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Octamer-binding transcription factor 4 ( OCT4 ) is a key regulatory gene that maintains the pluripotency and self-renewal properties of embryonic stem cells. Although there is emerging evidence that it can function as oncogene in several cancers, the role in mediating cervical cancer remains unexplored. Here we found that OCT4 protein expression showed a pattern of gradual increase from normal cervix to cervical carcinoma in situ and then to invasive cervical cancer. Overexpression of OCT4 in two types of cervical cancer cells promotes the carcinogenesis, and inhibits cancer cell apoptosis. OCT4 induces upregulation of miR-125b through directly binding to the promoter of miR-125b-1 confirmed by chromatin immunoprecipitation analysis. MiRNA-125b overexpression suppressed apoptosis and expression of BAK1 protein. In contrast, miR-125b sponge impaired the anti-apoptotic effect of OCT4, along with the upregulated expression of BAK1. Significantly, Luciferase assay showed that the activity of the wild-type BAK1 3′-untranslated region reporter was suppressed and this suppression was diminished when the miR-125b response element was mutated or deleted. In addition, we observed negative correlation between levels of BAK1 and OCT4, and positive between OCT4 and miR-125b in primary cervical cancers. These findings suggest an undescribed regulatory pathway in cervical cancer, by which OCT4 directly induces expression of miR-125b, which inhibits its direct target BAK1, leading to suppression of cervical cancer cell apoptosis.

Cancer patients regularly suffer from the behavioral symptoms of chemotherapy-induced nausea and vomiting. Particularly, it is involved in Pavlovian conditioning. Lithium chloride (LiCl) was used as the unconditioned stimulus (US) and contingent with the tastant, for example, a saccharin solution (i.e., the conditioned stimulus; CS), resulted in conditioned taste aversion (CTA) to the CS intake. The present study employed an animal model of LiCl-induced CTA to imitate chemotherapy-induced nausea and vomiting symptoms. Recently, the basolateral amygdala (BLA) was shown to mediate LiCl-induced CTA learning; however, which brain mechanisms of the BLA regulate CTA by LiCl remain unknown. The present study was designed to test this issue, and 4% lidocaine or D2 blocker haloperidol were microinjected into BLA between the 0.1% saccharin solution intake and 0.15M LiCl. The results showed lidocaine microinjections into the BLA could attenuate the LiCl-induced CTA. Microinjections of haloperidol blunted the CTA learning by LiCl. Altogether, BLA via the sodium chloride ion channel and D2 receptors control LiCl-induced conditioned saccharin solution intake suppression. The findings can provide some implications and contributions to cancer chemotherapy-induced nausea and vomiting side effects, and will help to develop novel strategies to prevent the side effects of cancer chemotherapy.

Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.

Environmental enrichment (EE) involves the presentation of various sensory, physical, social, and cognitive stimuli in order to alter neural activity in specific brain areas, which can ameliorate methamphetamine (MAMPH)-induced behavioral sensitization and comorbid anxiety symptoms. No previous studies have comprehensively examined which EE components are critical for effectively reducing MAMPH-induced behavioral sensitization and anxiety. This study examined different housing conditions, including standard housing (SH, No EE), standard EE (STEE), physical EE (PEE), cognitive EE (CEE), and social EE (SEE). In the beginning, mice were randomly assigned to the different combinations of housing conditions and injections, consisting of No EE/Saline, No EE/MAMPH, STEE/MAMPH, PEE/MAMPH, CEE/MAMPH, and SEE/MAMPH groups. Then, the mice received intraperitoneal injections of 1 mg/kg MAMPH or normal saline daily for 7 days, followed by a final injection of 0.5 mg/kg MAMPH or normal saline. After behavioral tests, all mice were examined for c-Fos immunohistochemical staining. The results showed that MAMPH induced behavioral sensitization as measured by distance traveled. MAMPH appeared to induce lowered anxiety responses and severe hyperactivity. All EE conditions did not affect MAMPH-induced lowered anxiety behaviors. STEE was likely more effective for reducing MAMPH-induced behavioral sensitization than PEE, CEE, and SEE. The c-Fos expression analysis showed that the medial prefrontal cortex (i.e., cingulate cortex 1 (Cg1), prelimbic cortex (PrL), and infralimbic cortex (IL)), nucleus accumbens (NAc), basolateral amygdala (BLA), ventral tegmental area (VTA), caudate-putamen (CPu), and hippocampus (i.e., CA1, CA3, and dentate gyrus (DG)) contributed to MAMPH-induced behavioral sensitization. The Cg1, IL, NAc, BLA, VTA, CPu, CA3, and DG also mediated STEE reductions in MAMPH-induced behavioral sensitization. This study indicates that all components of EE are crucial for ameliorating MAMPH-induced behavioral sensitization, as no individual EE component was able to effectively reduce MAMPH-induced behavioral sensitization. The present findings provide insight into the development of non-pharmacological interventions for reducing MAMPH-induced behavioral sensitization.

Alzheimer’s disease (AD) is a progressive neurodegenerative condition that causes cognitive impairment and other neuropsychiatric symptoms. Previously, little research has thus far investigated whether methamphetamine (MAMPH) can enhance cognitive function or ameliorate AD symptoms. This study examined whether a low dose of MAMPH can induce conditioned taste aversion (CTA) learning, or can increase plasma corticosterone levels, neural activity, and neural plasticity in the medial prefrontal cortex (mPFC) (responsible for cognitive function), the nucleus accumbens (NAc) and the amygdala (related to rewarding and aversive emotion), and the hippocampus (responsible for spatial learning). Furthermore, the excitations or lesions of the prelimbic cortex (PrL) can affect MAMPH-induced CTA learning, plasma corticosterone levels, and neural activity or plasticity in the mPFC [i.e., PrL, infralimbic cortex (IL), cingulate cortex 1 (Cg1)], the NAc, the amygdala [i.e., basolateral amygdala (BLA) and central amygdala (CeA)], and the hippocampus [i.e., CA1, CA2, CA3, and dentate gyrus (DG)]. In the experimental procedure, the rats were administered either saline or NMDA solutions, which were injected into the PrL to excite or destroy PrL neurons. Additionally, rats received 0.1% saccharin solution for 15 min, followed by intraperitoneal injections of either normal saline or 1 mg/kg MAMPH to induce CTA. A one-way ANOVA was performed to analyze the effects of saccharin intake on CTA, plasma corticosterone levels, and the expression of c-Fos and p-ERK. The results showed that the MAMPH induced CTA learning and increased plasma corticosterone levels. The mPFC, and particularly the PrL and IL and the DG of the hippocampus, appeared to show increased neural activity in c-Fos expression or neural plasticity in p-ERK expression. The excitation of the PrL neurons upregulated neural activity in c-Fos expression and neural plasticity in p-ERK expression in the PrL and IL. In summary, MAMPH may be able to improve cognitive and executive function in the brain and reduce AD symptoms. Moreover, the excitatory modulation of the PrL with MAMPH administration can facilitate MAMPH-induced neural activity and plasticity in the PrL and IL of the mPFC. The present data provide clinical implications for developing a possible treatment for AD in an animal model.

Pulsars radiate radio signals when they rotate. However, some old pulsars often stop radiating for some periods. The underlying mechanism remains unknown, as the magnetosphere during nulling phases is hard to probe due to the absence of emission measurements. Here we report the detection and accurate polarization measurements of sporadic, weak, narrow dwarf pulses detected in the ordinary nulling state of pulsar B2111+46 via the Five-Hundred-Meter Aperture Spherical radio Telescope. Further analysis shows that their polarization angles follow the average polarization angle curve of normal pulses, suggesting no change of the magnetic-field structure in the emission region in the two emission states. Whereas radio emission of normal individual pulses is radiated by a ‘thunderstorm’ of particles produced by copious discharges in regularly formed gaps, dwarf pulses are produced by one or a few ‘raindrops’ of particles generated by pair production in a fragile gap of this near-death pulsar.The intensity of radio emission from a pulsar is shown to relate to the quantity of particles discharging in the magnetosphere rather than to changes of the structure of the magnetic field in the magnetosphere itself.

Chromatin boundary elements or insulators are believed to regulate gene activity in complex genetic loci by organizing specialized chromatin structures. Here, we report that the enhancer-blocking activity of the Drosophila suHw insulator is sensitive to insulator copy number and position. Two tandem copies of suHw were ineffective in blocking various enhancers from a downstream promoter. Moreover, an enhancer was blocked more effectively from a promoter by two flanking suHw insulators than by a single intervening one. Thus, insulators may modulate enhancer-promoter interactions by interacting with each other and facilitating the formation of chromatin loop domains.

Many reports have shown that autophagy has a role as both a promoter and inhibitor in tumor development. However, the mechanism of this paradox is unknown. Tumor development is a multistep process. Therefore, we investigated whether the role of autophagy in hepatocarcinoma formation depended on the stage of tumor development. Based on our results, autophagy inhibition by chloroquine had a tumor-promotive effect in the rat model with N -diethylnitrosamine-induced hepatocarcinogenesis in its dysplastic stage (Ds) and a tumor-suppressive effect in its tumor-forming stage (Ts). In the Ds, autophagy inhibition enhanced cell proliferation, DNA damage and inflammatory cytokines expression in liver. These changes were dependent on the upregulation of reactive oxygen species (ROS) that was resulted from autophagy inhibition, and ultimately accelerated the process of hepatocarcinogenesis. However, in the Ts, autophagy inhibition restrained tumor formation by decreasing tumor cell survival and proliferation. In this stage, autophagy inhibition led to excessive ROS accumulation in the tumor, which promoted cell apoptosis, and prominently suppressed tumor cell metabolism. Taken together, our data suggested that autophagy suppressed hepatocarcinogenesis in the Ds by protecting normal cell stability and promoted hepatocarcinogenesis in the Ts by supporting tumor cells growth. Autophagy always had a role as a protector throughout the process of hepatocarcinoma development.

Objective: The aim of the present study was to explore the impact of the one-day clinic diabetes mellitus (DM) management model on perinatal outcomes in patients with gestational diabetes mellitus (GDM). Methods: A total of 995 patients who underwent prenatal checkups at our hospital and were diagnosed with GDM by oral glucose tolerance test (OGTT) screening at 24-28 weeks of gestational age were enrolled between December 2018 and August 2020. The patients were randomly divided into a study group (541 cases) and a control group (454 cases). One-day clinic intervention for DM was conducted in the study group, while individualized dietary interventions and exercise instruction were given in the control group. The perinatal outcomes of patients were compared between the two groups. Results: In the study group, maternal weight gain, fasting blood glucose before delivery, the incidence of abnormality in postpartum OGTT, and abnormality of pancreatic islet function were lower than in the control group, and the differences were statistically significant (P < 0.05). The percentage of patients with insulin treatment in the study group was higher than in the control group, and the difference was statistically significant (P < 0.05). The incidence of premature rupture of membranes, macrosomia, and neonatal jaundice was lower in the study group than in the control group, and the differences were statistically significant (P < 0.05). Conclusion: The one-day clinic DM management model can effectively control weight gain and blood glucose levels during pregnancy in patients with GDM, resulting in a higher recovery rate of blood glucose and islet function after delivery and a lower incidence of premature rupture of membranes, macrosomia, and neonatal jaundice. The one-day clinic DM management model could therefore have profound implications for reducing and delaying the onset of postpartum type 2 diabetes in patients with GDM. Keywords: gestational diabetes, one-day clinic, blood glucose, body weight, perinatal outcome