Photobiomodulation combination therapy as a new insight in neurological disorders: a comprehensive systematic review.

Preclinical and clinical studies have indicated that combining photobiomodulation (PBM) therapy with other therapeutic approaches may influence the treatment process in a variety of disorders. The purpose of this systematic review was to determine whether PBM-combined therapy provides additional benefits over monotherapies in neurologic and neuropsychiatric disorders. In addition, the review describes the most commonly used methods and PBM parameters in these conjunctional approaches.To accomplish this, a systematic search was conducted in Google Scholar, PubMed, and Scopus databases through January 2024. 95 potentially eligible articles on PBM-combined treatment strategies for neurological and neuropsychological disorders were identified, including 29 preclinical studies and 66 clinical trials.According to the findings, seven major categories of studies were identified based on disease type: neuropsychiatric diseases, neurodegenerative diseases, ischemia, nerve injury, pain, paresis, and neuropathy. These studies looked at the effects of laser therapy in combination with other therapies like pharmacotherapies, physical therapies, exercises, stem cells, and experimental materials on neurological disorders in both animal models and humans. The findings suggested that most combination therapies could produce synergistic effects, leading to better outcomes for treating neurologic and psychiatric disorders and relieving symptoms.These findings indicate that the combination of PBM may be a useful adjunct to conventional and experimental treatments for a variety of neurological and psychological disorders.

Magnetic hybrid nanovesicles for the precise diagnosis and treatment of central nervous system disorders.

INTRODUCTION: Central nervous system (CNS)-related disorders are increasingly being recognized as a global health challenge worldwide. There are significant challenges for effective diagnosis and treatment due to the presence of the CNS barriers which impede the management of neurological diseases. Combination of nanovesicles (NVs) and magnetic nanoparticles (MNPs), referred to as magnetic nanovesicles (MNVs), is now well suggested as a potential theranostic option for improving the management of neurological disorders with increased targeting efficiency and minimized side effects. AREAS COVERED: This review provides a summary of major CNS disorders and the physical barriers limiting the access of imaging/therapeutic agents to the CNS environment. A special focus on the unique features of MNPs and NV is discussed which make them attractive candidates for neuro-nanomedicine. Furthermore, a deeper understanding of MNVs as a promising combined strategy for diagnostic and/or therapeutic purposes in neurological disorders is provided. EXPERT OPINION: The multifunctionality of MNVs offers the ability to overcome the CNS barriers and can be used to monitor the effectiveness of treatment. The insights provided will guide future research toward better outcomes and facilitate the development of next-generation, innovative treatments for CNS disorders.

The efficacy and safety of interleukin-1 receptor antagonist in stroke patients: A systematic review.

Stroke is the leading cause of disability worldwide, yet there is currently no effective treatment available to mitigate its negative consequences. Pro-inflammatory cytokines, such as interleukin-1 (IL-1), are known to play a crucial role in exacerbating the aftermath of stroke. Thus, it is hypothesized that blocking inflammation and administering anti-inflammatory drugs at an optimal time and dosage may improve the long-term quality of life for stroke patients. This systematic review examines the effectiveness and safety of IL-1 receptor antagonist (IL-1Ra), commercially known as "anakinra," in clinical studies involving the treatment of stroke patients. A comprehensive literature search was conducted until October 2023 to identify relevant studies. The search yielded 1403 articles, out of which 598 were removed due to duplication. After a thorough review of 805 titles and abstracts, 797 articles were further excluded, resulting in 8 studies being included in this systematic review. The findings from all the included studies demonstrate that IL-1Ra is safe for use in acute ischemic and hemorrhagic stroke patients, with no significant adverse events reported. Additionally, biomarkers, clinical assessments, serious adverse events (AEs), and non-serious AEs consistently showed more favorable outcomes in IL-1Ra receiving patients. Stroke elevates the levels of several inflammatory cytokines, however, administration of IL-1RA directly or indirectly modulates these markers and improves some clinical outcomes, suggesting a potential therapeutic benefit of this intervention.

The effects of melatonin supplementation on neurobehavioral outcomes and clinical severity in rodent models of multiple sclerosis; a systematic review and meta-analysis.

BACKGROUND: Through the antioxidant and anti-inflammation pathways, melatonin is proposed as a safe and effective intervention in neurological diseases. This study aims to evaluate the effects of melatonin supplementation on the neurobehavioral and clinical outcomes in animal models of multiple sclerosis (MS). METHODS: This study was conducted following the PRISMA statement. Animal studies that reported the effects of melatonin in preclinical MS models, including the experimental autoimmune encephalomyelitis (EAE) and cuprizone model for demyelination are included in this study. A systematic search in PubMed, Web of Science, Embase, and Scopus up was conducted in April 2023. The collaborative Approach to Meta-Analysis and Review of Animal Experimental Studies (CAMARADES) critical appraisal tool was used for the quality assessment of the studies and the quantitative synthetizes were conducted using the comprehensive meta-analysis software. RESULTS: Out of 542 studies, finally 21 studies, including 14 studies in the EAE model and 7 studies of the toxic demyelination method with cuprizone were included. The route of administration was intraperitoneal in 18 studies, oral in 2 studies, and subcutaneous in 1 study. The quantitative synthesis of the EAE clinical severity scale was associated with significant differences (standardized mean difference [SDM]: - 2.52; - 3.61 to - 1.42; p value < 0.01). In subgroup analyses, the difference was statistically significant in the mouse subgroup (SMD: - 2.60; - 3.74 to - 1.46; p value < 0.01). DISCUSSION: This study encountered that melatonin may be associated with improved behavioral and cognitive outcomes of preclinical models of MS with acceptable safety profiles. FUNDING: The research was supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71005).

Sericin Improves Memory Impairment Via Activation of the PKA-CREB-BDNF Signaling Pathway and Suppression of Oxidative Stress in Ovariectomized Mice.

Menopause results in estrogen hormone deficiency which causes changes in brain morphology and cognitive impairments. The risk of breast and ovarian cancer increases with estrogen therapy. Thus, finding a substitute treatment option for women in menopause is necessary. In the current study, the impact of chronic sericin treatment (200 mg/kg/day for 6 weeks, gavage) on memory process, oxidative stress markers, synaptic neurotransmission, and acetylcholinesterase (AChE) activity in the hippocampus (HIP) of ovariectomized (OVX) mice was examined and compared to the effects of 17ß-estradiol (Es; 20 µg/kg, s.c.). The results demonstrated that sericin and Es administration improved spatial and recognition memory of the OVX animals in the both Lashley III maze and novel object recognition tests. Moreover, sericin-treated OVX mice showed decreased ROS levels, increased endogenous antioxidant defense capacity, and decreased AChE activity in the HIP. Additionally, sericin and Es therapy up-regulated pre-and-post-synaptic protein markers and increased BDNF, CREB, and protein kinase A (PKA) protein expressions in the HIP of OVX mice. Overall, the activation of the PKA-CREB-BDNF signaling pathway by sericin can provide protection against OVX-induced cognitive dysfunction, making it a potential alternative for managing cognitive deficits in postmenopausal women.

Transcranial photobiomodulation mitigates learning and memory impairments induced by hindlimb unloading in a mouse model of microgravity exposure by suppression of oxidative stress and neuroinflammation signaling pathways.

Prolonged microgravity exposure causes cognitive impairment. Evidence shows that oxidative stress and neuroinflammation are involved in the causation. Here, we explore the effectiveness of transcranial near-infrared photobiomodulation (PBM) on cognitive deficits in a mouse model of simulated microgravity. 24 adult male C57BL/6 mice were assigned into three groups (8 in each); control, hindlimb unloading (HU), and HU + PBM groups. After surgery to fit the suspension fixing, the animals were housed either in HU cages or in their normal cage for 14 days. The mice in the HU + PBM group received PBM (810 nm laser, 10 Hz, 8 J/cm2) once per day for 14 days. Spatial learning and memory were assessed in the Lashley III maze and hippocampus tissue samples were collected to assess oxidative stress markers and protein expression of brain-derived neurotrophic factor (BDNF), nuclear factor erythroid 2-related factor 2 (Nrf2), Sirtuin 1 (Sirt1), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Behavioral testing showed that the PBM-treated animals had a shorter latency time to find the target and fewer errors than the HU group. PBM decreased hippocampal lipid peroxidation while increasing antioxidant defense systems (glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) compared to HU mice. PBM increased protein expression of Sirt1, Nrf2, and BDNF while decreasing NF-κB compared to HU mice. Our findings suggested that the protective effect of PBM against HU-induced cognitive impairment involved the activation of the Sirt1/Nrf2 signaling pathway, up-regulation of BDNF, and reduction of neuroinflammation and oxidative stress in the hippocampus.

SIMOA-based analysis of plasma NFL levels in MCI and AD patients: a systematic review and meta-analysis.

BACKGROUND: The single-molecule array assay (SIMOA)-based detection of neurofilament light (NFL) chain could be useful in diagnosing mild cognitive impairment (MCI) and Alzheimer's disease (AD). This meta-analysis aimed to evaluate the circulating concentration of NFL in AD and MCI patients compared with healthy controls using the SIMOA technique. METHODS: To this end, Google Scholar, PubMed, Scopus, Web of Science, and the reference lists of relevant articles were systematically searched for studies reporting serum NFL chain levels in healthy controls, MCI, and AD patients. Appropriate statistical methods were employed to achieve the study purpose. RESULTS: Fifteen eligible studies including 3086 patients were pooled out of a total of 347 publications. Fixed effect model analysis showed that NFL chain level was significantly higher in the serum of patients with MCI (0.361 SMD, 95% CI, 0.286-0.435, p = 0.000, I2 = 49.179) and AD (0.808 SMD, 95% CI, 0.727-0.888, p = 0.000, I2 = 39.433) compared with healthy individuals. The analysis also showed that the NFL chain levels in plasma were significantly different between patients with MCI and AD (0.436 SMD, 95% CI, 0.359-0.513, p = 0.000, I2 = 37.44). The overall heterogeneity of the studies was modest. CONCLUSIONS: This study highlights the potential of serum NFL chain detected using SIMOA in differentiating MCI, AD, and healthy controls.

Sericin improves memory and sociability impairments evoked by transient global cerebral ischemia through suppression of hippocampal oxidative stress, inflammation, and apoptosis.

Sericin (Ser) is a natural neuroactive macromolecule with diverse pharmacological properties, and our previous findings have shown its neuroprotective potentials. This study aimed to investigate the therapeutic potential of Ser on cognitive dysfunction induced by transient global cerebral ischemia/reperfusion (tGI/R) and its mechanism of action. The tGI/R was induced in BALB/c mice by bilateral occlusion of the common carotid arteries for two 5 min followed by a 10-min reperfusion period. After 24 h, mice were treated with normal saline or different doses of Ser (100, 200, and 300 mg/kg) for 10 days. Cognitive performances were assessed using the Barnes maze and social interaction tasks. Oxidative stress markers including superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and malondialdehyde (MDA) as well as pro-inflammatory cytokines (interleukin (IL)-6 and tumor necrosis factor-alpha) and anti-inflammatory cytokine (IL-10) were assessed in the hippocampus. Markers of apoptosis (pro- and cleaved caspase-9 and 3, Bax, and Bcl-2) were assessed by Western blotting. Besides, transferase-mediated dUTP nick end-labeling assay was used to detect apoptotic cell death. We show here that Ser administration improved tGI/R-induced cognitive deficits, enhanced the activity of SOD and GPx, increased TAC levels, while reduced MDA levels. Notably, Ser decreased neuronal apoptotic cell death in the hippocampal dentate gyrus (DG) region, accompanied by suppression of neuroinflammation, downregulation of pro-apoptotic proteins (caspase-9, caspases-3, and Bax), and upregulation of anti-apoptotic protein, Bcl-2. Taken together, Ser administration protected hippocampal neurons from apoptotic cell death by impeding oxidative stress and inflammatory responses and, in turn, improved cognitive function in the tGI/R mice.

Simultaneous Pericytes and M2 Microglia Transplantation Improve Cognitive Function in Mice Model of mPFC Ischemia.

Cerebral ischemia is one of the major problems threatening global health. Many of the cerebral ischemia survivors would suffer from the physical and cognitive disabilities for their whole lifetime. Cell based-therapies have been introduced as a therapeutic approach for alleviating ischemia-enforced limitations. Photothrombotic stroke model was applied on the left medial prefrontal cortex (mPFC) of adult male BALB/c mice. Then, pericytes isolated from brain microvessels of adult male BALB/c mice, microglia isolated from brain cortices of the neonatal male BALB/c mice, and M2 phenotype shifted microglia by IL-4 treatment were used for transplantation into the injured area after 24 h of ischemia induction. The behavioural outcomes evaluated by social interaction and Barnes tests and the levels of growth associated protein (GAP)-43 and inflammatory cytokine interleukin (IL)-1 protein were assessed by western blotting 7 days after cell transplantation. Animals in both of the microglia + pericytes and microglia M2 + pericytes transplanted groups showed better performance in social memory as well as enhanced spatial learning and memory compared to ischemic controls. Also, improved escape latency was only observed in microglia M2 + pericytes (p < 0.01) group compared to ischemic controls. GAP-43 showed significant protein expression in microglia + pericytes and microglia M2 + pericytes groups compared to the control group. Conversely, IL-1 levels diminished in all of the pericytes microglia + pericytes, and microglia M2 + pericytes groups compared to the ischemic controls. Current study highlights efficiency of M2 microglia and pericytes combinatory transplantation therapeutic role on relieving ischemic stroke outcomes.

Effects of propofol and sevoflurane on social and anxiety-related behaviours in sleep-deprived rats.

BACKGROUND: Sleep disorders can profoundly affect neurological function. We investigated changes in social and anxiety-related brain functional connectivity induced by sleep deprivation, and the potential therapeutic effects of the general anaesthetics propofol and sevoflurane in rats. METHODS: Twelve-week-old male Sprague-Dawley rats were subjected to sleep deprivation for 20 h per day (from 14:00 to 10:00 the next day) for 4 consecutive weeks. They were free from sleep deprivation for the remaining 4 h during which they received propofol (40 mg kg-1 i.p.) or sevoflurane (2% for 2 h) per day or no treatment. These cohorts were instrumented for EEG/EMG recordings on days 2, 14, and 28. Different cohorts were used for open field and three-chambered social behavioural tests, functional MRI, nuclear magnetic resonance spectroscopy, and positron emission tomography imaging 48 h after 4 weeks of sleep deprivation. RESULTS: Propofol protected against sleep deprivation-induced anxiety behaviours with more time (44.7 [8.9] s vs 24.2 [4.1] s for the sleep-deprivation controls; P<0.001) spent in the central area of the open field test and improved social preference index by 30% (all P<0.01). Compared with the sleep-deprived rats, propofol treatment enhanced overall functional connectivity by 74% (P<0.05) and overall glucose metabolism by 30% (P<0.01), and improved glutamate kinetics by 20% (P<0.05). In contrast, these effects were not found after sevoflurane treatment. CONCLUSIONS: Unlike sevoflurane, propofol reduced sleep deprivation-induced social and anxiety-related behaviours. Propofol might be superior to sevoflurane for patients with sleep disorders who receive anaesthesia, which should be studied in clinical studies.

Cognitive effects of individual anticholinergic drugs: a systematic review and meta-analysis.

Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings. Objective: The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies. Methods: This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software. Results: Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM -1.84; 95%CI -2.48 to -1.21; p<0.01), immediate recall (SDM -1.82; 95%CI -2.35 to -1.30; p<0.01), matching to sample (SDM -1.76; 95%CI -2.57 to -0.96; p<0.01), delayed recall (SDM -1.54; 95%CI -1.97 to -1.10; p<0.01), complex memory tasks (SDM -1.31; 95%CI -1.78 to -0.84; p<0.01), free recall (SDM -1.18; 95%CI -1.63 to -0.73; p<0.01), cognitive function (SDM -0.95; 95%CI -1.46 to -0.44; p<0.01), attention (SDM -0.85; 95%CI -1.38 to -0.33; p<0.01), and digit span (SDM -0.65; 95%CI -1.21 to -0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders. Conclusion: The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence.

Os anticolinérgicos (ACs) estão entre os medicamentos mais prescritos. Investigar os domínios cognitivos prejudicados devido ao uso individual de ACs está associado a achados controversos. Objetivo: Investigar os efeitos de ACs individuais em diferentes aspectos da função cognitiva, com base em estudos de ensaios clínicos. Métodos: Esta revisão sistemática foi realizada em acordo com a declaração PRISMA. Uma busca sistemática foi realizada nos bancos de dados Embase, PubMed, Cochrane Library, Scopus e Web of Science. O risco de viés (risk of bias - RoB) foi avaliado pelas listas de verificação do Joanna Briggs Institute e a meta-análise foi realizada através do software CMA. Resultados: Foram incluídos 138 estudos dos 3.026 resultados da pesquisa. Trinta e oito estudos que avaliam os impactos cognitivos da escopolamina foram incluídos na meta-análise. Os estudos incluídos relataram efeitos cognitivos de escopolamina, mecamilamina, atropina, biperideno, oxibutinina, triexifenidil, benzhexol, diciclomina; no entanto, glicopirrolato, tróspio, tolterodina, darifenacina, fesoterodina, tiotrópio e ipratrópio não foram associados ao declínio cognitivo. Com base nas meta-análises, a escopolamina foi associada a reconhecimento reduzido (DPM -1,84; IC95% -2,48 a -1,21; p<0,01), recordação imediata (DPM -1,82; IC95% -2,35 a -1,30; p<0,01), correspondência com a amostra (DPM -1,76; IC95% -2,57 a -0,96; p<0,01), recordação atrasada (DPM -1,54; IC95% -1,97 a -1,10; p <0,01), tarefas de memória complexas (DPM -1,31; IC95% -1,78 a -0,84; p<0,01), recordação livre (DPM -1,18; IC95% -1,63 a -0,73; p<0,01), função cognitiva (DPM -0,95; IC95% -1,46 a -0,44; p<0,01), atenção (DPM -0,85; IC95% -1,38 a -0,33; p<0,01) e amplitude de memória de dígitos (DPM -0,65; IC95% -1,21 a -0,10; p=0,02). Houve um alto RoB em nosso estudo, especialmente quanto aos possíveis confundidores. Conclusão: As limitações deste estudo sugerem a necessidade de estudos mais bem delineados e com maior duração de acompanhamento sobre o tema para alcançar evidências mais confiáveis.

Deep brain stimulation for the treatment of Alzheimer's disease: A systematic review and meta-analysis.

Background: One of the experimental neuromodulation techniques being researched for the treatment of Alzheimer's disease (AD) is deep brain stimulation (DBS). To evaluate the effectiveness of DBS in AD, we performed a systematic review and meta-analysis of the available evidence. Methods: From the inception through December 2021, the following databases were searched: Medline via PubMed, Scopus, Embase, Cochrane Library, and Web of Science. The search phrases used were "Alzheimer's disease," "AD," "deep brain stimulation," and "DBS." The information from the included articles was gathered using a standardized data-collecting form. In the included papers, the Cochrane Collaboration methodology was used to evaluate the risk of bias. A fixed-effects model was used to conduct the meta-analysis. Results: Only five distinct publications and 6 different comparisons (one study consisted of two phases) were included out of the initial 524 papers that were recruited. DBS had no impact on the cognitive ability in patients with AD [0.116 SMD, 95% confidence interval (CI), -0.236 to 0.469, p = 0.518]. The studies' overall heterogeneity was not significant (κ2 = 6.23, T 2 = 0.053, df = 5, I 2 = 19.76%, p = 0.284). According to subgroup analysis, the fornix-DBS did not improve cognitive function in patients with AD (0.145 SMD, 95%CI, -0.246 to 0.537, p = 0.467). Unfavorable neurological and non-neurological outcomes were also reported. Conclusion: The inconsistencies and heterogeneity of the included publications in various target and age groups of a small number of AD patients were brought to light by this meta-analysis. To determine if DBS is useful in the treatment of AD, further studies with larger sample sizes and randomized, double-blinded, sham-controlled designs are required.

Synergistic effects of combined therapy with cerebrolysin and enriched environment on anxiety-like behavior and spatial cognitive deficits in posttraumatic stress disorder-like mouse model.

Posttraumatic stress disorder (PTSD) is a serious neuropsychiatric disorder that occurs after exposure to stressful, fearful, or troubling events. Cerebrolysin (CBL), consists of low molecular weights neurotrophic factors and amino acids obtained from purified porcine brain proteins. This study aimed to evaluate the possible therapeutic effects of enriched environment (EE) and CBL alone or combined for reducing anxiety and cognitive deficits in PTSD-like mouse models. For this purpose, inescapable electric foot shocks were delivered to Balb/c mice for two consecutive days. Then mice were treated with CBL (2.5 mL/kg) and/or were kept in EE (2 h per day) or received their combination for 14 consecutive days. The hole-board test and Lashley III paradigm were used to assess anxiety and spatial learning and memory, respectively. Changes in the serum corticosterone level and expression of synaptic elements, including; growth-associated protein 43, post-synaptic density 95, and synaptophysin were assessed in the hippocampus. This model caused anxiety and spatial memory impairment associated with increased serum corticosterone levels and decreased synaptic elements. Nevertheless, CBL and/or combination treatment could reverse behavioral and molecular alterations. Our findings indicated that CBL, separately or in combination with EE, is effective in reducing anxiety and spatial memory impairment in PTSD-like mice.

Hydroxychloroquine attenuated motor impairment and oxidative stress in a rat 6-hydroxydopamine model of Parkinson's disease.

PURPOSE: Parkinson's disease (PD) is associated with the destruction of dopaminergic neurons in the substantia nigra (SN). Hydroxychloroquine (HCQ) has the capability to cross the blood-brain barrier and promote a neuroprotective potential. This study evaluated the effects of HCQ on the 6-hydroxydopamine (6-OHDA)-induced PD model in rats. METHODS: Wistar rats were randomly divided into sham, PD, PD + levodopa and PD + HCQ groups. The PD model was induced by a stereotactic administration of 6-OHDA into the left SN pars compacta (SNpc) and confirmed by rotation and the Murprogo's tests. HCQ (100 mg/kg, p.o.) and levodopa (12 mg/kg, p.o.) were administered once a day for 21 days. Three weeks after surgery, the behavioral tests were performed. Brain lipid peroxidation index (MDA), glutathione peroxidase activity (GPx), total antioxidant capacity (TAC) levels and α-synuclein protein expression in the SN were also measured. RESULTS: The behavioral tests demonstrated that induction of PD increased the muscle rigidity and the number of rotations, which were reversed by HCQ treatment. Also, induction of PD was associated with an increase in α-synuclein protein levels and MDA and decreased TAC levels and GPx activity. However, HCQ decreased α-synuclein and MDA levels while increased TAC levels and GPx activity. In addition, histopathological data showed that HCQ protects dopaminergic neurons against 6-OHDA-induced toxicity. CONCLUSION: According to the results, HCQ has a beneficial effect in improving PD-related pathophysiology, in part, by mitigating oxidative stress and protecting the dopaminergic neurons in the SN.

Saffron as a promising therapy for diabetes and Alzheimer's disease: mechanistic insights.

The prevalence of both Alzheimer's disease (AD) and diabetes mellitus is increasing with the societies' aging and has become an essential social concern worldwide. Accumulation of amyloid plaques and neurofibrillary tangles (NFTs) of tau proteins in the brain are hallmarks of AD. Diabetes is an underlying risk factor for AD. Insulin resistance has been proposed to be involved in amyloid-beta (Aß) aggregation in the brain. It seems that diabetic conditions can result in AD pathology by setting off a cascade of processes, including inflammation, mitochondrial dysfunction, and ROS and advanced glycation end products (AGEs) synthesis. Due to the several side effects of chemical drugs and their high cost, using herbal medicine has recently attracted attention for the treatment of diabetes and AD. Saffron and its active ingredients have been used for its anti-inflammatory, anti-oxidant, anti-diabetic, and anti-AD properties. Therefore, in the present review paper, we take account of the clinical, in vivo and in vitro evidence regarding the anti-diabetic and anti-AD effects of saffron and discuss the preventive or postponing properties of saffron or its components on AD development via its anti-diabetic effects.

Nanoparticle and Stem Cell Combination Therapy for the Management of Stroke.

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, the available treatments for stroke are still extremely limited. Indeed, stem cell (SC) therapy is a new option for the treatment of stroke that could significantly expand the therapeutic time window of stroke. Some proposed mechanisms for stroke-based SC therapy are the incorporation of SCs into the host brain to replace dead or damaged cells/tissues. Moreover, acute cell delivery can inhibit apoptosis and decrease lesion size, providing immunomudolatory and neuroprotection effects. However, several major SC problems related to SCs such as homing, viability, uncontrolled differentiation, and possible immune response, have limited SC therapy. A combination of SC therapy with nanoparticles (NPs) can be a solution to address these challenges. NPs have received considerable attention in regulating and controlling the behavior of SCs because of their unique physicochemical properties. By reviewing the pathophysiology of stroke and the therapeutic benefits of SCs and NPs, we hypothesize that combined therapy will offer a promising future in the field of stroke management. In this work, we discuss recent literature in SC research combined with NP-based strategies that may have a synergistic outcome after stroke incidence.

Cognitive effects of individual anticholinergic drugs: a systematic review and meta-analysis / Efeitos cognitivos de drogas anticolinérgicas individuais: uma revisão sistemática e meta-análise

ABSTRACT. Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings. Objective: The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies. Methods: This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software. Results: Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM -1.84; 95%CI -2.48 to -1.21; p<0.01), immediate recall (SDM -1.82; 95%CI -2.35 to -1.30; p<0.01), matching to sample (SDM -1.76; 95%CI -2.57 to -0.96; p<0.01), delayed recall (SDM -1.54; 95%CI -1.97 to -1.10; p<0.01), complex memory tasks (SDM -1.31; 95%CI -1.78 to -0.84; p<0.01), free recall (SDM -1.18; 95%CI -1.63 to -0.73; p<0.01), cognitive function (SDM -0.95; 95%CI -1.46 to -0.44; p<0.01), attention (SDM -0.85; 95%CI -1.38 to -0.33; p<0.01), and digit span (SDM -0.65; 95%CI -1.21 to -0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders. Conclusion: The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence.

RESUMO. Os anticolinérgicos (ACs) estão entre os medicamentos mais prescritos. Investigar os domínios cognitivos prejudicados devido ao uso individual de ACs está associado a achados controversos. Objetivo: Investigar os efeitos de ACs individuais em diferentes aspectos da função cognitiva, com base em estudos de ensaios clínicos. Métodos: Esta revisão sistemática foi realizada em acordo com a declaração PRISMA. Uma busca sistemática foi realizada nos bancos de dados Embase, PubMed, Cochrane Library, Scopus e Web of Science. O risco de viés (risk of bias - RoB) foi avaliado pelas listas de verificação do Joanna Briggs Institute e a meta-análise foi realizada através do software CMA. Resultados: Foram incluídos 138 estudos dos 3.026 resultados da pesquisa. Trinta e oito estudos que avaliam os impactos cognitivos da escopolamina foram incluídos na meta-análise. Os estudos incluídos relataram efeitos cognitivos de escopolamina, mecamilamina, atropina, biperideno, oxibutinina, triexifenidil, benzhexol, diciclomina; no entanto, glicopirrolato, tróspio, tolterodina, darifenacina, fesoterodina, tiotrópio e ipratrópio não foram associados ao declínio cognitivo. Com base nas meta-análises, a escopolamina foi associada a reconhecimento reduzido (DPM -1,84; IC95% -2,48 a -1,21; p<0,01), recordação imediata (DPM -1,82; IC95% -2,35 a -1,30; p<0,01), correspondência com a amostra (DPM -1,76; IC95% -2,57 a -0,96; p<0,01), recordação atrasada (DPM -1,54; IC95% -1,97 a -1,10; p <0,01), tarefas de memória complexas (DPM -1,31; IC95% -1,78 a -0,84; p<0,01), recordação livre (DPM -1,18; IC95% -1,63 a -0,73; p<0,01), função cognitiva (DPM -0,95; IC95% -1,46 a -0,44; p<0,01), atenção (DPM -0,85; IC95% -1,38 a -0,33; p<0,01) e amplitude de memória de dígitos (DPM -0,65; IC95% -1,21 a -0,10; p=0,02). Houve um alto RoB em nosso estudo, especialmente quanto aos possíveis confundidores. Conclusão: As limitações deste estudo sugerem a necessidade de estudos mais bem delineados e com maior duração de acompanhamento sobre o tema para alcançar evidências mais confiáveis.

Association between miRNA-145 and miRNA-155 expression in peripheral blood mononuclear cells of patients with multiple sclerosis: a case-control study.

INTRODUCTION: MicroRNAs (miR or miRNA) are short regulatory RNAs, which modulate post-transcriptional gene expression. Dysregulation of these molecules contributes to pathogenicity of autoimmune disorders, such as multiple sclerosis (MS). AIMS: This study was conducted to investigate changed expression pattern of miRNA-145 and miRNA-155 in MS. METHODS: We collected blood samples of 75 patients with relapsing-remitting MS patients and 75 healthy controls. Ficoll-Hypaque density gradient method was used to isolate peripheral blood mononuclear cells. Also, total RNA was extracted and subjected to RT-PCR analysis. We used the Mann-Whitney U test to evaluate the differences in expression levels of target miRNAs between the groups. RESULTS: We found that expression of miRNA-145 (P = 0.012) and miRNA-155 (P = 0.005) were partly reduced in patients with relapse-remitting MS in comparison with healthy controls. The miRNA-145 had an area under curve (AUC) of 0.621 (P = 0.01) and miRNA-155 levels had an AUC of 0.625 (P = 0.008). CONCLUSION: Decreased expression of miRNA-145 and miRNA-155 contributes to development of relapse-remitting MS, while further large scale observational studies and meta-analyses are required.

The Link between Stroke Risk and Orodental Status-A Comprehensive Review.

One of the primary causes of disability and mortality in the adult population worldwide is stroke. A person's general health is significantly impacted by their oral and dental health. People who have poor oral health are more susceptible to conditions such as stroke. Stroke risk has long been linked to oral and dental conditions. The risk of stroke and its cost impact on the healthcare systems appear to be significantly reduced as a result of the decline in the incidence and prevalence of oral and dental illnesses. Hypothetically, better management of oral hygiene and dental health lead to reduced stroke risk. To the authors' best knowledge, for the first time, the potential link between dental health and stroke were cross-examined. The most typical stroke symptoms, oral and dental illnesses linked to stroke, and the role of oral healthcare professionals in stroke prevention are revealed. The potential mediating processes and subsequent long-term cognitive and functional neurological outcomes are based on the available literature. It must be noted that periodontal diseases and tooth loss are two common oral health measures. Lack of knowledge on the effects of poor oral health on systemic health together with limited access to primary medical or dental care are considered to be partially responsible for the elevated risk of stroke. Concrete evidence confirming the associations between oral inflammatory conditions and stroke in large cohort prospective studies, stratifying association between oral disease severity and stroke risk and disease effects on stroke survival will be desirable. In terms of clinical pathology, a predictive model of stroke as a function of oral health status, and biomarkers of systemic inflammation could be useful for both cardiologists and dentists.