Correction: Tumor Immunotherapy-Related Information on Internet-Based Videos Commonly Used by the Chinese Population: Content Quality Analysis.

[This corrects the article DOI: 10.2196/50561.].

Elucidating the changes in the heterogeneity and function of radiation-induced cardiac macrophages using single-cell RNA sequencing.

Purpose: A mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process. Methods: Cardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process. Results: Cardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes. Conclusion: We are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.

Tumor Immunotherapy-Related Information on Internet-Based Videos Commonly Used by the Chinese Population: Content Quality Analysis.

BACKGROUND: Tumor immunotherapy is an innovative treatment today, but there are limited data on the quality of immunotherapy information on social networks. Dissemination of misinformation through the internet is a major social issue. OBJECTIVE: Our objective was to characterize the quality of information and presence of misinformation about tumor immunotherapy on internet-based videos commonly used by the Chinese population. METHODS: Using the keyword "tumor immunotherapy" in Chinese, we searched TikTok, Tencent, iQIYI, and BiliBili on March 5, 2022. We reviewed the 118 screened videos using the Patient Education Materials Assessment Tool-a validated instrument to collect consumer health information. DISCERN quality criteria and the JAMA (Journal of the American Medical Association) Benchmark Criteria were used for assessing the quality and reliability of the health information. The videos' content was also evaluated. RESULTS: The 118 videos about tumor immunotherapy were mostly uploaded by channels dedicated to lectures, health-related animations, and interviews; their median length was 5 minutes, and 79% of them were published in and after 2018. The median understandability and actionability of the videos were 71% and 71%, respectively. However, the quality of information was moderate to poor on the validated DISCERN and JAMA assessments. Only 12 videos contained misinformation (score of >1 out of 5). Videos with a doctor (lectures and interviews) not only were significantly less likely to contain misinformation but also had better quality and a greater forwarding number. Moreover, the results showed that more than half of the videos contain little or no content on the risk factors and management of tumor immunotherapy. Overall, over half of the videos had some or more information on the definition, symptoms, evaluation, and outcomes of tumor immunotherapy. CONCLUSIONS: Although the quality of immunotherapy information on internet-based videos commonly used by Chinese people is moderate, these videos have less misinformation and better content. Caution must be exercised when using these videos as a source of tumor immunotherapy-related information.

Sintilimab-induced erythema multiforme drug eruption in the treatment of sigmoid colon cancer: A case report and literature review.

RATIONALE: Dermatologic toxicity has been reported as the most common immune-related side effect of programmed cell death 1 inhibitors. Previous reports related to Sintilimab include rash, pruritus, vitiligo, Stevens-Johnson syndrome, toxic epidermal necrolysis, and so on. PATIENT CONCERNS: A 66-year-old man was treated with Sintilimab as monotherapy for sigmoid colon cancer. After the second prescription, he developed a more severe and widespread rash. DIAGNOSES: The diagnose of erythema multiforme drug eruption induced by Sintilimab was considered. INTERVENTIONS: The patient received intravenous and oral methylprednisolone, routine antihistamines and topical gluccorticoids. OUTCOMES: The patient's symptoms were gradually relieved during hospitalization and was discharged following resolution of symptoms. He refused to continue using Sintilimab. LESSONS: This is the first reported case of Sintilimab-induced erythema multiforme drug eruption. It is advisable to inform patients of potential dermatologic toxicity that may occur after using immune checkpoint inhibitors, so that we may prevent the further development of it and avoid the discontinuation of immune checkpoint inhibitors.

Insights from multi-omics integration into seed germination of Taxus chinensis var mairei.

The transition from deep dormancy to seed germination is essential for the life cycle of plants, but how this process occurs in the gymnosperm Chinese yew (Taxus chinensis var mairei), the natural source of the anticancer drug paclitaxel, remains unclear. Herein, we analyse the transcriptome, proteome, spatial metabolome, and spatial lipidome of the Chinese yew and present the multi-omics profiles of dormant and germinating seeds. Our results show that abscisic acid and gibberellic acid 12 homoeostasis is closely associated with gene transcription and protein translation, and the balance between these phytohormones thereby determines if seeds remain dormant or germinate. We find that an energy supply of carbohydrates from glycolysis and the TCA cycle feed into the pentose phosphate pathway during seed germination, and energy supplied from lipids are mainly derived from the lipolysis of triacylglycerols. Using mass spectrometry imaging, we demonstrate that the spatial distribution of plant hormones and phospholipids has a remarkable influence on embryo development. We also provide an atlas of the spatial distribution of paclitaxel C in Chinese yew seeds for the first time. The data from this study enable exploration of the germination mechanism of Chinese yew seeds across several omics levels.

The value of RACK1 and peripheral blood M2/M1 monocyte ratio on the prognosis of patients with oral squamous cell carcinoma.

This study is to evaluate the effect of receptor for activated c kinase 1 (RACK1) and peripheral blood M2/M1 monocytes ratio on the prognosis of patients with oral squamous cell carcinoma (OSCC). A total of 115 OSCC patients who underwent radical surgery in North China University of Science and Technology Affiliated Hospital from January 2015 to December 2015 were included in the experimental group and 34 healthy individuals after a physical examination during the same period were included in the control group. Cancer and para-cancerous tissues were collected and the relationship between RACK1 and M2/M1 ratio and the prognosis of OSCC patients and its predictive value were analyzed. RACK1, M2/M1 ratio, clinical stages, lymphatic metastasis, recurrence and metastasis were considered independent factors for the prognosis of OSCC patients (p<0.05); In addition, RACK1 and the M2/M1 ratio were proven to be of significant predictive values for the prognosis of OSCC patients (p<0.05). RACK1 and peripheral blood M2/M1 monocytes ratio demonstrate great potential as prognostic predictors of OSCC patients.

BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Versus BEAM (Carmustine, Etoposide, Cytarabine, Melphalan) as Conditioning Regimen Before Autologous Haematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for selected patients with refractory/relapsed Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL), and it is also used as first-line clinical consolidation option for some aggressive NHL subtypes. Conditioning regimen prior to ASCT is one of the essential factors related with clinical outcomes post transplant. The conditioning regimen of carmustine, etoposide, cytarabine, and melphalan (BEAM) traditionally is considered the standard of care for patients with lymphoma who are eligible for transplantation. Replacement of carmustine with bendamustine (BeEAM) was described as an alternative conditioning regimen in the autograft setting for patients with lymphoma. Several studies have reported inconsistent clinical outcomes comparing BeEAM and BEAM. Therefore, in the lack of well-designed prospective comparative studies, the comparison of BeEAM versus BEAM is based on retrospective trials. To compare the clinical outcomes between BeEAM and BEAM, we performed a meta-analysis of 10 studies which compared the outcomes between BeEAM and BEAM in patients autografted for lymphoma disease (HL or NHL). We searched article titles and compared transplantation with BeEAM versus BEAM in MEDLINE (PubMed), Cochrane library, and EMBASE database. Here, we report the results of nine main endpoints in our meta-analysis comparing BeEAM and BEAM, including neutrophil engraftment (NE), platelet engraftment (PE), overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse rate (RR), grade 3 mucositis, renal toxicity, and cardiotoxicity. We discovered that the BeEAM regimen was associated with a slightly better PFS [pooled odds ratio (OR) of 0.70, 95% confidence interval (CI), 0.52-0.94, P = 0.02], lower RR (0.49, 95% CI, 0.31-0.76, P = 0.002), higher mucositis (3.43, 95% CI, 2.29-5.16, P = 0.001), renal toxicity (4.49, 95% CI, 2.68-7.51, P = 0.001), and cardiotoxicity (1.88, 95% CI, 1.03-3.40, P = 0.03). We also discovered that the two groups had equivalent NE (pooled WMD -0.64, 95% CI, -1.46 to 0.18, P = 0.13), PE (pooled WMD -0.3, 95% CI, -1.68 to 2.28, P = 0.77), OS (0.73, 95% CI, 0.52-1.01, P = 0.07), and NRM (1.51, 95% CI, 0.76-2.98, P = 0.24). The results of this meta-analysis show that the BeEAM regimen is a viable alternative to BEAM. More prospective comparisons between BeEAM and BEAM are required.

IL-23/IL-17 immune axis mediates the imiquimod-induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF-κB pathway in macrophages and keratinocytes.

The interleukin-23 (IL-23)/IL-17 immune axis has been linked to the pathology of psoriasis, but how this axis contributes to skin inflammation in this disease remains unclear. We measured inflammatory cytokines associated with the IL-23/IL-17 immune axis in the serum of patients with psoriasis using enzyme-linked immunosorbent assays. Psoriasis was induced in male C57BL/6J mice using imiquimod (IMQ) cream, and animals received intraperitoneal injections of recombinant mouse anti-IL-23A or anti-IL-17A antibodies for 7 days. The potential effects of the IL-23/IL-17 immune axis on skin inflammation were assessed based on pathology scoring, hematoxylin-eosin staining of skin samples, and quantitation of inflammatory cytokines. Western blotting was used to evaluate levels of the following factors in skin: ACT1, TRAF6, TAK1, NF-κB, and pNF-κB. The serum of psoriasis patients showed elevated levels of several cytokines involved in the IL-23/IL-17 immune axis: IL-2, IL-4, IL-8, IL-12, IL-17, IL-22, IL-23, and interferon-γ. Levels of IL-23p19 and IL-17 were increased in serum and skin of IMQ-treated mice, while ACT1, TRAF6, TAK1, NF-κB, and pNF-κB were upregulated in the skin. A large proportion of NF-κB p65 localized in nucleus of involucrin+ cells in the epidermis and in F4/80+ cells of the dermis of psoriatic lesional skin. Treating these animals with anti-IL-23 or anti-IL-17 antibodies improved pathological score and immune imbalance, mitigated skin inflammation and downregulated ACT1, TRAF6, TAK1, NF-κB, and pNF-κB in skin. Our results suggest that skin inflammation mediated by the IL-23/IL-17 immune axis in psoriasis involves activation of the ACT1/TRAF6/TAK1/NF-κB pathway in keratinocytes and macrophage.

Glucose-Dependent Insulinotropic Polypeptide and Substance P Mediate Emetic Response Induction by Masked Trichothecene Deoxynivalenol-3-Glucoside through Ca2+ Signaling.

Deoxynivalenol (DON), the most naturally-occurring trichothecenes, may affect animal and human health by causing vomiting as a hallmark of food poisoning. Deoxynivalenol-3-glucoside (D3G) usually co-occurs with DON as its glucosylated form and is another emerging food safety issue in recent years. However, the toxicity of D3G is not fully understood compared to DON, especially in emetic potency. The goals of this research were to (1) compare emetic effects to D3G by oral and intraperitoneal (IP) routes and relate emetic effects to brain-gut peptides glucose-dependent insulinotropic polypeptide (GIP) and substance P (SP) in mink; (2) determine the roles of calcium-sensing receptor (CaSR) and transient receptor potential (TRP) channel in D3G's emetic effect. Both oral and IP exposure to D3G elicited marked emetic events. This emetic response corresponded to an elevation of GIP and SP. Blocking the GIP receptor (GIPR) diminished emetic response induction by GIP and D3G. The neurokinin 1 receptor (NK-1R) inhibitor Emend® restrained the induction of emesis by SP and D3G. Importantly, CaSR antagonist NPS-2143 or TRP channel antagonist ruthenium red dose-dependently inhibited both D3G-induced emesis and brain-gut peptides GIP and SP release; cotreatment with both antagonists additively suppressed both emetic and brain-gut peptide responses to D3G. To summarize, our findings demonstrate that activation of CaSR and TRP channels contributes to D3G-induced emesis by mediating brain-gut peptide exocytosis in mink.

Emetic Response to T-2 Toxin Correspond to Secretion of Glucagon-like Peptide-17-36 Amide and Glucose-Dependent Insulinotropic Polypeptide.

The T-2 toxin, a major secondary metabolite of Fusarium Gramineae, is considered a great risk to humans and animals due to its toxicity, such as inducing emesis. The mechanism of emesis is a complex signal involving an imbalance of hormones and neurotransmitters, as well as activity of visceral afferent neurons. The T-2 toxin has been proven to induce emesis and possess the capacity to elevate expressions of intestinal hormones glucagon-like peptide-17-36 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), both of which are important emetic factors. In addition, the activation of calcium-sensitive receptor (CaSR) and transient receptor potential (TRP) channels are engaged in intestinal hormone release. However, it is unknown whether hormones GLP-1 and GIP mediate T-2 toxin-induced emetic response through activating CaSR and TRP channels. To further assess the mechanism of T-2 toxin-induced emesis, we studied the hypothesis that T-2 toxin-caused emetic response and intestinal hormones GLP-1 and GIP released in mink are associated with activating calcium transduction. Following oral gavage and intraperitoneal injection T-2 toxin, emetic responses were observed in a dose-dependent manner, which notably corresponded to the secretion of GLP-1 and GIP, and were suppressed by pretreatment with respective antagonist Exending9-39 and Pro3GIP. Additional research found that NPS-2143 (NPS) and ruthenium red (RR), respective antagonists of CaSR and TRP channels, dramatically inhibited both T-2 toxin-induced emesis response and the expression of plasma GLP-1 and GIP. According to these data, we observed that T-2 toxin-induced emetic response corresponds to secretion of GLP-1 and GIP via calcium transduction.

Mst1/2 Is Necessary for Satellite Cell Differentiation to Promote Muscle Regeneration.

The diminished ability for muscle to regenerate is associated with aging, diabetes, and cancers. Muscle regeneration depends on the activation and differentiation of satellite cells (SCs). Inactivation of Mst1/2 promotes cell proliferation by activating Yap, and that has been reported as a potential therapeutic target for improving many organ regeneration. However, the function of Mst1/2 in SCs fate decision and that effect on muscle regeneration remain unknown. By using inducible conditional knockout Mst1/2 in the SCs of mice and an inhibitor of Mst1/2, we found that inhibition of Mst1/2 in SCs significantly decrease Yap phosphorylation, thus causing Yap to accumulate in the nucleus and impairing SC differentiation; Mst1/2 were slightly elevated by irisin stimulation during SC differentiation; but inhibiting Mst1/2 in SCs significantly impaired irisin-induced muscle regeneration. These results indicate that Mst1/2 is necessary for SC differentiation and inhibiting Mst1/2 as a therapeutic target has potential risks for muscle regeneration.

Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans.

This secondary analysis sought to determine if plasma menthol glucuronide (MG) concentrations predict changes in three outcomes, subjective drug effects, urges to smoke, and heart rate, following concurrent inhaled menthol and intravenous nicotine. A total of 45 menthol and non-menthol cigarettes smokers (36 male, nine female, 20 Black, and 23 White) were included in this double-blind, placebo-controlled study. Across three test sessions, participants were assigned to a different flavor condition for each session: 0% (no menthol), 0.5%, or 3.2% menthol. In each test session, participants received in a random order one intravenous delivery of saline and two intravenous deliveries of nicotine (0.25 mg/70 kg and 0.5 mg/70 kg), each 1 h apart, concurrent with menthol delivery by e-cigarettes. The main outcomes were subjective drug effects, urges to smoke, and heart rate. The results showed that following e-cigarette inhalation, changes in plasma MG concentrations or "menthol boost" increased proportionally to the menthol concentration in the e-liquids. While changes in plasma MG concentrations were not predictive of increases in heart rate or subjective drug effects that are reflective of acute effects from nicotine (i.e., feel good effects, stimulated, aversive effects), they were predictive of cooling effect, a typical effect of menthol, but only in menthol smokers in the absence of concurrent active nicotine infusion. These findings demonstrate the utility of plasma MG as a biomarker both for acute menthol exposure by e-cigarette inhalation and for the examination of the concentration-dependent behavioral and physiological effects of menthol in humans.

E-cigarette device type and combustible tobacco use: Results from a pooled analysis of 10,482 youth.

INTRODUCTION: To understand whether using a certain e-cigarette device is more strongly associated with risk of combustible tobacco use among youth. METHODS: We conducted multivariable logistic regression analyses using cross-sectional data from 4 samples of youth in Connecticut and California (N = 10,482; ages 13-24), separately for each study using the total sample and the sample of past-month e-cigarette users, to understand the association between e-cigarette device type and past-month combustible tobacco use, while controlling for age, sex, race/ethnicity, socioeconomic status, school, and past-month marijuana use. Then, we conducted meta-analyses to calculate pooled associations for adolescents, young adults, and all individuals combined. RESULTS: Among the total sample, combustible tobacco use was associated with any e-cigarette device use (vs. no e-cigarette use) in the pooled analysis across all studies. Among past-month e-cigarette users, combustible tobacco use across all studies was 15.8%- 61.5%. Pooled associations among past-month e-cigarette users showed that using disposable devices (vs. pods; AOR=2.83, 95% CI: 1.73-4.61) and multiple devices most frequently (vs. pods; AOR=2.13, 95% CI: 1.16-3.90) was associated with greater odds of combustible tobacco use. Pooled associations also found that using multiple devices (vs. a single device) in the past month was associated with greater odds of combustible tobacco use (AOR 2.33, 95% CI: 1.74, 3.14). DISCUSSION: Using disposable e-cigarettes and multiple devices is associated with greater likelihood of combustible tobacco use among e-cigarette using youth. Future research should elucidate the trajectory of e-cigarette device used and combustible tobacco use among youth to inform prevention and product regulation.

Dihydroartemisinin represses oral squamous cell carcinoma progression through downregulating mitochondrial calcium uniporter.

Dysregulation of mitochondrial calcium uniporter (MCU) exerts a carcinogenic effect in several cancers. Nevertheless, the roles of MCU in oral squamous cell carcinoma (OSCC) remain elusive. It has been reported that dihydroartemisinin (DHA) may suppress the progression of OSCC but its associated mechanisms have not been investigated. The purpose of our research was to observe the biological function of MCU on OSCC and its regulatory relationship with DHA. MCU, MICU1, MICU2, N-cadherin, TGF-ß and vimentin expression was detected in OSCC and peritumoral tissues by immunohistochemistry and Western blot. Following DHA treatment, the expression of the aforementioned proteins was detected in CAL-27 cells transfected with shMCU or pcDNA3.1-MCU by Western blot or immunofluorescence. Furthermore, clone formation, mitochondrial membrane potential (MMP), wound healing and transwell assays were presented in CAL-27 cells treated with DHA, shMCU or pcDNA3.1-MCU. Our results showed that the members of MCU complex (MCU, MICU1 and MICU2) were overexpressed in OSCC than peritumoral tissues. Furthermore, TGF-ß and epithelial to mesenchymal transition (EMT) proteins (N-cadherin and vimentin) exhibited higher expression in OSCC. DHA treatment significantly lowered the expression of MCU in CAL-27 cells. MCU overexpression reversed the inhibitory effects of DHA on MICU1, MICU2, N-cadherin, TGF-ß and vimentin. MCU knockdown or DHA suppressed proliferation, MMP and migration of CAL-27 cells. DHA treatment could reverse the effects of MCU overexpression. Collectively, our study demonstrated that MCU was an oncogene of OSCC and DHA exerted a suppressive role on proliferation and migration of OSCC cells by suppressing MCU expression.

Analysis of M6A associated lncRNAs in prognosis and immune response of NSCLC patients.

Distinguishing between N6-methyladenosine (m6A)-associated long noncoding RNAs (lncRNAs) is crucial in non-small-cell lung cancer (NSCLC) patients. In this research, the prognosis and immunotherapeutic response of lncRNAs and m6A in NSCLC were examined. lncRNAs related to m6A were identified using co-expression analyses, and their prognostic impact on patients with NSCLC was assessed using univariate Cox regression analysis. Sixty-three m6A-associated lncRNAs were determined as prognostic lncRNAs, and on this basis, 25 m6A-associated lncRNAs were screened by least absolute shrinkage and selection operator (lasso) Cox regression. Multivariable Cox analysis obtained 14 m6A-associated lncRNAs for the construction of risk model. The NSCLC patients were grouped into different risk subgroups in accordance with the median of the risk fraction in each data, and we evaluated the differences of potential immunotherapeutic characteristics and drug sensitivity prediction between the two subgroups. By using this model to recombine patients, they can be effectively distinguished in terms of the immunotherapy response. Furthermore, candidate compounds for the differentiation of NSCLC subtypes were identified. The model based on 14 m6A-associated lncRNAs is a promising prognostic biomarker, which may help to predict the efficacy of immunotherapy in NSCLC patients and provide a theoretical basis for improving the outcome of patients.

E-cigarette use and adverse respiratory symptoms among adolescents and Young adults in the United States.

E-cigarette use among adolescents and young adults has been associated with adverse respiratory symptoms, including symptoms of asthma and bronchitis. This investigation examined whether such associations differ by primary type of e-cigarette device used. This cross-sectional study included data from four study populations in California and Connecticut, United States, ages 13-21 years (N = 10,483), who self-reported their tobacco use behaviors and health status from 2018 to 2020. Adverse respiratory symptoms were grouped as bronchitis, asthma exacerbation, and shortness of breath. Associations with e-cigarette use were examined by frequency of e-cigarette use (regardless of device type) and most-frequently use device type in the past 30 days (pod, pen/tank, disposable, or mod). Multivariable modeling accounted for demographic variables and use of other tobacco and cannabis. Results were pooled at the study level via random-effects meta-analysis. Across the four studies, e-cigarette use >5 days/month versus never use was associated with bronchitic symptoms (summary odds ratio, sOR: 1.56; 95% confidence interval, CI: 1.37, 1.77) and shortness of breath (sOR: 1.68; 95% CI: 1.35, 2.08) but not statistically significantly with asthma exacerbations (sOR: 1.36; 95% CI; 0.95, 1.95). Among past 30-day e-cigarette users, associations with respiratory symptoms did not differ by device type. In these populations, e-cigarette use was positively associated with symptoms of bronchitis and shortness of breath, but adjusted odds of symptoms did not differ meaningfully by device type. These findings suggest that risk of these respiratory outcomes is elevated among more frequent e-cigarette users regardless of device type used.

Antioral Squamous Cell Carcinoma Effects of Carvacrol via Inhibiting Inflammation, Proliferation, and Migration Related to Nrf2/Keap1 Pathway.

OBJECTIVE: To observe the therapeutic effect of Carvacrol on oral squamous cell carcinoma (OSCC) and dissect underlying molecular mechanisms. METHODS: Keap1/Nrf2, NALP3, Vimentin, and E-cadherin expression was detected in OSCC and normal oral mucosa (NOM) tissues using immunofluorescence or western blot. When treated with Carvacrol or tert-butylhydroquinone (TBHQ) that activates Nrf2, the expression of Keap1/Nrf2/HO-1, epithelial-mesenchymal transition- (EMT-) related proteins, and NALP3 was examined in OSCC cells. Nrf2 was silenced by treatment with sh-Nrf2 or ML385. After silencing Nrf2 or Carvacrol treatment, cell proliferation and migration were assessed by clone formation and scratch and transwell tests in OSCC cells. Moreover, the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 was detected. RESULTS: Keap1/Nrf2, NALP3, Vimentin, and E-cadherin proteins were all significantly upregulated in OSCC than NOM tissues. Carvacrol significantly suppressed Keap1/Nrf2/HO-1 activation. Carvacrol or silencing Nrf2 markedly inhibited the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 inflammasome in OSCC cells. Furthermore, clone formation and migration capacities were suppressed following treatment with Carvacrol or Nrf2 depletion. The opposite results were found when there is overexpression of Nrf2. However, Carvacrol distinctly improved the cancer-promoting effect induced by Nrf2 overexpression. CONCLUSION: Our findings suggested that Carvacrol ameliorated inflammation, proliferation, and migration for OSCC, which was related to inhibition of the Nrf2/Keap1 pathway.

The effect of varenicline on smoking and drinking outcomes among Black and White adults with alcohol use disorder and co-occurring cigarette smoking: A secondary analysis of two clinical trials.

INTRODUCTION: Varenicline is an FDA-approved medication for smoking cessation and has demonstrated promise in reducing alcohol use. This study sought to compare the efficacy of varenicline in reducing smoking and drinking among Black and White people seeking alcohol treatment. METHODS: Linear mixed modeling was conducted using data from two multi-site placebo-controlled randomized clinical trials examining the effects of varenicline for treatment of Alcohol Use Disorder (AUD; O'Malley et al., 2018; Litten et al., 2013) among Black and White adults with AUD and co-occurring cigarette smoking. The primary analyses were conducted in a sample of 117 adults (O'Malley trial: 29.1% female, 55.2% Black), and replicated in an independent sample of 73 adults (Litten trial: 23.3% female, 45.2% Black). RESULTS: Black participants smoked fewer cigarettes per day compared to White participants (O'Malley trial: F1,116 = 8.95, p = .003; Litten trial: F1,68.9 = 4.74p = .03). Linear mixed models revealed a marginal effect of varenicline on reducing cigarettes smoked per day regardless of race in the O'Malley trial (F1,109 = 3.34, p = .07), which was replicated in the Litten trial (F1,67.1 = 20.77p < .0001). Participants reduced the number of drinks consumed regardless of treatment condition or race in both trials (O'Malley trial: F1,98 = 131.69, p < .0001; Litten trial:F1,69 = 60.36, p < .0001). CONCLUSIONS: Our adjusted model findings suggest varenicline reduced smoking among Black and White people with AUD and co-occurring cigarette smoking. However, these findings should be replicated in a larger sample.