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1.
Artigo em Inglês | MEDLINE | ID: mdl-38743109

RESUMO

RATIONALE: Clinical and preclinical studies have demonstrated that estradiol withdrawal after delivery is one of important factors involved in the pathogenesis of postpartum depression (PPD). The infralimbic cortex (IL) is related to anxiety and mood disorders. Whether IL neurons mediate PPD is still unclear. OBJECTIVES: This study was to observe the antidepressant effect and expression of BDNF and ß-catenin in IL by allopregnanolone (ALLO) treatment or the selective activation or inhibition of IL neurons using a chemogenetic approach in a pseudopregnancy model of PPD. METHODS: Administration of estradiol combined with progesterone and the abrupt withdrawal of estradiol simulated the pregnancy and early postpartum periods to induce depression in ovariectomized rats. The relative expression levels of ß-catenin and BDNF were observed by western blotting. RESULTS: Immobility time was significantly increased in the forced swim test and open-arm movement was reduced in the elevated plus maze test in the estradiol-withdrawn rats. After ALLO treatment, the immobility time were lower and open-arm traveling times higher than those of the estradiol-withdrawn rats. Meanwhile, the expression level of BDNF or ß-catenin in the IL was reduced significantly in estradiol-withdrawn rats, which was prevented by treatment with ALLO. The hM3Dq chemogenetic activation of pyramidal neurons in the IL reversed the immobility and open-arm travel time trends in the estradiol-withdrawal rat model, but chemogenetic inhibition of IL neurons failed to affect this. Upregulated BDNF and ß-catenin expression and increased c-Fos in the basolateral amygdala were found following IL neuron excitation in model rats. CONCLUSIONS: Our results demonstrated that pseudopregnancy and estradiol withdrawal produced depressive-like behavior and anxiety. ALLO treatment or specific excitement of IL pyramidal neurons relieved abnormal behaviors and upregulated BDNF and ß-catenin expression in the IL in the PPD model, suggesting that hypofunction of IL neurons may be involved in the pathogenesis of PPD.

2.
Brain Sci ; 14(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38671986

RESUMO

Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second largest and most frequently seized group of new psychoactive substances. They are considered as ß-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health. Finally, the review discusses public health initiatives and efforts to reduce the hazards of synthetic cathinones, including harm reduction methods, education, and current clinical management strategies.

3.
Addict Biol ; 29(2): e13370, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38353028

RESUMO

N-Isopropylbenzylamine (N-ipb), a chain isomer of methamphetamine (METH) with similar physical properties, has been used as a substitute for METH in seized drug samples. However, the abuse potential of N-ipb remains unclear. Therefore, this study aimed to evaluate the abuse potential of N-ipb in comparison to METH, by using conditioned place preference (CPP), locomotor sensitization and intravenous self-administration tests. The results showed that N-ipb at a dose of 3 mg·kg-1 significantly induced CPP in mice, which was comparable to the effect of METH at 1 mg·kg-1 . Either acute or repeated N-ipb injections (1 or 3 mg·kg-1 ) failed to raise the locomotor activity. However, acute treatment with 10 mg·kg-1 N-ipb elevated the locomotor activity compared with saline, while chronic injection of 10 mg·kg-1 N-ipb induced a delayed and attenuated sensitization compared with 1 mg·kg-1 METH. Rats could acquire N-ipb self-administration at a dose of 1 mg·kg-1 ·infusion-1 , and a typical inverted U-shaped dose-response curve was obtained for N-ipb. The mean dose of N-ipb that maintained the maximum response was greater than that of METH, indicating that N-ipb is less potent for reinforcement than METH. In the economic behavioural analysis, comparison of essential values derived from the demand elasticity revealed that N-ipb is less efficacy as a reinforcer than METH. The present data demonstrate that N-ipb functions as a reinforcer and has a potential for abuse. However, the potency of psychomotor stimulation and the reinforcing effectiveness of N-ipb are lower than those of METH.


Assuntos
Aminas , Estimulantes do Sistema Nervoso Central , Metanfetamina , Camundongos , Ratos , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Roedores , Atividade Motora , Metanfetamina/farmacologia
4.
Front Cardiovasc Med ; 11: 1229299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414926

RESUMO

Background: Tongxinluo capsule (TXLC) is a common drug for treating angina pectoris of coronary heart disease (CHD). In recent years, many systematic reviews (SRs) and meta-analyses (MAs) have reported the efficacy and safety of TXLC for improving angina symptoms in patients with CHD. We aimed to comprehensively evaluate the existing SRs and MAs of TXLC in treating angina pectoris of CHD, summarize the evidence quality, and provide scientific evidence and recommendations. Methods: We searched seven databases for relevant SRs/MAs published up to 1 June 2023. Two reviewers independently completed the literature retrieval, screening, and data extraction. We used A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) to evaluate the methodological quality, the Risk of Bias in Systematic Reviews (ROBIS) to assess the risk of bias, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to determine the strength of the evidence. RevMan 5.3 was used to synthesize data. Results: We identified 15 SRs/MAs, including 329 RCTs and 33,417 patients. According to the evaluation results of AMSTAR-2, only one SR was of high methodological quality, the others were very low. ROBIS assessment showed that one SR (6.67%) had a low risk, 3 SRs (20%) had an unclear risk, and 11 SRs (73.33%) had a high risk. We assessed 42 outcomes by the GRADE, 10 (23.81%) for moderate-quality evidence, 17 (40.48%) for low-quality evidence, and 15 (35.71%) for very-low-quality evidence. Mate-analysis showed that TXLC combined with conventional western medications improved electrocardiogram efficacy (RR = 1.38, 95% CI: 1.23-1.43, P < 0.001) and angina efficacy (OR = 3.58, 95% CI: 3.02-4.24, P < 0.001), reduced angina attack frequency (SMD = -0.54, 95% CI: -0.64 to -0.44, P < 0.001) and angina duration (SMD = -0.42, 95% CI: -0.57 to -0.28, P < 0.001), with general heterogeneity. The pooled results showed that TXLC appears to have some efficacy in improving cardiac function and relieving angina symptoms, but there is limited evidence that it improves cardiovascular event rates, hemorheology, lipids, or hs-CRP. In the assessment of drug safety, TXLC was associated with different degrees of adverse drug reactions. Conclusion: Based on the evidence, TXLC may be effective as an adjuvant treatment for angina pectoris of CHD. However, the quality of the evidence is low, and the drug's safety must be carefully interpreted. In future studies, high-quality randomized controlled trials are needed to confirm the effectiveness and safety of TXLC. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022365372).

5.
Int J Obes (Lond) ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351251

RESUMO

BACKGROUND/OBJECTIVES: Adipose tissue macrophages (ATM) are key actors in the pathophysiology of obesity-related diseases. They have a unique intermediate M2-M1 phenotype which has been linked to endoplasmic reticulum (ER) stress. We previously reported that human M2 macrophages treated with the ER stress inducer thapsigargin switched to a pro-inflammatory phenotype that depended on the stress protein GRP94. In these conditions, GRP94 promoted cathepsin L secretion and was co-secreted with complement C3. As cathepsin L and complement C3 have been reported to play a role in the pathophysiology of obesity, in this work we studied the involvement of GRP94 in the pro-inflammatory phenotype of ATM. METHODS: GRP94, cathepsin L and C3 expression were analyzed in CD206 + ATM from mice, WT or obesity-resistant transgenic fat-1, fed a high-fat diet (HFD) or a standard diet. GRP94 colocalization with cathepsin L and C3 and its effects were analyzed in human primary macrophages using thapsigargin as a control to induce ER stress and palmitic acid (PA) as a driver of metabolic activation. RESULTS: In WT, but not in fat-1 mice, fed a HFD, we observed an increase in crown-like structures consisting of CD206 + pSTAT1+ macrophages showing high expression of GRP94 that colocalized with cathepsin L and C3. In vitro experiments showed that PA favored a M2-M1 switch depending on GRP94. This switch was prevented by omega-3 fatty acids. PA-induced GRP94-cathepsin L colocalization and a decrease in cathepsin L enzymatic activity within the cells (while the enzymatic activity in the extracellular medium was increased). These effects were prevented by the GRP94 inhibitor PU-WS13. CONCLUSIONS: GRP94 is overexpressed in macrophages both in in vivo and in vitro conditions of obesity-associated inflammation and is involved in changing their profile towards a more pro-inflammatory profile. It colocalizes with complement C3 and cathepsin L and modulates cathepsin L activity.

6.
Biosens Bioelectron ; 246: 115895, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38048720

RESUMO

Combined photothermal therapy and nitric oxide (NO)-mediated gas therapy has shown great potential as a cancer treatment. However, the on-demand release of NO at a high concentration presents a challenge owing to the lack of an ideal bio-transducer with a high loading capacity of NO donors and sufficient energy to induce NO release. Here, we present a new 2D BiTiS3 nanosheet that is synthesized, loaded with the NO donor (BNN6), and conjugated with PEG-iRGD to produce a multifunctional bio-transducer (BNN6-BiTiS3-iRGD) for the on-demand production of NO. The BiTiS3 nanosheets not only have a high loading capacity of NO donors (750%), but also exhibit a high photothermal conversion efficiency (59.5%) after irradiation by a 1064-nm laser at 0.5 W/cm2. As a result of the above advantages, the temporal-controllable generation of NO within a large dynamic range (from 0 to 344 µM) is achieved by adjusting power densities, which is among the highest efficiency values reported for NO generators so far. Moreover, the targeted accumulation of BNN6-BiTiS3-iRGD at tumor sites leads to spatial-controllable NO release. In vitro and in vivo assessments demonstrate synergistic NO gas therapy with mild photothermal therapy based on BNN6-BiTiS3-iRGD. Our work provides insights into the design and application of other 2D nanomaterial-based therapeutic platforms.


Assuntos
Técnicas Biossensoriais , Nanopartículas , Neoplasias , Animais , Óxido Nítrico , Bitis , Luz , Fototerapia , Linhagem Celular Tumoral , Neoplasias/terapia , Neoplasias/patologia
7.
Adv Sci (Weinh) ; 11(3): e2305762, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38115673

RESUMO

The photothermal performance of black phosphorus (BP) in the near infrared (NIR)-II bio-window (1000-1500 nm) is low, which limits its biomedical applications. Herein, ultrasmall nickel phosphide quantum dots (Ni2 P QDs) are synthesized with BP quantum dots (BPQDs) as the template by topochemical transformation. The size of Ni2 P QDs is ≈3.5 nm, similar to that of BPQDs, whereas the absorption and photothermal conversion efficiency of Ni2 P QDs at 1064 nm (43.5%) are significantly improved compared with those of BPQDs. To facilitate in vivo applications, an Ni2 P QDs-based liposomal nano-platform (Ni2 P-DOX@Lipo-cRGD) is designed by incorporation of Ni2 P QDs and doxorubicin (DOX) into liposomal bilayers and the interior, respectively. The encapsulated DOX is responsively released from liposomes upon 1064-nm laser irradiation owing to the photothermal effect of Ni2 P QDs, and the drug release rate and amount are controlled by the light intensity and exposure time. In vivo, experiments show that Ni2 P-DOX@Lipo-cRGD has excellent tumor target capability and biocompatibility, as well as complete tumor ablation through the combination of photothermal therapy and chemotherapy. The work provides a new paradigm for the NIR-II transformation of nano-materials and may shed light on the construction of multifunctional nano-platforms for cancer treatment.


Assuntos
Neoplasias , Pontos Quânticos , Humanos , Fototerapia , Fósforo , Doxorrubicina , Lipossomos , Neoplasias/tratamento farmacológico
8.
Biosens Bioelectron ; 241: 115665, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37716159

RESUMO

Nanozymes with enzyme-like characteristics have drawn wide interest but the catalytic activity and substrate selectivity of nanozymes still need improvement. Herein, Se-vacancy-rich TiSe2-x@Au nanocomposites are designed and demonstrated as nanozymes. The TiSe2-x@Au nanocomposites show excellent peroxidase-like activity and the chromogenic substrate p-phenylenediamine (PPD) can be selectively oxidized to compounds that exhibit an absorption peak at 413 nm that differs from that of self-oxidation or generally oxidized species, suggesting high catalytic activity and strong substrate selectivity. Theoretical calculations reveal that the PPD adsorption geometry at Se vacancies with an adsorption energy of -3.00 eV shows a unique spatial configuration and charge distribution, thereby inhibiting the free reaction and promoting both the activity and selectivity in PPD oxidation. The TiSe2-x@Au colorimetric system exhibits a wide linear range of 0.015 mM-0.6 mM and a low detection limit of 0.0037 mM in the detection of glucose. The blood glucose detection performance for human serum samples is comparable to that of a commercial glucose meter in the hospital (relative standard deviation < 6%). Our findings demonstrate a new strategy for rapid and accurate detection of blood glucose and our results provide insights into the future design of nanozymes.

9.
Mol Nutr Food Res ; 67(22): e2300269, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37726247

RESUMO

SCOPE: To summarize the effect of vitamin E-coated dialyzer membranes (VEMs) treatment or oral vitamin E intake on antioxidant molecules, such as superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant level in patients receiving dialysis. METHODS AND RESULTS: A literature search of PubMed, Embase, CNKI, and the Cochrane Library databases is performed from inception to July 1, 2023, with no language nor country restrictions. Twenty-four experimental studies involving 512 patients undergoing dialysis are selected for meta-analysis. The levels of antioxidant markers in the blood of patients receiving hemodialysis (HD) improve with long-term VEMs treatment (p = 0.016). According to the findings of each antioxidant index, there is a significant increase in the levels of erythrocyte-derived SOD (p = 0.047), CAT (p = 0.029), and plasma-derived total antioxidant level (p < 0.001). The antioxidant marker levels in patients receiving HD are significantly increased by oral vitamin E intake (p < 0.001). Erythrocyte-derived SOD (p = 0.003), GPX (p < 0.001), and CAT (p = 0.001) substantially improves after 2-6 months of intervention with oral vitamin E preparation. The antioxidant index of patients receiving peritoneal dialysis (PD) is unaffected by oral vitamin E treatment (p = 0.945). CONCLUSION: Vitamin E therapy has a favorable effect on the retention of antioxidant compounds in patients undergoing dialysis.


Assuntos
Antioxidantes , Vitamina E , Humanos , Antioxidantes/metabolismo , Vitamina E/farmacologia , Diálise Renal/efeitos adversos , Estresse Oxidativo , Catalase/farmacologia , Superóxido Dismutase , Glutationa Peroxidase
10.
Int J Biol Macromol ; 251: 126329, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37595718

RESUMO

The ε-polylysine (ε-PL) is a food-grade antimicrobial substance. The cationic ε-PL molecules may interact with anionic components of food matrix causing turbidity, sedimentation, and hampering the antimicrobial activity. Herein, sodium alginate (SA) was used as wall material to encapsulate ε-PL, thereby to synthesize ε-PL-SA nanoparticles (ε-PL-SA-NPs). Monosaccharide composition and molecular weight of SA were characterized. The synthetic scheme is optimized and physicochemical characteristics and antimicrobial potential was investigated. Findings indicate that SA primarily consisted of mannuronic acid (95.25 %), weight average molecular weight (Mw) of SA was 176.464 kDa, and the molecular configuration of SA was irregular line clusters. The encapsulation efficiency (EE) of ε-PL in ε-PL-SA-NPs made under optimum strategy (at pH 6.0, mass ratio of ε-PL to SA is 0.14, and SA concentration is 6 mg/mL) is about 99.74 %. The particle size of ε-PL-SA-NPs is ∼541.86 nm. The SEM image showed that the ε-PL-SA-NPs had a nearly spherical morphology. Zeta-potential and FTIR data reveal the interaction between ε-PL and SA was electrostatic and the hydrogen bonding. Agar diffusion assay exhibit that ε-PL-SA-NPs had antimicrobial activity against Escherichia coli and Staphylococcus aureus. The salmon preservation experiments reveal sustained antimicrobial efficacy of ε-PL-SA-NPs.

11.
Biosens Bioelectron ; 239: 115623, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37643492

RESUMO

Development of specific signal reporters with signal amplification effect are highly needed for sensitive and accurate detection of pathogen. Herein, we design a colorimetric immunosensing nanosystem based on liposome encapsulated quantum dots-sized MnO2 nanozyme (MnO2QDs@Lip) as a signal reporter for ultrasensitive and fast detection of SARS-CoV-2 antigen. The pathogenic antigens captured and separated by antibody-conjugated magnetic beads (MBs) are further connected with antibody-modified MnO2QDs@Lip to form a sandwich-like immunocomplex structure. After triggered release, MnO2 QDs efficiently catalyze colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB, which can be qualitatively observed by naked eyes and quantitatively analyzed by UV-Vis spectra or smartphone platforms. By taking advantages of immuno-magnetic separation, excellent peroxidase-like catalytic activity of MnO2 QDs, and high encapsulation efficiency of MnO2QDs@Lip, ultrasensitive detection of SARS-CoV-2 antigen ranging from 0.1 pg/mL to 100 ng/mL is achieved within 20 min. The limit of detection (LOD) is calculated to be 65 fg/mL in PBS buffer. Furthermore, real clinical samples of SARS-CoV-2 antigens can be effectively identified by this immunosensing nanosystem with excellent accuracy. This proposed detection nanosystem provides a strategy for simple, rapid and ultrasensitive detection of pathogens and may shed light on the development of new POCT detection platforms for early diagnosis of pathogens and surveillance in public health.


Assuntos
Técnicas Biossensoriais , Colorimetria , Imunoensaio , SARS-CoV-2 , Colorimetria/métodos , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Lipossomos/química , Antígenos Virais/análise , Antígenos Virais/imunologia , SARS-CoV-2/química , SARS-CoV-2/imunologia , Nanopartículas
12.
ChemSusChem ; 16(24): e202300829, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-37435816

RESUMO

Electro-chemically reducing CO2 in a highly acidic medium is promising for addressing the issue of carbonate accumulation. However, the hydrogen evolution reaction (HER) typically dominates the acidic CO2 reduction. Herein, we construct an efficient electro-catalyst for CO formation based on a core-shell structure, where nitrogen-doped Ni nanoparticles coexist with nitrogen-coordinated Ni single atoms. The optimal catalyst demonstrates a significantly improved CO faradaic efficiency (FE) of 96.7 % in the acidic electrolyte (pH=1) at an industrial-scale current density of 500 mA cm-2 . Notably, the optimal catalyst maintains a high FE of CO exceeding 90 % (current density=500 mA cm-2 ) in the electrolyte with a wide pH range from 0.67 to 14. In-situ spectroscopic characterization and density functional theory calculations show that the local electron density of Ni-N-C sites is enhanced by N-doped Ni particles, which facilitates the formation of *COOH intermediate and the adsorption of *CO. This study demonstrates the potential of a hybrid metal/Ni-N-C interface in boosting acidic CO2 electro-reduction.

13.
J Nanobiotechnology ; 21(1): 224, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443019

RESUMO

As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms.


Assuntos
Neoplasias Ósseas , Nanopartículas , Neoplasias , Osteossarcoma , Animais , Camundongos , Terapia Fototérmica , Antagomirs , Fototerapia/métodos , Osteossarcoma/terapia , Neoplasias/patologia , Neoplasias Ósseas/terapia , Linhagem Celular Tumoral
14.
Int J Clin Exp Pathol ; 16(4): 76-85, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168512

RESUMO

OBJECTIVE: Detection of gene rearrangements in MYC (a family of regulator genes and proto-oncogenes) and human B-cell lymphoma 6 (BCL6) using fluorescence in situ hybridization (FISH) are important in the evaluation of lymphomas, in particular diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Our current clinical MYC and BCL6 FISH workflow involves an overnight hybridization of probes with digital analysis using the GenASIs Scan and Analysis instrument (Applied Spectral Imaging). In order to improve assay turnaround time SureFISH probes were validated to reduce the hybridization time from 16 hours down to 1.5 hours. METHODS: Validation was a four-phase process involving initial development of the assays by testing new probes in a manual protocol, and cytogenetic studies to confirm the probe specificity, sensitivity, and localization. In the next phase, the assays were validated as a manual assay. The third phase involved development of the digital FISH assays by testing and optimizing the GenASIs Scan and Analysis instrument. In the final phase, the digital FISH assays were validated. RESULTS: Cytogenetic studies confirmed 100% probe sensitivity/specificity, and localization patterns. Negative reference range cutoffs calculated from 20 normal lymph nodes using the inverse of the beta cumulative probability density function (Excel BETAINV calculation) were 11% inclusive for both manual and digital MYC and BCL6 assays. There was 100% concordance between the manual and digital methods. The shortened hybridization time decreased the overall workflow time by 14.5 hours. CONCLUSIONS: This study validates the use of the SureFISH MYC and BCL6 probes on formalin fixed paraffin embedded (FFPE) tissue sections using a hybridization time of 1.5 hours that shortened the overall workflow by 14.5 hours. The process described also provides a standardized framework for validating digital FISH assays in the future.

15.
J Integr Neurosci ; 22(3): 76, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37258429

RESUMO

PURPOSE: Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. METHODS: Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. RESULTS: Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA). CONCLUSIONS: The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse.


Assuntos
Dependência de Heroína , Nootrópicos , Ratos , Animais , Heroína/farmacologia , Heroína/uso terapêutico , Donepezila/farmacologia , Sinais (Psicologia) , Nootrópicos/farmacologia , Condicionamento Operante , Dependência de Heroína/tratamento farmacológico , Dependência de Heroína/psicologia , Ratos Sprague-Dawley , Receptores Dopaminérgicos , Colinérgicos/uso terapêutico , Extinção Psicológica
16.
Molecules ; 28(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37241720

RESUMO

In this study, the flavor compounds of Camellia seed oils obtained by four processes were characterized by headspace solid phase microextraction/gas chromatography/mass spectrometry (HS-SPME/GC/MS). A variety of about 76 volatile flavor compounds were identified from all the oil samples. Of the four processing processes, the pressing process can retain a lot of volatile components. Among these, compounds nonanal and 2-undecenal were predominantly in the majority of the samples. Meanwhile, other compounds such as octyl ester formic acid, octanal and 2-nonenal (E), 3-acetyldihydro 2(3H)-furanone, (E)-2-decenal, dihydro-5-penty 2(3H)-furanone, nonanoic acid, and dodecane were also among the most consistently found compounds among the oil samples analyzed. The principal component analysis carried out to categorize the data produced seven clusters of the total oil samples based on the number of flavor compounds obtained in each sample. This categorization would lead to understanding the components which highly contributed to the characteristic volatile flavor and build up the flavor profile of Camellia seed oil.


Assuntos
Microextração em Fase Sólida , Compostos Orgânicos Voláteis , Microextração em Fase Sólida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Óleos de Plantas , Sementes/química , Análise de Componente Principal , Compostos Orgânicos Voláteis/análise
17.
Front Aging Neurosci ; 15: 1174341, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37181622

RESUMO

Background and objectives: Depression is a common comorbidity of dementia and may be a risk factor for dementia. Accumulating evidence has suggested that the cholinergic system plays a central role in dementia and depression, and the loss of cholinergic neurons is associated with memory decline in aging and Alzheimer's patients. A specific loss of cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) is correlated with depression and dysfunction of cognition in mice. In this study, we examined the potential regenerative mechanisms of knockdown the RNA-binding protein polypyrimidine tract binding protein (PTB) in reversing depression-like behaviors and cognition impairment in mice with lesioned cholinergic neurons. Methods: We lesioned cholinergic neurons in mice induced by injection of 192 IgG-saporin into HDB; then, we injected either antisense oligonucleotides or adeno-associated virus-shRNA (GFAP promoter) into the injured area of HDB to deplete PTB followed by a broad range of methodologies including behavioral examinations, Western blot, RT-qPCR and immunofluorescence. Results: We found that the conversion of astrocytes to newborn neurons by using antisense oligonucleotides on PTB in vitro, and depletion of PTB using either antisense oligonucleotides or adeno-associated virus-shRNA into the injured area of HDB could specifically transform astrocytes into cholinergic neurons. Meanwhile, knockdown of PTB by both approaches could relieve the depression-like behaviors shown by sucrose preference, forced swimming or tail-suspension tests, and alleviate cognitive impairment such as fear conditioning and novel object recognition in mice with lesioned cholinergic neurons. Conclusion: These findings suggest that supplementing cholinergic neurons after PTB knockdown may be a promising therapeutic strategy to revert depression-like behaviors and cognitive impairment.

18.
Front Psychiatry ; 14: 1160341, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37181871

RESUMO

The neurobiological mechanism underlying methamphetamine (MA) use disorder was still unclear, and no specific biomarker exists for clinical diagnosis of this disorder. Recent studies have demonstrated that microRNAs (miRNAs) are involved in the pathological process of MA addiction. The purpose of this study was to identify novel miRNAs for the diagnosis biomarkers of MA user disorder. First, members of the miR-320 family, including miR-320a-3p, miR-320b, and miR-320c, were screened and analyzed in the circulating plasma and exosomes by microarray and sequencing. Secondly, plasma miR-320 was quantified by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) in eighty-two MA patients and fifty age-gender-matched healthy controls. Meanwhile, we also analyzed exosomal miR-320 expression in thirty-nine MA patients and twenty-one age-matched healthy controls. Furthermore, the diagnostic power was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The expression of miR-320 significantly increased in plasma and exosomes of MA patients compared with healthy controls. The AUC of the ROC curves of miR-320 in plasma and exosomes of MA patients were 0.751 and 0.962, respectively. And the sensitivities of miR-320 were 0.900 and 0.846, respectively, whereas the specificities of miR-320 were 0.537 and 0.952, respectively, in plasma and exosomes in MA patients. And the increased plasma miR-320 was positively correlated with cigarette smoking, age of onset, and daily use of MA in MA patients. Finally, cardiovascular disease, synaptic plasticity, and neuroinflammation were predicted to be the target pathways related to miR-320. Taken together, our findings indicated that plasma and exosomal miR-320 might be used as a potential blood-based biomarker for diagnosing MA use disorder.

19.
Food Chem X ; 18: 100672, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37091512

RESUMO

The effects of different particle sizes of purple sweet potato flour (PSPF) on the structure and quality of noodles and the diffusion kinetics of anthocyanins during cooking were studied. As the particle size of the PSPF decreased (from 269 to 66 µm), the adverse effects of the addition of PSPF on the quality of noodles were reduced. The smaller particle size of PSPF was beneficial for the secondary structure orderliness and the tighter microstructure of PSP noodles. The diffusion of anthocyanins in noodles to the soup during cooking could be fitted well with Fick's second law, and diffusion coefficients were in the range of 8.3248-14.0893 × 10-9 m2/s. The noodles with 15% 66 µm PSPF showed the best cooking properties, the highest sensory score, the highest anthocyanin retention ability and a compact and orderly microstructure. Thus, they could be considered as noodles rich in anthocyanins for commercial application.

20.
Artigo em Inglês | MEDLINE | ID: mdl-37037245

RESUMO

Locality-sensitive hashing (LSH) has gained ever-increasing popularity in similarity search for large-scale data. It has competitive search performance when the number of generated hash bits is large, reversely bringing adverse dilemmas for its wide applications. The first purpose of this work is to introduce a novel hash bit reduction schema for hashing techniques to derive shorter binary codes, which has not yet received sufficient concerns. To briefly show how the reduction schema works, the second purpose is to present an effective bit reduction method for LSH under the reduction schema. Specifically, after the hash bits are generated by LSH, they will be put into bit pool as candidates. Then mutual information and data labels are exploited to measure the correlation and structural properties between the hash bits, respectively. Eventually, highly correlated and redundant hash bits can be distinguished and then removed accordingly, without deteriorating the performance greatly. The advantages of our reduction method include that it can not only reduce the number of hash bits effectively but also boost retrieval performance of LSH, making it more appealing and practical in real-world applications. Comprehensive experiments were conducted on three public real-world datasets. The experimental results with representative bit selection methods and the state-of-the-art hashing algorithms demonstrate that the proposed method has encouraging and competitive performance.

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