Effect of foot reflexology on an infant with sensorineural hearing loss: A case report.

BACKGROUND: Our study contributes to the further understanding of the mechanism of foot reflexology. Foot reflexology has been reported to affect hearing recovery, but no physiological evidence has been provided. This lack of evidence hampers the acceptance of the technique in clinical practice. CASE SUMMARY: A girl was taken to North Sichuan Medical University Affiliated Hospital for a hearing screen by her parents. Her parents reported that her hearing level was the same as when she was born. The girl was diagnosed with sensorineural hearing loss (SNHL) by a doctor in the otolaryngology department. After we introduced the foot reflexology project, the parents agreed to participate in the experiment. After 6 months of foot reflexology treatment, the hearing threshold of the girl recovered to a normal level, below 30 dB. CONCLUSION: Foot reflexology should be encouraged in clinical practice and for families of infants with SNHL.

Therapeutic effects and mechanisms of isoxanthohumol on DSS-induced colitis: regulating T cell development, restoring gut microbiota, and improving metabolic disorders.

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.

Clinical value of serum LINC02446 and S100B in early diagnosis and prognosis assessment of traumatic brain injury.

OBJECTIVE: To detect the expression levels of LINC02446 and S100B in serum of patients with traumatic brain injury (TBI) and explore their values as diagnostic and prognostic indicators for TBI. METHOD: Abnormal expressed RNAs in brain injury were screened from the dataset GSE1131475. Serums were collected from moderate to severe TBI patients at 1-3 and 4-12 h post injury. Quantitative polymerase chain reaction was used to detect the expression levels of LINC02446 and S100B in serum. The Glasgow Outcome Scale was used for prognostic evaluation. The diagnostic and prognostic efficacy of LINC02446 and S100B in TBI was evaluated using the receiver operating characteristic (ROC) curve. RESULT: The serum expression levels of LINC02446 and S100B in the TBI group were significantly increased. The expression levels of LINC02446 and S100B in the severe TBI group were significantly higher than those in the mild TBI group. ROC curve analysis showed that the combination of LINC02446 and S100B can distinguish TBI patients from healthy controls, as well as mild TBI from moderate to severe TBI. At the 6-month follow-up, the expression levels of LINC02446 and S100B in TBI patients with poor prognosis were significantly higher than those in patients with good prognosis, and ROC results showed their differentiation value. Moreover, the expression level of LINC02446 at 0-3 h can serve as an independent prognostic factor for poor prognosis. CONCLUSION: Serum LINC02446 and S100B hold clinical application value in the diagnosis and prognosis of TBI and are expected to become new potential biomarkers.

Identification and functional characterization of annexin A2 in half-smooth tongue sole (Cynoglossus semilaevis).

Annexin A2 (AnxA2), belonging to the annexin family, plays a crucial role in immune responses. In this study, the cDNA of the AnxA2 gene was identified in half-smooth tongue sole, Cynoglossus semilaevis. The transcript of AnxA2 gene in C. semilaevis (CsAnxA2) showed broad tissue distribution, with the highest expression level observed in the gut. CsAnxA2 expression was significantly up-regulated in the intestine, spleen, and kidney tissues following exposure to Shewanella algae. Immunohistochemical staining revealed that CsAnxA2 was predominantly expressed in epithelial cells and significantly elevated after S. algae challenge. Subcellular localization showed that CsAnxA2 was primarily localized in the cytoplasmic compartment. Moreover, proinflammatory cytokines (IL-6, IL-8 and IL-1ß) exhibited significant upregulation after CsAnxA2 was overexpressed in vivo. One hundred and fifty-eight CsAnxA2-interacting proteins were captured in the intestinal tissue, showing the top two normalized abundance observed for actin beta (ACTB) and protein S100-A10 (p11). Fifty-four high abundance CsAnxA2-interacting proteins (HIPs) were primary enriched in ten pathways, with the top three significantly enriched pathways being Salmonella infection, glycolysis/gluconeogenesis, and peroxisome proliferator-activated receptor (PPAR) signaling pathway. These results provide valuable information for further investigation into the functional mechanism of AnxA2 in C. semilaevis.

Hepatitis B virus and cytomegalovirus coinfection in an older patient: a case report.

Cytomegalovirus (CMV) infection involving the skin is relatively rare. We herein report a case involving a man in his late 70s with positive hepatitis B surface antigen who presented with multiform skin lesions, including a papuloid rash, papular urticaria, and purpura. The patient had taken no antiviral drugs for nearly 13 years but had recently developed severe liver injury. Laboratory examination revealed positive CMV immunoglobulin M, CMV polymerase chain reaction result of 1.09 × 102 copies/mL, and a slightly decreased CD4+ cell count; however, the CD8+ T-cell count was within the normal range. A skin biopsy was performed in the region of the papular eruption on the left inner thigh, and the pathologic findings were consistent with CMV infection. After admission, the patient began a combination of antiviral therapy for hepatitis B virus and CMV. After 3 weeks of treatment, the patient was discharged with skin lesions, and his liver function recovered.

Assembly and analysis of the genome of Notholithocarpus densiflorus.

Tanoak (Notholithocarpus densiflorus) is an evergreen tree in the Fagaceae family found in California and southern Oregon. Historically, tanoak acorns were an important food source for Native American tribes and the bark was used extensively in the leather tanning process. Long considered a disjunct relictual element of the Asian stone oaks (Lithocarpus spp.), phylogenetic analysis has determined that the tanoak is an example of convergent evolution. Tanoaks are deeply divergent from oaks (Quercus) of the Pacific Northwest and comprise a new genus with a single species. These trees are highly susceptible to 'sudden oak death' (SOD), a plant pathogen (Phytophthora ramorum) that has caused widespread mortality of tanoaks. Here, we set out to assemble the genome and perform comparative studies among a number of individuals that demonstrated varying levels of susceptibility to SOD. First, we sequenced and de novo assembled a draft reference genome of N. densiflorus using co-barcoded library processing methods and an MGI DNBSEQ-G400 sequencer. To increase the contiguity of the final assembly, we also sequenced Oxford Nanopore (ONT) long reads to 30X coverage. To our knowledge, the draft genome reported here is one of the more contiguous and complete genomes of a tree species published to date, with a contig N50 of ∼1.2 Mb, a scaffold N50 of ∼2.1 Mb, and a complete gene score of 95.5% through BUSCO analysis. In addition, we sequenced 11 genetically distinct individuals and mapped these onto the draft reference genome enabling the discovery of almost 25 million single nucleotide polymorphisms and ∼4.4 million small insertions and deletions. Finally, using co-barcoded data we were able to generate complete haplotype coverage of all 11 genomes.

Real-world implementation of a multilevel interventions program to prevent mother-to-child transmission of HBV in China.

Reducing hepatitis B virus (HBV) mother-to-child transmission (MTCT) is a fundamental step toward the HBV elimination goal. The multicentred, multilevel SHIELD program aimed to use an intense intervention package to reduce HBV MTCT in China. This study was conducted in diverse health settings across China, encompassing 30,109 pregnant women from 178 hospitals, part of the interim analysis of stage II of the SHIELD program, and 8,642 pregnant women from 160 community-level health facilities in stage III of the SHIELD program. The study found that the overall MTCT rate was 0.23% (39 of 16,908; 95% confidence interval (CI): 0.16-0.32%) in stage II and 0.23% (12 of 5,290; 95% CI: 0.12-0.40%) in stage III. The MTCT rate was lower among participants who were compliant with the interventions (stage II: 0.16% (95% CI: 0.10-0.26%); stage III: 0.03% (95% CI: 0.00-0.19%)) than among those who were noncompliant (3.16% (95% CI: 1.94-4.85%); 1.91% (95% CI: 0.83-3.73%); P < 0.001). Our findings demonstrate that the comprehensive interventions among HBV-infected pregnant women were feasible and effective in dramatically reducing MTCT.

Leptolyngbya sp. XZMQ and Bacillus XZM co-inoculation reduced sunflower arsenic toxicity by regulating rhizosphere microbial structure and enzyme activity.

Microorganisms are of great significance for arsenic (As) toxicity amelioration in plants as soil fertility is directly affected by microbes. In this study, we innovatively explored the effects of indigenous cyanobacteria (Leptolyngbya sp. XZMQ) and plant growth-promoting bacteria (PGPB) (Bacillus XZM) on the growth and As absorption of sunflower plants from As-contaminated soil. Results showed that single inoculation and co-inoculation stimulated the growth of sunflower plants (Helianthus annuus L.), enhanced enzyme activities, and reduced As contents. In comparison to the control group, single innoculation of microalgae and bacteria in the rhizosphere increased extracellular polymeric substances (EPS) by 21.99% and 14.36%, respectively, whereas co-inoculation increased them by 35%. Compared with the non-inoculated group, As concentration in the roots, stems and leaves of sunflower plants decreased by 38%, 70% and 41%, respectively, under co-inoculation conditions. Inoculation of Leptolyngbya sp. XZMQ significantly increased the abundance of nifH in soil, while co-inoculation of cyanobacteria and Bacillus XZM significantly increased the abundance of cbbL, indicating that the coupling of Leptolyngbya sp. XZMQ and Bacillus XZM could stimulate the activity of nitrogen-fixing and carbon-fixing microorganisms and increased soil fertility. Moreover, this co-inoculation increased the enzyme activities (catalase, sucrase, urease) in the rhizosphere soil of sunflower and reduced the toxic effect of As on plant. Among these, the activities of catalase, peroxidase, and superoxide dismutase decreased. Meanwhile, co-inoculation enables cyanobacteria and bacteria to attach and entangle in the root area of the plant and develop as symbiotic association, which reduced As toxicity. Co-inoculation increased the abundance of aioA, arrA, arsC, and arsM genes in soil, especially the abundance of microorganisms with aioA and arsM, which reduced the mobility and bioavailability of As in soil, hence, reduced the absorption of As by plants. This study provides a theoretical basis for soil microbial remediation in mining areas.

Efficacy and safety of utidelone plus capecitabine in advanced first-line therapy for metastatic breast cancer: A multicenter real-world study.

Background: The purpose of this study was to compare the efficacy and safety of utidelone plus capecitabine for advanced first-line versus second-line or above therapy in metastatic breast cancer patients who had previously received anthracycline and taxane. At the same time, we compared the efficacy of utidelone plus capecitabine and vinorelbine plus cisplatin in advanced first-line treatment of metastatic breast cancer. Patients and methods: A retrospective cohort of 11 patients with metastatic breast cancer previously treated with anthracycline and taxane (including neoadjuvant and adjuvant therapies) for advanced first-line with utidelone plus capecitabine, 32 patients treated with second-line or above, and 60 patients with vinorelbine plus cisplatin between October 2011 and August 2022 was collected. The first and second groups were treated with utidelone plus capecitabine, and the third group was treated with vinorelbine plus cisplatin. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), objective response rate (ORR), and treatment safety. Results: By 03/31/2023, median PFS reached 11.70 months (95 % CI 0.093-0.141) in utidelone plus capecitabine group in the advanced first-line therapy, compared to 5.60 months (95 % CI 0.025-0.079) in the second-line or above therapy [HR 0.42, (95 % CI 0.226-0.787), P = 0.0077]. In utidelone plus capecitabine, the median OS was not reached in the advanced first-line therapy, with a mean overall survival of 23.16 months (95 % CI 0.198-0.265); whereas the median OS in the second-line or above therapy was 19.50 months (95 % CI 0.083-0.307), with a mean overall survival of 16.89 months (95 % CI 0.136-0.202) [HR 0.26, (95 % CI 0.098-0.678), P = 0.0495]. The ORR for advanced first-line therapy was 27.27 % (95%CI 0.060, 0.610) compared with 15.63 % (95%CI 0.053, 0.328) for second-line or above. In advanced first-line therapy, utidelone plus capecitabine was superior to vinorelbine plus cisplatin with a median PFS of 6.12 months (95 % CI 0.051-0.072) [HR 0.49, (95 % CI 0.286-0.839), P = 0.0291]. Compared with utidelone plus capecitabine, the median OS in vinorelbine plus cisplatin advanced first-line therapy group was 35.37 months (95 % CI 0.258-0.449), and the mean overall survival was 40.79 months (95 % CI 0.315-0.501) [HR 0.54, (95 % CI 0.188-1.568), P = 0.2587]. The ORR for vinorelbine plus cisplatin was 18.33 % (95 % CI 0.095, 0.304). The most common adverse events in our study were neurological toxicity, hand-foot syndrome, hematological toxicity, gastrointestinal toxicity, and hepatic and renal function abnormalities. There were no deaths due to adverse effects during the utidelone plus capecitabine treatment period. Conclusions: In MBC, advanced first-line therapy with utidelone plus capecitabine resulted in more favorable PFS, OS, and ORR than second-line or above therapy. In advanced first-line therapy, utidelone plus capecitabine had superior PFS, and ORR compared with vinorelbine plus cisplatin. This study concludes that utidelone plus capecitabine is a more valuable chemotherapy option in advanced first-line MBC.

Deep Learning for the Prediction of the Survival of Midline Diffuse Glioma with an H3K27M Alteration.

BACKGROUND: The prognosis of diffuse midline glioma (DMG) patients with H3K27M (H3K27M-DMG) alterations is poor; however, a model that encourages accurate prediction of prognosis for such lesions on an individual basis remains elusive. We aimed to construct an H3K27M-DMG survival model based on DeepSurv to predict patient prognosis. METHODS: Patients recruited from a single center were used for model training, and patients recruited from another center were used for external validation. Univariate and multivariate Cox regression analyses were used to select features. Four machine learning models were constructed, and the consistency index (C-index) and integrated Brier score (IBS) were calculated. We used the receiver operating characteristic curve (ROC) and area under the receiver operating characteristic (AUC) curve to assess the accuracy of predicting 6-month, 12-month, 18-month and 24-month survival rates. A heatmap of feature importance was used to explain the results of the four models. RESULTS: We recruited 113 patients in the training set and 23 patients in the test set. We included tumor size, tumor location, Karnofsky Performance Scale (KPS) score, enhancement, radiotherapy, and chemotherapy for model training. The accuracy of DeepSurv prediction is highest among the four models, with C-indexes of 0.862 and 0.811 in the training and external test sets, respectively. The DeepSurv model had the highest AUC values at 6 months, 12 months, 18 months and 24 months, which were 0.970 (0.919-1), 0.950 (0.877-1), 0.939 (0.845-1), and 0.875 (0.690-1), respectively. We designed an interactive interface to more intuitively display the survival probability prediction results provided by the DeepSurv model. CONCLUSION: The DeepSurv model outperforms traditional machine learning models in terms of prediction accuracy and robustness, and it can also provide personalized treatment recommendations for patients. The DeepSurv model may provide decision-making assistance for patients in formulating treatment plans in the future.

Alfosbuvir plus Daclatasvir for Treatment of Chronic Hepatitis C Virus Infection in China.

INTRODUCTION: A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. METHODS: All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. RESULTS: Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%-99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p < 0.0001). The SVR12 rates were similar regardless of most baseline characteristics. The most common adverse event (AE) (≥ 10%) was hypercholesterolemia. Serious adverse events (SAEs) were reported in 25 (7.7%) patients, none of which was judged to be related to the study drug. The majority of AEs were mild to moderate in severity. CONCLUSIONS: Alfosbuvir plus daclatasvir for 12 weeks was highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3, or 6, suggesting that this regimen could be a promising option for HCV treatment in China irrespective of genotype. TRIAL REGISTRATION: ClinicalTrial.gov identifier, NCT04070235.

A quantitative study of airway ultrasound in predicting difficult laryngoscopy: A prospective study.

PURPOSE: As common clinical screening tests cannot effectively predict a difficult airway, and unanticipated difficult laryngoscopy remains a challenge for physicians. We herein used ultrasound to develop some point-of-care predictors for difficult laryngoscopy. METHODS: This prospective observational study included 502 patients who underwent laryngoscopy and a detailed sonographic assessment. Patients under 18 years old, or with maxillofacial deformities or fractures, limited mouth opening, limited neck movement or history of neck surgery were excluded from the study. Laryngoscopic views of all patients were scored and grouping using the modified Cormack-Lehane (CL) scoring system. The measurements acquired comprised tongue width, the longitudinal cross-sectional area of the tongue, tongue volume, the mandible-hyoid bone distance, the hyoid bone-glottis distance, the mandible-hyoid bone-glottis angle, the skin-thyrohyoid membrane distance, the glottis-superior edge of the thyroid cartilage distance (DGTC), the skin-hyoid bone distance, and the epiglottis midway-skin distance. ANOVA and Chi-square were used to compare differences between groups. Logistic regression was used to identify risk factors for difficult laryngoscopy and it was visualized by receiver operating characteristic curves and nomogram. R version 3.6.3 and SPSS version 26.0 were used for statistical analyses. RESULTS: Difficult laryngoscopy was indicated in 49 patients (CL grade Ⅲ - Ⅳ) and easy laryngoscopy in 453 patients (CL grade Ⅰ - Ⅱ). The ultrasound-measured mandible-hyoid bone-glottis angle and DGTC significantly differed between the 2 groups (p < 0.001). Difficult laryngoscopy was predicted by an area under the curve (AUC) of 0.930 with a threshold mandible-hyoid bone-glottis angle of 125.5° and by an AUC of 0.722 with a threshold DGTC of 1.22 cm. The longitudinal cross-sectional area of the tongue, tongue width, tongue volume, the mandible-hyoid distance, and the hyoid-glottis distance did not significantly differ between the groups. CONCLUSION: Difficult laryngoscopy may be anticipated in patients in whom the mandible-hyoid bone-glottis angle is smaller than 125.5° or DGTC is larger than 1.22 cm.

Prognostic nomogram models for predicting survival probability in elderly glioblastoma patients.

PURPOSE: To investigate the prognostic factors of survival and develop a predictive nomogram model for elderly GBM patients. METHODS: Elderly patients (> = 65 years) with histologically diagnosed GBM were extracted from the SEER database. Survival analysis of overall survival (OS) was performed by Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used to determine independent prognostic factors and these factors were used to further construct the nomogram model. RESULTS: A total of 9068 elderly GBM patients (5122 males and 3946 females) were included, with a median age of 72 years (65-96 years). All patients were divided randomly into the training group (n = 6044) and the validation group (n = 3024) by a ratio of 2:1. Cox regression analyses on OS showed eight independent prognostic factors (race, age, tumor side, tumor size, metastasis, surgery, radiotherapy, and chemotherapy) in the training cohort. Also, seven variables (except for race) were identified on CSS in the training group. By comprising these variables, the nomogram models on OS and CSS for predicting the 6-month, 1-year, and 2-year survival probability were constructed and exhibited moderate consistency, respectively. Then, they could be validated well in the validation cohort and by C-index, time-dependent ROC curve, calibration plot, and DCA curve. CONCLUSIONS: Nomogram models on OS and CSS could provide an applicable tool to predict the survival probability and provide clinical references regarding treatment strategies and prognosis.

Native microalgae and Bacillus XZM remediate arsenic-contaminated soil by forming biological soil crusts.

Biological soil crusts (BSCs) are a useful tool for immobilization of metal(loid)s in mining areas. Yet, the typical functional microorganisms involved in promoting the fast development of BSCs and their impacts on arsenic(As) contaminated soil remain unverified. In this study, As-contaminated soil was inoculated with indigenous Chlorella thermophila SM01 (C. thermophila SM01), Leptolyngbya sp. XZMQ, isolated from BSCs in high As-contaminated areas and plant growth-promoting (PGP) bacteria (Bacillus XZM) to construct BSCs in different manners. After 45 days of ex-situ culture experiment, Leptolyngbya sp. XZMQ and bacteria could form obvious BSCs. Compared to single-inoculated microalgae, the co-inoculation of Leptolyngbya sp. XZMQ and Bacillus XZM increased soil pH and water content by 10% and 26%, respectively, while decreasing soil EC and density by 19% and 14%, respectively. The soil catalase, alkaline phosphatase, sucrase, and urease activities were also increased by 30.53%, 96.24%, 154.19%, and 272.17%, respectively. The co-inoculation of Leptolyngbya sp. XZMQ and Bacillus XZM drove the formation of BSCs by producing large amounts of extracellular polymeric substances (EPS). The three-dimensional fluorescence spectroscopy (3D-EEM) analysis showed that induced BSCs increased As immobilization by enhancing the contents of tryptophan and tyrosine substances, fulvic acid, and humic acid in EPS. The presence of the -NH2 and -COOH functional groups in tryptophan residues were determined using Fourier Transform Infrared Spectroscopy (FTIR). X-Ray Diffraction (XRD) analysis showed that there were iron (hydrogen) oxides in BSCs, which could form ternary complexes with humic acid and As, thereby increasing the adsorption of As. Therefore, BSCs formed by co-inoculation of Leptolyngbya sp. XZMQ and Bacillus XZM increased the immobilization of As, thereby reducing the content of soluble As in the environment. In summary, our findings innovatively provided a new method for the remediation of As-contaminated soil in mining areas.

Deep learning-based prediction of H3K27M alteration in diffuse midline gliomas based on whole-brain MRI.

BACKGROUND: H3K27M mutation status significantly affects the prognosis of patients with diffuse midline gliomas (DMGs), but this tumor presents a high risk of pathological acquisition. We aimed to construct a fully automated model for predicting the H3K27M alteration status of DMGs based on deep learning using whole-brain MRI. METHODS: DMG patients from West China Hospital of Sichuan University (WCHSU; n = 200) and Chengdu Shangjin Nanfu Hospital (CSNH; n = 35) who met the inclusion and exclusion criteria from February 2016 to April 2022 were enrolled as the training and external test sets, respectively. To adapt the model to the human head MRI scene, we use normal human head MR images to pretrain the model. The classification and tumor segmentation tasks are naturally related, so we conducted cotraining for the two tasks to enable information interaction between them and improve the accuracy of the classification task. RESULTS: The average classification accuracies of our model on the training and external test sets was 90.5% and 85.1%, respectively. Ablation experiments showed that pretraining and cotraining could improve the prediction accuracy and generalization performance of the model. In the training and external test sets, the average areas under the receiver operating characteristic curve (AUROCs) were 94.18% and 87.64%, and the average areas under the precision-recall curve (AUPRC) were 93.26% and 85.4%. CONCLUSIONS: The developed model achieved excellent performance in predicting the H3K27M alteration status in DMGs, and its good reproducibility and generalization were verified in the external dataset.

Peroxisom proliferator-activated receptor-γ coactivator-1α in neurodegenerative disorders: A promising therapeutic target.

Neurodegenerative disorders (NDDs) are characterized by progressive loss of selectively vulnerable neuronal populations and myelin sheath, leading to behavioral and cognitive dysfunction that adversely affect the quality of life. Identifying novel therapies that attenuate the progression of NDDs would be of significance. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a widely expressed transcriptional regulator, modulates the expression of genes engaged in mitochondrial biosynthesis, metabolic regulation, and oxidative stress (OS). Emerging evidences point to the strong connection between PGC-1α and NDDs, suggesting its positive impaction on the progression of NDDs. Therefore, it is urgent to gain a deeper and broader understanding between PGC-1α and NDDs. To this end, this review presents a comprehensive overview of PGC-1α, including its basic characteristics, the post-translational modulations, as well as the interacting transcription factors. Secondly, the pathogenesis of PGC-1α in various NDDs, such as Alzheimer's (AD), Parkinson's (PD), and Huntington's disease (HD) is briefly discussed. Additionally, this study summarizes the underlying mechanisms that PGC-1α is neuroprotective in NDDs via regulating neuroinflammation, OS, and mitochondrial dysfunction. Finally, we briefly outline the shortcomings of current NDDs drug therapy, and summarize the functions and potential applications of currently available PGC-1α modulators (activator or inhibitors). Generally, this review updates our insight of the important role of PGC-1α on the development of NDDs, and provides a promising therapeutic target/ drug for the treatment of NDDs.