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Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis of AD is complex and diverse, and its occurrence and development is the result of the interaction of multiple factors. A number of studies have shown that mTOR signaling pathway is closely related to AD. In recent years, people in exploring relevant methods for the treatment of AD and the process of drugs, more and more studies have found that traditional Chinese medicine compound traditional Chinese medicine monomer, and can be applied to mTOR signaling pathway to improve symptoms in patients with AD. This paper will review the mechanism of action and treatment of TCM in Alzheimer's disease based on mTOR signaling pathway in recent years, so as to provide reference and expand thinking for the prevention and treatment of AD. [ABSTRACT FROM AUTHOR]

Orphan genes are genetic innovations that lack homologs in other lineages. Orphan genes can rapidly originate and become substantially functional, yet the mechanisms underlying their origins are still largely unknown in plants. Here, we investigated the origin of orphan genes in the Oryza sativa ssp. japonica "Nipponbare" genome using genome‐wide comparisons with 10 closely related Oryza species. We identified a total of 37 orphan genes in the Nipponbare genome that show short sequence lengths, elevated GC content, and absence of introns. Interestingly, half of the identified orphan genes originated by way of a distinctive mechanism that involved the generation of new coding sequences through independent and rapid divergence within the inserted transposable element. Our results provide valuable insight into genetic innovations in the model rice genome that formed on a very short timescale. [ABSTRACT FROM AUTHOR]

Clinical use of the chemotherapeutic agent vincristine (VCR) is limited by chemotherapy-induced peripheral neuropathy (CiPN). A new formulation of VCR encapsulated by nanoparticles has been proposed and developed to alleviate CiPN. We hypothesized in nonclinical animals that the nanoparticle drug would be less neurotoxic due to different absorption and distribution properties to the peripheral nerve from the unencapsulated free drug. Here, we assessed whether VCR encapsulation in nanoparticles alleviates CiPN using behavioral gait analysis (CatWalk), histopathologic and molecular biological (RT-qPCR) approaches. Adult male C57BL/6 mice were assigned to 3 groups (empty nanoparticle, nano-VCR, solution-based VCR, each n = 8). After 15 days of dosing, animals were euthanized for tissue collection. It was shown that intraperitoneal administration of nano-VCR (0.15 mg/kg, every other day) and the empty nanoparticle resulted in no changes in gait parameters; whereas, injection of solution-based VCR resulted in decreased run speed and increased step cycle and stance (P < 0.05). There were no differences in incidence and severity of degeneration in the sciatic nerves between the nano-VCR-dosed and solution-based VCR-dosed animals. Likewise, decreased levels of a nervous tissue-enriched microRNA-183 in circulating blood did not show a significant difference between the nano- and solution-based VCR groups (P > 0.05). Empty nanoparticle administration did not cause any behavioral, microRNA, or structural changes. In conclusion, this study suggests that the nano-VCR formulation may alleviate behavioral changes in CiPN, but it does not improve the structural changes of CiPN in peripheral nerve. Nanoparticle properties may need to be optimized to improve biological observations. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CiPN) is a frequent adverse effect in patients and a leading safety consideration in oncology drug development. Although behavioral assessment and microscopic examination of the nerves and dorsal root ganglia can be incorporated into toxicity studies to assess CiPN risk, more sensitive and less labor-intensive endpoints are often lacking. In this study, rats and mice administered vincristine (75 μg kg−1 day−1, i.p., for 10 days in rats and 100 μg kg−1 day−1, i.p., for 11 days in mice, respectively) were employed as the CiPN models. Behavioral changes were assessed during the dosing phase. At necropsy, the sural or sciatic nerve was harvested from the rats and mice, respectively, and assessed for mechanical and histopathological endpoints. It was found that the maximal load and the load/extension ratio were significantly decreased in the nerves collected from the animals dosed with vincristine compared with the vehicle-treated animals ( P < 0.05). Additionally, the gait analysis revealed that the paw print areas were significantly increased in mice ( P < 0.01), but not in rats following vincristine administration. Light microscopic histopathology of the nerves and dorsal root ganglia were unaffected by vincristine administration. We concluded that ex vivo mechanical properties of the nerves is a sensitive endpoint, providing a new method to predict CiPN in rodent. Gait analysis may also be a useful tool in these pre-clinical animal models. [ABSTRACT FROM AUTHOR]

Context: Selective inhibitors of glycine transporter type 1 (GlyT1) increase synaptic glycine concentrations and are being developed to treat cognitive and negative symptoms of schizophrenia. However, increases in systemic glycine levels have been associated with visual disturbances and electroretinogram (ERG) alternations. Objective: To determine whether the selective GlyT1 inhibitor PF-03463275 causes changes in ERG responses in albino rats. Materials and methods: Male Sprague-Dawley rats were administered PF-03463275 subcutaneously at 1, 3 and 10 mg/kg 1 h prior to ERG acquisition. Scotopic and photopic luminance responses, photopic adaptometry and flicker responses were measured. Plasma and vitreous samples were obtained at necropsy for determination of PF-03463275 concentrations. Results: A dose-dependent reduction (up to ∼70%) in the amplitude of the scotopic ERG oscillatory potentials (OPs) was observed following PF-03463275 administration. The amplitude of the OPs was also negatively correlated to the concentration of PF-03463275 in the vitreous humor ( r = −0.64, p < 0.0001). With the exception of a small increase in scotopic ERG a-wave amplitude and latency no effects were observed on other ERG parameters tested. Conclusions: We conclude that inhibition of the GlyT1 transporter in the retina causes ERG changes which may underlie recent reports of visual disturbance with GlyT1 inhibitors in clinical trials. [ABSTRACT FROM AUTHOR]

The potential for neurogenesis in the cranial (superior) cervical ganglia (SCG) of the sympathetic nervous system was evaluated. Eleven consecutive daily doses of guanethidine (100 mg/kg/d) were administered intraperitoneally to rats in order to destroy postganglionic sympathetic neurons in SCG. Following the last dose, animals were allowed to recover 1, 3, or 6 months. Right and left SCG from guanethidine-treated and age-matched, vehicle-treated control rats were harvested for histopathologic, morphometric, and stereologic evaluations. Both morphometric and stereologic evaluations confirmed neuron loss following guanethidine treatment. Morphometric analysis revealed a 50% to 60% lower number of tyrosine hydroxylase (TH)-positive neurons per unit area of SCG at both 3 and 6 months of recovery, compared to ganglia of age-matched controls, with no evidence of restoration of neuron density between 3 and 6 months. Reductions in TH-positive neurons following guanethidine treatment were corroborated by unbiased stereology of total hematoxylin and eosin-stained neuron numbers in SCG. Stereologic analyses revealed that total neuron counts were lower by 37% at 3 months of recovery when compared to age-matched vehicle controls, again with no obvious restoration between 3 and 6 months. Thus, no evidence was found that postganglionic neurons of the sympathetic nervous system in the adult rat have a neurogenic capacity.

Aim: To investigate the impact of postoperative antiviral treatment on tumor recurrence and survival of patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection-related primary hepatocellular carcinoma (HCC) after curative therapy., Methods: We performed a meta-analysis of randomized and non-randomized control trials from electronic search and manual search. The fixed effect model of Mantel-Haenszel method and the random effect model of Der Simonian and Laird method were used for homogeneous and heterogeneous studies, respectively. Seven HCV-related studies, three HBV-related studies and three studies on HBV or HCV-related HCC were identified., Results: A total of 1224 patients were included in this analysis. The estimated odds ratios (OR) for the 1-, 2-, 3- and 5-year recurrence were 0.54 [15.4% vs 24.1%, 95% confidence interval (CI): 0.32-0.89, P = 0.02], 0.42 (36.9% vs 58.0%, 95% CI: 0.19-0.90, P = 0.03), 0.37 (47.9% vs 63.8%, 95% CI: 0.19-0.71, P = 0.003), and 0.32 (66.7% vs 74.3%, 95% CI: 0.15-0.66, P = 0.002), respectively; and the OR for the 1-, 2-, 3-, 5- and 7-year mortality were 0.23 (1.2% vs 9.1%, 95% CI: 0.07-0.71, P = 0.01), 0.31 (6.4% vs 22.1%, 95% CI: 0.12-0.79, P = 0.01), 0.43 (12.7% vs 20.8%, 95% CI: 0.21-0.89, P = 0.02), 0.42 (25.1% vs 42.0%, 95% CI: 0.27-0.66, P = 0.0002) and 0.28 (31.9% vs 52.2%, 95% CI: 0.13-0.59, P = 0.0008)., Conclusion: This meta-analysis indicates the postoperative antiviral therapy, interferon in particular, may serve as a favorable alternative to reduce recurrence and mortality in patients with HBV/HCV related HCCs.

Objective: To explore and identify the non-coding RNAs related to tumors., Methods: We used RT-PCR and Northern blot to analyze non-coding RNAs in tumor tissues and cell lines., Results: Two predicted non-coding RNAs were confirmed to be expressed in cancer tissues and cell lines by RT-PCR and DNA sequencing. We detected the expression of two non-coding RNA transcripts by Northern blot. The length of NC28 was about 1800 nt, and that of NC119 was about 1200nt., Conclusions: NC28 and NC119 have a tumor-associated expression pattern. The non-coding RNAs may play a role in the development of tumors.