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Vitexin (VTX), a C-glycosylated flavone found in various medicinal herbs, is known for its antioxidant, anti-inflammatory, and neuroprotective properties. This study investigated the protective effects of VTX against orofacial dyskinesia (OD) in rats, induced by haloperidol (HPD), along with the neuroprotective mechanisms underlying these effects. OD was induced by administering HPD (1 mg/kg i.p.) to rats for 21 days, which led to an increase in the frequency of vacuous chewing movements (VCMs) and tongue protrusion (TP). VTX (10 and 30 mg/kg) was given intraperitoneally 60 min after each HPD injection during the same period. On the 21st day, following assessments of OD, the rats were sacrificed, and nitrosative and oxidative stress, antioxidant capacity, mitochondrial function, neuroinflammation, and apoptosis markers in the striatum were measured. HPD effectively induced OD, while VTX significantly reduced HPD-induced OD, decreased oxidative stress, enhanced antioxidant capacity, prevented mitochondrial dysfunction, and reduced neuroinflammatory and apoptotic markers in the striatum, and the protective effects of VTX on both behavioral and biochemical aspects of HPD-induced OD were significantly reduced when trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated pathway, was administered. These findings suggest that VTX provides neuroprotection against HPD-induced OD, potentially through the Nrf2 pathway, indicating its potential as a therapeutic candidate for the prevention or treatment of tardive dyskinesia (TD) in clinical settings. However, further detailed research is required to confirm these preclinical findings and fully elucidate VTX's therapeutic potential in human studies. [ABSTRACT FROM AUTHOR]

Herein, the combination of anionic Zr4L6 (L = embonate) cages and N, N-chelated transition-metal cations leads to a series of new cage-based architectures, including ion pair structures (PTC-355 and PTC-356), dimer (PTC-357), and 3D frameworks (PTC-358 and PTC-359). Structural analyses show that PTC-358 exhibits a 2-fold interpenetrating framework with a 3,4-connected topology, and PTC-359 shows a 2-fold interpenetrating framework with a 4-connected dia network. Both PTC-358 and PTC-359 can be stable in air and other common solvents at room temperature. The investigations of third-order nonlinear optical (NLO) properties indicate that these materials show different degrees of optical limiting effects. It is surprising that increasing coordination interactions between anion and cation moieties can effectively enhance their third-order NLO properties, which can be attributed to the formation of coordination bonds that facilitate charge transfer. In addition, the phase purity, UV-vis spectra, and photocurrent properties of these materials were also studied. This work provides new ideas for the construction of third-order NLO materials. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the most frequent form of dementia in aging population and is presently the world's sixth largest cause of mortality. With the advancement of therapies, several solutions have been developed such as passive immunotherapy against these misfolded proteins, thereby resulting in the clearance. Within this segment, encapsulated cell therapy (ECT) solutions that utilize antibody releasing cells have been proposed with a multitude of techniques under development. Hence, in this study, we utilized our novel and patented Microtube Array Membranes (MTAMs) as an encapsulating platform system with anti-pTau antibody-secreting hybridoma cells to study the impact of it on Alzheimer's disease. In vivo results revealed that in the water maze, the mice implanted with hybridoma cell MTAMs intracranially (IN) and subcutaneously (SC) showed improvement in the time spent the goal quadrant and escape latency. In passive avoidance, hybridoma cell loaded MTAMs (IN and SC) performed significantly well in step-through latency. At the end of treatment, animals with hybridoma cell loaded MTAMs had lower phosphorylated tau (pTau) expression than empty MTAMs had. Combining both experimental results unveiled that the clearance of phosphorylated tau might rescue the cognitive impairment associated with AD. [ABSTRACT FROM AUTHOR]

Background. An extensive body of research suggests that brain inflammation and oxidative stress are the underlying causes of Parkinson's disease (PD), for which no potent therapeutic approach exists to mitigate the degradation of dopamine neurons. Freshwater clams, an ancient health food of Chinese origin, have been documented to exhibit anti-inflammatory and antioxidant effects. We previously reported that freshwater clam extract (FCE) can attenuate astrocytic activation and subsequent proinflammatory cytokine production from substantia nigra in an MPTP-induced PD mouse model. This article provides insight into the potential mechanisms through which FCE regulates neuroinflammation in a glia model of injury. Materials and methods. In total, 1 μg/mL lipopolysaccharide (LPS) and 200 μM rotenone were conducted in primary glial cell cultures to mimic the respective neuroinflammation and oxidative stress during injury-induced glial cell reactivation, which is relevant to the pathological process of PD. Results. FCE markedly reduced LPS-induced neuroinflammation by suppressing NO and TNF-α production and the expression of pro-inflammatory cytokines. In addition, FCE was effective at reducing rotenone-induced toxicity by diminishing ROS production, promoting antioxidant enzymes (SOD, catalase, and GPx) and minimizing the decline in glial-cell-secreted neurotrophic factors (GDNF, BDNF). These impacts ultimately led to a decrease in glial apoptosis. Conclusions. Evidence reveals that FCE is capable of stabilizing reactive glia, as demonstrated by reduced neuroinflammation, oxidative stress, the increased release of neurotrophic factors and the inhibition of apoptosis, which provides therapeutic insight into neurodegenerative diseases, including PD. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM. [ABSTRACT FROM AUTHOR]

Malignant glioma (MG) is extremely aggressive and highly resistant to chemotherapeutic agents. Using electrospraying, the potent chemotherapeutic agent 7-ethyl-10-hydroxycamptothecia (SN-38) was embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs). The SMPs were stereotactically injected into the brain parenchyma of healthy rats and intratumorally injected into F98 glioma-bearing rats for estimating the pharmacodynamics and therapeutic efficacy. SN-38 was rapidly released after injection and its local (brain tissue) concentration remained much higher than that in the blood for more than 8 weeks. Glioma-bearing rats were divided into three groups—group A (n = 13; stereotactically injected pure PLGA microparticles), group B (n = 12; stereotactically injected Gliadel wafer and oral temozolomide), and group C (n = 13; stereotactic and intratumoral introduction of SMPs). The SMPs exhibited significant therapeutic efficacy, with prolonged survival, retarded tumor growth, and attenuated malignancy. The experimental results demonstrated that SMPs provide an effective and potential strategy for the treatment of MG. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is significantly associated with osteoarthritis (OA). This study investigated the effects of two resistance exercise approaches on glycated hemoglobin (HbA1c) level and function performance. Enrolled were 70 older patients with both T2DM and knee OA. The dynamic group performed resistance exercises with an elastic resistance band. The isometric group underwent isometric contraction exercises. After the 12-week intervention, a significant within-group improvement (all p < 0.001) was observed for the chair stand test (CST; 10.8%, vs. 7.1%), timed up and go (TUG) test (12.6% vs. 7.6%), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) physical function subscale (62.3% vs. 36.1%), and overall WOMAC (54.5% vs. 34.5%) in the dynamic and isometric group, respectively. In addition, in terms of between-group differences, the dynamic group had significant improvements in CST ( p = 0.011), TUG ( p < 0.001), WOMAC physical function subscale ( p = 0.033), and overall WOMAC ( p = 0.036) scores compared with the isometric group. However, no significant change in HbA1c was observed in either group. In conclusion, the dynamic resistance exercise significantly improved muscle strength, dynamic balance, and physical function in this comorbid population; however, there was no notable difference in change in HbA1c among different resistance exercises., Competing Interests: The authors declare no conflict of interest.

Autophagy, a self-eating machinery, has been reported as an adaptive response to maintain metabolic homeostasis when cancer cells encounter stress. It has been appreciated that autophagy acts as a double-edge sword to decide the fate of cancer cells upon stress factors, molecular subtypes, and microenvironmental conditions. Currently, the majority of evidence support that autophagy in cancer cells is a vital mechanism bringing on resistance to current and prospective treatments, yet whether autophagy affects the anticancer immune response remains unclear and controversial. Accumulated studies have demonstrated that triggering autophagy is able to facilitate anticancer immunity due to an increase in immunogenicity, whereas other studies suggested that autophagy is likely to disarm anticancer immunity mediated by cytotoxic T cells and nature killer (NK) cells. Hence, this contradiction needs to be elucidated. In this review, we discuss the role of autophagy in cancer cells per se and in cancer microenvironment as well as its dual regulatory roles in immune surveillance through modulating presentation of tumor antigens, development of immune cells, and expression of immune checkpoints. We further focus on emerging roles of autophagy induced by current treatments and its impact on anticancer immune response, and illustrate the pros and cons of utilizing autophagy in cancer immunotherapy based on preclinical references., Competing Interests: The authors declare no conflict of interest.