Advances in Brain Tumor Therapy Based on the Magnetic Nanoparticles.

Brain tumors, including primary gliomas and brain metastases, are one of the deadliest tumors because effective macromolecular antitumor drugs cannot easily penetrate the blood-brain barrier (BBB) and blood-brain tumor barrier (BTB). Magnetic nanoparticles (MNPs) are considered the most suitable nanocarriers for the delivery of brain tumor drugs because of their unique properties compared to other nanoparticles. Numerous preclinical and clinical studies have demonstrated the potential of these nanoparticles in magnetic targeting, nuclear magnetic resonance, magnetic thermal therapy, and ultrasonic hyperthermia. To further develop and optimize MNPs for the diagnosis and treatment of brain tumors, we attempt to outline recent advances in the use of MNPs to deliver drugs, with a particular focus on their efficacy in the delivery of anti-brain tumor drugs based on magnetic targeting and low-intensity focused ultrasound, magnetic resonance imaging for surgical real-time guidance, and magnetothermal and ultrasonic hyperthermia therapy. Furthermore, we summarize recent findings on the clinical application of MNPs and the research limitations that need to be addressed in clinical translation.

Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines.

Depression and obesity are both common disorders currently affecting public health, frequently occurring simultaneously within individuals, and the relationship between these disorders is bidirectional. The association between obesity and depression is highly co-morbid and tends to significantly exacerbate metabolic and related depressive symptoms. However, the neural mechanism under the mutual control of obesity and depression is largely inscrutable. This review focuses particularly on alterations in systems that may mechanistically explain the in vivo homeostatic regulation of the obesity and depression link, such as immune-inflammatory activation, gut microbiota, neuroplasticity, HPA axis dysregulation as well as neuroendocrine regulators of energy metabolism including adipocytokines and lipokines. In addition, the review summarizes potential and future treatments for obesity and depression and raises several questions that need to be answered in future research. This review will provide a comprehensive description and localization of the biological connection between obesity and depression to better understand the co-morbidity of obesity and depression.

Sex Differences in Depression Caused by Early Life Stress and Related Mechanisms.

Depression is a common psychiatric disease caused by various factors, manifesting with continuous low spirits, with its precise mechanism being unclear. Early life stress (ELS) is receiving more attention as a possible cause of depression. Many studies focused on the mechanisms underlying how ELS leads to changes in sex hormones, neurotransmitters, hypothalamic pituitary adrenocortical (HPA) axis function, and epigenetics. The adverse effects of ELS on adulthood are mainly dependent on the time window when stress occurs, sex and the developmental stage when evaluating the impacts. Therefore, with regard to the exact sex differences of adult depression, we found that ELS could lead to sex-differentiated depression through multiple mechanisms, including 5-HT, sex hormone, HPA axis, and epigenetics.

The Differential Expression of Circular RNAs in Type 2 Diabetes Mellitus and Latent Autoimmune Diabetes in Adults.

Objective: Expression of circular RNAs (circRNAs) in the peripheral blood of individuals with latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus (T2DM) were quantified to identify dysregulated circRNAs compared with control individuals. Methods: circRNAs were obtained from the peripheral blood serum of 12 healthy adults and 12 individuals with LADA and 12 type 2 diabetics. The circRNA expression profiles were analyzed by high-throughput RNA sequencing. The most highly dysregulated circular RNAs were validated by quantitative real-time polymerase chain reaction. A circular RNA-microRNA (miRNA) network diagram predicted the interactions of circular RNAs, miRNAs, and coding genes. Results: A total of 2334 differentially expressed circRNAs were detected among the three groups, with 277 circRNAs in the Group DM versus Group NG; 992 circRNAs in the Group LADA versus Group NG and 1065 circRNAs in the Group DM versus Group LADA. Six circRNAs were identified as the most distinctive differentially expressed targets (p < 0.05). The proposed molecular functions of these differentially expressed circRNAS included the tumor necrosis factor signaling pathway, the FoxO signaling pathway, cellular senescence, and long-term potentiation (all false discovery rate p < 0.05) which may contribute to T2DM and LADA. Conclusion: circRNAs are aberrantly expressed in the peripheral blood of patients with T2DM and LADA and may interact with miRNA and circRNA-derived peptides in the development of diabetes. Further investigations may illustrate the partial pathogenesis of diabetes mellitus. Clinical Trial Registration number: ChiCTR1900020644.

Pyrene-based ammonium bromides combined with g-C3N4 for the synergistically enhanced fixation reaction of CO2 and epoxides.

A new type of pyrene-based ammonium bromides (PABs) was synthesized via the reaction of bromomethyl pyrene and tertiary amines with different alkyl chains combined with graphitic carbon nitride (g-C3N4) through π-π stacking interactions. The new pyrene-based ammonium bromides were investigated both in homogenous phase and heterogeneous phase combining with g-C3N4 for the CO2 fixation reaction of epoxides under mild conditions. Obviously, the combination was proved to be an efficient system for the conversion of epoxides. The interaction between g-C3N4 and PABs was confirmed by quantum chemical calculations. g-C3N4/Py-C12 exhibited an excellent yield of cyclic carbonates (above 93%) at 80 °C, atmospheric pressure and solvent-free conditions. A preliminary kinetic study was performed using g-C3N4/Py-C12 and the activation energy was calculated to be 61.5 kJ mol-1.

Effect of Early Life Stress on the Epigenetic Profiles in Depression.

Depression is one of the most common mental disorders and has caused an overwhelming burden on world health. Abundant studies have suggested that early life stress may grant depressive-like phenotypes in adults. Childhood adversities that occurred in the developmental period amplified stress events in adulthood. Epigenetic-environment interaction helps to explain the role of early life stress on adulthood depression. Early life stress shaped the epigenetic profiles of the HPA axis, monoamine, and neuropeptides. In the context of early adversities increasing the risk of depression, early life stress decreased the activity of the glucocorticoid receptors, halted the circulation and production of serotonin, and reduced the molecules involved in modulating the neurogenesis and neuroplasticity. Generally, DNA methylation, histone modifications, and the regulation of non-coding RNAs programmed the epigenetic profiles to react to early life stress. However, genetic precondition, subtypes of early life stress, the timing of epigenetic status evaluated, demographic characteristics in humans, and strain traits in animals favored epigenetic outcomes. More research is needed to investigate the direct evidence for how early life stress-induced epigenetic changes contribute to the vulnerability of depression.

A Network Meta-Analysis to Compare the Efficacy of Steroid and Antiviral Medications for Facial Paralysis from Bell´s Palsy.

BACKGROUND: Facial paralysis is the most common cranial nerve injury. Bell's palsy is the name commonly used to describe an acute peripheral facial paralysis of unknown origin. The annual incidence of Bell's palsy is 20-30 cases per 100,000 persons, regardless of age and gender. OBJECTIVE: Our objective was to appraise the efficacy of steroid and antiviral treatments for facial paralysis. STUDY DESIGN: We conducted a network meta-analysis of studies of steroid and antiviral treatments for facial paralysis. SETTING: Second Hospital of Jilin University. METHODS: We performed a systematic search of PubMed and Embase databases to retrieve relevant studies. The efficacy outcome was overall recovery, measured in terms of the odds ratio (OR) and a corresponding 95% confidence interval (CI). The comprehensive ranking for each treatment with respect to overall recovery is presented as the value of the surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 23 articles representing 4,623 patients were eligible for our study. In terms of overall recovery, no significant differences were found in the pairwise meta-analysis. From the results of the network meta-analysis, antiviral combined with steroid treatment was superior to placebo treatment (OR = 3.25; 95% CI, 1.23-8.61), but neither steroid nor antiviral therapy alone resulted in significant benefit compared with placebo. According to the SUCRA, antiviral combined with steroid treatment was the most effective, with a SUCRA value of 0.96, and the probability of ranking first was 90%. Only a small difference was observed between the efficacies of steroid and antiviral treatments (SUCRA values of 0.55 and 0.36, respectively), and they were both better than the placebo (SUCRA value of 0.134). LIMITATIONS: The major limitation of our study is that, due to the limited number of related studies in the last several years, we were not able to evaluate the safety of these therapies. CONCLUSIONS: Antiviral combined with steroid therapy is significantly better than antiviral or steroid therapy alone with respect to overall recovery, and the efficacies of single antiviral medications or single steroid treatments are nearly equal. In addition, all 3 therapies are more effective than placebo, according to the SUCRA values. KEY WORDS: Facial paralysis, Bell´s palsy, steroids, antiviral drugs, efficacy, overall recovery, network meta-analysis, SUCRA.

A mixed treatment comparison on efficacy and safety of treatments for spasticity caused by multiple sclerosis: a systematic review and network meta-analysis.

OBJECTIVES: This study is aimed at providing a quantitative evaluation on different therapies of spasticity caused by multiple sclerosis. DATA SOURCES: PubMed and Embase database. REVIEW METHODS: We searched for randomized controlled trials that met the requirements. Percentages of improved patients' spasticity scale, mild adverse effect and severe adverse effect were extracted as outcomes. The forest plots accompanied with surface under the cumulative ranking curves were used to reveal the efficacy and safety of these therapies. RESULTS: In all, 23 randomized controlled trials with a total of 2720 patients were included in our study. Cannabinoids and botulinum toxin had shown a significantly better efficacy than placebo in the percentage of improved patients. Botulinum toxin also showed such significant difference compared with tizanidine and baclofen. No significant difference was found in spasticity scale. Cannabinoids, tizanidine and diazepam had significantly more mild adverse effect reports than placebo. Surface under the cumulative ranking curves suggested that cannabinoids, botulinum toxin and transcutaneous electric nerve stimulation were preferable therapies. CONCLUSIONS: We recommended botulinum toxin as the optimal intervention for multiple sclerosis-related spasticity. Cannabinoids and transcutaneous electric nerve stimulation could also be considered as multiple sclerosis-related spasticity treatments but their safety remained to be verified.

Efficacy of Drug Interventions for Chemotherapy-Induced Chronic Peripheral Neurotoxicity: A Network Meta-analysis.

Peripheral neurotoxicity is a disturbing issue for cancer patients who are treated with chemotherapy. Several medications have been developed for preventing chemotherapy-induced chronic neurotoxicity (CICNT) however; their relative efficacies have not yet been studied. In this study, we conducted a network meta-analysis to give intervention recommendations. The literature was searched in a variety of databases and eligible studies were chosen based on predefined criteria. Data extraction and statistical analysis was performed, and the results are displayed using the odds ratio (OR) and corresponding 95% credible intervals (CrI) with respect to overall and severe neurotoxicity. The medications were ranked according to their surface under cumulative ranking curve values. The consistency of direct and indirect evidence was also evaluated. We found that patients with amifostine or vitamin E (VE) treatment exhibited a lower risk of overall neurotoxicity compared to those using the placebo (amifostine: OR = 0.10, 95% CrI: 0.02-0.46; VE: OR = 0.08, 95% CrI: 0.01-0.99). In regard to preventing severe neurotoxicity, glutathione and amifostine treatment appeared to be significantly more effective than the placebo (glutathione: OR = 0.19, 95% CrI: 0.04-0.64; amifostine: OR = 0.12, 95% CrI: 0.02-0.48). In summary, amifostine, VE, and glutathione treatment is considered to be effective in lowering the risk of CICNT. However, further studies which consider safety are required.

A case report of overlapping Bickerstaff brainstem encephalitis and Guillain-Barre syndrome.

We report a case of a 23-year-old man diagnosed with overlapping Bickerstaff brainstem encephalitis (BBE) and Guillain-Barre syndrome (GBS). The patient initially presented with fever and headache and gradually developed ataxia, disturbance of consciousness, respiratory muscle paralysis, bilateral facial paralysis and quadriplegia accompanied by significant atrophy of limb, temporalis and masseter muscles. Brain MRI revealed abnormality in the left basal ganglia, thalamus, and rightside posterior limb of the internal capsule. Electromyogram indicated neurogenic damage (mainly axonal damage) in the upper and lower limbs and bilateral facial nerve damage. Cerebrospinal fluid (CSF) collected via lumbar puncture was colorless and transparent with a pressure of 330 mm H2O. The white blood cell count in CSF was 200×106/L, the protein concentration was 1.25 g/L, and Pandy's reaction was positive. Both the blood and CSF were negative for GQ1b antibody. The patient was clinically diagnosed with overlapping BBE and GBS. After treatment with ventilator assisted breathing, hormone therapy, neurotrophic and anti-infection therapies, and symptomatic and supportive care for more than three months, spontaneous breathing was restored. By the 5-month follow-up examination, the patient had completely recovered and returned to work. Like GBS and Fisher syndrome, BBE might be an anti-GQlb IgG antibody syndrome. Although the serum GQlb IgG antibody-positive rate for BBE is only 66%, a normal brainstem MRI or GQlb lgG antibody-negative finding cannot completely rule out BBE. Therefore, identifying critical illness polyneuropathy for patients with respiratory muscle paralysis and tracheal extubation difficulties at early stages is clinically important.