bluuebunny/crossref_metadata_2025 huggingface dataset:
The oncogenic role of SNRPB in human tumors: A pan-cancer analysis
Authors: Wu Juan , Lu Feng , Yu Bin , Wang Wenjun , Ye Xiaoqun
Published: October 2022

Purpose: The purpose of this study was to explore the oncogenic role of small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) in human tumors.

Materials and methods: Study cases were acquired from The Cancer Genome Atlas database, the Gene Expression Omnibus database, The Human Protein Atlas, and the Clinical Proteomic Tumor Analysis Consortium. We then used the R package and several online tools to analyze and visualize the role of SNRPB across tumors.

Results: We found that the expression of SNRPB was significantly increased in 28 of 33 tumors, and higher expression was observed in late pathological and TNM stages. Significantly decreased levels of SNRPB promoter methylation were observed in 12 tumors. SNRPB was found to be a risk factor for decreased overall survival in 10 tumors (p < 0.05), a risk factor for decreased disease-specific survival in 8 tumors (p < 0.05), and a risk factor for decreased progression-free interval in 7 tumors (p < 0.05). The PPI network of SNRPB and the top 100 coexpressed genes revealed that CDK1, CDC6, AURKB, CCNB1, CCNA2, and CDC45 were the most closely interacting genes across tumors. The GO and KEGG enrichment analyses revealed that SNRPB and the above genes were mainly enriched with respect to functions in cell cycle-related genetic material replication, assembly, and distribution. SNRPB was significantly associated with immune cell infiltration and the expression of immunomodulation-related genes in several but not all tumors.

Conclusion and limitations: The expression of SNRPB was significantly elevated in almost all tumors, and the decreased promoter methylation level may contribute to the elevated expression of SNRPB. SNRPB may facilitate the progression of pathological and TNM stages and is a risk factor for unfavorable prognosis across tumors. However, our research was based on data obtained from public databases, without further validation of our findings at the cellular and animal levels. Therefore, further studies are needed to clarify the oncogenic mechanism of SNRPB and its potential as a therapeutic target.
Microglial autophagy in cerebrovascular diseases
Authors: Chen Man , Zhang Hang , Chu Yun-Hui , Tang Yue , Pang Xiao-Wei , Qin Chuan , Tian Dai-Shi
Published: October 2022

Microglia are considered core regulators for monitoring homeostasis in the brain and primary responders to central nervous system (CNS) injuries. Autophagy affects the innate immune functions of microglia. Recently some evidence suggests that microglial autophagy is closely associated with brain function in both ischemic stroke and hemorrhagic stroke. Herein, we will discuss the interaction between autophagy and other biological processes in microglia under physiological and pathological conditions and highlight the interaction between microglial metabolism and autophagy. In the end, we focus on the effect of microglial autophagy in cerebrovascular diseases.
Hypocretin/orexin influences chronic sleep disruption injury in the hippocampus
Authors: Nick Henry , Fenik Polina , Zhu Yan , Veasey Sigrid
Published: October 2022

Chronic sleep disruption is a risk factor for Alzheimer’s disease (AD), yet mechanisms by which sleep disturbances might promote or exacerbate AD are not understood. Short-term sleep loss acutely increases hippocampal amyloid β (Aβ) in wild type (WT) mice and long-term sleep loss increases amyloid plaque in AD transgenic mouse models. Both effects can be influenced by the wake-promoting neuropeptide, hypocretin (HCRT), but whether HCRT influences amyloid accumulation independent of sleep and wake timing modulation remains unclear. Here, we induced chronic fragmentation of sleep (CFS) in WT and HCRT-deficient mice to elicit similar arousal indices, sleep bout lengths and sleep bout numbers in both genotypes. We then examined the roles of HCRT in CFS-induced hippocampal Aβ accumulation and injury. CFS in WT mice resulted in increased Aβ42 in the hippocampus along with loss of cholinergic projections and loss of locus coeruleus neurons. Mice with HCRT deficiency conferred resistance to CFS Aβ42 accumulation and loss of cholinergic projections in the hippocampus yet evidenced similar CFS-induced loss of locus coeruleus neurons. Collectively, the findings demonstrate specific roles for orexin in sleep disruption hippocampal injury.

Significance statement

Chronic fragmentation of sleep (CFS) occurs in common conditions, including sleep apnea syndromes and chronic pain disorders, yet CFS can induce neural injury. Our results demonstrate that under conditions of sleep fragmentation, hypocretin/orexin is essential for the accumulation of amyloid-β and loss of cholinergic projections in the hippocampus observed in response to CFS yet does not influence locus coeruleus neuron response to CFS.
Egocentric distance perception in older adults: Results from a functional magnetic resonance imaging and driving simulator study
Authors: Eudave Luis , Martínez Martín , Luis Elkin O. , Pastor María A.
Published: October 2022

The ability to appropriately perceive distances in activities of daily living, such as driving, is necessary when performing complex maneuvers. With aging, certain driving behaviors and cognitive functions change; however, it remains unknown if egocentric distance perception (EDP) performance is altered and whether its neural activity also changes as we grow older. To that end, 19 young and 17 older healthy adults drove in a driving simulator and performed an functional magnetic resonance imaging (fMRI) experiment where we presented adults with an EDP task. We discovered that (a) EDP task performance was similar between groups, with higher response times in older adults; (b) older adults showed higher prefrontal and parietal activation; and (c) higher functional connectivity within frontal and parietal-occipital-cerebellar networks; and (d) an association between EDP performance and hard braking behaviors in the driving simulator was found. In conclusion, EDP functioning remains largely intact with aging, possibly due to an extended and effective rearrangement in functional brain resources, and may play a role in braking behaviors while driving.
Effect of acupuncture for non-motor symptoms in patients with Parkinson’s disease: A systematic review and meta-analysis
Authors: Li Qinglian , Wu Chunxiao , Wang Xiaoling , Li Zhen , Hao Xiaoqian , Zhao Lijun , Li Mengzhu , Zhu Meiling
Published: October 2022

Background

Although non-motor symptoms of Parkinson’s disease (PD) are serious, effective treatments are still lacking. Acupuncture may have clinical benefits for non-motor symptoms of PD patients, but high-quality evidence supporting this possibility is still limited. Hence, we conducted this meta-analysis to evaluate the effect of acupuncture treatment on non-motor symptoms in patients with PD.

Methods

Randomized controlled trials (RCTs) of acupuncture treatment for PD were retrieved from the following electronic databases: Medline (OVID), Embase (OVID), Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, Chonqing VIP (CQVIP), and Wangfang database. Studies evaluating non-motor symptoms of PD were retrieved. Methodological quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions.

Results

A total of 27 RCTs were included, among which 8 outcomes related to non-motor symptoms were evaluated. The results showed that acupuncture combined with medication had benefits for PD-related insomnia relative to medication alone or sham acupuncture [standardized mean difference (SMD) = 0.517; 95% confidence interval (CI) = 0.242–0.793; p = 0.000], and acupuncture treatment had benefits at 8 weeks (SMD = 0.519; 95% CI = 0.181–0.857; p = 0.003). Regarding depression, acupuncture treatment was more effective (SMD = −0.353; 95% CI = −0.669 to −0.037; p = 0.029) within 2 months (SMD = −0.671; 95% CI = −1.332 to −0.011; p = 0.046). Regarding cognition, quality of life, and Unified Parkinson’s Disease Rating Scale (UPDRS) I and II scores, acupuncture treatment was effective [SMD = 0.878, 95% CI = 0.046–1.711, p = 0.039; SMD = −0.690, 95% CI = −1.226 to −0.155, p = 0.011; weighted mean difference (WMD) = −1.536, 95% CI = −2.201 to −0.871, p = 0.000; WMD = −2.071, 95% CI = −3.792 to −0.351, p = 0.018; respectively]. A significant difference was not found in terms of PD-related constipation. Only one study evaluated PD-related fatigue.

Conclusion

The results of the analysis suggested that acupuncture treatment could ameliorate the symptoms of depression, quality of life, cognition, total mentation, behavior and mood, and activities of daily living in PD patients. Nevertheless, more prospective, well-designed RCTs with larger sample sizes are required to confirm our findings.
Crosstalk between the aging intestinal microflora and the brain in ischemic stroke
Authors: Pluta Ryszard , Jabłoński Mirosław , Januszewski Sławomir , Czuczwar Stanisław J.
Published: October 2022

Aging is an inevitable phenomenon experienced by animals and humans, and its intensity varies from one individual to another. Aging has been identified as a risk factor for neurodegenerative disorders by influencing the composition of the gut microbiota, microglia activity and cognitive performance. The microbiota-gut-brain axis is a two-way communication path between the gut microbes and the host brain. The aging intestinal microbiota communicates with the brain through secreted metabolites (neurotransmitters), and this phenomenon leads to the destruction of neuronal cells. Numerous external factors, such as living conditions and internal factors related to the age of the host, affect the condition of the intestinal microflora in the form of dysbiosis. Dysbiosis is defined as changes in the composition and function of the gut microflora that affect the pathogenesis, progress, and response to treatment of a disease entity. Dysbiosis occurs when changes in the composition and function of the microbiota exceed the ability of the microflora and its host to restore equilibrium. Dysbiosis leading to dysfunction of the microbiota-gut-brain axis regulates the development and functioning of the host’s nervous, immune, and metabolic systems. Dysbiosis, which causes disturbances in the microbiota-gut-brain axis, is seen with age and with the onset of stroke, and is closely related to the development of risk factors for stroke. The review presents and summarizes the basic elements of the microbiota-gut-brain axis to better understand age-related changes in signaling along the microbiota-gut-brain axis and its dysfunction after stroke. We focused on the relationship between the microbiota-gut-brain axis and aging, emphasizing that all elements of the microbiota-gut-brain axis are subject to age-related changes. We also discuss the interaction between microbiota, microglia and neurons in the aged individuals in the brain after ischemic stroke. Finally, we presented preclinical and clinical studies on the role of the aged microbiota-gut-brain axis in the development of risk factors for stroke and changes in the post-stroke microflora.
Satellite Glial Cells: Morphology, functional heterogeneity, and role in pain
Authors: Andreeva Daria , Murashova Lada , Burzak Nikita , Dyachuk Vyacheslav
Published: October 2022

Neurons in the somatic, sympathetic, and parasympathetic ganglia are surrounded by envelopes consisting of satellite glial cells (SGCs). Recently, it has become clear that SGCs are highly altered after nerve injury, which influences neuronal excitability and, consequently, the development and maintenance of pain in different animal models of chronic pain. However, the exact mechanism underlying chronic pain is not fully understood yet because it is assumed that SGCs in different ganglia share many common peculiarities, making the process complex. Here, we review recent data on morphological and functional heterogeneity and changes in SGCs in various pain conditions and their role in response to injury. More research is required to decipher the role of SGCs in diseases, such as chronic pain, neuropathology, and neurodegenerative diseases.
Night skies through animals’ eyes—Quantifying night-time visual scenes and light pollution as viewed by animals
Authors: Stöckl Anna Lisa , Foster James Jonathan
Published: October 2022

A large proportion of animal species enjoy the benefits of being active at night, and have evolved the corresponding optical and neural adaptations to cope with the challenges of low light intensities. However, over the past century electric lighting has introduced direct and indirect light pollution into the full range of terrestrial habitats, changing nocturnal animals’ visual worlds dramatically. To understand how these changes affect nocturnal behavior, we here propose an animal-centered analysis method based on environmental imaging. This approach incorporates the sensitivity and acuity limits of individual species, arriving at predictions of photon catch relative to noise thresholds, contrast distributions, and the orientation cues nocturnal species can extract from visual scenes. This analysis relies on just a limited number of visual system parameters known for each species. By accounting for light-adaptation in our analysis, we are able to make more realistic predictions of the information animals can extract from nocturnal visual scenes under different levels of light pollution. With this analysis method, we aim to provide context for the interpretation of behavioral findings, and to allow researchers to generate specific hypotheses for the behavior of nocturnal animals in observed light-polluted scenes.
Case report: Bitter vertigo
Authors: Goldschagg Nicolina , Brem Christian , Strupp Michael
Published: October 2022

Background

There are many causes of episodes of vertigo and very few causes of episodes of changes in taste, and the combination of the two is very rare. Here, we describe a patient with recurrent short episodes of vertigo in combination with simultaneous episodes of recurrent paroxysmal dysgeusia and altered feeling on the left side of face. The symptoms were caused by compression of the vestibulocochlear nerve and the facial nerve due to dolichoectasia of the basilar artery.

Methods

The patient was diagnosed in our routine clinical practice and underwent a complete neurological and neuro-otological examination, including video head impulse test, caloric irrigation, ocular and cervical vestibular evoked myogenic potentials, acoustic-evoked potentials, neuro-orthoptic examination, cranial MRI, and MR angiography. The patient was seen twice for follow-up.

Case

A 71-year-old patient primarily presented with a 2-year history of recurrent short episodes of spinning vertigo. Each of the episodes began with an altered feeling on the left side of the face, followed by a bitter taste on the left half of the tongue, and subsequently vertigo lasting for up to 15 s. The frequency of the attacks was high: up to 80 times per day. Laboratory tests revealed signs of a peripheral vestibular deficit on the left side. There were no signs of sensory or motor deficits or of altered taste between the episodes. An MRI of the brain showed an elongated basilar artery leading to an indentation of the facial and vestibulocochlear nerves on the left side.

Conclusion

We propose a neurovascular compression in the proximal part of two cranial nerves because of pulsatile compression by the elongated basilar artery with ephatic discharges as the cause of the recurrent episodes. Consistent with the theory of ephatic discharges, treatment with the sodium channel blocker lacosamide for over six months with a final dosage of 200 mg per day p.o. led to a significant reduction of the attack frequency and intensity. This treatment option with a sodium channel blocker should therefore not only be considered in vestibular paroxysmia but also in cases of paroxysmal dysgeusia.
Case report: Visual snow as the presenting symptom in multiple evanescent white dot syndrome. Two case reports and literature review
Authors: Hang Chenyue , Yan Yan
Published: October 2022

Purpose

Multiple evanescent white dot syndrome (MEWDS) usually manifests as photopsia, enlarged blind spots, scotomas, and blurred vision, which can be classified into positive and negative visual phenomena. Visual snow and chromatopsia were rarely reported in these patients. Herein, we described two Chinese female patients with MEWDS who initially presented with visual snow, and one of them also had yellow-tinged vision.

Methods

First, we performed the chart review of two patients. Second, we reviewed the English literature for all cases of MEWDS through PubMed until December 2021, using the terms “MEWDS” or “multiple evanescent white dot syndrome.” We concluded on all the reported patients' demographic features and symptoms. The visual acuity of patients with/without positive or negative visual phenomena was compared through one-way ANOVA.

Results

Patient 1: A 27-year-old Chinese woman experienced continuous visual snow and yellow-tinged vision in the right eye for a week. She noticed tiny white and black dots involving the entire visual field and shimmering light inferiorly. Patient 2: A 22-year-old Chinese woman complained of a gray area with continuous visual snow in the temporal visual field of the left eye for 5 days. The ocular examinations, including fundus autofluorescence (FAF), optical coherence tomography (OCT), and indocyanine green angiography (ICGA), confirmed the diagnosis of MEWDS. Their symptoms resolved spontaneously without treatment. We found 60 MEWDS case reports (147 cases) in PubMed. The mean age was 31.2 years old. The mean LogMAR best-corrected visual acuity was 0.35 ± 0.39 at the first visit and 0.01 ± 0.16 at the last visit. The most common symptoms included blurred vision (72.8%), enlarged blind spot (42.2%), photopsia (37.4%), and scotoma (33.3%). We found the patients with only positive visual phenomena had significantly worse visual acuity at the first and last visit than patients with only negative visual phenomena (p = 0.008) or the patients with both positive and negative visual phenomena (p = 0.026). Four cases similar to visual snow were discovered. Compared to the MEWDS patients without visual snow, the patients with visual snow tend to have a larger proportion of females (p = 0.005) and a better visual acuity at the first visit (p = 0.007).

Conclusion

Herein, we expand upon the clinical manifestations of MEWDS with visual snow, and the symptoms attributable to visual snow could precede the onset of MEWDS. Neurologists and ophthalmologists should carefully rule out occult chorioretinopathy before diagnosing visual snow syndrome.
Transcranial direct current stimulation alters sensorimotor modulation during cognitive representation of movement
Authors: Bonassi Gaia , Lagravinese Giovanna , Putzolu Martina , Botta Alessandro , Bove Marco , Pelosin Elisa , Avanzino Laura
Published: October 2022

We recently demonstrated, by means of short latency afferent inhibition (SAI), that before an imagined movement, during the reaction time (RT), SAI decreases only in the movement-related muscle (sensorimotor modulation) and that a correlation exists between sensorimotor modulation and motor imagery (MI) ability. Excitatory anodal transcranial direct current stimulation (a-tDCS) on M1 could enhance the MI outcome; however, mechanisms of action are not completely known. Here, we assessed if a-tDCS on M1 prior to an MI task could affect sensorimotor modulation. Participants imagined abducting the index or little finger in response to an acoustic signal. SAI was evaluated from the first dorsal interosseus after the “go” signal, before the expected electromyographic (EMG) activity. Participants received 20-min 1.5 mA a-tDCS or sham-tDCS on M1 on two different days, in random order. Results showed that a-tDCS on M1 increases the sensorimotor modulation consisting of a weakening of SAI after the Go signal with respect to sham-tDCS, in the movement-related muscle right before the beginning of MI. These results suggest that a-tDCS on M1 further potentiate those circuits responsible for sensorimotor modulation in the RT phase of MI. Increased sensorimotor modulation during MI may be one of the mechanisms involved in MI improvement after a-tDCS over M1.
Modulation of Spectral Representation and Connectivity Patterns in Response to Visual Narrative in the Human Brain
Authors: Sabra Zahraa , Alawieh Ali , Bonilha Leonardo , Naselaris Thomas , AuYong Nicholas
Published: October 2022

The regional brain networks and the underlying neurophysiological mechanisms subserving the cognition of visual narrative in humans have largely been studied with non-invasive brain recording. In this study, we specifically investigated how regional and cross-regional cortical activities support visual narrative interpretation using intracranial stereotactic electroencephalograms recordings from thirteen human subjects (6 females, and 7 males). Widely distributed recording sites across the brain were sampled while subjects were explicitly instructed to observe images from fables presented in “sequential” order, and a set of images drawn from multiple fables presented in “scrambled” order. Broadband activity mainly within the frontal and temporal lobes were found to encode if a presented image is part of a visual narrative (sequential) or random image set (scrambled). Moreover, the temporal lobe exhibits strong activation in response to visual narratives while the frontal lobe is more engaged when contextually novel stimuli are presented. We also investigated the dynamics of interregional interactions between visual narratives and contextually novel series of images. Interestingly, the interregional connectivity is also altered between sequential and scrambled sequences. Together, these results suggest that both changes in regional neuronal activity and cross-regional interactions subserve visual narrative and contextual novelty processing.
Paradoxical markers of conscious levels: Effects of propofol on patients in disorders of consciousness
Authors: Maschke Charlotte , Duclos Catherine , Blain-Moraes Stefanie
Published: October 2022

Human consciousness is widely understood to be underpinned by rich and diverse functional networks, whose breakdown results in unconsciousness. Candidate neural correlates of anesthetic-induced unconsciousness include: (1) disrupted frontoparietal functional connectivity; (2) disrupted brain network hubs; and (3) reduced spatiotemporal complexity. However, emerging counterexamples have revealed that these markers may appear outside of the state they are associated with, challenging both their inclusion as markers of conscious level, and the theories of consciousness that rely on their evidence. In this study, we present a case series of three individuals in disorders of consciousness (DOC) who exhibit paradoxical brain responses to exposure to anesthesia. High-density electroencephalographic data were recorded from three patients with unresponsive wakefulness syndrome (UWS) while they underwent a protocol of propofol anesthesia with a targeted effect site concentration of 2 μg/ml. Network hubs and directionality of functional connectivity in the alpha frequency band (8–13 Hz), were estimated using the weighted phase lag index (wPLI) and directed phase lag index (dPLI). The spatiotemporal signal complexity was estimated using three types of Lempel-Ziv complexity (LZC). Our results illustrate that exposure to propofol anesthesia can paradoxically result in: (1) increased frontoparietal feedback-dominant connectivity; (2) posterior network hubs; and (3) increased spatiotemporal complexity. The case examples presented in this paper challenge the role of functional connectivity and spatiotemporal complexity in theories of consciousness and for the clinical evaluation of levels of human consciousness.
CT-guided radiofrequency ablation of the extracranial cranial nerve for the treatment of Meige’s syndrome
Authors: Huang Bing , Du Xin-dan , Yao Ming , Lin Hui-dan , Yu Wen-hua , Zhou Qing-he
Published: October 2022

Background

Meige’ s syndrome, a rare form of dystonia, lacks effective treatment. The purpose of this study was to determine the effects of CT-guided percutaneous extracranial radiofrequency ablation of the facial and/or trigeminal nerves in the treatment of Meige’s syndrome.

Methods

A total of 10 patients were enrolled in this study, with the numbers of blepharospasm dystonia syndrome (BDS), oromandibular dystonia syndrome (ODS), and blepharospasm combined with oromandibular dystonia syndrome (B-ODS) being 7, 1, and 2, respectively. BDS patients underwent radiofrequency ablation of the bilateral stylomastoid foramen facial nerve; ODS patients underwent radiofrequency ablation of the bilateral foramen oval trigeminal mandibular branch, and B-ODS patients underwent radiofrequency ablation of the bilateral stylomastoid foramen facial nerve and foramen oval trigeminal mandibular branch. The therapeutic effects and complications were observed.

Results

All 10 patients in this series experienced improved Meige’s syndrome-related symptoms after extracranial radiofrequency ablation of the cranial and/or mandibular branches of the extracranial trigeminal nerve. Adverse events included class II–III facial paralysis and/or mandibular skin numbness. Two patients had recurrences at the 18th and 22nd months postoperatively, respectively; the other patients were being followed up.

Conclusion

These results shown that CT-guided radiofrequency ablation of bilateral stylomastoid foramen facial nerve and/or oval foramen trigeminal mandibular branch can effectively treat the corresponding types of Meige’s syndrome. According to preliminary observations, the therapeutic effect may last more than 18 months.
A universal model of electrochemical safety limits in vivo for electrophysiological stimulation
Authors: Vatsyayan Ritwik , Dayeh Shadi A.
Published: October 2022

Electrophysiological stimulation has been widely adopted for clinical diagnostic and therapeutic treatments for modulation of neuronal activity. Safety is a primary concern in an interventional design leveraging the effects of electrical charge injection into tissue in the proximity of target neurons. While modalities of tissue damage during stimulation have been extensively investigated for specific electrode geometries and stimulation paradigms, a comprehensive model that can predict the electrochemical safety limits in vivo doesn’t yet exist. Here we develop a model that accounts for the electrode geometry, inter-electrode separation, material, and stimulation paradigm in predicting safe current injection limits. We performed a parametric investigation of the stimulation limits in both benchtop and in vivo setups for flexible microelectrode arrays with low impedance, high geometric surface area platinum nanorods and PEDOT:PSS, and higher impedance, planar platinum contacts. We benchmark our findings against standard clinical electrocorticography and depth electrodes. Using four, three and two contact electrochemical impedance measurements and comprehensive circuit models derived from these measurements, we developed a more accurate, clinically relevant and predictive model for the electrochemical interface potential. For each electrode configuration, we experimentally determined the geometric correction factors that dictate geometry-enforced current spreading effects. We also determined the electrolysis window from cyclic-voltammetry measurements which allowed us to calculate stimulation current safety limits from voltage transient measurements. From parametric benchtop electrochemical measurements and analyses for different electrode types, we created a predictive equation for the cathodal excitation measured at the electrode interface as a function of the electrode dimensions, geometric factor, material and stimulation paradigm. We validated the accuracy of our equation in vivo and compared the experimentally determined safety limits to clinically used stimulation protocols. Our new model overcomes the design limitations of Shannon’s equation and applies to macro- and micro-electrodes at different density or separation of contacts, captures the breakdown of charge-density based approaches at long stimulation pulse widths, and invokes appropriate power exponents to current, pulse width, and material/electrode-dependent impedance.
The role of ubiquitination in spinal and bulbar muscular atrophy
Authors: Sengupta Medha , Pluciennik Anna , Merry Diane E.
Published: October 2022

Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative and neuromuscular genetic disease caused by the expansion of a polyglutamine-encoding CAG tract in the androgen receptor (AR) gene. The AR is an important transcriptional regulator of the nuclear hormone receptor superfamily; its levels are regulated in many ways including by ubiquitin-dependent degradation. Ubiquitination is a post-translational modification (PTM) which plays a key role in both AR transcriptional activity and its degradation. Moreover, the ubiquitin-proteasome system (UPS) is a fundamental component of cellular functioning and has been implicated in diseases of protein misfolding and aggregation, including polyglutamine (polyQ) repeat expansion diseases such as Huntington’s disease and SBMA. In this review, we discuss the details of the UPS system, its functions and regulation, and the role of AR ubiquitination and UPS components in SBMA. We also discuss aspects of the UPS that may be manipulated for therapeutic effect in SBMA.
Deficiency of miR-29a/b1 leads to premature aging and dopaminergic neuroprotection in mice
Authors: Bai Xiaochen , Wang Jinghui , Zhang Xiaoshuang , Tang Yilin , He Yongtao , Zhao Jiayin , Han Linlin , Fang Rong , Liu Zhaolin , Dong Hongtian , Li Qing , Ge Jingyu , Ma Yuanyuan , Yu Mei , Sun Ruilin , Wang Jian , Fei Jian , Huang Fang
Published: October 2022

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of midbrain dopaminergic neurons. The miR-29s family, including miR-29a and miR-29b1 as well as miR-29b2 and miR-29c, are implicated in aging, metabolism, neuronal survival, and neurological disorders. In this study, the roles of miR-29a/b1 in aging and PD were investigated. miR-29a/b1 knockout mice (named as 29a KO hereafter) and their wild-type (WT) controls were used to analyze aging-related phenotypes. After challenged with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), dopaminergic injuries, glial activation, and mouse behaviors were evaluated. Primary glial cells were further cultured to explore the underlying mechanisms. Additionally, the levels of miR-29s in the cerebrospinal fluid (CSF) of PD patients (n = 18) and healthy subjects (n = 17) were quantified. 29a KO mice showed dramatic weight loss, kyphosis, and along with increased and deepened wrinkles in skins, when compared with WT mice. Moreover, both abdominal and brown adipose tissues reduced in 29a KO mice, compared to their WT counterpart. However, in MPTP-induced PD mouse model, the deficiency of miR-29a/b1 led to less severe damages of dopaminergic system and mitigated glial activation in the nigrostriatal pathway, and subsequently alleviated the motor impairments in 3-month-old mice. Eight-month-old mutant mice maintained such a resistance to MPTP intoxication. Mechanistically, the deficiency of miR-29a/b-1 promoted the expression of neurotrophic factors in 1-Methyl-4-phenylpyridinium (MPP+)-treated primary mixed glia and primary astrocytes. In lipopolysaccharide (LPS)-treated primary microglia, knockout of miR-29a/b-1 inhibited the expression of inflammatory factors, and promoted the expression of anti-inflammatory factors and neurotrophic factors. Knockout of miR-29a/b1 increased the activity of AMP-activated protein kinase (AMPK) and repressed NF-κB/p65 signaling in glial cells. Moreover, we found miR-29a level was increased in the CSF of patients with PD. Our results suggest that 29a KO mice display the peripheral premature senility. The combined effects of less activated glial cells might contribute to the mitigated inflammatory responses and elicit resistance to MPTP intoxication in miR-29a/b1 KO mice.
Protein phosphatase-1 inhibitor-2 promotes PP1γ positive regulation of synaptic transmission
Authors: Foley Karl , Altimimi Haider , Hou Hailong , Zhang Yu , McKee Cody , Papasergi-Scott Makaía M. , Yang Hongtian , Mayer Abigail , Ward Nancy , MacLean David M. , Nairn Angus C. , Stellwagen David , Xia Houhui
Published: October 2022

Inhibitor-2 (I-2) is a prototypic inhibitor of protein phosphatase-1 (PP1), a major serine-threonine phosphatase that regulates synaptic plasticity and learning and memory. Although I-2 is a potent inhibitor of PP1 in vitro, our previous work has elucidated that, in vivo, I-2 may act as a positive regulator of PP1. Here we show that I-2 and PP1γ, but not PP1α, positively regulate synaptic transmission in hippocampal neurons. Moreover, we demonstrated that I-2 enhanced PP1γ interaction with its major synaptic scaffold, neurabin, by Förster resonance energy transfer (FRET)/Fluorescence lifetime imaging microscopy (FLIM) studies, while having a limited effect on PP1 auto-inhibitory phosphorylation. Furthermore, our study indicates that the effect of I-2 on PP1 activity in vivo is dictated by I-2 threonine-72 phosphorylation. Our work thus demonstrates a molecular mechanism by which I-2 positively regulates PP1 function in synaptic transmission.
Role of brain-gut-muscle axis in human health and energy homeostasis
Authors: Yin Yunju , Guo Qiuping , Zhou Xihong , Duan Yehui , Yang Yuhuan , Gong Saiming , Han Mengmeng , Liu Yating , Yang Zhikang , Chen Qinghua , Li Fengna
Published: October 2022

The interrelationship between brain, gut and skeletal muscle plays a key role in energy homeostasis of the body, and is becoming a hot topic of research. Intestinal microbial metabolites, such as short-chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites, communicate with the central nervous system (CNS) by binding to their receptors. In fact, there is a cross-talk between the CNS and the gut. The CNS, under the stimulation of pressure, will also affect the stability of the intestinal system, including the local intestinal transport, secretion and permeability of the intestinal system. After the gastrointestinal tract collects information about food absorption, it sends signals to the central system through vagus nerve and other channels to stimulate the secretion of brain-gut peptide and produce feeding behavior, which is also an important part of maintaining energy homeostasis. Skeletal muscle has receptors for SCFAs and BAs. Therefore, intestinal microbiota can participate in skeletal muscle energy metabolism and muscle fiber conversion through their metabolites. Skeletal muscles can also communicate with the gut system during exercise. Under the stimulation of exercise, myokines secreted by skeletal muscle causes the secretion of intestinal hormones, and these hormones can act on the central system and affect food intake. The idea of the brain-gut-muscle axis is gradually being confirmed, and at present it is important for regulating energy homeostasis, which also seems to be relevant to human health. This article focuses on the interaction of intestinal microbiota, central nervous, skeletal muscle energy metabolism, and feeding behavior regulation, which will provide new insight into the diagnostic and treatment strategies for obesity, diabetes, and other metabolic diseases.
Comparison of waist-height ratio and other obesity indices in the prediction of diabetic peripheral neuropathy
Authors: Lawal Yakubu , Mshelia-Reng Rifkatu , Omonua Special O. , Odumodu Kenechukwu , Shuaibu Ramatu , Itanyi Ukamaka D. , Abubakar Amina I. , Kolade-Yunusa Hadijat O. , Songden Zumnan D. , Ehusani Caleb O. , Adediran Olufemi , Anumah Felicia E.
Published: October 2022

Background

Waist-height ratio (WHtR) is increasingly being studied as a simple and effective measure of central obesity. Reports have shown that WHtR is a better predictor of hypertension, diabetes, and cardiovascular diseases when compared to traditional obesity indices like body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR). This study is therefore aimed at comparing WHtR with other obesity indices in the prediction of peripheral neuropathy in persons with diabetes mellitus (DM).

Methodology

One thousand and forty persons with DM were enrolled following consent. Relevant details of history were obtained, followed by physical examinations. Data were analyzed using IBM-SPSS version 23. Logistic regression was used to compare the odds ratio of obesity indices in the prediction of peripheral neuropathy. The level of significance used was p = 0.05.

Results

Logistic regression showed that WHtR had the highest odds ratio (OR) for the prediction of “probable” diabetic peripheral neuropathy (OR 9.11, 95% CI 3.07–47.97, p = 0.002), followed by WC (OR 2.01, 95% CI 1.09–4.05, p = 0.004), and BMI (OR 1.26, 95% CI 1.00–3.99, p = 0.019) after correction for age; systemic hypertension; duration of DM; control of SBP, DBP, HbA1c, FPG, and 2HrPP.

Conclusion

WHtR has the highest odds ratio in the prediction of “probable” diabetic peripheral neuropathy in both genders, followed by WC in the males and BMI in the females.
Erythritol synthesis is elevated in response to oxidative stress and regulated by the non-oxidative pentose phosphate pathway in A549 cells
Authors: Ortiz Semira R. , Heinz Alexander , Hiller Karsten , Field Martha S.
Published: October 2022

Background

Erythritol is a predictive biomarker of cardiometabolic diseases and is produced from glucose metabolism through the pentose phosphate pathway (PPP). Little is known regarding the regulation of endogenous erythritol synthesis in humans.

Objective

In the present study, we investigated the stimuli that promote erythritol synthesis in human lung carcinoma cells and characterized potential points of regulation along the PPP.

Methods

Human A549 lung carcinoma cells were chosen for their known ability to synthesize erythritol. A549 cells were treated with potential substrates for erythritol production, including glucose, fructose, and glycerol. Using siRNA knockdown, we assessed the necessity of enzymes G6PD, TKT, TALDO, and SORD for erythritol synthesis. We also used position-specific13C-glucose tracers to determine whether the carbons for erythritol synthesis are derived directly from glycolysis or through the oxidative PPP. Finally, we assessed if erythritol synthesis responds to oxidative stress using chemical and genetic models.

Results

Intracellular erythritol was directly associated with media glucose concentration. In addition, siRNA knockdown of TKT or SORD inhibited erythritol synthesis, whereas siG6PD did not. Both chemically induced oxidative stress and constitutive activation of the antioxidant response transcription factor NRF2 elevated intracellular erythritol.

Conclusion

Our findings indicate that in A549 cells, erythritol synthesis is proportional to flux through the PPP and is regulated by non-oxidative PPP enzymes.
The new exploration of pure total flavonoids extracted from Citrus maxima (Burm.) Merr. as a new therapeutic agent to bring health benefits for people
Authors: Ding Shuning , Wang Peipei , Pang Xi , Zhang Leyin , Qian Lihui , Jia Xinru , Chen Wenqian , Ruan Shanming , Sun Leitao
Published: October 2022

The peel and fruit of Citrus varieties have been a raw material for some traditional Chinese medicine (TCM). Pure total flavonoids from Citrus maxima (Burm.) Merr. (PTFC), including naringin, hesperidin, narirutin, and neohesperidin, have been attracted increasing attention for their multiple clinical efficacies. Based on existing in vitro and in vivo research, this study systematically reviewed the biological functions of PTFC and its components in preventing or treating liver metabolic diseases, cardiovascular diseases, intestinal barrier dysfunction, as well as malignancies. PTFC and its components are capable of regulating glycolipid metabolism, blocking peroxidation and persistent inflammation, inhibiting tumor progression, protecting the integrity of intestinal barrier and positively regulating intestinal microbiota, while the differences in fruit cultivation system, picking standard, manufacturing methods, delivery system and individual intestinal microecology will have impact on the specific therapeutic effect. Thus, PTFC is a promising drug for the treatment of some chronic diseases, as well as continuous elaborate investigations are necessary to improve its effectiveness and bioavailability.
Replenishment of vitamin A for 7 days partially restored hepatic gene expressions altered by its deficiency in rats
Authors: Zhang Yan , Tian Kui , Chen Guoxun
Published: October 2022

We investigated the effects of vitamin A (VA) status on metabolism of Zucker rats with different genders and genotypes, and of short-term refeeding of a VA sufficient (VAS) diet on VA deficient (VAD) animals. First, male and female Zucker lean (ZL) and fatty (ZF) rats at weaning were fed a VAD or VAS diet for 8 weeks. Second, male VAD ZL rats were fed a VAS diet for 3 (VAD-VAS3d) or 7 (VAD-VAS7d) days. The body weight (BW), blood parameters, and hepatic expressions of genes for metabolism were determined. VA deficiency reduced BW gain in ZL and ZF rats of either gender. VAD ZL rats had lower plasma glucose, insulin, and leptin levels than VAS ZL rats. VAD-VAS3d and VAD-VAS7d rats had higher plasma glucose, insulin, and leptin levels than that in the VAD rats. The hepatic mRNA levels of Gck, Cyp26a1, Srebp-1c, Igf1, Rarb, Rxra, Rxrg, Pparg, and Ppard were lowered by VA deficiency. Refeeding of the VAS diet for 3 days restored the Gck and Cyp26a1 expressions, and for 7 days restored the Gck, Cyp26a1, Igf1, and Rxrb expressions significantly. The 7-day VA replenishment partially restored the hepatic gene expressions and metabolic changes in VAD ZL rats.
Outcomes with mismatched unrelated donor allogeneic hematopoietic stem cell transplantation in adults: A systematic review and meta-analysis
Authors: Mushtaq Muhammad Umair , Shahzad Moazzam , Tariq Ezza , Iqbal Qamar , Chaudhary Sibgha Gull , Zafar Muhammad U. , Anwar Iqra , Ahmed Nausheen , Bansal Rajat , Singh Anurag K. , Abhyankar Sunil H. , Callander Natalie S. , Hematti Peiman , McGuirk Joseph P.
Published: October 2022

Background

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for various hematologic disorders. Alternative donor strategies such as mismatched unrelated donors (MMUD) offer the option of HSCT to patients lacking a human leukocyte antigen (HLA)-matched donor. We conducted a systematic review and meta-analysis to evaluate outcomes after MMUD-HSCT.

Methods

A literature search was performed on PubMed, Cochrane Library, and ClinicalTrials.gov from the inception date through April 6, 2022. After screening 2477 manuscripts, 19 studies were included. Data was extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.

Results

A total of 3336 patients from 19 studies were included. The median age was 52.1 years, and 53% of recipients were males. The graft source was bone marrow in 19% and peripheral blood stem cells in 81% of recipients. The median time to transplant from hematologic diagnosis was 10 (1-247) months. Hematologic diagnoses included myeloid (82.9%), lymphoid (41.1%), and other disorders (3%). The reduced intensity and myeloablative conditioning were used in 65.6% and 32% of recipients, respectively. In-vivo T-cell depletion was performed in 56.7% of the patients. Most patients had one (87.9%) or two (11.4%) antigen HLA-mismatch. The pooled 1-year overall survival (OS) was 63.9% (95% CI 0.57-0.71, n=1426/2706), and the pooled 3-year OS was 42.1% (95% CI 0.34.2-0.50, n=907/2355). The pooled progression-free survival was 46.6% (95% CI 0.39-0.55, n=1295/3253) after a median follow-up of 1.8 (range 1-6) years. The pooled relapse rate was 26.8% (95% CI 0.22-0.32, n=972/3253) after a median follow-up of 2.25 (1-3) years. The pooled incidence of acute (grade II-IV) graft-versus-host disease (GVHD) and chronic GVHD was 36.4% (95% CI 0.31-0.42, n=1131/3030) and 41.2% (95% CI 0.35-0.48, n=1337/3228), respectively. The pooled non-relapse mortality was 22.6% (95% CI 0.17-0.29, n=888/3196) after a median follow-up of 2.6 (1-5) years.

Conclusion

MMUD-HSCT has demonstrated favorable outcomes with an acceptable toxicity profile. It represents a promising option in patients lacking an HLA-matched or haploidentical donor and may expand HSCT access to underrepresented racial and ethnic populations.
The complex interactions between the cellular and non-cellular components of the brain tumor microenvironmental landscape and their therapeutic implications
Authors: Faisal Syed M. , Comba Andrea , Varela Maria L. , Argento Anna E. , Brumley Emily , Abel Clifford , Castro Maria G. , Lowenstein Pedro R.
Published: October 2022

Glioblastoma (GBM), an aggressive high-grade glial tumor, is resistant to therapy and has a poor prognosis due to its universal recurrence rate. GBM cells interact with the non-cellular components in the tumor microenvironment (TME), facilitating their rapid growth, evolution, and invasion into the normal brain. Herein we discuss the complexity of the interactions between the cellular and non-cellular components of the TME and advances in the field as a whole. While the stroma of non-central nervous system (CNS) tissues is abundant in fibrillary collagens, laminins, and fibronectin, the normal brain extracellular matrix (ECM) predominantly includes proteoglycans, glycoproteins, and glycosaminoglycans, with fibrillary components typically found only in association with the vasculature. However, recent studies have found that in GBMs, the microenvironment evolves into a more complex array of components, with upregulated collagen gene expression and aligned fibrillary ECM networks. The interactions of glioma cells with the ECM and the degradation of matrix barriers are crucial for both single-cell and collective invasion into neighboring brain tissue. ECM-regulated mechanisms also contribute to immune exclusion, resulting in a major challenge to immunotherapy delivery and efficacy. Glioma cells chemically and physically control the function of their environment, co-opting complex signaling networks for their own benefit, resulting in radio- and chemo-resistance, tumor recurrence, and cancer progression. Targeting these interactions is an attractive strategy for overcoming therapy resistance, and we will discuss recent advances in preclinical studies, current clinical trials, and potential future clinical applications. In this review, we also provide a comprehensive discussion of the complexities of the interconnected cellular and non-cellular components of the microenvironmental landscape of brain tumors to guide the development of safe and effective therapeutic strategies against brain cancer.