatment of malignant melanoma.

Identification of drug compounds for keloids and hypertrophic scars: drug discovery based on text mining and DeepPurpose.

BACKGROUND: Keloids (KL) and hypertrophic scars (HS) are forms of abnormal cutaneous scarring characterized by excessive deposition of extracellular matrix and fibroblast proliferation. Currently, the efficacy of drug therapies for KL and HS is limited. The present study aimed to investigate new drug therapies for KL and HS by using computational methods. METHODS: Text mining and GeneCodis were used to mine genes closely related to KL and HS. Protein-protein interaction analysis was performed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape. The selection of drugs targeting the genes closely related to KL and HS was carried out using Pharmaprojects. Drug-target interaction prediction was performed using DeepPurpose, through which candidate drugs with the highest predicted binding affinity were finally obtained. RESULTS: Our analysis using text mining identified 69 KL- and HS-related genes. Gene enrichment analysis generated 25 genes, representing 7 pathways and 130 targeting drugs. DeepPurpose recommended 14 drugs as the final drug list, including 2 phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitors, 10 prostaglandin-endoperoxide synthase 2 (PTGS2) inhibitors and 2 vascular endothelial growth factor A (VEGFA) antagonists. CONCLUSIONS: Drug discovery using in silico text mining and DeepPurpose may be a powerful and effective way to identify drugs targeting the genes related to KL and HS.

Kindlin-2 regulates the differentiation of 3T3-L1 preadipocytes: implications for wound healing.

BACKGROUND: Adipose tissue has been proven to play a crucial role in wound healing, while kindlin-2, an integrin-associated protein, has been shown to regulate cell adhesion, migration, and differentiation. This study aimed to explore its involvement in the cell differentiation of 3T3-L1 preadipocytes and its role in wound healing. METHODS: Cell adhesion, Cell Counting Kit-8 (CCK-8), Transwell, and in vitro wound healing assays, along with adipogenic and osteogenic differentiation induction were performed in 3T3-L1 preadipocytes in which kindlin-2 was knocked down or overexpressed. In vivo, kindlin-2 (+/-) transgenic mice were constructed, and wound healing was analyzed by immunohistochemistry (IHC) in a mouse dorsal wound model. Real-time polymerase chain reaction (RT-PCR) and western blotting were performed to analyze the expression of adipokines and adipogenic markers in mouse wound tissues. Adipogenic differentiation induction of adipose tissue stromal vascular fraction (SVF) were performed, and the expression of adipogenic markers in SVF was detected by western blotting. The target signaling pathway highly related to adipogenic differentiation was explored by computational biology and verified by western blotting. RESULTS: Knockdown of kindlin-2 was found to inhibit the adhesion, migration, and adipogenic differentiation of 3T3-L1 preadipocytes while promoting their osteogenic differentiation. In contrast, kindlin-2 overexpression resulted in increased adhesion, migration, and adipogenic differentiation of 3T3-L1 preadipocytes while reducing osteogenic differentiation. In vivo, downregulation of kindlin-2 inhibited adipogenesis in kindlin-2 transgenic mice, resulting in delayed wound healing by inhibiting inflammation, angiogenesis, collagen remodeling, and wound contraction. Mechanistically, we found that kindlin-2 could regulate adipogenic differentiation through PI3K/AKT/mTOR signaling pathway. CONCLUSIONS: Our study revealed the essential role that kindlin-2 has in the differentiation and wound healing of 3T3-L1 preadipocytes, which offers a theoretical basis for further research and a novel strategy for wound healing.

Electroacupuncture for the treatment of functional dyspepsia: A systematic review and meta-analysis.

BACKGROUND: Functional dyspepsia (FD) is a common functional gastrointestinal disease. Acupuncture, including electroacupuncture (EA) is widely used as a complementary and alternative treatment for patients with FD. This study aimed to explore the effectiveness of EA for the treatment of FD. METHODS: We searched Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Cochrane Library) for randomized controlled trials of FD treated by EA from inception to February 3, 2020. Two reviewers will independently screen studies for data extraction and assess the quality and risk of bias. The Cochrane Collaboration's risk of bias tool, RevMan 5.3 software were used for meta-analysis. Data were pooled to calculate relative risk and 95% confidence intervals (CIs) of substantial improvement after treatment for dichotomous data and mean differences (SMDs) and 95% CIs for continuous data. RESULTS: Seven randomized clinical trials included 853 patients. This meta-analysis investigated the effectiveness of EA alone in the treatment of FD relative to sham-EA or pharmacologic medication (PM). The results showed that EA could significantly improve clinical symptoms. Compared with sham-EA, EA was more effective in reducing symptom scores (SMD -3.44, 95% CI -4.21 to -2.67) and increasing normal slow waves of electrogastrogram (SMD 0.93, 95% CI -0.30 to1.55). When EA was combined with PM, there was no significant difference in reducing symptom scores (SMD -0.18, 95% CI -0.51 to 0.16), increasing the effective rate of clinical symptoms (risk ratio 1.04, 95% CI 0.96 to 1.13), enhancing the level of plasma motilin (SMD 0.93, 95% CI -0.30 to1.55), and reducing gastric half-emptying time (SMD 0.02, 95% CI -0.16 to 0.20). The results also showed that there were very few adverse events reported. CONCLUSION: This meta-analysis suggests that EA is better than the placebo (sham-EA) in treating FD, and the therapeutic effect of EA on FD is equivalent to that of PM on FD. Compared with PM, EA for FD is safer and has fewer adverse reactions. Despite limitations due to the quality and number of the included studies, EA might be used as an effective and safe treatment for FD.

The effect of body mass index and creatinine clearance on serum trough concentration of vancomycin in adult patients.

BACKGROUND: The aim of this study was to evaluate the influence of patient body mass index (BMI) and estimated creatinine clearance (CrCl) on serum vancomycin concentrations to define a possible optimal dosage regimen in overweight patients based on data obtained during therapeutic drug monitoring. METHODS: This retrospective study used data collected from January 2017 to January 2019. Adult patients (n = 204) received vancomycin treatment at a dose of 1000 mg every 12 h and underwent serum monitoring. Data collected included patient disease category, sex, age, height, weight, vancomycin concentrations, and serum creatinine. The CrCl values were estimated using the Cockcroft-Gault formula. In this study, statistical comparisons were performed on the results of patients according to serum vancomycin concentration. RESULTS: Serum vancomycin concentration was significantly related to BMI (P <  0.001) and CrCl (P <  0.05) in adult patients. Furthermore, the trough serum vancomycin concentration showed a logarithmic correlation with BMI (R = - 0.5108, 95% CI: - 0.6082 to - 0.3982, P <  0.001) and CrCl (R = - 0.5739, 95% CI: - 0.6616 to - 0.4707, P <  0.001). The multivariate analysis showed that BMI and CrCl are independent contributors to the trough vancomycin concentration. Moreover, some of the patients with higher BMI (≥ 24 kg/m2) met the goal trough concentration after an adjustment from 1000 mg every 12 h to 1000 mg every 8 h. CONCLUSIONS: Serum vancomycin concentration decreases progressively with increasing BMI and the augmentation in CrCl in adult patients. The trough concentration of vancomycin should be continuously monitored for patients with a BMI ≥ 24 kg/m2, and the dosage regimen should be adjusted to reach the target trough concentration in these patients to reduce the impact of BMI.

Prognostic genes of melanoma identified by weighted gene co-expression network analysis and drug repositioning using a network-based method.

Melanoma is one of the most malignant types of skin cancer. However, the efficacy and utility of available drug therapies for melanoma are limited. The objective of the present study was to identify potential genes associated with melanoma progression and to explore approved therapeutic drugs that target these genes. Weighted gene co-expression network analysis was used to construct a gene co-expression network, explore the associations between genes and clinical characteristics and identify potential biomarkers. Gene expression profiles of the GSE65904 dataset were obtained from the Gene Expression Omnibus database. RNA-sequencing data and clinical information associated with melanoma obtained from The Cancer Genome Atlas were used for biomarker validation. A total of 15 modules were identified through average linkage hierarchical clustering. In the two significant modules, three network hub genes associated with melanoma prognosis were identified: C-X-C motif chemokine receptor 4 (CXCR4), interleukin 7 receptor (IL7R) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG). The receiver operating characteristic curve indicated that the mRNA levels of these genes exhibited excellent prognostic efficiency for primary and metastatic tumor tissues. In addition, the proximity between candidate genes associated with melanoma progression and drug targets obtained from DrugBank was calculated in the protein interaction network, and the top 15 drugs that may be suitable for treating melanoma were identified. In summary, co-expression network analysis led to the selection of CXCR4, IL7R and PIK3CG for further basic and clinical research on melanoma. Utilizing a network-based method, 15 drugs that exhibited potential for the treatment of melanoma were identified.

Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology.

BACKGROUND: Obesity-with its increased risk of obesity-associated metabolic diseases-has become one of the greatest public health epidemics of the twenty-first century in affluent countries. To date, there are no ideal drugs for treating obesity. Studies have shown that activation of brown adipose tissue (BAT) can promote energy consumption and inhibit obesity, which makes browning of white adipose tissue (WAT) a potential therapeutic target for obesity. Our objective was to identify genes and molecular pathways associated with WAT and the activation of BAT to WAT browning, by using publicly available data and computational tools; this knowledge might help in targeting relevant signaling pathways for treating obesity and other related metabolic diseases. RESULTS: In this study, we used text mining to find out genes related to brown fat and white fat browning. Combined with biological process and pathway analysis in GeneCodis and protein-protein interaction analysis by using STRING and Cytoscape, a list of high priority target genes was developed. The Human Protein Atlas was used to analyze protein expression. Candidate drugs were derived on the basis of the drug-gene interaction analysis of the final genes. Our study identified 18 genes representing 6 different pathways, targetable by a total of 33 drugs as possible drug treatments. The final list included 18 peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, 4 beta 3 adrenoceptor (ß3-AR) agonists, 1 insulin sensitizer, 3 insulins, 6 lipase clearing factor stimulants and other drugs. CONCLUSIONS: Drug discovery using in silico text mining, pathway, and protein-protein interaction analysis tools may be a method of exploring drugs targeting the activation of brown fat or white fat browning, which provides a basis for the development of novel targeted therapies as potential treatments for obesity and related metabolic diseases.

Text mining­based drug discovery in cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. However, the efficacy and utility of the available drug therapies are limited. The objective of the present study was to determine the genes and molecular pathways associated with cSCC by using computational tools and publicly available data, and to explore drugs targeting the relevant molecular pathways for cSCC treatment. In this study, we used text mining and GeneCodis to mine genes which were highly related to cSCC. Protein­protein interaction (PPI) analysis was performed by using STRING and Cytoscape. By using the data analytical tool cBioPortal, we analyzed the characteristics of candidate genes for the purpose of drug selection. Based on the drug­gene interaction analysis of the final genes, candidate drugs were then derived. Our analysis identified 121 genes related to cSCC from the text mining searches. Gene enrichment analysis yielded 11 genes representing 10 pathways, targetable by a total of 55 drugs as possible drug treatments for cSCC. The final list included 25 chemotherapy agents, 21 tyrosine kinase inhibitors (TKIs), 7 PI3K/AKT/mTOR inhibitors, 2 MAPK inhibitors, 2 cyclin­dependent kinase (CDK) inhibitors, 1 histone deacetylase (HDAC) inhibitor, 3 nonsteroidal anti­inflammatory drugs (NSAIDs) and 3 other drugs, which directly affect the most enriched pathways. In conclusions, drug discovery using in silico text mining and pathway analysis tools may be a method of exploring candidate drugs which target the genes/pathways relevant to cSCC, to identify potential treatments.