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1.
Infect Genet Evol ; 123: 105634, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950667

RESUMO

BACKGROUND: Aedes albopictus is an important vector of chikungunya, dengue, yellow fever and Zika viruses. Insecticides are often the most effective tools for rapidly decreasing the density of vector populations, especially during arbovirus disease outbreaks. However, the intense use of insecticides, particularly pyrethroids, has led to the selection of resistant mosquito populations worldwide. Mutations in the voltage-gated sodium channel (VGSC) gene are one of the main drivers of insecticide resistance in Ae. albopictus and are also known as "knockdown resistance" (kdr) mutations. Knowledge about genetic mutations associated with insecticide resistance is a prerequisite for developing techniques for rapid resistance diagnosis. Here, we report studies on the origin and dispersion of kdr haplotypes in samples of Ae. albopictus from the Yangtze River Basin, China; METHODS: Here, we report the results of PCR genotyping of kdr mutations in 541 Ae. albopictus specimens from 22 sampling sites in 7 provinces and municipalities in the Yangtze River Basin. Partial DNA sequences of domain II and domain III of the VGSC gene were amplified. These DNA fragments were subsequently sequenced to discover the possible genetic mutations mediating knockdown resistance (kdr) to pyrethroids. The frequency and distribution of kdr mutations were assessed in 22 Ae. albopictus populations. Phylogenetic relationships among the haplotypes were used to infer whether the kdr mutations had a single or multiple origins; RESULTS: The kdr mutation at the 1016 locus had 2 alleles with 3 genotypes: V/V (73.38%), V/G (26.43%) and G/G (0.18%). The 1016G homozygous mutation was found in only one case in the CQSL strain in Chongqing, and no 1016G mutations were detected in the SHJD (Shanghai), NJDX (Jiangsu) or HBQN (Hubei) strains. A total of 1532 locus had two alleles and three genotypes, I/I (88.35%), I/T (8.50%) and T/T (3.14%). A total of 1534 locus had four alleles and six genotypes: F/F (49.35%), F/S (19.96%), F/C (1.48%) and F/L (0.18%); S/S (23.66%); and C/C (5.36%). Haplotypes with the F1534C mutation were found only in Ae. albopictus populations in Chongqing and Hubei, and C1534C was found only in three geographic strains in Chongqing. Haplotypes with the 1534S mutation were found only in Ae. albopictus populations in Sichuan and Shanghai. F1534L was found only in HBYC. The Ae. albopictus populations in Shanghai were more genetically differentiated from those in the other regions (except Sichuan), and the genetic differentiation between the populations in Chongqing and those in the middle-lower reaches of the Yangtze River (Huber, Jiangsu, Jiangxi, and Anhui) was lower. Shanghai and Sichuan displayed low haplotype diversity and low nucleotide diversity. Phylogenetic analysis and sequence comparison revealed that the 1016 locus was divided into three branches, with the Clade A and Clade B branches bearing the 1016 mutation occurring mostly in Jiangsu and the Clade C branch bearing the 1016 mutation occurring mostly in Chongqing, suggesting at least two origins for 1016G. IIIS6 phylogenetic analysis and sequence comparison revealed that F1534S, F1534C and I1532T can be divided into two branches, indicating that IIIS6 has two origins; CONCLUSIONS: Combined with the distribution of kdr mutations and the analysis of population genetics, we infer that besides the local selection of pyrethroid resistance mutations, dispersal and colonization of Ae. albopictus from other regions may explain why kdr mutations are present in some Ae. albopictus populations in the Yangtze River Basin.

2.
Neuro Oncol ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38989697

RESUMO

BACKGROUND: Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. CONCLUSIONS: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.

3.
J Nucl Med ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38991752

RESUMO

[177Lu]Lu-PSMA is an effective class of therapy for patients with metastatic castration-resistant prostate cancer (mCRPC); however, progression is inevitable. The limited durability of response may be partially explained by the presence of micrometastatic deposits, which are energy-sheltered and receive low absorbed radiation with 177Lu due to the approximately 0.7-mm mean pathlength. 161Tb has abundant emission of Auger and conversion electrons that deposit a higher concentration of radiation over a shorter path, particularly to single tumor cells and micrometastases. 161Tb has shown in vitro and in vivo efficacy superior to that of 177Lu. We aim to demonstrate that [161Tb]Tb-PSMA-I&T will deliver effective radiation to sites of metastatic prostate cancer with an acceptable safety profile. Methods: This single-center, single-arm, phase I/II trial will recruit 30 patients with mCRPC. Key eligibility criteria include a diagnosis of mCRPC with progression after at least one line of taxane chemotherapy (unless medically unsuitable) and androgen receptor pathway inhibitor; prostate-specific membrane antigen-positive disease on [68Ga]Ga-PSMA-11 or [18F]DCFPyL PET/CT (SUVmax ≥ 20); no sites of discordance on [18F]FDG PET/CT; adequate bone marrow, hepatic, and renal function; an Eastern Cooperative Oncology Group performance status of no more than 2, and no prior treatment with another radioisotope. The dose escalation is a 3 + 3 design to establish the safety of 3 prespecified activities of [161Tb]Tb-PSMA-I&T (4.4, 5.5, and 7.4 GBq). The maximum tolerated dose will be defined as the highest activity level at which a dose-limiting toxicity occurs in fewer than 2 of 6 participants. The dose expansion will include 24 participants at the maximum tolerated dose. Up to 6 cycles of [161Tb]Tb-PSMA-I&T will be administered intravenously every 6 wk, with each subsequent activity reduced by 0.4 GBq. The coprimary objectives are to establish the maximum tolerated dose and safety profile (Common Terminology Criteria for Adverse Events version 5.0) of [161Tb]Tb-PSMA-I&T. Secondary objectives include measuring absorbed radiation dose (Gy), evaluating antitumor activity (prostate-specific antigen 50% response rate, radiographic and prostate-specific antigen progression-free survival, overall survival, objective response rate), and evaluating pain (Brief Pain Inventory-Short Form) and health-related quality of life (Functional Assessment of Cancer Therapy-Prostate and Functional Assessment of Cancer Therapy-Radionuclide Therapy). Conclusion: Enrollment was completed in February 2024. Patients are still receiving [161Tb]Tb-PSMA-I&T.

4.
J Sci Food Agric ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958073

RESUMO

BACKGROUND: The formation of ice crystals will have adverse effects on aquatic products, and the key to ensure the long-term preservation and better quality preservations of the product is to evaluate the intercellular ice crystal formation to find suitable refrigeration conditions and cryoprotectants. RESULTS: The ice crystal formation was successfully captured by using an inverted microscope cryomicroscopic system equipped with a low-temperature stage, the ice crystals formed under different freezing methods between tuna muscle cells were observed directly, the deformation degree of muscle tissue pores during crystallization was evaluated, and the effect of freeze-thaw times on tuna samples was analyzed. The effects of the use of cryoprotectant such as cellobiose and carboxylated cellulose nanofibers on ice-growth inhibition were investigated, and the reliability of the ice crystal observation results was further verified by the determination of physical properties. The results showed that carboxylated cellulose nanofibers had the best ice-growth inhibition effect, they prevented about 50% cell deformation compared with the control group, and also reduced the minimum size of ice crystal formation. In addition, the addition of cellobiose and sodium tripolyphosphate gave the ice crystals a more uniform size and roundness. CONCLUSION: The experiment proposed a stable and clear observation method for the process of intercellular ice crystal formation, and the accuracy of the observation method was further verified by some physical indicators. This may help in the selection of suitable measurement methods to directly observe ice crystal formation behavior and screen cryoprotectants. © 2024 Society of Chemical Industry.

5.
Int J Biol Macromol ; 275(Pt 1): 133584, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960271

RESUMO

The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNsD) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.

6.
Adv Sci (Weinh) ; : e2401855, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973158

RESUMO

Clinically, chronic pain and depression often coexist in multiple diseases and reciprocally reinforce each other, which greatly escalates the difficulty of treatment. The neural circuit mechanism underlying the chronic pain/depression comorbidity remains unclear. The present study reports that two distinct subregions in the paraventricular thalamus (PVT) play different roles in this pathological process. In the first subregion PVT posterior (PVP), glutamatergic neurons (PVPGlu) send signals to GABAergic neurons (VLPAGGABA) in the ventrolateral periaqueductal gray (VLPAG), which mediates painful behavior in comorbidity. Meanwhile, in another subregion PVT anterior (PVA), glutamatergic neurons (PVAGlu) send signals to the nucleus accumbens D1-positive neurons and D2-positive neurons (NAcD1→D2), which is involved in depression-like behavior in comorbidity. This study demonstrates that the distinct thalamo-subcortical circuits PVPGlu→VLPAGGABA and PVAGlu→NAcD1→D2 mediated painful behavior and depression-like behavior following spared nerve injury (SNI), respectively, which provides the circuit-based potential targets for preventing and treating comorbidity.

7.
Adv Sci (Weinh) ; : e2309471, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38889269

RESUMO

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

8.
Cell Biol Toxicol ; 40(1): 45, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864940

RESUMO

MALT1 has been implicated as an upstream regulator of NF-κB signaling in immune cells and tumors. This study determined the regulatory mechanisms and biological functions of MALT1 in non-small cell lung cancer (NSCLC). In cell culture and orthotopic xenograft models, MALT1 suppression via gene expression interference or protein activity inhibition significantly impaired malignant phenotypes and enhanced radiation sensitivity of NSCLC cells. CSN5, the core subunit of COP9 signalosome, was firstly verified to stabilize MALT1 via disturbing the interaction with E3 ligase FBXO3. Loss of FBXO3 in NSCLC cells reduced MALT1 ubiquitination and promoted its accumulation, which was reversed by CSN5 interference. An association between CSN5/FBXO3/MALT1 regulatory axis and poor prognosis in NSCLC patients was identified. Our findings revealed the detail mechanism of continuous MALT1 activation in NF-κB signaling, highlighting its significance as predictor and potential therapeutic target in NSCLC.


Assuntos
Complexo do Signalossomo COP9 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , NF-kappa B , Transdução de Sinais , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/metabolismo , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Complexo do Signalossomo COP9/metabolismo , Complexo do Signalossomo COP9/genética , NF-kappa B/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Animais , Linhagem Celular Tumoral , Camundongos , Camundongos Nus , Ubiquitinação , Peptídeo Hidrolases/metabolismo , Peptídeo Hidrolases/genética , Progressão da Doença , Camundongos Endogâmicos BALB C , Feminino , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Peptídeos e Proteínas de Sinalização Intracelular
9.
Heliyon ; 10(11): e31919, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38841485

RESUMO

Background: The ageing population presents a substantial challenge to conventional care services for older adults in China. College students' voluntary service constitutes an integral component of youth volunteerism, and investigating their continuing willingness to engage in volunteer services to benefit older adults holds immense importance for fostering a stable and enduring framework for China's older adults' care team. Method: Drawing on the extended theory of reasoned action, this study establishes an analytical framework to examine the willingness of Chinese college students to engage in volunteer services for older adults. Using micro-survey data, we employ structural equation modelling and the bootstrap mediation effect test method to empirically investigate the influencing mechanism behind this willingness. Results: (1) Attitude has the strongest influence on the continuing willingness of Chinese college students to engage in volunteer services for older adults, and plays a mediating role between subjective norms and continuing willingness to engage in volunteer services, which reveals the special role of attitude in the continuing engagement of Chinese college students in volunteer services for older adults. (2) Personality trait has a substantial positive impact on Chinese college students' willingness to engage continuously in volunteer service for older adults, and subjective norms and attitudes have a chain mediating effect in this influence relationship. (3) The theoretical model constructed in this study is reasonable, reliable and robust. Conclusion: This study elucidates the potential relationship between attitude, subjective norms, personality traits and the willingness to engage in volunteer services, offering a novel perspective for understanding the continuing willingness of Chinese college students to engage in volunteer services for older adults. Furthermore, it highlights the value of incorporating the extended theory of reasoned action into the policy design of college students' engagement in such services.

10.
Int J Biol Macromol ; 274(Pt 1): 133276, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906360

RESUMO

Chitosan is a natural polymer material with antibacterial, biodegradable and biocompatibility. At present, the research is mainly to enhance the antibacterial and antioxidant activity of chitosan by grafting with phenolic acids to further expand its application in food. In this study, the effect of chitosan-g-gentisic acid graft copolymer (CS-g-GA) on the shelf life of refrigerated seabass (Lateolabrax maculatus) was investigated. The results of microbial analysis demonstrated that GA and CS-g-GA treatment could effectively inhibit the growth of microorganisms. In addition, physicochemical analysis showed that GA and CS-g-GA treatment could reduce the increase of pH value, thiobarbituric acid reactive substances (TBARS), total volatile base nitrogen (TVB-N) and K-value, delay water loss, maintain texture and color, and postpone the decrease of sensory score. Compared with the control sample, CS-g-GA could keep the quality of Lateolabrax japonicus and extend its shelf-life for another 9 days. In summary, CS-g-GA has good application and development prospects for the preservation of seabass.

11.
Ultrason Sonochem ; 107: 106945, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38857567

RESUMO

In this study, large yellow croaker (Larimichthys crocea) was frozen using multi-frequency ultrasound-assisted freezing (MUIF) with different powers (160 W, 175 W, and 190 W, respectively) and stored at -18 °C for ten months. The effect of different ultrasound powers on the myofibrillar protein (MP) structures and lipid oxidation of large yellow croaker was investigated. The results showed that MUIF significantly slowed down the oxidation of MP by inhibiting carbonyl formation and maintaining high sulfhydryl contents. These treatments also held a high activity of Ca2+-ATPase in the MP. MUIF maintained a higher ratio of α-helix to ß-sheet during frozen storage, thereby protecting the secondary structure of the tissue and stabilizing the tertiary structure. In addition, MUIF inhibited the production of thiobarbituric acid reactive substances value and the loss of unsaturated fatty acid content, indicating that MUIF could better inhibit lipid oxidation of large yellow croaker during long-time frozen storage.


Assuntos
Congelamento , Oxirredução , Perciformes , Animais , Fatores de Tempo , Armazenamento de Alimentos , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Ondas Ultrassônicas , ATPases Transportadoras de Cálcio/metabolismo
12.
Bioresour Technol ; 406: 130968, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38876277

RESUMO

This study evaluated the reflection of long-term anaerobic system exposed to sulfate and propionate. Fe@C was found to efficiently mitigate anaerobic sulfate inhibition and enhance propionate degradation. With influent propionate of 12000mgCOD/L and COD/SO42- ratio of 3.0, methane productivity and sulfate removal were only 0.06 ± 0.02L/gCOD and 63 %, respectively. Fe@C helped recover methane productivity to 0.23 ± 0.03L/gCOD, and remove sulfate completely. After alleviating sulfate stress, less organic substrate was utilized to form extracellular polymeric substances for self-protection, which enhanced mass transfer in anaerobic sludge. Microbial community succession, especially for alteration of key sulfate-reducing bacteria and propionate-oxidizing bacteria, was driven by Fe@C, thus enhancing sulfate reduction and propionate degradation. Acetotrophic Methanothrix and hydrogenotrophic unclassified_f_Methanoregulaceae were enriched to promote methanogenesis. Regarding propionate metabolism, inhibited methylmalonyl-CoA degradation was a limiting step under sulfate stress, and was mitigated by Fe@C. Overall, this study provides perspective on Fe@C's future application on sulfate and propionate rich wastewater treatment.

13.
Front Psychol ; 15: 1411055, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915426

RESUMO

In the emerging post-pandemic era (the 'wavelet' era), humans must coexist with viruses for the foreseeable future, and personal protective behaviors will largely replace national-level preventive measures. In this new normal, encouraging the public to implement proper personal protective behaviors against the coronavirus disease (COVID-19) is vital to the sustainable development of cities and communities. This knowledge-attitude-practice (KAP) survey conducted in Chengdu (N = 900) narrowed the knowledge gap regarding post-pandemic public practices of protective behavior. Findings show that:(1) approximately 1/3 of the respondents are currently not concerned about COVID-19 at all; (2) respondents with different demographics and individual COVID-19-related factors showed significant differences in practice behaviors indoors and outdoors; (3) vulnerable groups performed better in practice behavior indoors/outdoors; (4) because the public may relax their vigilance outdoors, public places may become a transmission threat in the next outbreak; (5) attitudes are important, but limited incentives for practice; and (6) when knowledge increases beyond a threshold (68.75-75% in this study), protective behaviors decrease. Our results suggest that authorities must continue to educate and motivate the public, extending measures to cover personal protective practices, and have targeted policies for specific demographics to ensure equity in healthcare in the event of another pandemic (COVID-19 and alike crisis). Besides, comparing the results of the current study with similar studies conducted in other parts of the world can provide insights into how different populations respond to and adopt COVID-19 protective behaviors. The epidemiologists can use the data collected by this and other KAP surveys to refine epidemiologic models, which can help predict the spread of the virus and the impact of interventions in different settings.

14.
Int J Artif Organs ; : 3913988241259975, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904358

RESUMO

OBJECTIVE: To investigate the effects of different blood purification modes on left ventricular remodeling and its relationship with serum cardiac troponin I (cTnI) in patients with end-stage renal disease (ESRD). METHOD: A total of 108 patients with ESRD were selected, 55 cases were divided into hemodialysis combined with hemoperfusion (HD + HP) group, in which patients participants accepted routine hemodialysis for three times/week and hemoperfusion for three times/month; 53 cases in hemodialysis combined with hemodialysis filtration (HD + HDF) group, routine hemodialysis three times/week + hemodialysis filtration three times/month. The total duration of dialysis in the study was 1 year. Cardiac troponin I (cTnI) levels were measured before dialysis and 1 year after treatment, and related parameters were measured by echocardiography, including ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVEDs), and left ventricular myocardial mass index (LVMI). The paired t test was used within the group. Correlation analysis was performed using Spearman correlation analysis. RESULT: After treatment, the levels of cTnI, IVST, LVPWT, LVEDd, LVEDs, and LVMI in the two groups were increased, and the results were statistically significant (all p < 0.05). In addition, cTnI of the two groups was significantly correlated with IVST, LVPWT, LVEDd, LVEDs, and LVMI (all p < 0.05). CONCLUSION: Left ventricular remodeling is common in patients with ESRD, HD + Hp, and HD + HDF cannot reduce the phenomenon of left ventricular remodeling, cTnI can be used as a predictor of left ventricular hypertrophy and enlargement.

15.
Biochim Biophys Acta Mol Cell Res ; 1871(7): 119788, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38879132

RESUMO

Chondrocytes rely heavily on glycolysis to maintain the metabolic homeostasis and cartilage matrix turnover. Glycolysis in chondrocytes is remodeled by diverse biochemical and biomechanical factors due to the sporty joint microenvironment. Transforming growth factor-ß2 (TGF-ß2), one of the most abundant TGF-ß superfamily members in chondrocytes, has increasingly attracted attention in cartilage physiology and pathology. Although previous studies have emphasized the importance of TGF-ß superfamily members on cell metabolism, whether and how TGF-ß2 modulates glycolysis in chondrocytes remains elusive. In the current study, we investigated the effects of TGF-ß2 on glycolysis in chondrocytes and explored the underlying biomechanisms. The results showed that TGF-ß2 could enhance glycolysis in chondrocytes by increasing glucose consumption, up-regulating liver-type ATP-dependent 6-phosphofructokinase (Pfkl) expression, and boosting lactate production. The TGF-ß2 signal entered chondrocytes via TGF-ß receptor type I (TßRI), and activated p-Smad3 signaling to regulate the glycolytic pathway. Subsequent experiments employing specific inhibitors of TßRI and p-Smad3 further substantiated the role of TGF-ß2 in enhancement of glycolysis via TßRI/p-Smad3 axis in chondrocytes. The results provide new understanding of the metabolic homeostasis in chondrocytes induced by TGF-ß superfamily and might shed light on the prevention and treatment of related osteoarticular diseases.

16.
Polymers (Basel) ; 16(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38932098

RESUMO

Increasing concern over the safety of consumable products, particularly aquatic products, due to freshness issues, has become a pressing issue. Therefore, ensuring the quality and safety of aquatic products is paramount. To address this, a dual-mode colorimetric-fluorescence sensor utilizing Ce-MOF as a mimic peroxidase to detect H2S was developed. Ce-MOF was prepared by a conventional solvothermal synthesis method. Ce-MOF catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by hydrogen peroxide (H2O2) to produce blue oxidized TMB (oxTMB). When dissolved, hydrogen sulfide (H2S) was present in the solution, and it inhibited the catalytic effect of Ce-MOF and caused the color of the solution to fade from blue to colorless. This change provided an intuitive indication for the detection of H2S. Through steady-state dynamic analysis, the working mechanism of this sensor was elucidated. The sensor exhibited pronounced color changes from blue to colorless, accompanied by a shift in fluorescence from none to light blue. Additionally, UV-vis absorption demonstrated a linear correlation with the H2S concentration, ranging from 200 to 2300 µM, with high sensitivity (limit of detection, LOD = 0.262 µM). Fluorescence intensity also showed a linear correlation, ranging from 16 to 320 µM, with high selectivity and sensitivity (LOD = 0.156 µM). These results underscore the sensor's effectiveness in detecting H2S. Furthermore, the sensor enhanced the accuracy of H2S detection and fulfilled the requirements for assessing food freshness and safety.

17.
Chin J Nat Med ; 22(6): 530-540, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38906600

RESUMO

Although various anti-inflammatory medications, such as ephedrine, are employed to manage cough-variant asthma, their underlying mechanisms are yet to be fully understood. Recent studies suggest that exosomes derived from airway epithelial cells (AECs) contain components like messenger RNAs (mRNAs), micro-RNAs (miRNAs), and long noncoding RNA (lncRNA), which play roles in the occurrence and progression of airway inflammation. This study investigates the influence of AEC-derived exosomes on the efficacy of ephedrine in treating cough-variant asthma. We established a mouse model of asthma and measured airway resistance and serum inflammatory cell levels. Real-time polymerase chain reaction (RT-qPCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA) analyses were used to assess gene and protein expression levels. Exosomes were isolated and characterized. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to examine the interaction between hnRNPA2B1 and lnc-TRPM2-AS1. In the ovalbumin (OVA)-challenged mouse model, ephedrine treatment reduced inflammatory responses, airway resistance, and Th1/Th2 cell imbalance. Exosomes from OVA-treated AECs showed elevated levels of lnc-TRPM2-AS1, which were diminished following ephedrine treatment. The exosomal lnc-TRPM2-AS1 mediated the Th1/Th2 imbalance in CD4+ T cells, with its packaging into exosomes being facilitated by hnRNPA2B1. This study unveils a novel mechanism by which ephedrine ameliorates OVA-induced CD4+ T cell imbalance by suppressing AEC-derived exosomal lnc-TRPM2-AS1. These findings could provide a theoretical framework for using ephedrine in asthma treatment.


Assuntos
Asma , Efedrina , Células Epiteliais , Exossomos , Camundongos Endogâmicos BALB C , Ovalbumina , Células Th2 , Animais , Asma/tratamento farmacológico , Asma/imunologia , Efedrina/farmacologia , Exossomos/metabolismo , Camundongos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Feminino , RNA Longo não Codificante/genética , Humanos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Modelos Animais de Doenças
18.
Front Cell Infect Microbiol ; 14: 1394955, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912208

RESUMO

Background: Accumulated evidences indicate that dysbiosis of the urinary microbiota is associated with kidney stone formation. In the present study, we aimed to investigate the urinary microbiota composition and functionality of patients with calcium oxalate stones and compare it with those of healthy individuals. Method: We collected bladder urine samples from 68 adult patients with calcium oxalate stones and 54 age-matched healthy controls by transurethral catheterization. 16S rRNA gene and shotgun sequencing were utilized to characterize the urinary microbiota and functionality associated with calcium oxalate stones. Results: After further exclusion, a total of 100 subjects was finally included and analyzed. The diversity of the urinary microbiota in calcium oxalate stone patients was not significantly different from that of healthy controls. However, the urinary microbiota structure of calcium oxalate stone formers significantly differed from that of healthy controls (PERMANOVA, r = 0.026, P = 0.019). Differential representation of bacteria (e.g., Bifidobacterium) and several enriched functional pathways (e.g., threonine biosynthesis) were identified in the urine of calcium oxalate stone patients. Conclusion: Our results showed significantly different urinary microbiota structure and several enriched functional pathways in calcium oxalate stone patients, which provide new insight into the pathogenesis of calcium oxalate stones.


Assuntos
Bactérias , Oxalato de Cálcio , Microbiota , RNA Ribossômico 16S , Humanos , Oxalato de Cálcio/urina , Oxalato de Cálcio/metabolismo , Masculino , Feminino , RNA Ribossômico 16S/genética , Pessoa de Meia-Idade , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/isolamento & purificação , Cálculos Renais/urina , Cálculos Renais/microbiologia , Urina/microbiologia , Urina/química , Disbiose/microbiologia , Estudos de Casos e Controles , Idoso
19.
ESC Heart Fail ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937863

RESUMO

AIMS: This study aimed to analyse the global prevalence and disability trends of heart failure (HF) from 1990 to 2019, considering both sexes and country-specific economic strata. METHODS: This study conducted a secondary analysis employing data from the Global Burden of Disease (GBD) study. The analysis is stratified by sex and Socio-demographic Index (SDI) levels. Through age-period-cohort and Joinpoint regression analyses, we investigated the temporal trends in HF prevalence and years lived with disability (YLDs) during this period. RESULTS: Between 1990 and 2019, the global prevalence of HF surged by 106.3% (95% uncertainty interval: 99.3% to 114.3%), reaching 56.2 million cases in 2019. While all-age prevalence and YLDs increased over the 30 year span, age-standardized rates decreased by 2019. Countries with higher SDI experienced a more pronounced percentage decrease compared with those with lower SDI. Longitudinal analysis revealed an overall improvement in both prevalence and YLDs for HF, albeit with notable disparities between SDI quintiles and sexes. Ischaemic heart disease and hypertensive heart disease emerged as the most rapidly increasing and primarily contributing causes of HF, albeit with variations observed across different countries. The average annual percentage change for prevalence and YLDs over the period was -0.26% and -0.25%, respectively. CONCLUSIONS: This study offers valuable insights into the global burden of HF, considering factors such as population aging, regional disparities, sex differences and aetiological variations. The findings hold significant implications for healthcare planning and resource allocation. Continued assessment of these trends and innovative strategies for HF prevention and management are crucial for addressing this pressing global health concern.

20.
Vaccines (Basel) ; 12(6)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38932330

RESUMO

The effectiveness of COVID-19 vaccines depends on widespread vaccine uptake. Employing a telephone-administered weighted survey with 19,502 participants, we examined the determinants of COVID-19 vaccine acceptance among adults in Texas. We used multiple regression analysis with LASSO-selected variables to identify factors associated with COVID-19 vaccine uptake and intentions to receive the vaccine among the unvaccinated. The prevalence of unvaccinated individuals (22%) was higher among those aged 18-39, males, White respondents, English speakers, uninsured individuals, those facing financial challenges, and individuals expressing no concern about contracting the illness. In a fully adjusted regression model, higher odds of being unvaccinated were observed among males (aOR 1.11), the uninsured (aOR 1.38), smokers (aOR 1.56), and those facing financial struggles (aOR 1.62). Conversely, Asians, Blacks, and Hispanics were less likely to be unvaccinated compared to Whites. Among the unvaccinated, factors associated with stronger intent to receive the vaccine included age (over 65 years), Black and Hispanic ethnicity, and perceived risk of infection. Hispanic individuals, the uninsured, those covered by public insurance, and those facing financial challenges were more likely to encounter barriers to vaccine receipt. These findings underscore the importance of devising tailored strategies, emphasizing nuanced approaches that account for demographic, socioeconomic, and attitudinal factors in vaccine distribution and public health interventions.

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