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1.
J Environ Sci (China) ; 147: 153-164, 2025 Jan.
Article de Anglais | MEDLINE | ID: mdl-39003036

RÉSUMÉ

Heavy metal(loid) (HM) pollution in agricultural soils has become an environmental concern in antimony (Sb) mining areas. However, priority pollution sources identification and deep understanding of environmental risks of HMs face great challenges due to multiple and complex pollution sources coexist. Herein, an integrated approach was conducted to distinguish pollution sources and assess human health risk (HHR) and ecological risk (ER) in a typical Sb mining watershed in Southern China. This approach combines absolute principal component score-multiple linear regression (APCS-MLR) and positive matrix factorization (PMF) models with ER and HHR assessments. Four pollution sources were distinguished for both models, and APCS-MLR model was more accurate and plausible. Predominant HM concentration source was natural source (39.1%), followed by industrial and agricultural activities (23.0%), unknown sources (21.5%) and Sb mining and smelting activities (16.4%). Although natural source contributed the most to HM concentrations, it did not pose a significant ER. Industrial and agricultural activities predominantly contributed to ER, and attention should be paid to Cd and Sb. Sb mining and smelting activities were primary anthropogenic sources of HHR, particularly Sb and As contaminations. Considering ER and HHR assessments, Sb mining and smelting, and industrial and agricultural activities are critical sources, causing serious ecological and health threats. This study showed the advantages of multiple receptor model application in obtaining reliable source identification and providing better source-oriented risk assessments. HM pollution management, such as regulating mining and smelting and implementing soil remediation in polluted agricultural soils, is strongly recommended for protecting ecosystems and humans.


Sujet(s)
Agriculture , Antimoine , Surveillance de l'environnement , Métaux lourds , Mine , Polluants du sol , Antimoine/analyse , Appréciation des risques , Métaux lourds/analyse , Polluants du sol/analyse , Surveillance de l'environnement/méthodes , Chine , Sol/composition chimique
2.
J Agric Food Chem ; 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39088660

RÉSUMÉ

Ferroptosis is a form of regulated cell death triggered by iron-dependent lipid peroxidation and has been associated with heart diseases. However, there are currently no approved drugs that specifically inhibit ferroptosis in clinical practice, which largely limits the translational potential of this novel target. Here, we demonstrated that ß-caryophyllene (BCP; 150 µM), a natural dietary cannabinoid, protects cardiomyocytes against ferroptotic cell death induced by cysteine deprivation or glutathione peroxidase 4 (GPX4) inactivation. Moreover, BCP preserved the mitochondrial morphology and function during ferroptosis induction. Unexpectedly, BCP supported ferroptosis resistance independent of canonical antiferroptotic pathways. Our results further suggested that BCP may terminate radical chain reactions through interactions with molecular oxygen, which also explains why its oxidation derivative failed to suppress ferroptosis. Finally, oral BCP administration (50 mg/kg, daily) significantly alleviated doxorubicin (15 mg/kg, single i.p. injection)-induced cardiac ferroptosis and cardiomyopathy in mice. In conclusion, our data revealed the role of BCP as a natural antiferroptotic compound and suggest pharmacological modification based on BCP as a promising therapeutic strategy for treating ferroptosis-associated heart disorders.

3.
Biochem Pharmacol ; 227: 116444, 2024 Jul 20.
Article de Anglais | MEDLINE | ID: mdl-39038551

RÉSUMÉ

Regenerating family protein 2 (Reg2) is a trophic factor which stimulates ß-cell replication and resists islet destruction. However, Reg2 also serves as an islet autoantigen, which makes it complicated to judge the effectiveness in treating diabetes. How Reg2 treatment behaves in non-obese diabetic (NOD) mice is to be investigated. NOD mice were treated with recombinant Reg2 protein, Complete Freund's adjuvant (CFA) + PBS and CFA+Reg2 vaccinations, CFA+PBS- and CFA+Reg2-immunized antisera, and single chain variable fragment (scFv)-Reg2 and mIgG2a-Reg2 antibodies. Glycemic level, bodyweight, serum Reg2 antibody titer, glucose tolerance, and insulin secretion were determined. Islet morphological characteristics, insulitis, cell apoptosis, islet cell components, and T cell infiltration were analyzed by histological examinations. The autoantigenicity of constructed Reg2C and Reg2X fragments was determined in healthy BALB/c mice, and the bioactivity in stimulating cell proliferation and survival was assessed in insulinoma MIN6 cells. Reg2 administration alleviated diabetes in NOD mice with improved glucose tolerance and insulin secretion but elevated serum Reg2 autoantibodies. Histomorphometry showed reduced inflammatory area, TUNEL signal and CD8 + T cell infiltration, and increased ß-cell proportion in support of the islet-protective effect of Reg2 treatment. CFA+PBS and CFA+Reg2 immunizations prevented diabetic onset and alleviated insulitis while injections of the antisera offered mild protections. Antibody treatments accelerated diabetic onset without increasing the overall incidence. Reg2C fragment depletes antigenicity, but reserves protective activity in streptozotocin (STZ)-treated MIN6 cells. In conclusion, Reg2 treatment alleviates type 1 diabetes (T1D) by preserving islet ß-cells, but induces Reg2 autoantibody production which poses a potential risk of accelerating diabetic progression.

4.
Int J Epidemiol ; 53(4)2024 Jun 12.
Article de Anglais | MEDLINE | ID: mdl-38990179

RÉSUMÉ

BACKGROUND: This study aimed to estimate population-level and state-level lead-attributable mortality burdens stratified by socioeconomic status (SES) class in the USA. METHODS: Based on the National Health and Nutrition Examination Survey (NHANES), we constructed individual-level SES scores from income, employment, education and insurance data. We assessed the association between the blood lead levels (BLL) and all-cause mortality by Cox regression in the NHANES cohort (n = 31 311, 4467 deaths). With estimated hazard ratios (HR) and prevalences of medium (2-5 µg/dL) and high (≥ 5 µg/dL) BLL, we computed SES-stratified population-attributable fractions (PAFs) of all-cause mortality from lead exposure across 1999-2019. We additionally conducted a systematic review to estimate the lead-attributable mortality burden at state-level. RESULTS: The HR for every 2-fold increase in the BLL decreased from 1.23 (1.10-1.38) for the lowest SES class to 1.05 (0.90-1.23) for the highest SES class. Across all SES quintiles, medium BLL exhibited a greater mortality burden. Individuals with lower SES had higher lead-attributable burdens, and such disparities haver persisted over the past two decades. In 2017-19, annually 67 000 (32 000-112 000) deaths in the USA were attributable to lead exposure, with 18 000 (2000-41 000) of these deaths occurring in the lowest SES class. Substantial disparities in the state-level mortality burden attributable to lead exposure were also highlighted. CONCLUSIONS: These findings suggested that disparities in lead-attributable mortality burden persisted within US adults, due to heterogeneities in the effect sizes of lead exposure as well as in the BLL among different SES classes.


Sujet(s)
Plomb , Enquêtes nutritionnelles , Classe sociale , Humains , États-Unis/épidémiologie , Femelle , Mâle , Plomb/sang , Plomb/effets indésirables , Adulte d'âge moyen , Adulte , Sujet âgé , Intoxication par le plomb/mortalité , Exposition environnementale/effets indésirables , Modèles des risques proportionnels , Mortalité/tendances , Jeune adulte , Prévalence
5.
Inflammation ; 2024 Jul 18.
Article de Anglais | MEDLINE | ID: mdl-39023831

RÉSUMÉ

Hemorrhagic shock/resuscitation (HS/R) can lead to acute kidney injury, mainly manifested as oxidative stress and inflammatory injury in the renal tubular epithelial cells, as well as abnormal autophagy and apoptosis. Sulforaphane (SFN), an agonist of the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) signaling pathway, is involved in multiple biological activities, such as anti-inflammatory, antioxidant, autophagy, and apoptosis regulation. This study investigated the effect of SFN on acute kidney injury after HS/R in mice. Hemorrhagic shock was induced in mice by controlling the arterial blood pressure at a range of 35-45 mmHg for 90 min within arterial blood withdrawal. Fluid resuscitation was carried out by reintroducing withdrawn blood and 0.9% NaCl. We found that SFN suppressed the elevation of urea nitrogen and serum creatinine levels in the blood induced by HS/R. SFN mitigated pathological alterations including swollen renal tubules and renal casts in kidney tissue of HS/R mice. Inflammation levels and oxidative stress were significantly downregulated in mouse kidney tissue after SFN administration. In addition, the kidney tissue of HS/R mice showed high levels of autophagosomes as observed by electron microscopy. However, SFN can further enhance the formation of autophagosomes in the HS/R + SFN group. SFN also increased autophagy-related proteins Beclin1 expression and suppressed P62 expression, while increasing the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II and LC3-I (LC3-II/LC3-I). SFN also effectively decreased cleaved caspase-3 level and enhanced the ratio of anti-apoptotic protein B cell lymphoma 2 and Bcl2-associated X protein (Bcl2/Bax). Collectively, SFN effectively inhibited inflammation and oxidative stress, enhanced autophagy, thereby reducing HS/R-induced kidney injury and apoptosis levels in mouse kidneys.

6.
Signal Transduct Target Ther ; 9(1): 182, 2024 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-39004647

RÉSUMÉ

A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0-57.9), and a disease control rate of 95.3% (95% CI 84.2-99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1-15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.


Sujet(s)
Carcinome pulmonaire non à petites cellules , Immunoconjugués , Tumeurs du poumon , Mutation , Récepteur ErbB-2 , Humains , Carcinome pulmonaire non à petites cellules/génétique , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/anatomopathologie , Femelle , Adulte d'âge moyen , Mâle , Sujet âgé , Récepteur ErbB-2/génétique , Récepteur ErbB-2/antagonistes et inhibiteurs , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , Adulte , Immunoconjugués/effets indésirables , Immunoconjugués/usage thérapeutique , Sujet âgé de 80 ans ou plus
7.
Sci Rep ; 14(1): 16345, 2024 Jul 16.
Article de Anglais | MEDLINE | ID: mdl-39014093

RÉSUMÉ

During rock drilling, a drill bit will wear as it breaks the rock. However, there is no uniform grading standard for rock abrasiveness. To solve this problem, the wear mechanisms of a polycrystalline diamond compact (PDC) bit and the formation it is drilling into are analyzed in depth, and an abrasiveness evaluation method based on the fractal dimension of the rock surface topography is established. Initially, a three-dimensional digital model is generated from a scanning electron microscope image of the rock after drilling; next, an evaluation of the irregularities on the rock surface is performed using an adapted Weierstrass-Mandelbrot (W-M) function to ascertain the fractal dimensionality. Then, the microcontact characteristics of the contact surface between the formation and the PDC bit are analyzed, and the distribution of the microconvex contact points of the two-body friction pair in a region is obtained. Because the sliding friction between the drill bit and the rock produces a large amount of heat, according to the contact area formula of the friction surface and heat conduction theory, the temperature rise and overall temperature distribution of the formation and PDC bit under the condition of sliding friction are revealed, and the real contact area between the formation and the drill bit within a certain temperature range is obtained. Finally, the evaluation index of rock abrasiveness under sliding conditions is established by adopting the wear weight loss of the rock cutting tool per unit volume as the index of rock abrasiveness, and the model is verified by a microdrilling experiment. The research in this paper is highly important for improving the rock-breaking efficiency and bit service life during drilling.

8.
PLoS One ; 19(7): e0302826, 2024.
Article de Anglais | MEDLINE | ID: mdl-38950315

RÉSUMÉ

Can the information technology revolution lead to carbon emission reduction for firms? This study extends the limited evidence in the literature and investigate the role and mechanism of digital inclusive finance on enterprises' carbon emissions using panel data of 247 prefectural-level cities and 6019 industrial enterprises in China. Our findings indicate that digital inclusive finance can promote enterprise carbon emission reduction, and this effect remains significant after the instrumental variable estimation test. The effect has regional heterogeneity and the development of digital inclusive finance in the area east of Hu Huanyong line has a significant impact on reducing enterprise carbon emission. The role of digital inclusive finance is heterogeneous in enterprise ownership, with a remarkable effect in non-state-owned enterprises. Sub-dimension analysis indicates that the breadth of coverage, depth of use, and degree of digitalization of digital inclusive finance have differential effects on reducing enterprise carbon emissions. The stepwise regression method shows that the impact of digital inclusive finance on enterprise carbon emissions can be passed through effect of technological progress, environmental protection investment and financing constrain. This study has significant reference value for evaluating the impact of financial inclusion and policy implications in formulating differentiated strategies for achieving carbon emission reduction efficiency in enterprises.


Sujet(s)
Carbone , Carbone/métabolisme , Chine , Villes , Industrie/économie
9.
Nat Commun ; 15(1): 5502, 2024 Jun 29.
Article de Anglais | MEDLINE | ID: mdl-38951519

RÉSUMÉ

Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.


Sujet(s)
Antinéoplasiques , Systèmes CRISPR-Cas , Résistance aux médicaments antinéoplasiques , Irinotécan , Oxaliplatine , Protein-Serine-Threonine Kinases , Résistance aux médicaments antinéoplasiques/génétique , Humains , Lignée cellulaire tumorale , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Oxaliplatine/pharmacologie , Irinotécan/pharmacologie , Systèmes CRISPR-Cas/génétique , Protein-Serine-Threonine Kinases/génétique , Protein-Serine-Threonine Kinases/métabolisme , Protein-Serine-Threonine Kinases/antagonistes et inhibiteurs , Tumeurs colorectales/génétique , Tumeurs colorectales/traitement médicamenteux , Animaux , Tumeurs/génétique , Tumeurs/traitement médicamenteux , Clustered regularly interspaced short palindromic repeats/génétique , Souris , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques
11.
Heliyon ; 10(11): e32522, 2024 Jun 15.
Article de Anglais | MEDLINE | ID: mdl-38961909

RÉSUMÉ

Objectives: Dihydroartemisinin (DHA), an artemisinin derivative extracted from the traditional Chinese medicinal herb Artemisia annua, has the potential to suppress head and neck squamous cell carcinoma (HNSCC) progression. However, the mechanisms underlying these effects remain unclear. Therefore, we aimed to examine the mechanisms underlying the effects of DHA on tumor invasion and migration. Methods: Human HNSCC cell lines CAL-27 and FaDu were exposed to varying DHA concentrations (0, 5, 20, and 80 µM) for 24 h. Cell proliferation, invasion, and migration were assessed using CCK8, transwell, and wound-healing assays, respectively. Quantitative real-time PCR, western blotting, and immunofluorescence were used to assess the expression levels of the target genes and proteins. Results: DHA suppressed the invasion and migration of CAL-27 and FaDu cells. Additionally, miR-195-5p suppressed the invasion and migration of HNSCC cells. This study revealed significant differences in the expression of miR-195-5p and TENM2 between clinical samples and multiple public databases. DHA treatment and miR-195-5p overexpression significantly reduced TENM2 expression in HNSCC cells, which suggested that miR-195-5p overexpression enhanced the inhibitory effect of DHA on TENM2. Conclusions: This study provides the first evidence that DHA inhibits cell invasion and migration by regulating the miR-195-5p/TENM2 axis in HNSCC cells, suggesting it as a potentially effective treatment strategy for HNSCC.

13.
Physiol Mol Biol Plants ; 30(6): 877-891, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38974354

RÉSUMÉ

Natural leaf senescence is critical for plant fitness. Drought-induced premature leaf senescence affects grape yield and quality. However, reports on the regulatory mechanisms underlying premature leaf senescence under drought stress are limited. In this study, two-year-old potted 'Muscat Hamburg' grape plants were subjected to continuous natural drought treatment until mature leaves exhibited senescence symptoms. Physiological and biochemical indices related to drought stress and senescence were monitored. Transcriptome and transgenic Arabidopsis were used to perform expression analyses and functional identification of drought-induced senescence-associated genes. Twelve days of continuous drought stress was sufficient to cause various physiological disruptions and visible senescence symptoms in mature 'Muscat Hamburg' leaves. These disruptions included malondialdehyde and H2O2 accumulation, and decreased catalase activity and chlorophyll (Chl) levels. Transcriptome analysis revealed that most genes involved in photosynthesis and Chl synthesis were downregulated after 12 d of drought treatment. Three key Chl catabolic genes (SGR, NYC1, and PAO) were significantly upregulated. Overexpression of VvSGR in wild Arabidopsis further confirmed that SGR directly promoted early yellowing of cotyledons and leaves. In addition, drought treatment decreased expression of gibberellic acid signaling repressors (GAI and GAI1) and cytokinin signal components (AHK4, AHK2, RR22, RR9-1, RR9-2, RR6, and RR4) but significantly increased the expression of abscisic acid, jasmonic acid, and salicylic acid signaling components and responsive transcription factors (bZIP40/ABF2, WRKY54/75/70, ANAC019, and MYC2). Moreover, some NAC members (NAC0002, NAC019, and NAC048) may also be drought-induced senescence-associated genes. These results provide extensive information on candidate genes involved in drought-induced senescence in grape leaves. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01465-2.

14.
Medicine (Baltimore) ; 103(30): e39089, 2024 Jul 26.
Article de Anglais | MEDLINE | ID: mdl-39058871

RÉSUMÉ

RATIONALE: Desmoid tumor (DT) is a rare soft tissue tumor that can occur anywhere in the body. Abdominal wall DT presents unique clinical challenges due to its distinctive manifestations, treatment modalities, and the lack of biomarkers for diagnosis and recurrence prediction, making clinical decisions exceedingly complex. PATIENT CONCERNS: A 32-year-old female who underwent radical resection combined with patch reinforcement for rectus abdominis DT, successfully alleviating abdominal discomfort, with no recurrence during the 6-month follow-up after surgery. DIAGNOSES: Based on the imaging studies and medical history, the patient underwent radical surgical resection. Histopathology reveals that the tumor cells predominantly composed of proliferative fibroblasts with local collagen deposition. The lesional cells show positive staining for ß-catenin, indicating a diagnosis of DT. INTERVENTIONS: The patient underwent radical surgical resection with patch reinforcement to repair the abdominal wall defect. Pathology confirmed negative margins, achieving an R0 resection, and genetic testing identified a T41A mutation in CTNNB1. Consequently, no additional adjuvant therapy was administered postoperatively. OUTCOMES: The patient was discharged with the incision healing well after 3 days postoperation. Upon reexamination 6 months later, no recurrence or adverse complications were observed. LESSONS: Abdominal wall DT treatment requires personalized plans from multidisciplinary team discussions. Genetic testing plays a crucial role in identifying novel biomarkers for abdominal wall DT. We have once again demonstrated the significant clinical significance of CTNNB1 mutations in the diagnosis and progression of abdominal wall DT. Additionally, genes such as CCND1, CYP3A4, SLIT1, RRM1, STIM1, ESR2, UGT1A1, among others, may also be closely associated with the progression of abdominal wall DT. Future research should delve deeper into and systematically evaluate the precise impact of these genetic mutations on treatment selection and prognosis for abdominal wall DT, in order to better guide patient management and treatment decisions.


Sujet(s)
Fibromatose agressive , Muscle droit de l'abdomen , Humains , Femelle , Adulte , Fibromatose agressive/chirurgie , Fibromatose agressive/diagnostic , Fibromatose agressive/génétique , Fibromatose agressive/anatomopathologie , Muscle droit de l'abdomen/chirurgie , bêta-Caténine/génétique , Tumeurs de l'abdomen/chirurgie , Tumeurs de l'abdomen/génétique , Tumeurs de l'abdomen/diagnostic , Tumeurs de l'abdomen/anatomopathologie
15.
Food Res Int ; 191: 114702, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39059909

RÉSUMÉ

Sterilization of Northern shrimp (Pandalus borealis) is a key tool to ensure their freshness for post-production transportation. However, in the face of the specific problem of quality deterioration caused by the increase of storage environment temperature due to unexpected circumstances or the prolongation of temporary storage time, it is still a technical challenge to realize intelligent decision-making and higher sterilization efficiency. In this paper, we propose an intelligent UV-Ozone sterilization system suitable for cold chain transportation of Northern shrimp (Pandalus borealis). Using hierarchical analysis, equipartition method and the prediction method of generalized linear model, combined with the technology of intelligent control and remote control, we realized the automatic control of the system's UV irradiance from 324 âˆ¼ 1620 J/m2, and ozone concentration from21.4 ∼ 107 mg/cm3 in a graded manner. The accuracy of the predicted structure was verified using a combination of direct measurement and simulation. In addition, the key model of the system, the intensity level decision model, was tested, and the test results showed that the decision model was able to accurately make decisions during the sterilization of Northern shrimp (Pandalus borealis), and the system was able to achieve a sterilization effect of 1-3 orders of magnitude. This reduces quality loss due to unexpected conditions, facilitates real-time monitoring of transported samples by staff, extends the shelf life of the samples, and improves the accuracy of sterilization, increasing the economic value of Northern shrimp (Pandalus borealis).


Sujet(s)
Stockage des aliments , Ozone , Pandalidae , Stérilisation , Rayons ultraviolets , Animaux , Stérilisation/méthodes , Stockage des aliments/méthodes , Conservation aliments/méthodes , Fruits de mer , Réfrigération
16.
J Autoimmun ; 148: 103289, 2024 Jul 25.
Article de Anglais | MEDLINE | ID: mdl-39059058

RÉSUMÉ

Patients with primary biliary cholangitis (PBC) commonly experience extrahepatic rheumatic diseases. However, the epidemiologic and genetic associations as well as causal relationship between PBC and these extrahepatic conditions remain undetermined. In this study, we first conducted systematic review and meta-analyses by analyzing 73 studies comprising 334,963 participants across 17 countries and found strong phenotypic associations between PBC and rheumatic diseases. Next, we utilized large-scale genome-wide association study summary data to define the shared genetic architecture between PBC and rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Sjögren's syndrome (SS). We observed significant genetic correlations between PBC and each of the four rheumatic diseases. Pleiotropy and heritability enrichment analysis suggested the involvement of humoral immunity and interferon-associated processes for the comorbidity. Of note, we identified four variants shared between PBC and RA (rs80200208), SLE (rs9843053), and SSc (rs27524, rs3873182) using cross-trait meta-analysis. Additionally, several pleotropic loci for PBC and rheumatic diseases were found to share causal variants with gut microbes possessing immunoregulatory functions. Finally, Mendelian randomization revealed consistent evidence for a causal effect of PBC on RA, SLE, SSc, and SS, but no or inconsistent evidence for a causal effect of extrahepatic rheumatic diseases on PBC. Our study reveals a profound genetic overlap and causal relationships between PBC and extrahepatic rheumatic diseases, thus providing insights into shared biological mechanisms and novel therapeutic interventions.

17.
Biomed Pharmacother ; 178: 117176, 2024 Jul 24.
Article de Anglais | MEDLINE | ID: mdl-39059350

RÉSUMÉ

The class-III histone deacetylase SIRT1 is the most extensively investigated sirtuin deacetylase. It is resistant to the broad deacetylase inhibitor trichostatin A and depends on oxidized nicotinamide adenine nucleotide (NAD+). SIRT1 plays a crucial role in the tumorigenesis of numerous types of cancers, including colorectal cancer (CRC). Accumulating evidence indicates that SIRT1 is a therapeutic target for CRC; however, the function and underlying mechanism of SIRT1 in CRC still need to be elucidated. Herein, we provide a detailed and updated review to illustrate that SIRT1 regulates many processes that go awry in CRC cells, such as apoptosis, autophagy, proliferation, migration, invasion, metastasis, oxidative stress, resistance to chemo-radio therapy, immune evasion, and metabolic reprogramming. Moreover, we closely link our review to the clinical practice of CRC treatment, summarizing the mechanisms and prospects of SIRT1 inhibitors in CRC therapy. SIRT1 inhibitors as monotherapy in CRC or in combination with chemotherapy, radiotherapy, and immune therapies are comprehensively discussed. From epigenetic regulation to its potential therapeutic effect, we hope to offer novel insights and a comprehensive understanding of SIRT1's role in CRC.

18.
Front Oncol ; 14: 1386597, 2024.
Article de Anglais | MEDLINE | ID: mdl-38947889

RÉSUMÉ

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

19.
J Oleo Sci ; 73(8): 1125-1134, 2024.
Article de Anglais | MEDLINE | ID: mdl-39085085

RÉSUMÉ

In recent years, there has been a growing interest in regulating lipid digestion through the construction of various interfacial structures. In the present work, a series of complex interfacial structures were designed by combining Tween 80 in the aqueous phase and lecithin in the oil phase at different concentration ratios. The emulsification properties, the roles in regulating lipid digestion, and the interfacial dilatational rheological properties of the composite emulsifying systems were characterized. The results showed that the combination of Tween 80 and lecithin at different ratios could effectively modulate the rate of lipid digestion. The polyoxyethylene chains of Tween 80 formed a network, that provided a spatial obstacle for the adsorption of bile salts and lipases. Thus, Tween 80 significantly delayed the lipid digestion. The introduction of lecithin gradually replaced Tween 80 molecules at the interface, thus providing space for the adsorption of bile salts and lipases. In addition, as the ratio of lecithin concentration to Tween 80 increased, lecithin gradually became the dominant factor in the interfacial properties. As a result, the rate of lipid digestion was accelerated. Therefore, by compounding different ratios of lecithin and Tween 80, a series of emulsions with different lipid digestion rates were obtained. This research provides a basis for rationally designing food emulsions according to specific needs.


Sujet(s)
Acides et sels biliaires , Émulsions , Lécithines , Triacylglycerol lipase , Polysorbates , Polysorbates/composition chimique , Lécithines/composition chimique , Adsorption , Triacylglycerol lipase/composition chimique , Triacylglycerol lipase/métabolisme , Acides et sels biliaires/composition chimique , Rhéologie , Digestion , Métabolisme lipidique , Nanostructures/composition chimique , Lipides/composition chimique , Eau/composition chimique
20.
J Fungi (Basel) ; 10(7)2024 Jul 19.
Article de Anglais | MEDLINE | ID: mdl-39057384

RÉSUMÉ

Based on phylogenetic analysis, Candolleomyces (Psathyrellaceae, Agaricales) was established with Psathyrella candolleana as the type species. The basidiomes range from small to large and are typically terrestrial, lignicolous, and rarely fimicolous. We analysed the Candolleomyces species collected during five years in China, and based on morphological and molecular data (nrITS, nrLSU, and tef-1α), we propose seven new Candolleomyces species viz. C. brevisporus, C. gyirongicus, C. lignicola, C. luridus, C. shennongdingicus, C. shennongjianus, and C. sichuanicus. Full descriptions, colour photographs, illustrations, phylogenetic analyses results, and comparisons with related Candolleomyces species of the new taxa are provided. This study enriches the species diversity of Candolleomyces in China.

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