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1.
Front Public Health ; 12: 1403729, 2024.
Article in English | MEDLINE | ID: mdl-39354996

ABSTRACT

Objective: Childhood hearing impairment has potential repercussions on the mental well-being of both children and their parents. As a vulnerable population in accessing health care services, they may face specific challenges, especially during the COVID-19 pandemic. This cross-sectional study aims to investigate the association between childhood hearing impairment and the mental health of children and their parents, and to assess health care utilization of hearing-impaired children and its impact on mental outcomes for both during the COVID-19 pandemic. Methods: Using the National Health Interview Survey (NHIS) database, we analyzed data for 15,989 children aged 5-17 and their corresponding parents. The correlations between childhood hearing impairment and mental outcomes were examined using logistic regression models. The 2020 (quarter 3 and quarter 4)-2021 NHIS data was singled out and re-analyzed, focusing on the utilization of medical care during the COVID-19 pandemic. Results: After accounting for covariates, hearing-impaired children exhibited a higher frequency of anxiety (OR 2.33, 95% CI 1.79-3.02) or depression (OR 2.14, 95% CI 1.59-2.88). Parents of hearing-impaired children had significantly higher odds of a higher frequency of anxiety (OR 1.55, 95% CI 1.20-2.01) or depression (OR 1.73, 95% CI 1.30-2.29). Interaction effect of hearing impairment with survey year on parents' mental health outcomes was observed (p for interaction <0.1). Children with hearing loss had higher odds of reporting delayed medical care (OR 2.00, 95% CI 1.11-3.59) or canceled medical care (OR 1.96, 95% CI 0.98-3.96, p = 0.059) due to the pandemic. Delayed medical care (OR 12.41, 95% CI 2.78-55.46) or canceled medical care (OR 6.26, 95% CI 1.28-30.75) due to the COVID-19 pandemic significantly contributed to the increase of anxiety frequency in hearing-impaired children. Conclusion: Childhood hearing impairment exhibits a substantial impact on children's and parental mental health, which is further exacerbated by the COVID-19 pandemic. Families of hearing-impaired children appear to be in a vulnerable position during public health emergencies such as the COVID-19 pandemic, which can further exacerbate their mental outcomes.


Subject(s)
Anxiety , COVID-19 , Hearing Loss , Parents , Humans , COVID-19/epidemiology , COVID-19/psychology , Child , Male , Female , Cross-Sectional Studies , Parents/psychology , Adolescent , Child, Preschool , Hearing Loss/epidemiology , Hearing Loss/psychology , Anxiety/epidemiology , Depression/epidemiology , Pandemics , SARS-CoV-2 , Mental Health/statistics & numerical data , Adult , Patient Acceptance of Health Care/statistics & numerical data , Patient Acceptance of Health Care/psychology
2.
Apoptosis ; 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39404933

ABSTRACT

Pulsed electromagnetic field (PEMF) therapy is a potential non-invasive treatment to modulate immune responses and inhibit tumor growth. Cervical cancer (CC) is influenced by IL-37-mediated immune regulation, making PEMF therapy a potential strategy to impede CC progression. This study aimed to elucidate the effects of PEMF on IL-37 regulation and its molecular mechanisms in CC. CC cell-xenografted mouse models, including IL-37 transgenic (IL-37tg) mice, were used to assess tumor growth through in vivo fluorescence imaging and analyze CC cell apoptosis via flow cytometry. TCGA-CESC transcriptome and clinical data were analyzed to identify key inflammation and immune-related genes. CD8+ T cell models were stimulated with PEMF, and apoptosis, oxidative stress, and inflammatory factor expression were analyzed through RT-qPCR, Western blot, and flow cytometry. PEMF treatment significantly inhibited IL-37 expression (p < 0.05), promoted inflammatory factor release (TNF-α and IL-6), and activated oxidative stress, leading to increased CC cell apoptosis (p < 0.05). IL-37 interaction with SMAD3 impacted the p38/NF-κB signaling pathway, modulating CD8+ T cell activity and cytotoxicity. Co-culture of Hela cells with CD8+ T cells under PEMF treatment showed reduced proliferation (by 40%), migration, and invasion (p < 0.05). In vivo experiments with CC-bearing mice demonstrated that PEMF treatment downregulated IL-37 expression (p < 0.05), enhanced CD8+ T cell function, and inhibited tumor growth (p < 0.05). These molecular mechanisms were validated through RT-qPCR, Western blot, and immunohistochemistry. Thus, PEMF therapy inhibits CC progression by downregulating IL-37 and improving CD8+ T cell function via the SMAD3/p38/NF-κB signaling pathway.

3.
JAMA Oncol ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39298141

ABSTRACT

Importance: Chimeric antigen receptor (CAR) T-cell therapy (CART) has transformed the treatment landscape of hematologic cancer, but has negligible effects for adult solid cancers. In this trial, an autologous CAR T-cell product demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer (mCRC). Objective: To evaluate the safety and efficacy of guanylate cyclase-C (GCC19) CART in participants with metastatic colorectal cancer (mCRC). Design, Setting, and Participants: This single-arm, nonrandomized, phase 1 trial was conducted at the First Hospital of Jilin University from December 3, 2020, to April 13, 2022. Data analysis was conducted from May 2022 to April 2024. Adults with relapsed and refractory mCRC expressing GCC were treated with GCC19CART, a mixture of autologous CAR T cells transduced with lentiviral vectors expressing genes that encode either CD-19 CAR or GCC CAR. Main Outcomes and Measures: Safety and tolerability of CAR T-cell therapy targeting GCC in patients with mCRC without therapeutic options is capable of conferring a reasonable likeliness of clinical benefit. Other outcomes included objective response rate, progression-free survival, overall survival, and immune activation. Results: Of 15 patients 9 (60%) were women, and the median (range) age was 44 (33-61) years. Treatment with GCC19CART was associated with the development of cytokine release syndrome and diarrhea in most patients, all of which were self-limited and manageable. The objective response rate was 40%, with a partial response in 2 of 8 and 4 of 7 patients treated with either 1 × 106 cells/kg or 2 × 106 cells/kg. Median overall survival was 22.8 months (95% CI, 13.4-26.1) at data cutoff; the median progress-free survival was 6.0 months in the high dose level group (95% CI, 3.0 to not available). Conclusions and Relevance: The results of this nonrandomized clinical trial suggest that GCC19CART was safe and tolerable in heavily pretreated patients with mCRC and is the first CAR T-cell therapy known to produce objective clinical activity in refractory cancer. Given the paucity of effective therapeutics developed for colorectal cancer in recent decades, the observation that CD-19 CART target engagement can robustly induce GCC19CART target engagement sufficient to produce objective activity may serve as a foundation to develop effective cellular therapy in mCRC and other solid cancers. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000040645.

4.
Subst Use Misuse ; : 1-9, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39285635

ABSTRACT

BACKGROUND: Fatal drug overdoses have involved both xylazine and fentanyl. Xylazine is a non-opioid substance used in veterinary medicine. This study aimed to model changes in fatal xylazine-involved drug overdose deaths from 2019 to 2023 in Connecticut using overdose death data from the Office of the Chief Medical Examiner. METHODS: Xylazine-involved drug overdose fatality rates were calculated by number of deaths per year per 100,000 population from 2019 to 2023. We used joinpoint regression modeling to evaluate quarterly overdose rates across age, number of drugs, and drug types with a significance level of p < 0.05. RESULTS: From 2019 to 2023, there were 1116 xylazine-involved fatal overdoses with a cumulative rate of 31.3 deaths per 100,000. Xylazine-involved overdose death rates were significantly higher in Hispanic populations compared to both non-Hispanic White and Black populations (p < 0.05). The joinpoint analyses showed that xylazine-fentanyl mortality rates significantly increased by 0.18 per 100,000 per quarter from 2019 to 2022. Xylazine-fentanyl overdoses involving at least 4 or 5 substances significantly increased. Windham, Hartford, New London, and New Haven counties had the highest xylazine-involved death rates. CONCLUSION: Xylazine-fentanyl deaths increased from 2019 to 2023, and often involved multiple substances (e.g., cocaine, ethanol, benzodiazepines, and oxycodone). Results show Hispanic populations, those aged 35-49, and 50+ experienced high rates of xylazine-fentanyl overdose deaths. Vulnerable populations in Connecticut for special consideration for future intervention and local resource allocation are recommended.

5.
Heliyon ; 10(17): e36770, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39290260

ABSTRACT

Background and aim: Accurately predicting microvascular invasion (MVI) before surgery is beneficial for surgical decision-making, and some high-risk hepatocellular carcinoma (HCC) patients may benefit from postoperative adjuvant transarterial chemoembolization (PA-TACE). The purpose of this study was to develop and validate a novel nomogram for predicting MVI and assessing the survival benefits of selectively receiving PA-TACE in HCC patients. Methods: The 1372 HCC patients who underwent hepatectomy at four medical institutions were randomly divided into training and validation datasets according to a 7:3 ratio. We developed and validated a nomogram for predicting MVI using preoperative clinical data and further evaluated the survival benefits of selective PA-TACE in different risk subgroups. Results: The nomogram for predicting MVI integrated alpha-fetoprotein, tumor diameter, tumor number, and tumor margin, with an area under the curve of 0.724, which was greater than that of any single predictive factor. The calibration curve, decision curve, and clinical impact curve demonstrated that the nomogram had strong predictive performance. Risk stratification based on the nomogram revealed that patients in the low-risk group did not achieve better DFS and OS with PA-TACE (all p > 0.05), while patients in the medium-to-high risk groups could benefit from higher DFS (Medium-risk, p = 0.039; High-risk, p = 0.027) and OS (Medium-risk, p = 0.001; High-risk, p = 0.019) with PA-TACE. Conclusions: The nomogram predicting MVI demonstrated strong predictive performance, and its risk stratification aided in identifying different subgroups of HCC patients who may benefit from PA-TACE with improved survival outcomes.

6.
J Phys Chem Lett ; 15(32): 8265-8271, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39106046

ABSTRACT

The properties of liquid-liquid interfaces are intricately linked to its structure, with a particular focus on the concentration distribution within the interface. To obtain precise information regarding the concentration distribution, we have developed a high-resolution soft X-ray imaging method for liquid-liquid interfaces. This work focused on representative partially miscible systems, analyzing the interfacial concentration distribution profiles of water-alkanols under both steady-state and dynamic processes, and obtaining the diffusion coefficients of different water concentrations in alkanols. Significant disparities in concentration distributions and the concentration-related diffusion coefficients were observed despite comparable diffusion distances within the same system across different states. Meanwhile, it was found that alkanols exhibit adsorption phenomena at the interface. This newfound knowledge serves as a crucial stepping stone toward a deeper understanding of partially miscible systems. Our study opens a way to explore liquid-liquid interface information with high-resolution.

7.
Se Pu ; 42(8): 805-811, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39086250

ABSTRACT

Tobacco flavor, an important tobacco additive, is an essential raw material in cigarette production that can effectively improve the quality of tobacco products, add aroma and taste, and increase the suction flavor. The quality consistency of tobacco flavors affects the quality stability of branded cigarettes. Therefore, the quality control of tobacco flavors is a major concern for cigarette and flavor manufacturers. Physical and chemical indices, odor similarity, and sensory efficacy are employed to evaluate the quality of tobacco flavors, and the analysis of chemical components in tobacco flavors is usually conducted using gas chromatography (GC) and high performance liquid chromatography (HPLC). However, because the composition of tobacco flavors is complex, their quality cannot be fully reflected using a single component or combination of components. Therefore, establishing an objective analytical method for the quality control of tobacco flavors is of extreme importance. Chromatographic fingerprint analysis is routinely used for the discriminative analysis of tobacco flavors. Chromatographic fingerprints refer to the general characteristics of the concentration profiles of different chemical compounds. In the daily procurement process, fingerprints established by GC and HPLC are effective for the evaluation and identification of tobacco flavors. However, given continuous improvements in aroma-imitation technology, some flavors with high similarity cannot be directly distinguished using existing methods. In this study, a method for the determination of organic acids and inorganic anions in tobacco flavors based on ion chromatography (IC) was developed to ensure the quality consistency of tobacco flavors. A 1.0 g sample of tobacco flavors and 10 mL of deionized water were mixed and vibrated for 30 min. The aqueous sample solution was passed through a 0.45 µm membrane filter and RP pretreatment column in succession to eliminate interferences and then subjected to IC. Standard solutions containing nine organic acids and seven inorganic anions were used to identify the anions in the tobacco flavors, and satisfactory reproducibility was obtained. The relative standard deviations (RSDs) for retention times and peak areas were <0.71% and <6.02%, respectively. The chromatographic fingerprints of four types of tobacco flavors (samples A-D) from five different batches were obtained. Nine tobacco flavor samples from different manufacturers (samples AY1-AY3, BY1-BY2, CY1-CY2, DY1-DY2) were also analyzed to obtain their chromatographic fingerprints. Hierarchical cluster and similarity analyses were used to evaluate the quality of tobacco flavors from different manufacturers. Hierarchical clustering refers to the process of subdividing a group of samples into clusters that exhibit a high degree of intracluster similarity and intercluster dissimilarity. The dendrograms obtained using SPSS 12.0 indicated good quality consistency among the samples in different batches. Samples AY3, BY2, CY2, and DY1 clustered with the batches of standard tobacco flavors. Therefore, hierarchical cluster analysis can effectively distinguish the quality of products from different manufacturers. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (version 2.0) was used to evaluate the similarity between the standard tobacco flavors and products from different manufacturers. Among the samples analyzed, samples AY3, BY2, CY2, and DY1 showed the highest similarity values (>97.7%), which was consistent with the results of the hierarchical cluster analysis. This finding indicates that IC combined with chromatographic fingerprint analysis could accurately determine the quality of tobacco flavors. GC combined with ultrasonic-assisted liquid-liquid extraction was also used to analyze the tobacco flavors and verify the accuracy of the proposed method. Compared with GC coupled with ultrasonic-assisted liquid-liquid extraction, IC demonstrated more significant quality differences among certain tobacco flavors.


Subject(s)
Nicotiana , Quality Control , Nicotiana/chemistry , Flavoring Agents/analysis , Tobacco Products/analysis , Chromatography, High Pressure Liquid/methods , Chromatography, Gas/methods , Chromatography, Ion Exchange/methods
8.
Chem Commun (Camb) ; 60(61): 7926-7929, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38982972

ABSTRACT

A highly enantioselective allylation/lactonization cascade was developed, which provides a concise and efficient route to chiral γ-butenolides under mild conditions. Most of the reaction examples can be completed in 10 minutes with high selectivity.

9.
Org Lett ; 26(29): 6120-6124, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-38989859

ABSTRACT

A novel Ag-catalyzed ring opening of unsymmetric cyclopropenones for the stereoselective synthesis of a diverse range of α-alkylidene lactones has been developed. In this protocol, two different C-C(O) bonds were distinguished, demonstrating selective C-C bond activation. This reaction features a wide substrate scope, good functional group compatibility, and high atom economy, providing a versatile and general approach to the construction of α-alkylidene lactones.

10.
Front Nutr ; 11: 1364835, 2024.
Article in English | MEDLINE | ID: mdl-39077156

ABSTRACT

Objective: Recent studies have demonstrated that the Dietary Inflammatory Index (DII) is relevant to abnormal gut health. However, there is a lack of studies that have explicitly explored the link between fecal incontinence (FI) and DII. The current study aims to explore the relationship between DII and FI. Methods: The cross-sectional study enrolled a total of 11,747 participants aged 20-85 from NHANES 2005-2010. Weighted logistic regression was conducted to evaluate the relationship between DII and FI, and restricted cubic spline (RCS) was employed to assess the dose-response relationship between DII and FI. Subgroup analyses were performed according to age, gender, race, and BMI. Result: DII levels were found to be significantly higher in patients with FI than in the normal population (p = 0.016). After adjusting for all covariates, DII was found to be significantly correlated with FI (model 2: Q4 vs. Q1, OR = 1.49, 95% CI: 1.04-2.14, p = 0.032, p for trend = 0.039). The dose-response curve revealed that there was no non-linear correlation between DII and FI (p-non-linear = 0.234). Subsequent subgroup analyses uncovered that DII was notably associated with FI in the old (Q4 vs. Q1, OR = 1.84, 95% CI: 1.07-3.18, p = 0.030), female (Q4 vs. Q1: OR = 2.02, 95% CI: 1.23-3.33, p = 0.008), non-Hispanic white (Q4 vs. Q1: OR = 1.70, 95% CI: 1.12-2.59, p = 0.015) populations. Conclusion: DII was positively associated with FI, particularly among old, female and non-Hispanic white individuals. Decreasing daily dietary inflammatory levels may be an effective tactic to prevent FI, but the precise mechanisms need to be further investigated.

11.
Nano Lett ; 24(31): 9675-9682, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39058271

ABSTRACT

Feeding silkworms with functional materials as additives to produce naturally modified silk is a facile, diverse, controllable, and environmentally friendly method with a low cost of time and investment. Among various additives, carbon dots (CDs) show unique advantages due to their excellent biocompatibility and fluorescence stability. Here, a new type of green fluorescent carbon dots (G-CDs) is synthesized with a high oil-water partition ratio of 147, a low isoelectric point of 5.16, an absolute quantum yield of 71%, and critically controlled surface states. After feeding with G-CDs, the silkworms weave light yellow cocoons whose green fluorescence is visible to the naked eye under UV light. The luminous silk is sewn onto the cloth to create striking patterns with beautiful fluorescence. Such G-CDs have no adverse effect on the survival rate and the life cycle of silkworms and enable their whole bodies to glow under UV light. Based on the strong fluorescence, chemical stability, and biological safety, G-CDs are found in the digestive tracts, silk glands, feces, cocoons, and even moth bodies. G-CDs accumulate in the posterior silk glands where fibroin protein is secreted, indicating its stronger combination with fibroin than sericin, which meets the requirements for practical applications.


Subject(s)
Bombyx , Carbon , Quantum Dots , Silk , Animals , Silk/chemistry , Carbon/chemistry , Quantum Dots/chemistry , Fibroins/chemistry , Ultraviolet Rays , Fluorescence , Fluorescent Dyes/chemistry , Surface Properties
12.
Front Biosci (Landmark Ed) ; 29(7): 243, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39082336

ABSTRACT

BACKGROUND: The tumour mutation burden (TMB) is a valuable indicator of the accumulation of somatic mutations, and is thought to be associated with the biological behaviour and prognosis of tumours. However, the related genetic mechanism for these association is still unclear. The aim of the present study was to identify the key gene(s) associated with TMB in hepatocellular carcinoma (HCC) and to investigate its biological functions, downstream transcription factors, and mechanism of action. METHODS: Patients in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database were classified according to TMB signature-related genes. Key genes related to the TMB signature and tumour prognosis were identified. Immunohistochemistry and Quantitative Real-Time Polymerase Chain Reaction (qPCR) were then used to assess gene expression in clinical HCC tissues and HCC cells. Cells with altered gene expression were evaluated for the effect on cell proliferation and apoptosis, both in vitro and in vivo. Three independent databases and cell sequencing data were used to identify the mechanisms involved and the downstream transcription factors. The mechanism was also studied by altering the expression of downstream transcription factors in vitro. RESULT: The integrated cluster (IC) 2 group, characterized by 99 TMB signature-related genes, showed a significant different TMB score compared to the IC1 group (p < 0.001), as well as more favourable tumour prognosis (p = 0.031). We identified five key prognostic genes that were differentially expressed between IC2 and IC1 and were associated with overall survival. The expression of one of these key prognostic genes, RCAN2, was negatively correlated with TMB in 18 out of 33 tumour types examined. A high level of RCAN2 was correlated with better overall survival in HCC (p = 0.0009). Overexpression of RCAN2 enhanced apoptosis in vitro and in vivo, whereas knockdown of RCAN2 attenuated apoptosis. The mechanism by which RCAN2 promotes apoptosis may involve upregulation of the expression of ETS homologous factor (EHF) and of death receptor 5 (DR5). CONCLUSIONS: Downregulation of RCAN2 expression was found to correlate with elevated TMB in multiple cancer types. RCAN2 was also found to be a biomarker of HCC prognosis, and to promote the apoptosis of HCC cells through the EHF/DR5 pathway. These findings provide a new perspective on systemic treatment for advanced HCC with a high TMB.


Subject(s)
Apoptosis , Carcinoma, Hepatocellular , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Muscle Proteins , Receptors, TNF-Related Apoptosis-Inducing Ligand , Transcription Factors , Animals , Female , Humans , Male , Mice , Middle Aged , Apoptosis/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Mice, Nude , Muscle Proteins/genetics , Muscle Proteins/metabolism , Mutation , Prognosis , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Signal Transduction/genetics , Up-Regulation/genetics , Transcription Factors/metabolism
13.
Chem Biol Drug Des ; 104(1): e14589, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39031926

ABSTRACT

Previous studies have indicated that heterocyclic substituted dihydropyrazole derivatives, particularly MW-19, potentially exert anticancer activity in vitro; however, the underlying mechanism remains unknown. The present study was designed to investigate the mechanisms underlying MW-19 activity in triple-negative breast cancer cells. A sulforhodamine B assay was performed to evaluate cell proliferation inhibition rates, and the antitumor effect of MW-19 was evaluated in mice with HCC-1806 xenografts. Apoptosis was analyzed by Hoechst 33342 and annexin V/propidium iodide staining. Expression of pro- and antiapoptotic proteins and mRNA were analyzed by western blotting and reverse transcription-quantitative (RT-q) PCR, respectively. We found that MW-19 significantly inhibited HCC-1806 cell proliferation in a dose- and time-dependent manner, and significantly inhibited MDA-MB-231 cell migration. Importantly, oral administration of MW-19 significantly inhibited HCC-1806 tumor growth in BALB/c-nu/nu mice. Moreover, MW-19 treatment induced marked apoptosis and G2/M arrest in the sensitive cell line, HCC-1806. RT-qPCR analysis showed that levels of proapoptotic genes (Bax, caspase-3, caspase-7, and Fas) were considerably increased in the MW-19 group relative to the control group, while those of antiapoptotic factors (Bcl-2, C-MYC) were dramatically decreased. Consistently, Bax, caspase-3, and caspase-7 were significantly induced after MW-19 treatment, while levels of phosphorylated (p-)AKT, p-PI3K, p-ERK, and the antiapoptotic protein, Bcl-2, were clearly diminished, and the P38 MAPK signaling pathway was activated. Furthermore, P38 pharmacological inhibitors abrogated MW-19-induced apoptosis. Together, our findings indicate that MW-19 exerts antitumor effects by targeting PI3K/AKT and ERK/P38 signaling pathways.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Mice, Inbred BALB C , Pyrazoles , Triple Negative Breast Neoplasms , Apoptosis/drug effects , Humans , Animals , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , Female , Cell Line, Tumor , Pyrazoles/chemistry , Pyrazoles/pharmacology , Pyrazoles/chemical synthesis , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cell Proliferation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Mice, Nude , Cell Movement/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism , Xenograft Model Antitumor Assays , Phosphatidylinositol 3-Kinases/metabolism
14.
Mol Cell Endocrinol ; 592: 112292, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38830447

ABSTRACT

RESEARCH QUESTION: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients? DESIGN: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition. RESULTS: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM. CONCLUSIONS: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients.


Subject(s)
Granulosa Cells , Mitochondria , Polycystic Ovary Syndrome , RNA-Binding Proteins , Humans , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/pathology , Female , Granulosa Cells/metabolism , Granulosa Cells/pathology , Mitochondria/metabolism , Mitochondria/genetics , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Adult , Reactive Oxygen Species/metabolism , Gene Expression Regulation , Adenosine Triphosphate/metabolism , Glycolysis/genetics , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism
15.
Front Pharmacol ; 15: 1332036, 2024.
Article in English | MEDLINE | ID: mdl-38835658

ABSTRACT

We previously revealed that Cang-ai volatile oil (CAVO) regulates T-cell activity, enhancing the immune response in people with chronic respiratory diseases. However, the effects of CAVO on allergic rhinitis (AR) have not been investigated. Herein, we established an ovalbumin (OVA)-induced AR rat model to determine these effects. Sprague-Dawley (SD) rats were exposed to OVA for 3 weeks. CAVO or loratadine (positive control) was given orally once daily for 2 weeks to OVA-exposed rats. Behavior modeling nasal allergies was observed. Nasal mucosa, serum, and spleen samples of AR rats were analyzed. CAVO treatment significantly reduced the number of nose rubs and sneezes, and ameliorated several hallmarks of nasal mucosa tissue remodeling: inflammation, eosinophilic infiltration, goblet cell metaplasia, and mast cell hyperplasia. CAVO administration markedly upregulated expressions of interferon-γ, interleukin (IL)-2, and IL-12, and downregulated expressions of serum tumor necrosis factor-α, IL-4, IL-5, IL-6, IL-13, immunoglobulin-E, and histamine. CAVO therapy also increased production of IFN-γ and T-helper type 1 (Th1)-specific T-box transcription factor (T-bet) of the cluster of differentiation-4+ T-cells in splenic lymphocytes, and protein and mRNA expressions of T-bet in nasal mucosa. In contrast, levels of the Th2 cytokine IL-4 and Th2-specific transcription factor GATA binding protein-3 were suppressed by CAVO. These cumulative findings demonstrate that CAVO therapy can alleviate AR by regulating the balance between Th1 and Th2 cells.

16.
Biomedicines ; 12(5)2024 May 03.
Article in English | MEDLINE | ID: mdl-38790970

ABSTRACT

Preclinical evidence indicates the potential anti-tumor capabilities of cannabinoids in prostate cancer (PC). We undertook a cross-sectional study using National Survey on Drug Use and Health data from 2002 to 2020, involving 2503 participants in the USA. The independent variable was marijuana use status (current, former, never), while the dependent variable was self-reported PC (yes, no). Eleven other demographic variables were assessed as covariates. PC prevalence was lower among current marijuana users (46/145, 31.7%) and former users (323/1021, 31.6%) compared to non-users (534/1337, 39.9%, p < 0.001). PC prevalence was lower among users versus non-users in the elderly (≥65) (36.4% vs. 42.4%, p = 0.016) and non-Hispanic white subgroups (28.9% vs. 38.3%, p < 0.001). There were no significant PC prevalence differences between users and non-users in the younger population (50-64) or other race/ethnicity. In the multivariable analyses, former marijuana use was associated with lower PC compared to never using (odd ratio = 0.74, 95% CI 0.62-0.90, p = 0.001). Current use was also suggestive of reduced prevalence but was not statistically significant (odd ratio = 0.77, 95% CI 0.52-1.14, p = 0.198), possibly due to low sample size. Our findings from a large national survey provide additional data to link marijuana use with lower PC prevalence.

17.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2776-2782, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812178

ABSTRACT

This study explore the molecular mechanism of the synergistic effect of Chinese Yam polysaccharides and nucleoside analogues(NAs) on hepatitis B virus(HBV) resistance. Different concentrations of Chinese Yam polysaccharide and entecavir were ad-ded to HepG2.2.15 cells. After the cytotoxicity was detected by cell counting kit-8(CCK-8), the optimal concentration and time of the two drugs to inhibit HepG2.2.15 cells were screened out. They were divided into control group, Chinese Yam polysaccharide group, entecavir group and combination drug group(Chinese Yam polysaccharide + entecavir). The drugs were added to HepG2.2.15 cells, ELISA was used to detect the effects of each group of drugs on the secretion of hepatitis B virus surface antigen(HBsAg) and hepatitis B virus e antigen(HBeAg) in cell supernatant, probe quantitative real-time PCR(probe qRT-PCR) was used to detect the effects of drugs on HBV-DNA in HepG2.2.15 cells, and Western blot was used to detect the effects of each group of drugs on the expression of p38 MAPK, p-p38 MAPK, NTCP proteins in HepG2.2.15 cells. The qRT-PCR was used to detect the effect of drugs on the expression of p38 MAPK and NTCP mRNA in HepG2.2.15 cells. The results showed that compared with control group, the concentrations of HBeAg and HBsAg in Chinese Yam polysaccharide group, entecavir group and combination group decreased(P<0.01 or P<0.001), and both of them inhibited HBV-DNA in HepG2.2.15 cells(P<0.01), and the HBV-DNA inhibition of HepG2.2.15 cells in the combination group was more obvious(P<0.001), and the protein expression levels of p-p38 MAPK and NTCP were significantly decreased(P<0.05 or P<0.01), the mRNA expression level of p38 MAPK increased, and the mRNA expression level of NTCP decreased(P<0.05 or P<0.01). To sum up, Chinese Yam polysaccharide can reduce the expression of NTCP protein and mRNA through p38 MAPK signaling pathway and cooperate with entecavir in anti-HBV.


Subject(s)
Antiviral Agents , Dioscorea , Hepatitis B virus , Polysaccharides , p38 Mitogen-Activated Protein Kinases , Humans , Hepatitis B virus/drug effects , Hepatitis B virus/genetics , Polysaccharides/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolism , p38 Mitogen-Activated Protein Kinases/genetics , Hep G2 Cells , Antiviral Agents/pharmacology , Dioscorea/chemistry , Drug Synergism , Nucleosides/pharmacology , MAP Kinase Signaling System/drug effects , Hepatitis B Surface Antigens/metabolism , Hepatitis B Surface Antigens/genetics , Hepatitis B e Antigens/metabolism , Hepatitis B/drug therapy , Hepatitis B/virology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Guanine/analogs & derivatives , Guanine/pharmacology
18.
Article in English | MEDLINE | ID: mdl-38662058

ABSTRACT

Impaired basic academic skills (e.g., word recognition) are common in children with Attention Deficit Hyperactivity Disorder (ADHD). The underlying neuropsychological and neural correlates of impaired Chinese reading skills in children with ADHD have not been substantially explored. Three hundred and two children with ADHD (all medication-naïve) and 105 healthy controls underwent the Chinese language skill assessment, and 175 also underwent fMRI scans (84 ADHD and 91 controls). Between-group and mediation analyses were applied to explore the interrelationships of the diagnosis of ADHD, cognitive dysfunction, and impaired reading skills. Five ADHD-related brain functional networks, including the default mode network (DMN) and the dorsal attention network (DAN), were built using predefined regions of interest. Voxel-based group-wise comparisons were performed. The ADHD group performed worse than the control group in word-level reading ability tests, with lower scores in Chinese character recognition (CR) and word chains (WS) (all P < 0.05). With full-scale IQ and sustained attention in the mediation model, the direct effect of ADHD status on the CR score became insignificant (P = 0.066). The underlying neural correlates for the orthographic knowledge (OT) and CR differed between the ADHD and the control group. The ADHD group tended to recruit more DMN regions to maintain their reading performance, while the control group seemed to utilize more DAN regions. Children with ADHD generally presented impaired word-level reading skills, which might be caused by impaired sustained attention and lower IQ. According to the brain functional results, we infer that ADHD children might utilize a different strategy to maintain their orthographic knowledge and character recognition performance.

19.
Org Lett ; 26(17): 3530-3535, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38656165

ABSTRACT

State-of-the-art strategies for alkene-hydroxyazidation, which yield a mixture of ß-azido alcohol and ß-azido peroxide, must rely on phosphine reagents to improve the chemoselectivity. To overcome the above problems, we present a photochemical hydroxyazidation of alkenes via Mn-mediated ligand-to-metal charge transfer (LMCT) in O2, which activates N3- to •N3 and incorporates O2 to be used as an oxygen source in the hydroxyazidation products. Broad alkene range and step-economy chemistry for the hydroxyazidation transformation were also demonstrated.

20.
World J Clin Cases ; 12(12): 2122-2127, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38680266

ABSTRACT

BACKGROUND: Crossed renal ectopia (CRE) occurs when one kidney crosses the midline from the primary side to the contralateral side while the ureter remains on the primary side. Rectal cancer, one of the most common malignant tumors of the digestive tract, refers to cancer from the dentate line to the rectosigmoid junction. The concurrent presentation of CRE alongside rectal cancer is an uncommon clinical observation. CASE SUMMARY: Herein, we report a 69-year-old male patient with rectal cancer who was diagnosed with CRE via computed tomography during hospitalization. Following thorough preoperative evaluations, the patient underwent Dixon surgery. CONCLUSION: We performed laparoscopic radical resection of rectal cancer and adequate lymph node removal in a patient with CRE with no postoperative discomfort.

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