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1.
J Ethnopharmacol ; 333: 118394, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38823663

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Piper methysticum G. Forst (Piperaceae) is traditionally consumed in Polynesian culture. The roots are used to produce an entheogenic drink and traditional medicine with sedative and anxiolytic properties. There is also evidence that it functions as a pain reliever. Kavalactones, its main active ingredients, exhibit psychoactive effects on the central nervous system. However, the active ingredients and pharmacological mechanisms underlying the analgesic effect of kavalactones are unclear. AIM OF THE STUDY: This study investigated the effects of kavain and yangonin on nociception, inflammatory hyperalgesia, and neuropathic mechanical allodynia at the spinal level. MATERIALS AND METHODS: Male Sprague-Dawley rats were administered kavain and yangonin (27.14 and 19.36 nmol/rat) via intrathecal injection. Tail-flick tests were performed to evaluate the anti-nociceptive properties. The efficacy of kavain and yangonin on inflammatory hyperalgesia was examined using a plantar test in rats with carrageenan-induced paw inflammation. The von Frey test was used to assess mechanical allodynia induced by partial sciatic nerve ligation. RESULTS: Intrathecal injection of yangonin demonstrated a relatively potent anti-nociceptive effect and attenuated carrageenan-induced hyperalgesia. These effects were completely reversed by the co-administration of PF 514273, a cannabinoid 1 (CB1) receptor antagonist. However, yangonin did not affect mechanical allodynia at the spinal level. Kavain, another abundant kavalactone, did not affect nociception, hyperalgesia, or mechanical allodynia at the spinal level. CONCLUSIONS: Overall, our study demonstrated that yangonin exerts anti-nociception and anti-inflammatory hyperalgesia effects via CB1 receptors at the spinal level. We identified a single kavalactone, yangonin, extracted from kava as a promising treatment for pain.

2.
J Biomed Sci ; 31(1): 38, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38627765

RESUMO

BACKGROUND: Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood. METHODS: In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse. RESULTS: Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae. CONCLUSION: Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.


Assuntos
Doenças Mitocondriais , Doença de Parkinson , Camundongos , Animais , Dopamina/metabolismo , Citocromos c/metabolismo , Citocromos c/farmacologia , Citocromos c/uso terapêutico , Doença de Parkinson/genética , Mitocôndrias , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/metabolismo , Modelos Animais de Doenças
3.
Angew Chem Int Ed Engl ; 63(22): e202404202, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38525500

RESUMO

Endowing perovskite quantum dots (PQDs) with circularly polarized luminescence (CPL) offers great promise for innovative chiroptical applications, but the existing strategies are inefficient in acquiring stimuli-responsive flexible chiral perovskite films with large, tunable dissymmetry factor (glum) and long-term stability. Here, we report a strategy for the design and synthesis of luminescent cholesteric liquid crystal elastomer (Lumin-CLCE) films with mechanically tunable CPL, which is enabled by liquid crystal-templated chiral self-assembly and in situ covalent cross-linking of judiciously designed photopolymerizable CsPbX3 (X=Cl, Br, I) PQD nanomonomers into the elastic polymer networks. The resulting Lumin-CLCE films showcase circularly polarized structural color in natural light and noticeable CPL with a maximum glum value of up to 1.5 under UV light. The manipulation of CPL intensity and rotation direction is achieved by controlling the self-assembled helicoidal nanostructure and the handedness of soft helices. A significant breakthrough lies in the achievement of a reversible, mechanically tunable perovskite-based CPL switch activated by biaxial stretching, which enables flexible, dynamic anti-counterfeiting labels capable of decrypting preset information in specific polarization states. This work can provide new insights for the development of advanced chiral perovskite materials and their emerging applications in information encryption, flexible 3D displays, and beyond.

4.
Ren Fail ; 46(1): 2319327, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38419565

RESUMO

Nanostructures composed of liposomes and polydopamine (PDA) have demonstrated efficacy as carriers for delivering plasmids, effectively alleviating renal cell carcinoma. However, their role in acute kidney injury (AKI) remains unclear. This study aimed to investigate the effects of the plasmid-encoded lncRNA-OIP5-AS1@PDA nanoparticles (POP-NPs) on renal ischemia/reperfusion (RI/R) injury and explore the underlying mechanisms. RI/R or OGD/R models were established in mice and HK-2 cells, respectively. In vivo, vector or POP-NPs were administered (10 nmol, IV) 48 h after RI/R treatment. In the RI/R mouse model, the OIP5-AS1 and Nrf2/HO-1 expressions were down-regulated, while miR-410-3p expression was upregulated. POP-NPs treatment effectively reversed RI/R-induced renal tissue injury, restoring altered levels of blood urea nitrogen, creatinine, malondialdehyde, inflammatory factors (IL-8, IL-6, TNF-α), ROS, apoptosis, miR-410-3p, as well as the suppressed expression of SOD and Nrf2/HO-1 in the model mice. Similar results were obtained in cell models treated with POP-NPs. Additionally, miR-410-3p mimics could reverse the effects of POP-NPs on cellular models, partially counteracted by Nrf2 agonists. The binding relationship between OIP5-AS1 and miR-410-3p, alongside miR-410-3p and Nrf2, has been substantiated by dual-luciferase reporter and RNA pull-down assays. The study revealed that POP-NPs can attenuate RI/R-induced injury through miR-410-3p/Nrf2 axis. These findings lay the groundwork for future targeted therapeutic approaches utilizing nanoparticles for RI/R-induced AKI.


Assuntos
Injúria Renal Aguda , MicroRNAs , Nanopartículas , RNA Longo não Codificante , Traumatismo por Reperfusão , Animais , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator 2 Relacionado a NF-E2/genética , Traumatismo por Reperfusão/genética , Injúria Renal Aguda/genética , Injúria Renal Aguda/terapia
5.
Eur Arch Otorhinolaryngol ; 281(4): 1933-1940, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38197935

RESUMO

PURPOSE: The endoscopic endonasal approach (EEA) is a minimally invasive and promising modality for treating traumatic superior orbital fissure (SOF) syndrome (tSOFS). Recently, the endoscopic transorbital approach (ETOA) has been considered an alternative method for reaching the anterolateral skull base. This study accessed the practicality of using the ETOA to treat SOF decompression using both cadaveric dissection and clinical application. METHODS: Bilateral anatomic dissections were performed on four adult cadaveric heads using the ETOA and EEA to address SOF decompression. The ETOA procedure for SOF decompression is described, and the extent of SOF decompression was compared between the ETOA and EEA. The clinical feasibility of the ETOA for treating SOF decompression was performed in two patients diagnosed with tSOFS. RESULTS: ETOA allowed for decompression over the lateral aspect of the SOF, from the meningo-orbital band superolaterally to the maxillary strut inferomedially. By contrast, the EEA allowed for decompression over the medial aspect of the SOF, from the lateral opticocarotid recess superiorly to the maxillary strut inferiorly. In both patients treated using the ETOA and SOF decompression, the severity of ophthalmoplegia got obvious improvement. CONCLUSIONS: Based on the cadaveric findings, ETOA provided a feasible access pathway for SOF decompression with reliable outcomes, and our patients confirmed the clinical efficacy of the ETOA for managing tSOFS.


Assuntos
Procedimentos Neurocirúrgicos , Órbita , Adulto , Humanos , Procedimentos Neurocirúrgicos/métodos , Órbita/cirurgia , Endoscopia/métodos , Cadáver , Descompressão
6.
Peptides ; 173: 171150, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38190970

RESUMO

Our previous studies have established that intrathecal oxytocin (OT) and angiotensin IV (Ang IV) injections induce antihyperalgesia and antiallodynia in rodents. Ang IV, a renin-angiotensin system hexapeptide, acts as an endogenous inhibitor that inhibits the oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP). The pain inhibitory effects by Ang IV were found to be through its inhibition on IRAP to potentiate the effect of OT. However, these effects were found to be with a significant sex difference, which could be partially due to the higher expression of IRAP at the spinal cords of female. Therefore, we synthesized Ang IV and OT conjugates connected with a peptide bond and tested for their effects on hyperalgesia and allodynia. Carrageenan-induced hyperalgesia and partial sciatic nerve ligation (PSNL) were performed using rat models. Conjugates Ang IV-OT (Ang IV at the N-terminal) and OT-Ang IV (OT at the N-terminal) were synthesized and intrathecally injected into male and female rats. Our results showed that Ang IV-OT exhibited prominent antihyperalgesia in male rats, particularly during hyperalgesia recovery, whereas OT-Ang IV was more effective during development stage. Ang IV-OT showed clear antihyperalgesia in female rats, but OT-Ang IV had no significant effect. Notably, both conjugates alleviated neuropathic allodynia in male rats; however, OT-Ang IV had no effect in female rats, whereas Ang IV-OT induced significant antiallodynia. In conclusion, Ang IV-OT has greater therapeutic potential for treating hyperalgesia and allodynia than OT-Ang IV. Its effects were not affected by sex, unlike those of OT and OT-Ang IV, extending its possible clinical applications.


Assuntos
Angiotensina II/análogos & derivados , Hiperalgesia , Ocitocina , Ratos , Feminino , Masculino , Animais , Ocitocina/farmacologia , Ocitocina/uso terapêutico , Ocitocina/fisiologia , Hiperalgesia/tratamento farmacológico , Cistinil Aminopeptidase/metabolismo , Angiotensina II/farmacologia , Aminopeptidases , Injeções Espinhais
7.
Sci Rep ; 13(1): 22351, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102208

RESUMO

Wi-Fi fingerprinting has been a popular indoor localization due to the widespread layout of indoor WLAN. However, the signal fluctuations in the complex environments make it difficult to maintain high accuracy localization for the received signal strength (RSS) fingerprinting. Various positioning solutions have emerged to address this challenge, either working in stand-alone mode or in collaborative mode. In the former case, the user only utilizes his own RSS observation to request location service, while the latter usually requires information transfer between users. Considering the spatial correlation of wireless signal distribution, we propose an online joint localization scheme (JointLoc) that does not require direct interaction between users. The fact that the signals observed by users in physical proximity characterize the surroundings is used by JointLoc to identify neighboring users for joint localization. Besides this, JointLoc further integrates a novel subset-based localization scheme, thus the influence of anomalous RSS signals is eliminated before making the final location decision. We have fully evaluated the performance of JointLoc in two RSS datasets collected in real environments. Compared with conventional algorithms and the latest ones, results show that JointLoc is robust against signal fluctuations, and achieves good localization accuracy.

8.
Cancer Epidemiol Biomarkers Prev ; 32(12): 1726-1733, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37721479

RESUMO

BACKGROUND: This study aimed to explore the relationship between diabetes risk reduction diet (DRRD) and bladder cancer risk in Prostate, Lung, Colorectal, Ovarian (PLCO) cohort. METHODS: Data from 99,001 participants in the PLCO Cancer Screening Trial were analyzed using Cox proportional hazards regression models to estimate HRs and 95% confidence intervals (CI) for the association between DRRD score and bladder cancer incidence. Subgroup analyses were conducted to assess whether variables such as age, sex, body mass index, cigarette smoking status, and history of diabetes influenced the observed association. The DRRD score was formulated on the basis of nine nutrient intake indicators derived from the Dietary History Questionnaire. RESULTS: During the median follow-up of 11.7 years, 761 new bladder cancer cases were identified. Participants with highest DRRD scores exhibited a reduced risk of bladder cancer compared with those in the lowest quartile (unadjusted analysis, HR, 0.65; 95% CI, 0.53-0.82); multivariable adjusted analysis, HR, 0.79; 95% CI, 0.64-0.98; Ptrend = 0.007). A similar risk reduction was seen solely in transitional cell carcinoma (HR, 0.79; 95% CI, 0.64-0.99; P = 0.007). In addition, the significant negative association between DRRD scores and bladder cancer risk persisted even after excluding participants with unique characteristics. CONCLUSIONS: This large prospective population-based study suggests that adherence to a DRRD may contribute to the prevention of bladder cancer. IMPACT: The DRRD could potentially mitigate bladder cancer risk, which warrants further validation in diverse populations.


Assuntos
Neoplasias Colorretais , Diabetes Mellitus , Neoplasias da Bexiga Urinária , Masculino , Feminino , Humanos , Próstata/patologia , Estudos Prospectivos , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/prevenção & controle , Dieta , Pulmão/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Comportamento de Redução do Risco , Fatores de Risco
9.
Int J Mol Sci ; 24(14)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37511141

RESUMO

Chlamydomonas reinhardtii is a unicellular green alga that can grow heterotrophically by using acetate as a carbon source. Carotenoids are natural pigments with biological activity and color, which have functions such as antioxidant, anti-inflammatory, vision protection, etc., and have high commercial value and prospects. We transformed Chlamydomonas reinhardtii with the BKT genes from Phaffia rhodozyma (PrBKT) and Chlamydomonas reinhardtii (CrBKT) via plasmid vector, and screened out the stable transformed algal strains C18 and P1. Under the condition that the cell density of growth was not affected, the total carotenoid content of C18 and P1 was 2.13-fold and 2.20-fold higher than that of the WT, respectively. CrBKT increased the levels of ß-carotene and astaxanthin by 1.84-fold and 1.21-fold, respectively, while PrBKT increased them by 1.11-fold and 1.27-fold, respectively. Transcriptome and metabolome analysis of C18 and P1 showed that the overexpression of CrBKT only up-regulated the transcription level of BKT and LCYE (the gene of lycopene e-cyclase). However, in P1, overexpression of PrBKT also led to the up-regulation of ZDS (the gene of ζ-carotene desaturase) and CHYB (the gene of ß-carotene hydroxylase). Metabolome results showed that the relative content of canthaxanthin, an intermediate metabolite of astaxanthin synthesis in C18 and P1, decreased. The overall results indicate that there is a structural difference between CrBKT and PrBKT, and overexpression of PrBKT in Chlamydomonas reinhardtii seems to cause more genes in carotenoid pathway metabolism to be up-regulated.


Assuntos
Carotenoides , Chlamydomonas reinhardtii , Carotenoides/metabolismo , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/metabolismo , Oxigenases/genética , Oxigenases/metabolismo
10.
Head Neck ; 45(9): 2438-2448, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37431182

RESUMO

BACKGROUND: Transpterygoid transposition of the temporoparietal fascia flap (TPFF) is a feasible selection for ventral skull base defect (VSBD) reconstruction, but not anterior skull base defect (ASBD) reconstruction, after expanded endoscopic endonasal approach (EEEA). The goal of this study is to introduce the transorbital transposition of the TPFF for skull base defects reconstruction after EEEA, and make quantitative comparison between the transpterygoid transposition and transorbital transposition. METHODS: Cadaveric dissections were performed in five adult cadaveric heads with creating three transporting corridors bilaterally, encompassing superior transorbital corridor, inferior transorbital corridor, and transpterygoid corridor. For each transporting corridor, the minimum necessary length of the TPFF for skull base defects reconstruction was measured. RESULTS: The areas of ASBD and VSBD were 1019.63 ± 176.32 mm2 and 572.99 ± 126.21 mm2 . The length of the harvested TPFF was 149.38 ± 6.21 mm. In contrast to the transpterygoid transposition with incomplete coverage, transorbital transposition of the TPFF allowed full coverage of ASBD with a minimum necessary length of 109.75 ± 8.31 mm. For VSBD reconstruction, transorbital transposition of the TPFF needs shorter minimum necessary length (123.88 ± 4.49 mm) than transpterygoid transposition (138.00 ± 6.28 mm). CONCLUSIONS: Transorbital corridor is a novel pathway for transporting the TPFF into the sinonasal cavity for skull base defects reconstruction after EEEA. In comparison with transpterygoid transposition, transorbital transposition provides wider coverage of skull base defects with a fixed length of the TPFF.


Assuntos
Procedimentos de Cirurgia Plástica , Adulto , Humanos , Retalhos Cirúrgicos/cirurgia , Base do Crânio/cirurgia , Fáscia/transplante , Cadáver , Endoscopia
11.
ACS Appl Mater Interfaces ; 15(22): 27195-27205, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37227697

RESUMO

Wireless actuation of electrically driven soft actuators is of paramount importance for the development of bioinspired soft robotics without physical connection or on-board batteries. Here, we demonstrate untethered electrothermal liquid crystal elastomer (LCE) actuators based on emerging wireless power transfer (WPT) technology. We first design and fabricate electrothermal LCE-based soft actuators that consist of an active LCE layer, a conductive liquid metal-filled polyacrylic acid (LM-PA) layer, and a passive polyimide layer. LM can function not only as an electrothermal transducer to endow resulting soft actuators with electrothermal responsiveness but also as an embedded sensor to track the resistance changes. Various shape-morphing and locomotive modes such as directional bending, chiral helical deformation, and inchworm-inspired crawling can be facilely obtained through appropriately controlling the molecular alignment direction of monodomain LCEs, and the reversible shape-deformation behaviors of resulting soft actuators can be monitored in real-time through resistance changes. Interestingly, untethered electrothermal LCE-based soft actuators have been achieved by designing a closed conductive LM circuit within the actuators and combining it with inductive-coupling WPT technology. When the resulting soft actuator approaches a commercially available wireless power supply system, an induced electromotive force can be generated within the closed LM circuit, which results in Joule heating and wireless actuation. As proof-of-concept illustrations, wirelessly driven soft actuators that can exhibit programmable shape-morphing behaviors are demonstrated. The research disclosed herein can provide insights into the development of bioinspired somatosensory soft actuators, battery-free wireless soft robots, and beyond.

12.
Nat Commun ; 14(1): 3036, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37236989

RESUMO

In nature, many plants have evolved diverse flight mechanisms to disperse seeds by wind and propagate their genetic information. Inspired by the flight mechanism of the dandelion seeds, we demonstrate light-driven dandelion-inspired microfliers based on ultralight and super-sensitive tubular-shaped bimorph soft actuator. Like dandelion seeds in nature, the falling velocity of the as-proposed microflier in air can be facilely controlled by tailoring the degree of deformation of the "pappus" under different light irradiations. Importantly, the resulting microflier is able to achieve a mid-air flight above a light source with a sustained flight time of ~8.9 s and a maximum flight height of ~350 mm thanks to the unique dandelion-like 3D structures. Unexpectedly, the resulting microflier is found to exhibit light-driven upward flight accompanied by autorotating motion, and the rotation mode can be customized in either a clockwise or counterclockwise direction by engineering the shape programmability of bimorph soft actuator films. The research disclosed herein can offer new insights into the development of untethered and energy-efficient artificial aerial vehicles that are of paramount significance for many applications from environmental monitoring and wireless communication to future solar sail and robotic spacecraft.

13.
Neurosurg Rev ; 46(1): 73, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36944828

RESUMO

The supracerebellar infratentorial (SCIT) approach is commonly used to gain access to the lateral mesencephalic sulcus (LMS), which has been established as a safe entry point into the posterolateral midbrain. This study describes a lateral variant of the SCIT approach, the supreme-lateral SCIT approach, for accessing the LMS through the presigmoid retrolabyrinthine craniectomy and quantitatively compares this approach with the paramedian and extreme-lateral SCIT approaches. Anatomical dissections were performed in four cadaveric heads. In each head, the supreme-lateral SCIT approach was established on one side, following a detailed description of each step, whereas the paramedian and supreme-lateral SCIT approaches were established on the other side. Quantitative measurements of the exposed posterolateral midbrain, the angles of LMS entry, and the depth of surgical corridors were recorded and compared between the three SCIT approach variants. The supreme-lateral (67.70 ± 23.14 mm2) and extreme-lateral (70.83 ± 24.99 mm2) SCIT approaches resulted in larger areas of exposure anterior to the LMS than the paramedian SCIT approach (38.61 ± 9.84 mm2); the supreme-lateral SCIT approach resulted in a significantly smaller area of exposure posterior to the LMS (65.24 ± 6.81 mm2) than the other two variants (paramedian = 162.75 ± 31.98 mm2; extreme-lateral = 143.10 ± 23.26 mm2; both P < .001). Moreover, the supreme-lateral SCIT approach resulted in a surgical corridor with a shallower depth and a smaller angle relative to the horizontal plane than the other two variants. The supreme-lateral SCIT approach is a more lateral approach than the extreme-lateral SCIT approach, providing a subtemporal approach with direct LMS visualization. The supreme-lateral SCIT offers the benefits of both subtemporal and SCIT approaches and represents a suitable option for the management of selected midbrain pathologies.


Assuntos
Mesencéfalo , Procedimentos Neurocirúrgicos , Humanos , Procedimentos Neurocirúrgicos/métodos , Mesencéfalo/cirurgia , Craniotomia/métodos , Dissecação , Cadáver
15.
Int J Mol Sci ; 24(5)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36902115

RESUMO

To determine the efficacy of PT320 on L-DOPA-induced dyskinetic behaviors, and neurochemistry in a progressive Parkinson's disease (PD) MitoPark mouse model. To investigate the effects of PT320 on the manifestation of dyskinesia in L-DOPA-primed mice, a clinically translatable biweekly PT320 dose was administered starting at either 5 or 17-weeks-old mice. The early treatment group was given L-DOPA starting at 20 weeks of age and longitudinally evaluated up to 22 weeks. The late treatment group was given L-DOPA starting at 28 weeks of age and longitudinally observed up to 29 weeks. To explore dopaminergic transmission, fast scan cyclic voltammetry (FSCV) was utilized to measure presynaptic dopamine (DA) dynamics in striatal slices following drug treatments. Early administration of PT320 significantly mitigated the severity L-DOPA-induced abnormal involuntary movements; PT320 particularly improved excessive numbers of standing as well as abnormal paw movements, while it did not affect L-DOPA-induced locomotor hyperactivity. In contrast, late administration of PT320 did not attenuate any L-DOPA-induced dyskinesia measurements. Moreover, early treatment with PT320 was shown to not only increase tonic and phasic release of DA in striatal slices in L-DOPA-naïve MitoPark mice, but also in L-DOPA-primed animals. Early treatment with PT320 ameliorated L-DOPA-induced dyskinesia in MitoPark mice, which may be related to the progressive level of DA denervation in PD.


Assuntos
Antiparkinsonianos , Discinesia Induzida por Medicamentos , Receptor do Peptídeo Semelhante ao Glucagon 1 , Levodopa , Doença de Parkinson , Animais , Camundongos , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Modelos Animais de Doenças , Dopamina/efeitos adversos , Dopamina/uso terapêutico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Levodopa/efeitos adversos , Levodopa/uso terapêutico , Oxidopamina , Doença de Parkinson/tratamento farmacológico
16.
Cell Death Dis ; 14(2): 128, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36792604

RESUMO

During intracerebral hemorrhage (ICH), hematoma formation at the site of blood vessel damage results in local mechanical injury. Subsequently, erythrocytes lyse to release hemoglobin and heme, which act as neurotoxins and induce inflammation and secondary brain injury, resulting in severe neurological deficits. Accelerating hematoma resorption and mitigating hematoma-induced brain edema by modulating immune cells has potential as a novel therapeutic strategy for functional recovery after ICH. Here, we show that intracerebroventricular administration of recombinant human cerebral dopamine neurotrophic factor (rhCDNF) accelerates hemorrhagic lesion resolution, reduces peri-focal edema, and improves neurological outcomes in an animal model of collagenase-induced ICH. We demonstrate that CDNF acts on microglia/macrophages in the hemorrhagic striatum by promoting scavenger receptor expression, enhancing erythrophagocytosis and increasing anti-inflammatory mediators while suppressing the production of pro-inflammatory cytokines. Administration of rhCDNF results in upregulation of the Nrf2-HO-1 pathway, but alleviation of oxidative stress and unfolded protein responses in the perihematomal area. Finally, we demonstrate that intravenous delivery of rhCDNF has beneficial effects in an animal model of ICH and that systemic application promotes scavenging by the brain's myeloid cells for the treatment of ICH.


Assuntos
Edema Encefálico , Lesões Encefálicas , Animais , Humanos , Hemorragia Cerebral/complicações , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/patologia , Inflamação/complicações , Hematoma/tratamento farmacológico , Hematoma/complicações , Hematoma/metabolismo , Imunidade Inata , Modelos Animais de Doenças , Edema Encefálico/complicações , Fatores de Crescimento Neural/uso terapêutico
17.
Nicotine Tob Res ; 25(7): 1251-1260, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-36520961

RESUMO

INTRODUCTION: Tobacco products are addictive, with nicotine serving as the major addictive ingredient. Chronic tobacco use or chronic administration of nicotine alone results in both physiological and psychological dependence. Our previous studies indicated that dextromethorphan (DM) could effectively attenuate the dependence of morphine and methamphetamine. Thus, we further investigated the possible effects of DM on nicotine dependence. AIMS AND METHODS: Conditioned place preference (CPP) test was used to examine nicotine-induced rewarding effects as well as the drug-seeking-related behavior in rats. Nicotine dependence was induced by continuous subcutaneous infusion of nicotine via an osmotic minipump for 7 days and abstinence was initiated by removal of the pump. Withdrawal signs were observed and quantified. Locomotor activity was measured to determine the behavioral sensitization induced by nicotine. To investigate the activity of mesolimbic dopaminergic neuronal activity in correlation with the effects of nicotine, the animals were sacrificed and the nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC) were dissected and used to determine the contents of dopamine (DA) and its metabolites using high-performance liquid chromatography (HPLC). RESULTS: Our results showed that DM could suppress nicotine-induced rewarding effect and drug-seeking-related behavior. In addition, co-administration and post-treatment of DM could both attenuate nicotine withdrawal signs. Moreover, DM could suppress nicotine-induced behavioral sensitization. Neurochemical experiments show that co-administration and post-treatment of DM abolished nicotine-induced increase of the DA turnover rate in the mPFC, but not in the NAc and DS. CONCLUSIONS: The results suggest that DM has a great therapeutic potential in the treatment of nicotine dependence. IMPLICATIONS: Our results showed that DM could suppress nicotine-induced rewarding effect and drug-seeking-related behavior. In addition, co-administration and post-treatment of DM could both attenuate nicotine withdrawal signs. Moreover, DM could suppress nicotine-induced behavioral sensitization. Neurochemical experiments show that co-administration and post-treatment of DM abolished nicotine-induced increase of the DA turnover rate in the mPFC, but not in the NAc and DS. These results suggest that DM has a great therapeutic potential in the treatment of nicotine dependence.


Assuntos
Síndrome de Abstinência a Substâncias , Tabagismo , Ratos , Animais , Nicotina/efeitos adversos , Nicotina/metabolismo , Dextrometorfano/farmacologia , Dextrometorfano/metabolismo , Ratos Sprague-Dawley , Tabagismo/tratamento farmacológico , Tabagismo/metabolismo , Recompensa , Núcleo Accumbens/metabolismo , Dopamina/metabolismo , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/metabolismo
18.
Foods ; 13(1)2023 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-38201094

RESUMO

Proteins from Flammulina filiformis were prepared by sodium chloride extraction and fractionated by ammonium sulfate precipitation with increasing saturation degrees to obtain the protein fractions Ffsp-30, Ffsp-50, Ffsp-70, Ffsp-90, and Ffp-90. Among these protein fractions, Ffsp-50 possessed the most significant cytotoxic effect against three human gastrointestinal cancer cell lines, viz. HT-29, SGC-7901, and HepG2. SDS-PAGE and MALDI-TOF/TOF MS/MS analyses revealed that flammutoxin (FTX) was present as a dominating protein in Ffsp-50, which was further evidenced by HPLC-MS/MS determination. Furthermore, native FTX was purified from Ffsp-50 with a molecular weight of 26.78 kDa, exhibiting notable cytotoxicity against gastrointestinal cancer cell lines. Both Ffsp-50 and FTX exposure could enhance intercellular reactive oxygen species (ROS) generation and induce significant apoptosis in HepG2 cells. FTX was identified to be relatively conserved in basidiomycetes according to phylogenetic analysis, and its expression was highly upregulated in the primordium as well as the pileus of the fruiting body from the elongation and maturation stages, as compared with that in mycelium. Taken together, FTX could remarkably inhibit cell growth and induce ROS and apoptosis in HepG2 cells, potentially participating in the growth and development of the fruiting body. These findings from our investigation provided insight into the antigastrointestinal cancer activity of FTX, which could serve as a biological source of health-promoting and biomedical applications.

19.
Crit Rev Food Sci Nutr ; : 1-28, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36377724

RESUMO

Currently, the whole world is facing hunger due to the increase in the global population and the rising level of food consumption. Unfortunately, the impact of environmental, climate, and political issues on agriculture has resulted in limited global food resources. Thus, it is important to develop new food sources that are environmentally friendly and not subject to climate or space limitations. Microalgae represent a potential source of nutrients and bioactive components for a wide range of high-value products. Advances in cultivation and genetic engineering techniques provide prospective approaches to widen their application for food. However, there are currently problems in the microalgae food industry in terms of assessing nutritional value, selecting processes for microalgae culture, obtaining suitable commercial strains of microalgae, etc. Additionally, the limitations of real data of market opportunities for microalgae make it difficult to assess their actual potential and to develop a better industrial chain. This review addresses the current status of the microalgae food industry, the process of commercializing microalgae food and breeding methods. Current research progress in addressing the limitations of microalgae industrialization and future prospects for developing microalgae food products are discussed.

20.
Nanomicro Lett ; 15(1): 1, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36441443

RESUMO

In nature, many living organisms exhibiting unique structural coloration and soft-bodied actuation have inspired scientists to develop advanced structural colored soft actuators toward biomimetic soft robots. However, it is challenging to simultaneously biomimic the angle-independent structural color and shape-morphing capabilities found in the plum-throated cotinga flying bird. Herein, we report biomimetic MXene-based soft actuators with angle-independent structural color that are fabricated through controlled self-assembly of colloidal SiO2 nanoparticles onto highly aligned MXene films followed by vacuum-assisted infiltration of polyvinylidene fluoride into the interstices. The resulting soft actuators are found to exhibit brilliant, angle-independent structural color, as well as ultrafast actuation and recovery speeds (a maximum curvature of 0.52 mm-1 can be achieved within 1.16 s, and a recovery time of ~ 0.24 s) in response to acetone vapor. As proof-of-concept illustrations, structural colored soft actuators are applied to demonstrate a blue gripper-like bird's claw that can capture the target, artificial green tendrils that can twine around tree branches, and an artificial multicolored butterfly that can flutter its wings upon cyclic exposure to acetone vapor. The strategy is expected to offer new insights into the development of biomimetic multifunctional soft actuators for somatosensory soft robotics and next-generation intelligent machines.

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