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1.
Phytomedicine ; 134: 155973, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39241384

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease marked by chronic tissue inflammation that alters the integrity and function of the gut, seriously impacting patient health and quality of life. Aucklandiae Radix (AR), known as Mu Xiang in Chinese, is a traditional Chinese medicine documented in Chinese Pharmacopoeia with effects of strengthening the intestine and stopping diarrhea. However, the potential of AR in treating intestinal inflammation and its underlying mechanism have yet to be further elucidated. PURPOSE: The objective of this study was to explore the protective effect and the potential mechanism attributable to AR for treating ulcerative colitis (UC). STUDY DESIGN AND METHODS: A murine model of UC was constructed using dextran sulfate sodium (DSS) to examine the therapeutic potential of AR in alleviating inflammation and modulating the immune response. Advanced techniques such as photocrosslinking target fishing technique, click chemistry, Western blot analysis, real-time quantitative PCR, flow cytometry, immunofluorescence, and immunohistochemistry were employed to unveil the therapeutic mechanism of AR for treating IBD. RESULTS: AR decreased disease activity index (DAI) score to alleviate the course of IBD through ameliorating intestinal barrier function in DSS-induced mice. Furthermore, AR suppressed NF-κB and NLRP3 pathways to reduce the release of pro-inflammatory factors interleukin-6 and 1ß (IL-6 and IL-1ß) and tumor necrosis factor α (TNF-α), allowing to alleviate the inflammatory response. Flow cytometry revealed that AR could reduce the accumulation of intestinal macrophages and neutrophils, maintaining intestinal immune balance by regulating the ratio of Treg to Th17 cells. It was worth noting that pyruvate kinase isozyme type M2 (PKM2) served as a potential target of AR using the photocrosslinking target fishing technology, which was further supported by cellular thermal shift assay (CETSA), drug affinity target stability (DARTS), and PKM2 knockdown experiments. CONCLUSION: AR targeted PKM2 to inhibit NF-κB and NLRP3 pathways, thereby modulating the inflammatory response and immunity to alleviate DSS-induced UC. These findings suggested the potential of AR in the treatment of UC and AR as a candidate for developing PKM2 regulators.


Subject(s)
Colitis, Ulcerative , Dextran Sulfate , Disease Models, Animal , Drugs, Chinese Herbal , Pyruvate Kinase , Animals , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Mice , Pyruvate Kinase/metabolism , Drugs, Chinese Herbal/pharmacology , Mice, Inbred C57BL , Male , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Carrier Proteins/metabolism , Membrane Proteins/metabolism
2.
World J Clin Cases ; 12(26): 5868-5876, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39286371

ABSTRACT

BACKGROUND: Orthodontic treatment can easily cause local soft tissue reactions in the oral cavity of patients under mechanical stress, leading to oral mucosal ulcers and affecting their quality of life. At present, only limited literature has explored the factors leading to oral ulcers in orthodontic treatment, and these research results are still controversial. AIM: To investigate the current status and related factors of oral mucosal ulcers during orthodontic treatment, aiming to provide a valuable reference for preventing this disease in clinical practice. METHODS: A total of 587 patients who underwent orthodontic treatment at the Peking University School of Stomatology and Hospital of Stomatology between 2020 and 2022 were selected and allocated to an observation or control group according to the incidence of oral mucosal ulcers during orthodontic therapy. A questionnaire survey was constructed to collect patient data, including basic information, lifestyle and eating habits, treatment details, mental factors, and trace element levels, and a comparative analysis of this data was performed between the two groups. RESULTS: A logistic regression model with oral ulcers as the dependent variable was established. The regression results showed that age (≥ 60 years: odds ratio [OR]: 6.820; 95% confidence interval [CI]: 2.226-20.893), smoking history (smoking: OR: 4.434; 95%CI: 2.527-7.782), toothbrush hardness (hard: OR: 2.804; 95%CI: 1.746-4.505), dietary temperature (hot diet: OR: 1.399; 95%CI: 1.220-1.722), treatment course (> 1 year: OR: 3.830; 95%CI: 2.203-6.659), and tooth brushing frequency (> 1 time per day: OR: 0.228; 95%CI: 0.138-0.377) were independent factors for oral mucosal ulcers (P < 0.05). Furthermore, Zn level (OR: 0.945; 95%CI: 0.927-0.964) was a protective factor against oral ulcers, while the SAS (OR: 1.284; 95%CI: 1.197-1.378) and SDS (OR: 1.322; 95%CI: 1.231-1.419) scores were risk factors. CONCLUSION: Age ≥ 60 years, smoking history, hard toothbrush, hot diet, treatment course for > 1 year, tooth brushing frequency of ≤ 1 time per day, and mental anxiety are independent risk factors for oral mucosal ulcers. Therefore, these factors should receive clinical attention and be incorporated into the development and optimization of preventive strategies for reducing oral ulcer incidence.

3.
Eur Radiol ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261335

ABSTRACT

OBJECTIVES: The Baveno VII consensus recommends endoscopic screening for varicose veins in cases of liver stiffness measurement (LSM) ≥ 20 kPa or platelet count ≤ 150 × 109/L. Whether this approach was appropriate for patients with primary biliary cholangitis (PBC) remains uncertain. This study expanded the observed risk factors by adding analysis of ultrasound images as a non-invasive tool to predict the risk of esophageal or fundic varices. METHODS: We enrolled 111 patients with PBC whose complete ultrasound images, measurement data, and LSM data were available. The value of the periportal hypoechoic band (PHB), splenic area, and LSM in determining the risk of varicose veins and variceal rupture was analyzed. A prospective cohort of 67 patients provided external validation. RESULTS: The area under the receiver operating characteristic curve (AUC) for predicting varicose veins using LSM > 12.1 kPa or splenic areas > 41.2 cm2 was 0.806 (95% confidence interval (CI): 0.720-0.875) and 0.852 (95% CI: 0.772-0.912), respectively. This finding could assist in avoiding endoscopic screening by 76.6% and 83.8%, respectively, with diagnostic accuracy surpassing that suggested by Baveno VII guidelines. The AUCs for predicting variceal rupture using splenic areas > 56.8 cm2 was 0.717 (95% CI: 0.623-0.798). The diagnostic accuracy of PHB for variceal rupture was higher than LSM and splenic areas (75.7% vs. 50.5% vs. 68.5%). CONCLUSION: We recommend LSM > 12.1 kPa as a cutoff value to predict the risk of varicosity presence in patients with PBC. Additionally, the splenic area demonstrated high accuracy and relevance for predicting varicose veins and variceal rupture, respectively. The method is simple and reproducible, allowing endoscopy to be safely avoided. CLINICAL RELEVANCE STATEMENT: The measurement of the splenic area and identification of the periportal hypoechoic band (PHB) on ultrasound demonstrated high accuracy and relevance for predicting the risk of esophageal or fundic varices presence and variceal rupture, respectively. KEY POINTS: Predicting varices in patients with primary biliary cholangitis (PBC) can reduce the morbidity and mortality of gastrointestinal hemorrhage. Transient elastography (TE) and ultrasound play an important role in predicting patients with PBC with varices. TE and ultrasound can predict varicose veins and variceal rupture. Liver stiffness measurement and splenic area measurements can allow endoscopy to be safely avoided.

4.
Hypertens Res ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261700

ABSTRACT

Superselective adrenal artery embolization (SAAE) offers a novel approach for treating primary aldosteronism (PA). In this study, we aimed to assess the efficacy and safety of SAAE for the treatment of PA based on the lateralization results obtained from adrenal vein sampling (AVS).In this prospective study, we enrolled 40 patients with PA who underwent SAAE. The patients were categorized into two groups, unilateral PA and bilateral PA, based on AVS results. Clinical parameters and biochemical markers were assessed at 3 and 12 months postoperatively. The primary outcomes were changes in blood pressure and defined daily dose (DDD) of antihypertensive medications compared to baseline. Thirty-eight patients achieved technical success, with favorable clinical and biochemical efficacy rates. At three months postoperatively, the clinical efficacy rates were 79.2% and 78.6% for the UPA and BPA groups, respectively. At 12 months, the rates were 83.3% and 71.4%, respectively. Both groups exhibited a significant decrease in average blood pressure at 3 and 12 months compared with baseline (P < 0.001), and there was also a notable reduction in DDD (P < 0.05). At three months, the biochemical efficacy rates were 61.9% and 58.3% in the UPA and BPA groups, respectively. Due to loss to follow-up, biochemical indicators were not assessed at 12 months postoperatively. No severe adverse reactions occurred during or after SAAE. Patients with both UPA and BPA can benefit from SAAE. The superiority of bilateral adrenal artery embolization in the treatment of BPA over unilateral adrenal artery embolization requires further investigation.

5.
Infect Agent Cancer ; 19(1): 42, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261841

ABSTRACT

High-grade B-cell lymphoma with 11q aberration (HGBL-11q) is a distinct lymphoma entity according to the 5th edition of the WHO classification of hematolymphoid tumors. It lacks MYC translocation but carries proximal gains and/or telomeric losses of chromosome 11q. This rare type of B-cell lymphoma is less frequently reported in people living with HIV (PLWH), and its exact frequency remains unclear. Our goal was to retrospectively analyze its frequency in a cohort of aggressive B-cell lymphomas in PLWH, including Burkitt lymphoma (BL, n = 35), diffuse large B-cell lymphoma (DLBCL, n = 48), high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS, n = 13), which was diagnosed as AIDS-related lymphoma (ARL) at our institution. In total, 10/96 (10.4%) cases harbored the typical 11q aberration pattern, predominantly those that had been classified as BL (6/35, 17.1%), DLBCL (2/48, 4.2%), and HGBL, NOS (2/13, 15.4%). We also evaluated 7 cases of AIDS-related HGBL-11q (AR-HGBL-11q) reported in the literature. The median age of our cohort was 35 years, and all the patients were male. Most cases (70%) had a history of HIV infection for over 1 year, and all were involved in lymph nodes (100%), frequently involved extranodal sites (60%), and Ann Arbor stage III/IV. In histomorphology, the cases exhibited diverse cytological features, reminiscent of BL (6 cases), DLBCL (2 cases), and HGBL (2 cases). A comparison of the combined cohort of 17 AR-HGBL-11q cases with 11 ARL cases that lacked both MYC rearrangement and 11q aberration at our institution showed that HGBL-11q cases were characterized by strikingly coarse apoptotic debris (P < 0.001), background rich in eosinophils (P = 0.002), higher expression of the germinal centre marker LMO2 (P = 0.080), lower expression of MUM1 (P = 0.004), BCL2 (P = 0.007), and LEF1 (P = 0.080), and lower positivity for EBER in situ hybridisation (P = 0.027). Notably, one case in our series was EBV-positive, a finding not previously reported in the literature. Furthermore, comparing the prognosis between these two groups, AR-HGBL-11q showed a relatively favorable prognosis (P = 0.15), although the difference was not statistically significant. We analyzed this rare lymphoma entity in the HIV setting and highlighted the importance of integrating histomorphological and immunophenotypic features in its diagnosis and classification.

7.
Int J Environ Health Res ; : 1-15, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39234625

ABSTRACT

In this study, based on a cross-sectional study among 9597 preschoolers in Shandong of China, we quantitatively evaluated influences of lifestyle behaviors and air treatment equipment on indoor damp exposures and thus on risks of childhood pneumonia. In the two-level multivariate logistic regression analyses, childhood pneumonia was significantly associated with parent-reported damp clothing/bedding and visible mold spots or damp stains. These associations were weaker among preschoolers from families who frequently opened the child's bedroom windows, frequently cleaned the child's bedroom, and frequently exposed beddings to sunshine (references: not frequently), as well as among preschoolers without usage of air humidifier and air conditioner and with usage of air purifier. Our results indicate that frequently keeping household ventilation and cleanness, and exposing beddings to sunshine, as well using air purifier could decrease the effects of household damp-related exposures on childhood pneumonia, but using air humidifier and air conditioner could increase the effects.

8.
Gene ; : 148944, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39284557

ABSTRACT

BACKGROUND: N6 methyladenosine (m6A) regulates the ferroptosis in different diseases. However, there is no report about the role of the m6A regulator in the ferroptosis process of septic cardiomyopathy (SCM). This study aims to find the potential m6A regulator that participates in the ferroptosis process of SCM. METHODS: Genes related to m6A were identified through bioinformatics analysis in GSE142615. Then, the expression of Rrp8, Trmt6, Trmt61a, Ythdf1, and ZC3H13 was detected in lipopolysaccharide (LPS)-treated HL-1 cells using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). After overexpression or interference with ZC3H13, Cell Counting Kit-8 measured cell proliferation, flow cytometry detected apoptosis and reactive oxygen species (ROS) accumulation was observed. Then, we identified the potential downstream genes of ZC3H13 through further bioinformatics analysis followed by qRT-PCR and western blotting validation. RESULTS: There were five differentially expressed genes related to m6A, including Rrp8, Trmt6, Trmt61a, Ythdf1, and ZC3H13. The expression of Rrp8, Trmt6, Trmt61a, Ythdf1, and ZC3H13 mRNA was significantly up-regulated in the LPS-treated HL-1 cells, with ZC3H13 having the highest expression. Furthermore, overexpression of ZC3H13 inhibited the proliferation of HL-1 cells and promoted apoptosis and ROS accumulation. While, interfering with ZC3H13 promoted the proliferation of LPS-treated HL-1 cells, and reduced apoptosis and ROS accumulation. Additionally, si-ZC3H13 promoted the expression of Pnn, GPX4, and SLC7A11; while inhibiting the expression of Rbm25 and Caspase 3. CONCLUSIONS: In a word, the silence of ZC3H13 increased the proliferation and ferroptosis-related protein expression, decreased apoptosis and ROS accumulation, as well as maybe by regulating Pnn and Rbm25 expression.

9.
Int J Biol Macromol ; 278(Pt 1): 134457, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39111487

ABSTRACT

The optimization of hydrogel structure is crucial for adsorption capacity, mechanical stability, and reusability. Herein, a chitosan and laponite-XLS co-doped poly(acrylic acid-co-acrylamide) hydrogel (CXAA) with honeycomb-like porous structures is synthesized by cooperative cross-linking of 2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) and laponite-XLS in reticular frameworks of acrylic acid (AAc) and acrylamide (AM). The CXAA exhibits extraordinary mechanical performances including tough tensile strength (3.36 MPa) and elasticity (2756 %), which facilitates recycling in practical adsorption treatment and broadens potential applications. Since the regular porous structures can fully expose numerous adsorption sites and electronegative natures within polymer materials, CXAA displays efficient and selective adsorption properties for cationic dyes like methylene blue (MB) and malachite green (MG) from mixed pollutants and can reach record-high values (MB = 6886 mg g-1, MG = 11,381 mg g-1) compared with previously reported adsorbents. Therefore, CXAA exhibits promising potential for separating cationic and anionic dyes by their charge disparities. Mechanism studies show that the synergistic effects of HACC, laponite-XLS, and functional groups in monomers promote highly efficient adsorption. Besides, the adsorption capacity of CXAA remains stable even after undergoing five cycles of regeneration. The results confirm that CXAA is a promising adsorbent for effectively removing organic dyes in wastewater.


Subject(s)
Cations , Coloring Agents , Hydrogels , Hydrogels/chemistry , Adsorption , Coloring Agents/chemistry , Coloring Agents/isolation & purification , Porosity , Cations/chemistry , Chitosan/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Methylene Blue/chemistry , Silicates/chemistry , Mechanical Phenomena , Water Purification/methods , Acrylamide/chemistry , Rosaniline Dyes
10.
Environ Pollut ; 360: 124768, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39163946

ABSTRACT

The neurotoxic effects of neonicotinoids (NEOs) have been widely reported in relation to the poisoning of wild birds, yet the underlying molecular mechanism has remained elusive. This study employed Japanese quails (Coturnix japonica) and primary quail embryonic neurons as in vivo and ex vivo models, respectively, to investigate the neurotoxic effects and mechanism of thiamethoxam (TMX), a representative neonicotinoid insecticide, at environmentally relevant concentrations. Following a 28-day exposure to TMX, metabolomic analysis of quail brain revealed TMX-induced changes in glutamatergic, GABA-ergic, and dopaminergic function. Subsequent ex vivo and in silico experimentation revealed that the activation of nicotinic acetylcholine receptors and calcium signaling, induced by clothianidin (CLO), the primary metabolite of TMX, served as upstream events for the alterations in neurotransmitter synthesis, metabolism, release, and uptake. Our findings propose that the disruption of the central nervous system, caused by environmentally significant concentrations of NEOs, may account for the avian poisoning events induced by NEOs.


Subject(s)
Coturnix , Insecticides , Thiamethoxam , Animals , Thiamethoxam/toxicity , Coturnix/metabolism , Insecticides/toxicity , Central Nervous System/drug effects , Central Nervous System/metabolism , Neonicotinoids/toxicity , Thiazoles/toxicity , Brain/metabolism , Brain/drug effects , Computer Simulation , Neurons/drug effects , Neurons/metabolism , Guanidines/toxicity , Oxazines/toxicity , Receptors, Nicotinic/metabolism
11.
Fish Shellfish Immunol ; 153: 109844, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39168290

ABSTRACT

Cystatins play an important role in various physiological and pathological processes of organisms, including regulating protein metabolism, antigen processing, inflammatory response, nutritional disorders, and controlling enzyme activity. However, research on immunity functions of fish cystatin M is limited. In this study, Pampus argenteus cystatin M (Pacystatin M) was identified and analyzed. Its amino acid sequence was highly conserved in teleosts, and included the conserved cystatin cysteine protease inhibitor motifs. Pacystatin M was highly expressed in the gill, spleen, and intestine, whereas the expression levels of liver and kidney were lower. Furthermore, Nocardia seriolae infection up-regulated the expression of Pacystatin M in the kidney, spleen and liver, with particularly significant expression observed in the liver on day 15 post-infection. Functional analysis indicated that the recombinant Pacystatin M showed increasing inhibitory activity against papain within a certain concentration range, suggesting that the inhibition was likely competitive. Additionally, Pacystatin M demonstrated the ability to inhibit bacterial growth and high thermal stability. These results suggested that Pacystatin M might be involved in the immune response to microbial invasion and provided new reference addressing disease issues in the large-scale farming of silver pomfret.


Subject(s)
Amino Acid Sequence , Cystatins , Fish Diseases , Fish Proteins , Immunity, Innate , Nocardia , Perciformes , Sequence Alignment , Animals , Fish Diseases/immunology , Cystatins/genetics , Cystatins/immunology , Cystatins/chemistry , Fish Proteins/genetics , Fish Proteins/immunology , Fish Proteins/chemistry , Immunity, Innate/genetics , Perciformes/immunology , Perciformes/genetics , Nocardia/immunology , Nocardia Infections/immunology , Nocardia Infections/veterinary , Phylogeny , Gene Expression Regulation/immunology , Gene Expression Profiling/veterinary
12.
Proc Natl Acad Sci U S A ; 121(34): e2405986121, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39145928

ABSTRACT

RAS GTPases associate with the biological membrane where they function as molecular switches to regulate cell growth. Recent studies indicate that RAS proteins oligomerize on membranes, and disrupting these assemblies represents an alternative therapeutic strategy. However, conflicting reports on RAS assemblies, ranging in size from dimers to nanoclusters, have brought to the fore key questions regarding the stoichiometry and parameters that influence oligomerization. Here, we probe three isoforms of RAS [Kirsten Rat Sarcoma viral oncogene (KRAS), Harvey Rat Sarcoma viral oncogene (HRAS), and Neuroblastoma oncogene (NRAS)] directly from membranes using mass spectrometry. We show that KRAS on membranes in the inactive state (GDP-bound) is monomeric but forms dimers in the active state (GTP-bound). We demonstrate that the small molecule BI2852 can induce dimerization of KRAS, whereas the binding of effector proteins disrupts dimerization. We also show that RAS dimerization is dependent on lipid composition and reveal that oligomerization of NRAS is regulated by palmitoylation. By monitoring the intrinsic GTPase activity of RAS, we capture the emergence of a dimer containing either mixed nucleotides or GDP on membranes. We find that the interaction of RAS with the catalytic domain of Son of Sevenless (SOScat) is influenced by membrane composition. We also capture the activation and monomer to dimer conversion of KRAS by SOScat. These results not only reveal the stoichiometry of RAS assemblies on membranes but also uncover the impact of critical factors on oligomerization, encompassing regulation by nucleotides, lipids, and palmitoylation.


Subject(s)
Cell Membrane , Protein Multimerization , Proto-Oncogene Proteins p21(ras) , Proto-Oncogene Proteins p21(ras)/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/chemistry , Humans , Cell Membrane/metabolism , Membrane Proteins/metabolism , Membrane Proteins/chemistry , Membrane Proteins/genetics , GTP Phosphohydrolases/metabolism , GTP Phosphohydrolases/chemistry , GTP Phosphohydrolases/genetics , Lipoylation , ras Proteins/metabolism , ras Proteins/chemistry , Guanosine Triphosphate/metabolism , Guanosine Diphosphate/metabolism
13.
BMC Surg ; 24(1): 242, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39182043

ABSTRACT

OBJECTIVE: This study aimed to assess the efficacy and safety of bilateral superselective adrenal arterial embolization (SAAE) in patients with bilateral idiopathic hyperaldosteronism (IHA), a subtype of PA. METHODS: Ninety-eight patients with bilateral IHA underwent bilateral SAAE between August 2022 and August 2023. Sixty-eight patients were followed up for up to 12 months. The study outcomes were evaluated using the criteria provided by the Primary Aldosteronism Surgical Outcome (PASO) guidelines. RESULTS: The mean reductions in systolic and diastolic blood pressure were 27.4 ± 21.3 mmHg and 23.1 ± 17.4 mmHg, respectively (p < 0.001). The rates of clinical success and biochemical success after adrenal artery ablation were 63.2% (43/68) and 39.7% (27/68), respectively. Overall, there were significant reductions in daily defined doses (DDD), aldosterone/renin ratio (ARR), and plasma aldosterone levels (p < 0.001). Plasma renin levels increased by a mean value of 10.4 ± 39.0 pg/mL (p = 0.049), and potassium levels increased by 0.40 ± 0.63 mmol/L (p < 0.001). No significant adverse events were reported during SAAE or the follow-up period of up to one year. Additionally, no abnormalities were detected by adrenal 68Ga-Pentixafor PET/CT scans before or after SAAE. CONCLUSION: Bilateral SAAE appears to lead to sustained improvements in blood pressure and biochemical parameters in patients with bilateral PA, with minimal adverse effects. This suggests that bilateral SAAE could serve as an effective alternative approach for treating bilateral IHA, potentially curing this condition.


Subject(s)
Adrenal Glands , Embolization, Therapeutic , Hyperaldosteronism , Humans , Hyperaldosteronism/therapy , Hyperaldosteronism/surgery , Hyperaldosteronism/diagnosis , Hyperaldosteronism/blood , Female , Male , Prospective Studies , Middle Aged , Embolization, Therapeutic/methods , Treatment Outcome , Adult , Adrenal Glands/blood supply , Follow-Up Studies , Aldosterone/blood
14.
Bioact Mater ; 41: 137-157, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39131627

ABSTRACT

Non-small cell lung cancer (NSCLC) is a major disease with high incidence, low survival rate and prone to develop drug resistance to chemotherapy. The mechanism of secondary drug resistance in NSCLC chemotherapy is very complex, and studies have shown that the abnormal activation of STAT3 (Signal Transducer and Activator of Transcription 3) plays an important role in it. In this study, the pGPU6/GFP/Neo STAT3-shRNA recombinant plasmid was constructed with STAT3 as the precise target. By modifying hydrophilic and hydrophobic blocks onto chitosan, a multifunctional vitamin E succinate-chitosan-polyethylene glycol monomethyl ether histidine (VES-CTS-mPEG-His) micelles were synthesized. The micelles could encapsulate hydrophobic drug doxorubicin through self-assembly, and load the recombinant pGPU6/GFP/Neo STAT3-shRNA (pDNA) through positive and negative charges to form dual-loaded nanoparticles DOX/VCPH/pDNA. The co-delivery and synergistic effect of DOX and pDNA could up-regulate the expression of PTEN (Phosphatase and Tensin Homolog), down-regulate the expression of CD31, and induce apoptosis of tumor cells. The results of precision targeted therapy showed that DOX/VCPH/pDNA could significantly down-regulate the expression level of STAT3 protein, further enhancing the efficacy of chemotherapy. Through this study, precision personalized treatment of NSCLC could be effectively achieved, reversing its resistance to chemotherapy drugs, and providing new strategies for the treatment of drug-resistant NSCLC.

15.
Geriatr Nurs ; 59: 630-638, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39197354

ABSTRACT

BACKGROUND: Web- and mobile-based physical activity interventions effectively promote physical and mental health among older adults, but participation and adherence are suboptimal. METHODS: This qualitative review used the mega-aggregation approach. Searches were conducted in five databases from the earliest to November 2023. Quality assessment and data extraction used JBI tools. Data synthesis used the COM-B model as a guide. RESULTS: Sixteen sub-themes were identified from the eight studies and categorized into the COM-B model. Sub­themes were physical and psychological changes, digital skills and knowledge, older adult-friendly design, integration into daily routines, social influence, family engagement and support, health benefits and impairments, accessibility and flexibility, low cost, visibility and interaction, instructions and feedback, personalization and progression, incentives, self-efficacy, visual cues, self-monitoring. DISCUSSION: Web- and mobile-based interventions motivate older adults to engage in physical activity, but modifications are necessary. This includes age-appropriate interfaces and contents, tailored behavioral change techniques, and family engagement.

17.
J Cancer Res Clin Oncol ; 150(7): 366, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39052126

ABSTRACT

PURPOSE: Kinase interacting with stathmin (KIS) is a serine/threonine kinase involved in RNA processing and protein phosphorylation. Increasing evidence has suggested its involvement in cancer progression. The aim of this study was to investigate the role of KIS in the development of lung adenocarcinoma (LUAD). Dual luciferase assay was used to explore the relationship between KIS and SOX4, and its effect on ID1/ß-catenin pathway. METHODS: Real-time qPCR and western blot were used to assess the levels of KIS and other factors. Cell proliferation, migration, and invasion were monitored, and xenograft animal model were established to investigate the biological functions of KIS in vitro and in vivo. RESULTS: In the present study, KIS was found to be highly expressed in LUAD tissues and cell lines. KIS accelerated the proliferative, migratory and invasive abilities of LUAD cells in vitro, and promoted the growth of LUAD in a mouse tumor xenograft model in vivo. Mechanistically, KIS activated the ß-catenin signaling pathway by modulating the inhibitor of DNA binding 1 (ID1) and was transcriptionally regulated by SOX4 in LUAD cells. CONCLUSION: KIS, a target of SOX4, regulates the ID1-mediated enhancement of ß-catenin to facilitate LUAD cell invasion and metastasis.


Subject(s)
Adenocarcinoma of Lung , Cell Proliferation , Inhibitor of Differentiation Protein 1 , Lung Neoplasms , SOXC Transcription Factors , beta Catenin , Humans , Animals , SOXC Transcription Factors/metabolism , SOXC Transcription Factors/genetics , Inhibitor of Differentiation Protein 1/metabolism , Inhibitor of Differentiation Protein 1/genetics , beta Catenin/metabolism , Mice , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/genetics , Cell Line, Tumor , Mice, Nude , Neoplasm Metastasis , Cell Movement , Mice, Inbred BALB C , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Male , Female , Gene Expression Regulation, Neoplastic , Xenograft Model Antitumor Assays
19.
Exp Appl Acarol ; 93(1): 197-210, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38869725

ABSTRACT

The goji berry psyllid, Bactericera gobica Logniova (Homoptera: Psyllidae), is one of the most important pests on goji berry plants (Lycium barbarum L.), whose fruits are widely used in traditional Chinese medicine and food. However, chemical control is still the predominant control strategy of this pest. Recently, two species of predatory mites, Neoseiulus setarius Ma, Meng & Fan and Neoseiulus barkeri Hughes were found to be associated with B. gobica in China. To assess their predation potential against B. gobica, the functional responses of these two phytoseiid species feeding on different densities (2, 4, 8, 12, 16, 24 and 32 individuals) of B. gobica eggs and 1st instar nymphs were compared at a temperature of 25ºC ± 1º C. Logistic regression analysis revealed that both predatory mite species exhibited type Holling-II functional responses on eggs and 1st instar nymphs of B. gobica, with the predation number increased for both predators as the density of prey increased. Overall, N. setarius consumed more prey compared to N. barkeri across all levels of prey densities. Meanwhile, the highest attack rate (α = 0.0283), the lowest handling time (Th = 1.1324 h prey- 1), and the highest estimated maximum predation rate (T/Th = 21.19 prey day- 1) were all observed for N. setarius fed with 1st instar nymphs of B. gobica. These findings suggest that it is worthy considering utilizing N. setarius and N. barkeri as candidate biocontrol agents of B. gobica, with N. setarius appearing to be a more effective predator than N. barkeri.


Subject(s)
Hemiptera , Mites , Nymph , Ovum , Pest Control, Biological , Predatory Behavior , Animals , Mites/physiology , Nymph/growth & development , Nymph/physiology , Ovum/physiology , Ovum/growth & development , Hemiptera/physiology , Female , Population Density
20.
IEEE J Biomed Health Inform ; 28(9): 5509-5518, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38829757

ABSTRACT

Clinical studies have proved that both structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) are implicitly associated with neuropsychiatric disorders (NDs), and integrating multi-modal to the binary classification of NDs has been thoroughly explored. However, accurately classifying multiple classes of NDs remains a challenge due to the complexity of disease subclass. In our study, we develop a heterogeneous neural network (H-Net) that integrates sMRI and fMRI modes for classifying multi-class NDs. To account for the differences between the two modes, H-Net adopts a heterogeneous neural network strategy to extract information from each mode. Specifically, H-Net includes an multi-layer perceptron based (MLP-based) encoder, a graph attention network based (GAT-based) encoder, and a cross-modality transformer block. The MLP-based and GAT-based encoders extract semantic features from sMRI and features from fMRI, respectively, while the cross-modality transformer block models the attention of two types of features. In H-Net, the proposed MLP-mixer block and cross-modality alignment are powerful tools for improving the multi-classification performance of NDs. H-Net is validate on the public dataset (CNP), where H-Net achieves 90% classification accuracy in diagnosing multi-class NDs. Furthermore, we demonstrate the complementarity of the two MRI modalities in improving the identification of multi-class NDs. Both visual and statistical analyses show the differences between ND subclasses.


Subject(s)
Brain , Magnetic Resonance Imaging , Mental Disorders , Neural Networks, Computer , Humans , Magnetic Resonance Imaging/methods , Mental Disorders/diagnostic imaging , Mental Disorders/classification , Brain/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Adult , Male , Female , Algorithms
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