Depression and the risk of non-alcohol fatty liver disease: Results from a cross-sectional study and a Mendelian randomization analysis.

BACKGROUND: Previous studies have suggested that psychiatric factors may be pathogenic for NAFLD. However, the association between depression and NAFLD is not been consistent, and whether depression plays a causal role in the development of NAFLD remains unclear. METHODS: We extracted data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 to assess the correlation between depression and NAFLD risk. Based on previous genome-wide association studies (GWAS) meta-analyses on NAFLD and depression, we performed a Mendelian randomization (MR) analysis to explore the causal effect of depression on NAFLD. The primary analysis method used in the MR analysis was inverse variance weighted. RESULTS: We ultimately extracted the data from 3878 individuals in the NHANES database to perform the cross-sectional study. Multivariable-adjusted logistic regression showed that depressed individuals had a higher risk of NAFLD than controls (odds ratio [OR] 1.33, 95 % CI 1.03-1.72, p = 0.027) among women. Based on GWAS data, we included 36 genetic variants as instrumental variables to estimate the causal effect of depression on NAFLD risk. The MR analysis revealed a causal association between genetically predicted depression and an increased risk of NAFLD (OR = 1.504, 95 % CI 1.13-2.00, p = 0.005). LIMITATIONS: The consistency of these findings in Eastern populations requires further longitudinal studies. CONCLUSIONS: This cross-sectional study suggested that depression might increase the risk of NAFLD in women. The MR analysis demonstrated that there exists a causal association between genetically predicated depression and NAFLD risk.

Unveiling the Impact of BMP9 in Liver Diseases: Insights into Pathogenesis and Therapeutic Potential.

Bone morphogenetic proteins (BMPs) are a group of growth factors belonging to the transforming growth factor ß(TGF-ß) family. While initially recognized for their role in bone formation, BMPs have emerged as significant players in liver diseases. Among BMPs with various physiological activities, this comprehensive review aims to delve into the involvement of BMP9 specifically in liver diseases and provide insights into the complex BMP signaling pathway. Through an enhanced understanding of BMP9, we anticipate the discovery of new therapeutic options and potential strategies for managing liver diseases.

Prevalence of overweight and obesity, dietary behaviors, and physical activities among sixth graders: a cross-sectional study in Ho Chi Minh City, Vietnam.

The prevalence of overweight and obesity among adolescents has been increasing worldwide and is a significant public health challenge. Obesity is linked to several non-communicable diseases. This study aimed to determine the prevalence of overweight and obesity based on three growth references and described physical activities and dietary patterns among sixth graders in Ho Chi Minh City (HCMC). From 2018 to 2020, a cross-sectional study was conducted on 1375 students from 16 junior high schools in HCMC. We applied Probability Proportional to Size sampling to select schools. Anthropometric measurements, pubertal status assessment, and diet and physical activity data were collected through Food Frequency and Physical Activity Questionnaires. The study revealed a high prevalence of overweight and obesity among grade 6 students, with ∼45%-56% of students classified as overweight or obese using various growth references. Moreover, most students did not meet the World Health Organization's physical activity and sedentary behavior recommendations. Most students spent <60 min/day on moderate to vigorous physical activity, and over 70% spent at least 120 min/day on sedentary activities during weekdays and weekends. The diet of the students was also imbalanced, with high intakes of protein, lipids, and carbohydrates and low consumption of fruits and vegetables. Nutritionists and policymakers should inform and encourage opportunities for healthier food and more daily activity for children, starting before the sixth-grade, so they can learn how to make healthier choices and change their behavior before they reach adolescence.

The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy.

The global burden of hepatitis B virus (HBV) infection remains high, with chronic hepatitis B (CHB) patients facing a significantly increased risk of developing cirrhosis and hepatocellular carcinoma (HCC). The ultimate objective of antiviral therapy is to achieve a sterilizing cure for HBV. This necessitates the elimination of intrahepatic covalently closed circular DNA (cccDNA) and the complete eradication of integrated HBV DNA. This review aims to summarize the oncogenetic role of HBV integration and the significance of clearing HBV integration in sterilizing cure. It specifically focuses on the molecular mechanisms through which HBV integration leads to HCC, including modulation of the expression of proto-oncogenes and tumor suppressor genes, induction of chromosomal instability, and expression of truncated mutant HBV proteins. The review also highlights the impact of antiviral therapy in reducing HBV integration and preventing HBV-related HCC. Additionally, the review offers insights into future objectives for the treatment of CHB. Current strategies for HBV DNA integration inhibition and elimination include mainly antiviral therapies, RNA interference and gene editing technologies. Overall, HBV integration deserves further investigation and can potentially serve as a biomarker for CHB and HBV-related HCC.

Association between Ureaplasma urealyticum colonization and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis.

Background: Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease in preterm infants. Studies have shown that Ureaplasma urealyticum (UU) infection is linked to its pathogenesis. However, it remains controversial whether UU colonization in preterm infants increases the risk of developing BPD. Objective: This study aimed to conduct a systematic review and meta-analysis to summarize the correlation between UU and BPD. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, Wanfang Database, Chinese National Knowledge Infrastructure Database, Chinese Science and Technique Journal Database, and the China Biology Medicine disc from their inception to March 15, 2024. We included cohort and case-control studies investigating the association between UU infections and BPD in preterm infants, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle-Ottawa Scale was used for quality assessment. The outcome was defined as the continued need for oxygen or respiratory support at 28 days after birth (BPD28) or at 36 weeks postmenstrual age (BPD36). Considering the potential publication bias in observational studies, we used a random-effects meta-analysis model, assessed heterogeneity (I2), performed subgroup analyses, evaluated publication bias, and graded the quality of evidence. Results: The meta-analysis included 36 cohort studies encompassing 5,991 participants. Among these, 20 reported on BPD28, 13 on BPD36, and 3 on both. The results indicated a significant association between UU colonization and BPD28 (odds ratio (OR): 2.26, 95% confidence interval (CI): 1.78-2.85, P < 0.00001, 23 studies, very low certainty of evidence) and BPD36 (OR: 2.13, 95% CI: 1.47-3.07, P < 0.0001, 16 studies, very low certainty of evidence). Conclusion: There is a correlation between UU colonization and the development of BPD in preterm infants. Future research should prioritize well-designed, large-scale, high-quality randomized controlled trials (RCTs) to comprehensively assess the risk of BPD in neonates following UU infection and to provide stronger evidence for clinical screening and prevention strategies to improve the prognosis of affected newborns. Systematic Review Registration: https://www.crd.york.ac.uk/, identifier (CRD42024524846).

Disseminated Mycobacterium tilburgii infection in a person with AIDS: A case report.

Background: Mycobacterium tilburgii is a nonculturable, nontuberculous mycobacterium that occasionally causes serious infections in individuals with immune deficiencies. Owing to its nonculturable nature, its antimicrobial susceptibility has not been assessed, and the optimal treatment regimen is unclear. Herein, we report a case of disseminated M. tilburgii infection in a person with AIDS, identified using metagenomics next-generation sequencing (mNGS) and polymerase chain reaction (PCR). Case presentation: A 33-year-old man presented with a 3-month history of abdominal pain, lymphadenopathy, intermittent night hot flashes, night sweats, and weight loss. No pathogen was detected during initial routine investigations. M. tilburgii was subsequently identified in a left cervical lymph node sample using mNGS. Furthermore, M. tilburgii infection was detected in a bone marrow sample based on PCR of 16S rRNA and hsp65 gene sequencing. The person was treated with a combination of moxifloxacin, clarithromycin, ethambutol, rifabutin, and amikacin. The laboratory results improved, and the patient's symptoms resolved. Conclusion: M. tilburgii may be missed in diagnostic tests because it cannot be grown using routine culture techniques. Early diagnosis and timely and effective treatment are critical in patients with M. tilburgii infection; therefore, molecular techniques are recommended for patients with suspected M. tilburgii infection.

Beat-by-Beat Estimation of Hemodynamic Parameters in Left Ventricle Based on Phonocardiogram and Photoplethysmography Signals Using a Deep Learning Model: Preliminary Study.

Beat-by-beat monitoring of hemodynamic parameters in the left ventricle contributes to the early diagnosis and treatment of heart failure, valvular heart disease, and other cardiovascular diseases. Current accurate measurement methods for ventricular hemodynamic parameters are inconvenient for monitoring hemodynamic indexes in daily life. The objective of this study is to propose a method for estimating intraventricular hemodynamic parameters in a beat-to-beat style based on non-invasive PCG (phonocardiogram) and PPG (photoplethysmography) signals. Three beagle dogs were used as subjects. PCG, PPG, electrocardiogram (ECG), and invasive blood pressure signals in the left ventricle were synchronously collected while epinephrine medicine was injected into the veins to produce hemodynamic variations. Various doses of epinephrine were used to produce hemodynamic variations. A total of 40 records (over 12,000 cardiac cycles) were obtained. A deep neural network was built to simultaneously estimate four hemodynamic parameters of one cardiac cycle by inputting the PCGs and PPGs of the cardiac cycle. The outputs of the network were four hemodynamic parameters: left ventricular systolic blood pressure (SBP), left ventricular diastolic blood pressure (DBP), maximum rate of left ventricular pressure rise (MRR), and maximum rate of left ventricular pressure decline (MRD). The model built in this study consisted of a residual convolutional module and a bidirectional recurrent neural network module which learnt the local features and context relations, respectively. The training mode of the network followed a regression model, and the loss function was set as mean square error. When the network was trained and tested on one subject using a five-fold validation scheme, the performances were very good. The average correlation coefficients (CCs) between the estimated values and measured values were generally greater than 0.90 for SBP, DBP, MRR, and MRD. However, when the network was trained with one subject's data and tested with another subject's data, the performance degraded somewhat. The average CCs reduced from over 0.9 to 0.7 for SBP, DBP, and MRD; however, MRR had higher consistency, with the average CC reducing from over 0.9 to about 0.85 only. The generalizability across subjects could be improved if individual differences were considered. The performance indicates the possibility that hemodynamic parameters could be estimated by PCG and PPG signals collected on the body surface. With the rapid development of wearable devices, it has up-and-coming applications for self-monitoring in home healthcare environments.

TFEB alleviates periodontitis by activating autophagy and inhibiting inflammation.

Periodontitis is a chronic inflammatory oral disease that impaired the tooth-supporting apparatus, including gingival tissue destruction and alveolar bone resorption. The initiation of periodontitis is linked to the presence of oral bacteria, particularly P. gingivalis within pathogenic biofilms. Here, we demonstrated the central role of the autophagy regulator Transcription Factor EB (TFEB) in orchestrating autophagy activation and modulating the host immune response against P. gingivalis in periodontitis. Upregulation of TFEB expression at the protein level and heightened nuclear localization occurred during the progressive stages of periodontitis. Functionally, TFEB overexpression emerges as a potent alleviator of periodontitis-associated phenotypes, operating through the activation of autophagy and the inhibition of the NF-κB pathway in both in vivo and in vitro models. In addition, TFEB knockdown exacerbates the inflammatory response by upregulating pro-inflammatory cytokines. The dual regulatory role of TFEB in governing both autophagy and inflammatory responses unveils novel insights into periodontitis pathogenesis, positioning TFEB as a promising therapeutic target for periodontitis intervention.

Invasive Pulmonary Aspergillosis in Patients with HBV-Related Acute on Chronic Liver Failure.

BACKGROUND: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). METHODS: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. RESULTS: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. CONCLUSIONS: The WBC count might be used to monitor patients' progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels.

Development of a Novel System Consisting of a Reductase-Like Nanozyme and the Reaction of Resazurin and Ammonia Borane for Sensitive Fluorometric Sensing.

We report a novel system consisting of a redox reaction and a highly efficient reductase-like nanozyme, silica-palladium nanoparticles (Pd@SiO2 NPs), as a novel detection platform for fluorometric sensing. In a proof-of-concept demonstration using an oligonucleotide as the detection target, a glass fiber-based sensor is fabricated by covalently conjugating two oligo probes, which are complementary to the adjacent segments of the target oligonucleotide, on Pd@SiO2 NPs and glass fiber, respectively. In the presence of the target oligonucleotide, the two probes are drawn together by the target through sequence-specific hybridization, bringing the Pd@SiO2 NPs to the glass fiber. When the glass fiber is subsequently immersed in a mixture of resazurin and ammonia borane solution, the Pd@SiO2 NPs on the glass fiber trigger the catalytic conversion of resazurin (blue, slightly fluorescent) to resorufin (pink, highly fluorescent) with massive signal amplification, indirectly signaling the presence of the target oligonucleotide. We show that the glass fiber-based fluorometric sensor can detect a target oligonucleotide associated with the BRAF mutation linearly in the concentration range of 20 to 400 pM with a detection limit (LOD) of 15 pM and the specificity to differentiate targets with single-base difference. These results demonstrate a new frontier for the development of a sensitive, specific, and inexpensive nonenzyme-based fluorometric sensing platform as an alternative to conventional enzyme-based assays.

Production of Martian fiber by in-situ resource utilization strategy.

Many countries and commercial organizations have shown great interest in constructing a Martian base. In situ resource utilization (ISRU) provides a cost-effective way to achieve this ambitious goal. In this article, we proposed to use Martian soil simulant to produce a fiber to satisfy material requirement for the construction of Martian base. The composition, melting behavior, and fiber forming process of the soil simulant was studied, and continuous fiber with maximum strength of 1320 MPa and elastic modulus of 99 GPa was obtained on a spinning facility. The findings of this study demonstrate the feasibility of ISRU to prepare Martian fiber from the soil on the Mars, offering a new way to obtain key materials for the construction of a Martian base.

N-doped lignin-based activated carbon aerogel derived from bamboo black pulp liquor for efficient removal of malachite green in wastewater.

In this study, a lignin-based aerogel (LA) was prepared through acid precipitation of BPBL, followed by sol-gel method and freeze-drying. Additionally, a one-step activation-carbonization method was used to acquire nitrogen-doped lignin-based activated carbon aerogel (NLACA). The adsorption and catalytic degradation performance for malachite green (MG) were examined. The specific surface area of NLACA after N-doping was 2644.5 m2/g. The adsorption capacity for MG was increased to 3433 mg/g with the presence of nitrogenous functional groups on surface of NLACA compared without N-doping. Meanwhile, non-radical singlet oxygen is the primary active substance and degradation efficiency arrives at 91.8% after the catalytic degradation within 20 min and it has good stability and reuse. Three possible degradation pathways during degradation were analyzed by LC-MS technique. The adsorption isotherm and kinetic data demonstrated conformity with both the Langmuir model and the pseudo-second-order kinetic model. The primary mechanisms of the adsorption for MG dyes on NLACA include hydrogen bonding, π-π interactions, attraction of electrostatic and pore filling. Hence, NLACA derived from BPBL acts as a cost-effective and high-performance adsorbent and catalyst for removal of MG in dye wastewater. This concept introduces an innovative approach of "treatment of waste with waste" for developing a low-consumption, high-efficiency dye wastewater treatment and provides significant reference to treatment dye wastewater.

Helicobacter pylori Outer Membrane Vesicles: Biogenesis, Composition, and Biological Functions.

Helicobacter pylori has been recognized not only as a causative agent of a spectrum of gastroduodenal diseases including chronic gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer, but also as the culprit in several extra-gastric diseases. However, the association of H. pylori infection with extra-gastric diseases remains elusive, prompting a reevaluation of the role of H. pylori-derived outer membrane vesicles (OMVs). Like other gram-negative bacteria, H. pylori constitutively sheds biologically active OMVs for long-distance delivery of bacterial virulence factors in a concentrated and protected form, averting the need of direct bacterial contact with distant host cells to induce extra-gastric diseases associated with this gastric pathogen. Additionally, H. pylori-derived OMVs contribute to bacterial survival and chronic gastric pathogenesis. Moreover, the immunogenic activity, non-replicable nature, and anti-bacterial adhesion effect of H. pylori OMVs make them a desirable vaccine candidate against infection. The immunogenic potency and safety concerns of the OMV contents are challenges in the development of H. pylori OMV-based vaccines. In this review, we discuss recent advances regarding H. pylori OMVs, focusing on new insights into their biogenesis mechanisms and biological functions.

Carvacrol ameliorates skin allograft rejection through modulating macrophage polarization by activating the Wnt signalling pathway.

Post-transplantation immune rejection remains an important factor for transplant patients. However, conventional immunosuppressants are associated with substantial adverse effects. Natural immunosuppressants present a promising alternative to conventional counterparts, boasting exceptional biological activity, minimal toxicity and reduced side effects. We identified carvacrol as a prospective immunosuppressive agent following T cell proliferation experiment and validated carvacrol's immunosuppressive efficacy in the murine allogeneic skin graft model. T cell proliferation assay was used to screen natural small molecule compounds and the immunosuppressive effect of compounds was evaluated in MHC-mismatched murine allogeneic skin graft model. H&E and immunohistochemical staining were applied to evaluate the pathological grade. Furthermore, flow cytometry was uitlized to analyse the immunophenotype changes of immune cells. Western blotting and q-PCR were used to detect the expression of key molecules in macrophages. In vitro, carvacrol demonstrates significant inhibition of the proliferation of CD4+ T and CD8+ T cells. It notably reduces inflammatory factor expression within the allografts, suppresses T cell differentiation toward Th1 phenotype and expansion. Furthermore, carvacrol prominently hinders M1-type macrophages polarization by activating Wnt signaling. Notably, the anti-rejection efficacy of carvacrol was significantly weakened upon the removal of macrophages in mice using chlorophosphate liposomes. Carvacrol could significantly inhibit T cell proliferation, alleviate graft rejection and has outstanding toxicological safety. The molecular mechanism of the anti-rejection effect of carvacrol is closely related to its mediating activation of macrophage Wnt pathway, inhibiting M1 polarization and inducing T cell differentiation.

B. glomerulata promotes neuroprotection against ischemic stroke by inhibiting apoptosis through the activation of PI3K/AKT/mTOR pathway.

BACKGROUND: Brassaiopsis glomerulata (Blum) Regel (B.glomerulata) is recognized as a traditional Chinese medicine (TCM) primarily used for promoting blood circulation and removing stasis. It is frequently utilized in the treatment of injuries resulting from falls and bumps. PURPOSE: Despite its effective use in clinical treatment for ischemic stroke (IS), there are currently no reports on its composition and mechanism of action, which affects its promotion. The study investigated the chemical components and molecular mechanisms of B.glomerulata, with the following components: UPLC-Q-TOF-MS, network pharmacology Analysis and experimental verification in vivo and vitro. METHODS: The effect of B.glomerulata on interfering with ischemic stroke was assessed on MCAO/R rats and ORD cell model. Then the compositional analysis was conducted using UPLC-Q-TOF-MS. Furthermore, network pharmacology and molecular docking techniques were explored to identify potential targets and pathways. The predicted mechanisms of action were ultimately confirmed by immunohistochemistry and protein blotting. RESULTS: B. glomerulata exhibited neuroprotective effects in MCAO/R rats by reductions in hippocampal and cortical neuronal damage, brain infarction, and cerebral edema. Both in vivo and in vitro experiments demonstrated that it decreased ROS and MDA levels, increased SOD and GSH levels, thereby inhibiting oxidative stress. Moreover, the improvements in neuronal morphology and the modulation of Nissl bodies suggested a potential mechanism underlying its neuroprotective action. Additionally, B.glomerulata exhibited concentration-dependent reductions in Bax and Caspase-3 expressions, along with increases in GFAP, Bcl2/Bax ratio, p-PI3K, p-AKT, and p-mTOR levels. CONCLUSION: B.glomerulata exhibited neuroprotective effects against cerebral ischemia-reperfusion injury both in vivo and in vitro. It prevented oxidative stress damage and inhibited apoptosis of ischemic stroke through the PI3K/AKT/mTOR pathway.

Three Ru(II) complexes modulate the antioxidant transcription factor Nrf2 to overcome cisplatin resistance.

Here, we designed, synthesized and characterized three new cyclometalated Ru(II) complexes, [Ru(phen)2(1-(4-Ph-Ph)-IQ)]+ (phen = 1,10-phenanthroline, IQ = isoquinoline, RuIQ9), [Ru(phen)2(1-(4-Ph-Ph)-7-OCH3-IQ)]+ (RuIQ10), and [Ru(phen)2(1-(4-Ph-Ph)-6,7-(OCH3)2-IQ)]+ (RuIQ11). The cytotoxicity experiments conducted on both 2D and 3D multicellular tumor spheroids (MCTSs) indicated that complexes RuIQ9-11 exhibited notably higher cytotoxicity against A549 and A549/DDP cells when compared to the ligands and precursor compounds as well as clinical cisplatin. Moreover, the Ru(II) complexes displayed low toxicity when tested on normal HBE cells in vitro and exposed to zebrafish embryos in vivo. In addition, complexes RuIQ9-11 could inhibit A549 and A549/DDP cell migration and proliferation by causing cell cycle arrest, mitochondrial dysfunction, and elevating ROS levels to induce apoptosis in these cells. Mechanistic studies revealed that RuIQ9-11 could suppress the expression of Nrf2 and its downstream antioxidant protein HO-1 by inhibiting Nrf2 gene transcription in drug-resistant A549/DDP cells. Simultaneously, they inhibited the expression of efflux proteins MRP1 and p-gp in drug-resistant cells, ensuring the accumulation of the complexes within the cells. This led to an increase in intracellular ROS levels in drug-resistant cells, ultimately causing damage and cell death, thus overcoming cisplatin resistance. More importantly, RuIQ11 could effectively inhibit the migration and proliferation of drug-resistant cells within zebrafish, addressing the issue of cisplatin resistance. Accordingly, the prepared Ru(II) complexes possess significant potential for development as highly effective and low-toxicity lung cancer therapeutic agents to overcome cisplatin resistance.

PER2 binding to PDK1 enhances the cisplatin sensitivity of oral squamous cell carcinoma through inhibition of the AKT/mTOR pathway.

Cisplatin (CDDP) is a cornerstone chemotherapeutic agent used to treat oral squamous cell carcinoma (OSCC) and many solid cancers. However, the mechanisms underlying tumor resistance to CDDP obscure the enhancement of its therapeutic efficacy. In this study, we unveil diminished expression of the biological clock gene PER2 in OSCC, negatively correlated with the expression of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1). The overexpression of PER2 suppressed MDR1 and MRP1 expression and increased intracellular CDDP levels and DNA damage, thereby bolstering OSCC cell sensitivity to CDDP. In vivo tumorigenic assays corroborated that PER2 overexpression notably increased OSCC sensitivity to CDDP, augmenting the suppression of OSCC tumorigenesis. Co-immunoprecipitation, GST pull-down, and cycloheximide tracking assays revealed that PER2, via its C-terminal domain, bound to and diminishes PDK1 stability. The degradation of PDK1 was further dependent on the suppression of the AKT/mTOR pathway to enhance the sensitivity of OSCC cells to CDDP. Our study supports PER2 as a target for improving CDDP sensitivity in OSCC, and the combination of PER2 and CDDP is a novel strategy with potential clinical therapeutic value.

RNA Adduction Resulting from the Metabolic Activation of Myristicin by P450 Enzymes and Sulfotransferases.

Myristicin (MYR) mainly occurs in nutmeg and belongs to alkoxy-substituted allylbenzenes, a class of potentially toxic natural chemicals. RNA interaction with MYR metabolites in vitro and in vivo has been investigated in order to gain a better understanding of MYR toxicities. We detected two guanosine adducts (GA1 and GA2), two adenosine adducts (AA1 and AA2), and two cytosine adducts (CA1 and CA2) by LC-MS/MS analysis of total RNA extracts from cultured primary mouse hepatocytes and liver tissues of mice after exposure to MYR. An order of nucleoside adductions was found to be GAs > AAs > CAs, and the result of density functional theory calculations was in agreement with that detected by the LC-MS/MS-based approach. In vitro and in vivo studies have shown that MYR was oxidized by cytochrome P450 enzymes to 1'-hydroxyl and 3'-hydroxyl metabolites, which were then sulfated by sulfotransferases (SULTs) to form sulfate esters. The resulting sulfates would react with the nucleosides by SN1 and/or SN2 reactions, resulting in RNA adduction. The modification may alter the biochemical properties of RNA and disrupt RNA functions, perhaps partially contributing to the toxicities of MYR.

Resveratrol Inhibits Nasopharyngeal Carcinoma (NPC) by Targeting the MAPK Signaling Pathway.

BACKGROUND: With conventional cancer treatments facing limitations, interest in plant-derived natural products as potential alternatives is increasing. Although resveratrol has demonstrated antitumor effects in various cancers, its impact and mechanism on nasopharyngeal carcinoma remain unclear. OBJECTIVE: This study aimed to systematically investigate the anti-cancer effects of resveratrol on nasopharyngeal carcinoma using a combination of experimental pharmacology, network pharmacology, and molecular docking approaches. METHODS: CCK-8, scratch wound, and transwell assays were employed to confirm the inhibitory effect of resveratrol on the proliferation, migration, and invasion of nasopharyngeal carcinoma cells. H&E and TUNEL stainings were used to observe the morphological changes and apoptosis status of resveratrol-treated cells. The underlying mechanisms were elucidated using a network pharmacology approach. Immunohistochemistry and Western blotting were utilized to validate key signaling pathways. RESULTS: Resveratrol inhibited the proliferation, invasion, and migration of nasopharyngeal carcinoma cells, ultimately inducing apoptosis in a time- and dose-dependent manner. Network pharmacology analysis revealed that resveratrol may exert its anti-nasopharyngeal carcinoma effect mainly through the MAPK pathway. Immunohistochemistry results from clinical cases showed MAPK signaling activation in nasopharyngeal carcinoma tissues compared to adjacent tissues. Western blotting validated the targeting effect of resveratrol, demonstrating significant inhibition of the MAPK signaling pathway. Furthermore, molecular docking supported its multi-target role with MAPK, TP53, PIK3CA, SRC, etc. Conclusion: Resveratrol has shown promising potential in inhibiting human nasopharyngeal carcinoma cells by primarily targeting the MAPK pathway. These findings position resveratrol as a potential therapeutic agent for nasopharyngeal carcinoma.