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Glucagon-like peptide-1 (GLP-1) receptor agonists became the most prescribed drugs for weight loss. This study aimed to investigate adverse events of GLP-1 receptor agonists using Twitter and KIDS-KAERS database (KIDS-KD). 116 Korean tweets on Twitter and 1,701 liraglutide-adverse event combinations from KIDS-KD were used for analysis. The most common adverse events were nausea (37.76%), vomiting (12.59%), dyspepsia (9.79%), dizziness (4.90%), and somnolence (4.90%) on Twitter. Adverse events observed in the post-marketing surveillance such as somnolence, myalgia, chest pain/ discomfort, and parosmia were found on Twitter. In KIDS-KD, injection site rash (13.46%), injection site pruritus (10.76%), nausea (10.64%), vomiting (6.41%), and injection site reaction (5.29%) were commonly reported. Signals were injection site rash (reporting odds ratio [ROR] = 616.1), injection site pruritus (ROR = 477.7), vomiting (ROR = 2.4), injection site reaction (ROR = 222.0), pruritus (ROR = 2.5), injection site bruising (ROR = 45.8), injection site pain (ROR = 36.3). Subgroup analysis revealed that injection site rash (n = 16, ROR = 46.6) and acne (n = 3, ROR = 39.2) met signal criteria in men and women, respectively. Twitter analysis identified adverse events that were not found in clinical trials, and KIDS-KD subgroup analysis suggested the possibility of acne being a safety signal. Social media and KIDS-KD were useful for pharmacovigilance.

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Social media offer valuable knowledge about opioid narcotics’ risks but are also commonly used to sell them. To determine how drug dealers avoid social media surveillance, the cross-sectional study used fentanyl-related data from Twittersphere and Tumblrsphere.The three-stagee process with data collection, preprocessing, and forensic tracking of fentanyl sales and promotion was performed. Twitter data were consistent between January and June 2021, while Tumblr data were more up-to-date. From January to June 2021, 12189 tweets and, from January 2020 to July 2021, 1240, Tumblr posts related to fentanyl were gathered. A higher proportion of Tumblr data (192, 15.56%) was classified as fentanyl sales and promotion, compared with Twitter data (1, 0.01%). Twitter has been successful in limiting the sale of opioids. However, more attention should be paid to non-English languages. Researchers, governments, and social media companies must collaborate to positively maintain social networking platforms to prevent the illicit sale of drugs through them.

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Coffee is a widely consumed beverage with multifaceted health benefits. While several studies have explored its effects on various diseases, limited reports have investigated its association with liver disease. Therefore, this review aimed to explore the effects of coffee consumption and its major coffee components on liver disease. Meta-analysis results have suggested that coffee consumption may reduce the risk of non-alcoholic fatty liver disease, hepatic fibrosis, and hepatocellular carcinoma, but the molecular mechanisms underlying these beneficial actions of coffee consumption remain elusive. Studying the individual components of coffee could help us better understand the mechanisms behind its liver protective effects. To clarify a more precise mechanism of coffee-related liver protective effects, the experimentally determined effects of each coffee component on liver diseases are also reviewed.

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Although the inflammatory response is an important process in the host defense system, it has been found to cause serious complications in disease in response to various stresses. Cyclic nucleotide monophosphates (cAMP and cGMP) are related to the inflammatory response, however, their mechanism is unclear. Although the antioxidative and neuroprotective mechanisms of the phosphodiesterase 2 (PDE2) inhibitor have been extensively studied in relation to heart failure and neuropsychiatric diseases, the PDE2 inhibitor’s role in inflammatory immune responses caused by bacterial endotoxin has not been elucidated. In the present study, the anti-inflammatory effects of the PDE2 selective inhibitor BAY 60-7550 were investigated in the murine macrophage cell line RAW 264.7 after being induced by lipopolysaccharide (LPS). BAY 60-7550 showed no cytotoxicity in RAW 264.7 cells and suppressed the LPS-induced overexpression of oxidative stress factors such as an inducible nitric oxide synthase (iNOS), nitric oxide (NO), and reactive oxygen species (ROS). The oxidative stress-induced activation of the mitogen-activated protein kinase (MAPK) pathway, especially the phosphorylation of the extracellular signal-regulated kinases (ERK)1/2 and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, was also inhibited by the application of BAY 60-7550. Moreover, the expression of COX-2, PGE₂, and pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β was significantly reduced by the application of BAY 60-7550. In conclusion, BAY 60-7550 has an anti-inflammatory effect through the regulation of the ERK1/2-associated MAPK and NF-κB pathways. Thus, this finding shows the potential of the PDE2 selective inhibitor as a new therapeutic candidate for infectious inflammatory diseases.

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Although N⁶-adenosine methyltransferase (METTL3) is frequently upregulated in breast cancer patients, the anticancer effect of small-molecule inhibitors targeting METTL3 has not yet been studied. The present study aimed to investigate the anti-tumorigenic effects of STM2457, a METTL3 inhibitor, on a panel of breast cancer cells representing distinct clinical subtypes. Measurement of cell viability using MTT assay demonstrated dose- and time-dependent reduction in viability in MCF7, SKBR3, and MDA-MB-231 cells, which are representative of luminal A, HER2-positive, and triple-negative breast cancer subtypes, respectively. Immunoblotting analysis revealed that STM2457 induced pro-apoptotic effects in breast cancer cells, as evidenced by the cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3. In addition, analysis of cell cycle distribution with flow cytometry revealed that it induced cell cycle arrest at G0/G1-phase. Consistently, treatment with STM2457 increased the Annexin V-stained cell population, corroborating the pro-apoptotic effects of the compound. Moreover, analysis of colonies formed by breast cancer cells in a soft agar matrix showed that STM2457 reduced the anchorage-independent growth of breast cancer cells, suggesting its potential to inhibit colony formation. Together, these findings indicate that STM2457 exerts cytotoxic and pro-apoptotic effects in breast cancer cells. Our study demonstrates the therapeutic potential of METTL3 inhibitor STM2457 in treating breast cancer patients.

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Adriamycin is currently used in the treatment of breast cancer, however, acquired resistance to adriamycin is a critical problem. This study examined the gene expression involved in resistance to adriamycin in MCF-7 breast cancer cells, with a particular focus on the epithelial-mesenchymal transition (EMT). The level of E-cadherin, an epithelial marker, was significantly decreased, however, an obvious increase was observed in the levels of mesenchymal markers in adriamycin-resistant MCF-7 (MCF-7/ADR) cells, implying that EMT is induced by adriamycin resistance. In the evaluation of target transcription factors involved in EMT, Slug is predominantly expressed in MCF-7/ADR cells. Knockdown of Slug in MCF-7/ADR cells resulted in significant recovery of the epithelial characteristics. Of particular significance, the downregulation of Slug using siRNA resulted in repressed P-glycoprotein (P-gp) as well as increased sensitivity to adriamycin. Taken together, these findings suggest the potential importance of Slug in the acquisition of mesenchymal characteristics as well as the expression of P-gp in adriamycin-resistant MCF-7 cells.

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We compared the risk of diabetic complications between diabetes patients with dementia and those without dementia in elderly type 2 diabetes patients using the data from insurance claims in South Korea. We performed 1:4 propensity score matching between the two groups using gender, age, and the type of National Health Security program in which they were enrolled. In this retrospective cross-sectional study, logistic regression analysis was used to assess the association between dementia and the prevalence and hospitalization rate of diabetes complications. The adjusted odds ratio obtained for the incidence of diabetic complications by logistic regression analysis of comorbid dementia was 1.328 (95% confidence interval (CI): 1.244-1.417). The hospitalization rate for diabetic complications was 1.371 times (95% CI: 1.240-1.516) higher in diabetic patients with dementia than in those without. The adjusted odds ratio for the risk of diabetic complication (prevalence) decreased to 1.248 (95% CI: 1.169-1.333), after accounting for baseline health status using Carlson Comorbidity Index, however, hospitalization risk increased to 1.748 (95% CI: 1.575-1.939). Our results suggest that patients with diabetes accompanied by dementia were more likely to experience both mild and severe diabetic complications, implying that diabetes patients with dementia are disproportionately vulnerable to problems with glycemic level management.

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The development of therapy resistance in cancer is a complex mechanism with multifaceted and catastrophic consequences. BCRP (Breast Cancer Resistance Protein/ATP-Binding Cassette Subfamily G member 2; ABCG2), a drug efflux transporter, is recognized as a key regulator in obtaining multidrug resistance properties of cancer cells. NRF2 (Nuclear Factor Erythroid 2-Like 2; NFE2L2) plays an essential role in maintaining cellular redox homeostasis by regulating the expression of an array of antioxidant and detoxifying genes. In contrast to its protective roles in normal cells, a substantial body of evidence has demonstrated the negative aspects of NRF2 accumulation in cancer cells, including facilitated tumor growth, stemness, and therapy resistance. This review focuses on the linkage between BCRP and NRF2 in cancer and its consequences in acquiring therapy resistance. In particular, we highlight the role of the NRF2/BCRP axis in photodynamic therapy resistance and cancer stem cell maintenance, demonstrating that inhibition of this axis can be a beneficial strategy to overcome resistance to cancer therapy. A comprehensive understanding of the NRF2/BCRP regulating pathway will lead to the development of new therapeutic approaches and improve the prognosis of cancer patients.

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The CYP2C19 gene has a high proportion of poor metabolizers (PMs) in Asians, including Koreans, with the CYP2C19*2 and *3 alleles accounting for most of the PMs. CYP2C19*10 is a mutation that differs by 1 bp from CYP2C19*2 and cannot be distinguished by the conventional PCR-RFLP method using SmaI. Thus, the frequency of CYP2C19*10 may appear high in an ethnic group with a high frequency of CYP2C19*2. We classified CYP2C19*2 and *10 using the pyrosequencing method and carried out a study to accurately confirm their frequency. Four hundred and thirty-two healthy Korean subjects were studied. CYP2C19 alleles (CYP2C19*2, *3, *10, and *17) were detected using pyrosequencing assays. The allele frequencies observed here were 63.0% for CYP2C19*1, 26.4% for CYP2C19*2, 9.4% for CYP2C19*3, and 1.3% for CYP2C19*17. The CYP2C19*10 allele was not detected. The frequencies of the CYP2C19 normal metabolizer, rapid metabolizer, intermediate metabolizer, and PM phenotypes were 40.0%, 1.6%, 45.1%, and 13.2%, respectively. Similar to previous studies, the frequencies of CYP2C19*2 and *3 were relatively high, and the frequency of CYP2C19*17 was low. Finally, in Koreans, the frequency of CYP2C19*10 seems to be extremely low.

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Complications associated with diabetes have increased along with diabetes prevalence. Cataract in diabetic patients is a significant cause of vision loss. We aimed to investigate related factors such as comorbidities and co-medications to provide evidence for cataract prevention and management in diabetic patients. A nested case-control study was performed using the Korean National Insurance Health Service Database. Patients diagnosed with cataract after type 2 diabetes were defined as the case group and control group included patients never diagnosed with cataract. In a total of 117,610 subjects, the case group consisted of 14,352 patients after 1:1 risk set sampling. Among the covariates included in the analysis, atopic disorder was associated with increased development of cataracts in diabetes whereas dementia was associated with decreased prevalence of cataracts. Regarding dementia medications, patients with memantine and donepezil showed a significantly lowered risk of developing cataracts. The National Health Insurance System database may differ from actual medical treatment data to insurance claim date, and the effect on outcome cannot be measured due to a lack of clinical data on clinical measurement and severity. It is necessary to manage diabetic patients' comorbidities and co-medications in coordination with ocular complications.