Olfactory dysfunction and the role of stem cells in the regeneration of olfactory neurons.

The prevalence of COVID-19 has drawn increasing attention to olfactory dysfunction among researchers. Olfactory dysfunction manifests in various clinical types, influenced by numerous pathogenic factors. Despite this diversity, the underlying pathogenesis remains largely elusive, contributing to a lack of standardized treatment approaches. However, the potential regeneration of olfactory neurons within the nasal cavity presents a promising avenue for addressing olfactory dysfunction effectively. Our review aims to delve into the current research landscape and treatment modalities concerning olfactory dysfunction, emphasizing etiology, pathogenesis, clinical interventions, and the role of stem cells in regenerating olfactory nerves. Through this comprehensive examination, we aim to provide valuable insights into understanding the onset, progression, and treatment of olfactory dysfunction diseases.

P300 correlates with tDCS response in minimally conscious state patients.

BACKGROUND: Several recent studies indicated that transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (DLPFC) showed promising results in patients in a minimally conscious state (MCS). However, the neurological characteristics of patients in MCS considered to be tDCS responders have not been firmly established. OBJECTIVES: In the current study, we aimed to explore a reliable electrophysiological biomarker of tDCS response before the patients' inclusion in a tDCS protocol. METHOD: A hierarchical auditory event-related potential (ERP) pattern was applied to thirty-one MCS patients who subsequently received 20 anodal tDCS sessions of the left DLPFC over 10 consecutive working days. The patients were divided into responders and non-responders according to the Coma Recovery Scale-Revised (CRS-R) behavioral evaluation, and the differences in cortical information processing were compared using the P300 component in the ERP pattern. RESULTS: For the Tone-SON (TO) paradigm, CRS-R score (OR = 2.229, 95% CI: 1.241-4.005, P = 0.007) at admission was independently associated with tDCS response, while in the SDN-SON (DO) paradigm, CRS-R score at admission (OR = 2.369, 95% CI: 1.143-4.908, P = 0.020) and P300 (OR = 22.795, 95% CI: 1.823-285.038, P = 0.015) were independently associated with tDCS response in MCS patients. CONCLUSION: Our findings showed that higher total CRS-R score and presence of P300 in the hierarchical auditory ERP pattern, especially P300 in the DO paradigm, are associated with tDCS response in MCS patients. We speculate that P300 in the DO paradigm indicates patients with more preserved semantic processing abilities, and a priority to recover. The results provide important information for guidelines on the use of tDCS in MCS patients.

Music Therapy Alleviates Motor Dysfunction in Rats With Focal Cerebral Ischemia-Reperfusion Injury by Regulating BDNF Expression.

Background/Aim: Music-based therapy plays a role in central nervous system diseases. We aimed to explore the effect of different doses and durations of music therapy on motor function recovery after stroke and the underlying molecular mechanisms. Methods: Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, which was followed by reperfusion. In experiment 1, the rats that survived 1 week after MCAO surgery were randomly allocated into four groups (n = 10 per group): MCAO group, 1 h music group (Mozart K.448 music therapy 1 h per day for 2 weeks), 12 h music group (Mozart K.448 music therapy 12 h/day for 2 weeks), and accelerated music group (reversely accelerated music therapy 12 h for 2 weeks, AM group). In experiment 2, the survived rats were randomly divied into three groups: MCAO group, 12 h music group (music therapy 12 h/day for 3 weeks), and 12 h music-R group (music therapy 12 h/day for 2 weeks and rest for 1 week). Three neuroscores were evaluated daily, starting on the first day after surgery until the end of the experiment. The rats were killed 3 weeks after MCAO surgery in experiment 1 or 4 weeks after surgery in experiment 2. Nissl staining of infart core, peri-infarct zone, and motor cortex was performed to assess neuronal survival and regeneration. Western blot and immunofluorescence were used to detect the expression and distribution of brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) in ipsilateral hemispheres. Results: In the experiment of different music therapy doses, the motor function in the 12-h music group but not in the 1-h music group and AM group was significantly improved compared with that of the MCAO group. The BDNF protein level of the ipsilateral hemisphere motor cortex in the 12-h music group and the 1-h music group was higher than that of the MCAO group. The neurons and Nissl bodies were more in the 12-h music group than in the MCAO group. Immunofluorescence assay showed that a 12 h music therapy induces BDNF and GFAP accumulation at the damage boundary. In the experiment of different music therapy durations, 3 weeks music therapy (12 h music group) induced more longer cell synapses and more clearer cell-to-cell connections than 2 weeks music intervention (12 h music-R group). Moreover, the GFAP morphology in the 12-h music group was more similar to mature activated astrocytes than that in the 12-h music-R group. Conclusions: Music therapy may improve poststroke motor function and promote neuronal repair in the long term. The mechanism may be through stimulating BDNF and GFAP secretion in the injured motor cortex.

Apoptosis-antagonizing transcription factor is involved in rat post-traumatic epilepsy pathogenesis.

The present study aimed to explore the pathogenesis behind post-traumatic epilepsy (PTE). In the present study, a chloride ferric injection-induced rat PTE model was established. The expression levels of apoptosis-antagonizing transcription factor (AATF), cleaved caspase-3, p53, Bcl-2 and Bax were measured by western blotting or immunofluorescence staining (IF). The expression of AATF in vivo was downregulated by microinjection of lentiviral-mediated short-hairpin RNA. Compared with control and sham groups, at day 5 after PTE, neuron apoptosis was significantly increased and the expression levels of AATF, p53, cleaved caspase-3 and Bax were significantly upregulated. In addition, IF revealed co-localization of AATF and cleaved caspase-3 in the cortex. Additionally, AATF was expressed mainly in neurons and astrocytes. Following AATF inhibition, the expression levels of p53 and cleaved caspase-3 were significantly reduced as compared with the control group. Taken together, these findings suggested that following PTE, AATF is involved in neuronal apoptosis and may serve as a potential target for its alleviation.

Exploring the neural correlates of self-related names in healthy subjects.

OBJECTIVES: This study aimed to clarify the neural correlates and underlying mechanisms of the subject's own name (SON) and the unique name derived from the SON (SDN). METHODS: A name that was most familiar to the subject (SFN) was added as a self-related reference. We used 4 auditory stimuli-pure tone (1000 Hz), SON, SDN, and SFN-to evaluate the corresponding activated brain areas in 19 healthy subjects by using functional magnetic resonance imaging. RESULTS: Our results demonstrated that pure tone activated the fewest brain regions. Although SFN was a very strong self-related stimulus, it failed to activate many midline structures. The brain regions activated by SON and SDN were very similar. SFN as a self-related stimulus was less self-related compared with SDN. What's more, the additionally activated fusiform gyrus and parahippocampal gyrus of SDN might revealed its processing path. CONCLUSIONS: SDN, which has created by us, is a new and self-related stimulus similar to SON. They might provide a useful reference for consciousness assessment with SON and SDN.

Recovery from prolonged disorders of consciousness: A dual-center prospective cohort study in China.

BACKGROUND: Recent innovations in intensive care have improved the prognosis of patients with severe brain injuries and brought more patients with disorders of consciousness (DoC). Data are lacking regarding the long-term outcomes of those patients in China. It is necessary to study the long-term outcomes of patients with prolonged DoC in light of many factors likely to influence crucial decisions about their care and their life. AIM: To present the preliminary results of a DoC cohort. METHODS: This was a two-center prospective cohort study of inpatients with vegetative state (VS)/unresponsive wakefulness syndrome (UWS). The study outcomes were the recovery from VS/UWS to minimally conscious state (MCS) and the long-term status of patients with prolonged DoC considered in VS/UWS or MCS for up to 6 years. The patients were evaluated using the Glasgow coma scale, coma recovery scale-revised, and Glasgow outcome scale. The endpoint of follow-up was recovery of full consciousness or death. The changes in the primary clinical outcome improvement in clinical diagnosis were evaluated at 12 mo compared with baseline. RESULTS: The study population included 93 patients (62 VS/UWS and 31 MCS). The post-injury interval range was 28-634 d. Median follow-up was 20 mo (interquartile range, 12-37 mo). At the endpoint, 33 transitioned to an emergence from MCS or full consciousness, eight had a locked-in syndrome, and there were 35 patients remaining in a VS/UWS and 11 in an MCS. Seven (including one locked-in syndrome) patients (7.5%) died within 12 mo of injury. Compared with the unresponsive group (n = 52) at 12 mo, the responsive group (n = 41) had a higher proportion of males (87.8% vs 63.5%, P = 0.008), shorter time from injury (median, 40.0 d vs 65.5 d, P = 0.006), higher frequency of vascular etiology (68.3% vs 38.5%, P = 0.007), higher Glasgow coma scale score at admission (median, 9 vs 6, P < 0.001), higher coma recovery scale-revised score at admission (median, 9 vs 2.5, P < 0.001), at 1 mo (median, 14 vs 5, P < 0.001), and at 3 mo (median, 20 vs 6, P < 0.001), lower frequency of VS/UWS (36.6% vs 90.0%, P < 0.001), and more favorable Glasgow outcome scale outcome (P < 0.001). CONCLUSION: Patients with severe DoC, despite having strong predictors of poor prognosis, might recover consciousness after a prolonged time of rehabilitation. An accurate initial diagnosis of patients with DoC is critical for predicting outcome and a long-term regular follow-up is also important.

Lin28 is associated with astrocytic proliferation during intracerebral hemorrhage.

As an evolutionarily conserved RNA-binding protein, LIN28 is known to be involved in the regulation of the translation and stability of a large number of mRNAs and the biogenesis of certain miRNAs. Increasing evidence indicates that LIN28 regulates many cellular processes, such as embryonic stem cell proliferation, cell fate succession, developmental timing, and oncogenesis. However, the expression and function of LIN28 after intracerebral hemorrhage (ICH) are still unclear. In this study, we performed an intracranial hemorrhage model in adult rats and western blot, immunohistochemistry, as well as immunofluorescence showed that LIN28 was obviously up-regulation in neurons adjacent to the hematoma after ICH. Besides, the transitory increase of LIN28 expression was paralleled with the up-regulation of proliferating cell nuclear antigen (PCNA) as well as GFAP. Hence, LIN28 might play an important role in astrocyte proliferation after ICH.

miR­145 suppresses ovarian cancer progression via modulation of cell growth and invasion by targeting CCND2 and E2F3.

MicroRNAs (miRNA/miRs) have been demonstrated to be critical post­transcriptional modulators of gene expression during tumorigenesis. Numerous miRNAs have been revealed to be downregulated in human epithelial ovarian cancer (EOC). In the present study, it was observed that the expression of miR­145 was decreased in EOC tissues and cell lines. Overexpression of miR­145 inhibited the proliferation, migration and invasion of EOC cells. The D­type cyclin 2, cyclin D2 (CCND2), and E2F transcription factor 3 (E2F3) were confirmed to be targets of miR­145. In addition, restoration of these 2 genes significantly reversed the tumor suppressive effects of miR­145. Collectively, the results indicated that miR­145 serves a critical role in suppressing the biological behavior of EOC cells by targeting CCND2 and E2F3. Therefore, miR­145 was suggested to be a potential miRNA­based therapeutic target in ovarian cancer.

Hippocampal FXR plays a role in the pathogenesis of depression: A preliminary study based on lentiviral gene modulation.

As a well-known bile acid receptor, the role of Farnesoid X receptor (FXR) in the digestive system and cardiovascular system has been widely explored. However, there are very few studies involving FXR in the central nervous system. In this study, we explored the role of FXR in the pathogenesis of depression, a serious and worldwide neuropsychiatric disease. It was found that chronic unpredictable mild stress (CUMS) fully enhanced the protein and mRNA expressions of FXR in hippocampus, but not medial prefrontal cortex (mPFC). Overexpression of hippocampal FXR induced notable depressive-like behaviors and decreased expression of brain-derived neurotrophic factor (BDNF) in naïve rats, while knockdown of hippocampal FXR fully prevented the effects of CUMS on rat behaviors and hippocampal BDNF expression. Taken together, our research extends the knowledge of FXR's role in the central nervous system, and may provide a potential and novel therapeutic target for treating depression.

Association between CYP1B1 gene polymorphisms and risk factors and susceptibility to laryngeal cancer.

BACKGROUND: The aim of this study was to investigate the association between polymorphism of the cytochrome P450 1B1 (CYP1B1) gene, a metabolic enzyme gene, and the susceptibility to laryngeal cancer among the Chinese Han population. MATERIAL/METHODS: In a case-control study, we investigated polymorphisms in the CYP1B1 gene (rs10012, rs1056827, and rs1056836) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 300 Chinese Han patients with laryngeal cancer and 300 healthy Chinese Han subjects in a control group. We also studied the interactions between genetic polymorphism and risk factors such as smoking and alcohol consumption in the pathogenesis of laryngeal cancer. RESULTS: There were statistically significant differences in the distributions of the rs1056827 and rs1056836 genotypes between the 2 groups. Regarding rs1056827, carriers of the T allele had a significantly higher risk of laryngeal cancer than the G-allele carriers (OR=1.4339, 95% CI: 1.1268-1.8247; P=0.0034). The difference was still statistically significant after adjusting for factors such as age, sex, smoking, and drinking (adjusted OR=1.743, 95% CI: 1.124-3.743, P<0.001). However, regarding rs1056836, the G allele carriers had a significantly lower risk of laryngeal cancer than the C allele carriers (OR=0.5557, 95% CI: 0.3787-0.8154; P=0.0027). The difference was statistically significant even after adjusting for factors such as age, sex, smoking, and drinking (adjusted OR=0.5641, 95% CI: 0.3212-0.8121, P=0.001). Subjects who carry the C-T-C haplotype have a significantly increased incidence of laryngeal cancer. We also found that CYP1B1 rs1056827 polymorphism had synergistic effects with smoking or alcohol consumption regarding the risk of laryngeal cancer. CONCLUSIONS: CYP1B1 gene polymorphism is closely related to the onset of laryngeal cancer. There is a mutually synergistic effect between smoking, alcohol consumption, and CYP1B1 gene polymorphisms regarding laryngeal cancer.

[Effect of acupoint catgut embedding on motor function and serum high sensitivity C-reactive protein and IL-6 levels in patients with acute cerebral infarction].

OBJECTIVE: To evaluate the effect of acupoint catgut embedding on motor function in patients with acute cerebral infarction (ACI), and to explore its mechanism. METHODS: Sixty-three ACI patients were randomly assigned to acupuncture group (n = 30) and catgut embedding group (n = 33). Patients of the acupuncture group received acupuncture stimulation of Baihui (GV 20), Neiguan (P 6), Sanyinjiao (SP 6), Taichong (LR 3), etc. and scalp-point Motor Area, Sensory Area, Balance Area, once daily, 5 times a week for 20 times. Patients of the catgut embedding group received catgut embedding at the acupoints same to acupuncture group, once every 10 days, 3 times altogether. Additionally, both groups received regular treatment of neurology (controlling blood pressure, blood sugar and blood lipids levels, physical therapy, etc.) and early rehabilitation training (limb otor training). The patients' functional mobility was evaluated by simplified Fugl-Meyer Assessment Scale (FMA) and Modified Bathel Index Scale (MBI). The level of serum high sensitivity C-reactive protein (hs-CRP) was detected using latex agglutination reaction method; and serum in terleukin-6 (IL-6) content measured by enzyme-linked immunosorbent assay. RESULTS: lts After 30 days' treatment, the mean scores of FMA and MBI were significantly increased in both acupuncture group and catgut embedding grou p (P < 0.05), suggesting an improvement of the cerebral infarction patient's functional mobility after the treatment. The therapeutic effect of the catgut embedding was obviously superior to that of the acupuncture grou p (P < 0. 05). The mean contents of serum IL-6 and hs-CRP of the two groups were significantly decreased after the treatmen t (P < 0.05), suggesting a reduction of proinflammatory cytokine and inflammatory mediator levels, respectively. The levels of both serum IL-6 and hs-CRP of the catgut embedding group were markedly lower than those of the acupuncture group ( P < 0.05). CONCLUSION: ion Acupoint catgut embedding therapy is effective in improving cerebral infarction patients' functional mobility, which is related to its action in inhibiting inflammatory reaction in the early stage of cerebral ischemic injury.

Carbenoxolone pretreatment and treatment of posttraumatic epilepsy.

Gap junction blocking agents can inhibit spontaneous discharge frequency in cells. We established a rat model of posttraumatic epilepsy induced using ferric ions. Rats were intraperitoneally injected with carbenoxolone, 20 mg/kg, prior to and 30 minutes after model establishment, once a day for 14 consecutive days. Immunohistochemistry showed glial cell proliferation around a cortical focus and significantly increased connexin expression in posttraumatic epilepsy. However, carbenoxolone pretreatment or treatment significantly reduced connexin expression in the cortex, inhibited glial fibrillary acidic protein expression and ameliorated seizure degree in rats. These findings indicate that large amounts of glial cell proliferation and abnormal gap junction generation play a role in posttraumatic epilepsy, and that carbenoxolone may prevent and treat this disease.