Epidemiological and Clinical Characteristics of Neonatal Ureaplasma urealyticum Infection.

Purpose: To understand the epidemiology and clinical features of Ureaplasma urealyticum (UU) infection in hospitalized neonates due to vertical transmission from mother to child. Methods: Respiratory secretions were collected from neonates hospitalized in the neonatology department of the Maternal and Child Health Hospital of Hubei Province from July 2020 to June 2022, and PCR was used to detect UU-DNA in respiratory secretions. The neonates were divided into UU-positive and UU-negative groups, the epidemiological and clinical characteristics of two groups, were statistically analyzed. Results: A total of 7257 hospitalized neonates were included in this study, of whom 561 were UU positive and 6696 were UU negative, with a UU detection rate of 7.73%. The detection rate among female neonates was higher than male neonates, and the highest detection rate was found in the period from 1-7 days after birth; the detection rate was highest in spring and fall, and the lowest in winter, but the overall difference was not statistically significant (P>0.05). Compared with the UU-negative group, neonates in the UU-positive group were more likely to be preterm, have a lower birth weight, be delivered vaginally, and have maternal preterm rupture of membranes. In addition, neonates in the UU-positive group were more likely to be co-infected with pathogens and to have complications related to UU infections, which were all statistically significant (P<0.05). Conclusion: Neonatal UU infections are detected more frequently in female infants, with the highest detection rate occurring in 1-7 days after birth, and the most prevalent periods for infection being spring and fall. Vaginal delivery and premature rupture of membranes may lead to an increased risk of vertical UU transmission from mother to child, and UU infection is strongly associated with preterm labor, low birth weight, pathogen co-infection, and related complications.

Isobavachalcone attenuates liver fibrosis via activation of the Nrf2/HO-1 pathway in rats.

Liver fibrosis, a progression of chronic liver disease, is a significant concern worldwide due to the lack of effective treatment modalities. Recent studies have shown that natural products play a crucial role in preventing and treating liver fibrosis. Isobavachalcone (IBC) is a chalcone compound with anti-inflammatory, antioxidant, and anti-cancer properties. However, its potential antifibrotic effects remain to be elucidated. This study aimed to investigate the antifibrotic effects of IBC on liver fibrosis and its underlying mechanisms in rats. The results showed that IBC significantly ameliorated the pathological damage and collagen deposition in liver tissues; it also reduced the levels of hydroxyproline (HYP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). In addition, IBC activated Nuclear factor E2-associated factor 2/Hemeoxygenase-1 (Nrf2/HO-1) signaling, leading to the nuclear translocation of Nrf2. This translocation subsequently increased the levels of superoxide dismutase (SOD) and glutathione (GSH) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), thereby alleviating oxidative stress-induced damage. Moreover, it inhibited the expression of nuclear factor kappa B (NF-κB), which further reduced the levels of downstream inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 beta (IL-1ß), thereby suppressing the activation of HSCs and weakening liver fibrosis. In HSC-T6 cell experiments, changes observed in inflammatory responses, oxidative stress indicators, and protein expression were consistent with the in vivo results. Furthermore, the Nrf2 inhibitor (ML385) attenuated the effect of IBC on inhibiting the activation of quiescent HSCs. Consequently, IBC could alleviate liver fibrosis by activating Nrf2/ HO-1 signaling.

Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients: An interim analysis of post-marketing surveillance.

BACKGROUND: Schizophrenia is a psychiatric disorder characterized by chronic or recurrent symptoms. Lurasidone was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/d. However, post-market surveillance (PMS) with an adequate sample size is required for further validation of the drug's safety profile and effectiveness. AIM: To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese population. METHODS: A prospective, multicenter, open-label, 12-wk surveillance was conducted in mainland China. All patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for enrollment. Safety assessments included adverse events (AEs), adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, use of EPS drugs, weight gain, and laboratory values as metabolic parameters and the QTc interval. The effectiveness was assessed using the brief psychiatric rating scale (BPRS) from baseline to the end of treatment. RESULTS: A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim analysis. The average daily dose was 61.7 ± 19.08 mg (mean ± SD) during the treatment. AEs and ADRs were experienced by 101 patients (11.3%) and 78 patients (8.7%), respectively, which were mostly mild. EPS occurred in 25 individuals with a 2.8% incidence, including akathisia in 20 individuals (2.2%). Moreover, 59 patients received drugs for treating EPS during the treatment, with an incidence of 6.6% which dropped to 5.4% at the end of the treatment. The average weight change was 0.20 ± 2.36 kg (P = 0.01687) with 0.8% of patients showing a weight gain of ≥ 7% at week 12 compared with that at the baseline. The mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal ranges. The mean changes in total BPRS scores were -8.9 ± 9.76 (n = 959), -13.5 ± 12.29 (n = 959), and -16.8 ± 13.97 (n = 959) after 2/4, 6/8, and 12 wk, respectively (P < 0.001 for each visit compared with the baseline) using the last-observation-carried-forward method. CONCLUSION: The interim analysis of the PMS of adult patients with schizophrenia demonstrate the safety and effectiveness of lurasidone in the Chinese population. No new safety or efficacy concerns were identified.

Dietary Galactooligosaccharides Supplementation as a Gut Microbiota-Regulating Approach to Lower Early Life Arsenic Exposure.

Prebiotics may stimulate beneficial gut microorganisms. However, it remains unclear whether they can lower the oral bioavailability of early life arsenic (As) exposure via regulating gut microbiota and altering As biotransformation along the gastrointestinal (GI) tract. In this study, weanling mice were exposed to arsenate (iAsV) via diet (7.5 µg As g-1) amended with fructooligosaccharides (FOS), galactooligosaccharides (GOS), and inulin individually at 1% and 5% (w/w). Compared to As exposure control mice, As concentrations in mouse blood, liver, and kidneys and As urinary excretion factor (UEF) were reduced by 43.7%-74.1% when treated with 5% GOS. The decrease corresponded to a significant proliferation of Akkermansia and Psychrobacter, reduced percentage of inorganic arsenite (iAsIII) and iAsV by 47.4% and 65.4%, and increased proportion of DMAV in intestinal contents by 101% in the guts of mice treated with 5% GOS compared to the As control group. In contrast, FOS and inulin either at l% or 5% did not reduce As concentration in mouse blood, liver, and kidneys or As UEF. These results suggest that GOS supplementation may be a gut microbiota-regulating approach to lower early life As exposure via stimulating the growth of Akkermansia and Psychrobacter and enhancing As methylation in the GI tract.

[Electroacupuncture combined with bone marrow mesenchymal stem cell transplantation promotes repair of thin endometrium by regulating SDF-1/CXCR4 signaling].

OBJECTIVE: It is to explore, based on stromal cell derived factor 1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signal axis, whether the electroacupuncture (EA) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation can promote thin endometrium regeneration and improve endometrial receptivity, so as to further study its mechanisms underlying improvement of promoting BMSCs homing to repair thin endometrium. METHODS: Thirty matured female SD rats were randomly divided into normal control , model , BMSCs transplantation (BMSCs), BMSCs+AMD3100 (a specific antagonist of CXCR4, BMSCs+AMD3100), BMSCs+EA, and BMSCs+EA+AMD3100 groups, with 5 rats in each group. The thin endometrial model was established by intrauterine injection of 95% ethanol during the period of estrus. Rats of the model group received intravenous injection of PBS solution (tail vein) on day 1, 3 and 7 of modeling and intraperitoneal injection of normal saline once daily for 3 estrous cycles. Rats of the BMSCs group received intravenous injection of BMSCs suspension on day 1,3 and 7 of modeling, and those of the BMSCs+EA group received BMSCs transplantation and EA stimulation. EA (2 Hz/15 Hz, 1 mA) was applied to "Guanyuan" (CV4) and bilateral "Sanyinjiao"(SP9), "Zigong" (EX-CA1) for 15 min, once daily for 3 estrous cycles. Rats of the BMSCs+AMD3100 group received intravenous injection of BMSCs suspension (1×106/mL) and intraperitoneal injection of AMD3100 (5 mg/kg), and those of the BMSCs+EA+AMD3100 group received administration of BMSCs, AMD3100 and EA, with both groups being once daily for 3 estrous cycles. H.E. staining was used to observe histopathological changes of endometrium tissues, and immunohistochemistry was used to detect the expressions of cytokeratin (CK19) and vimentin in endometrium (for evaluating the damage and repair of endometrium). The expression levels of homeobox A10 (HOXA10), leukemia inhibitory factor (LIF), SDF-1 and CXCR4 proteins were detected by Western blot, and those of SDF-1 and CXCR4 mRNAs in the endometrium detected by real-time PCR. RESULTS: In comparison with the normal control group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression leve-ls of HOXA10, LIF and CXCR4 proteins and CXCR4 mRNA were significantly down-regulated (P<0.01), and the expression levels of SDF-1 protein and mRNA significantly up-regulated (P<0.05) in the model group. Compared with the model group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, and the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs group, and the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA, and SDF-1 protein and mRNA in the BMSCs+EA group were significantly up-regulated (P<0.05, P<0.01). Compared to the BMSCs group, the number of endometrial glands, and the expression levels of LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+EA group were up-regulated (P<0.01, P<0.05)； the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+AMD3100 group were down-regulated (P<0.01). Compared to the BMSCs+EA group, the number of endometrial glands, the immunoactivity of CK19 and vimentin, the expression levels of HOXA10, LIF, CXCR4 proteins and CXCR4 mRNA in the BMSCs+EA+AMD3100 group were down-regulated (P<0.01). Results of H.E. staining showed thin endometrium with absence of epithelial cells, and sparse glands and blood vessels, with smaller glandular cavity in the model group, which was relative milder in BMSCs and BMSCs+EA groups. CONCLUSION: EA can promote the transfer of transplanted BMSCs to the damaged site through SDF-1/CXCR4 signaling related stem cell homing, thereby promoting thin endometrial regeneration, repairing endometrial injury, and improving endometrial tolerance in rats with thin endometrium.

A new formulation of dezocine, Cyc-dezocine, reduces oxycodone self-administration in female and male rats.

Dezocine is a partial mu opioid receptor agonist previously used as an analgesic for perioperative acute pain in the US and is now the most used perioperative analgesic in China. In general, dezocine is well-tolerated, with relatively minimal risk of fatal respiratory depression. To our knowledge, there are no reports of dezocine addiction, which suggests that the abuse liability of dezocine is low. The overarching goal of this study was to determine the efficacy of a novel formulation of dezocine (Cyc-dezocine), developed for intraperitoneal or intranasal administration, to reduce voluntary opioid taking in rats. One cohort of male rats self-administered intravenous oxycodone on a fixed-ratio 5 schedule of reinforcement. Once oxycodone taking stabilized, rats were pretreated with systemic injections of vehicle or Cyc-dezocine. Cyc-dezocine dose-dependently reduced intravenous oxycodone self-administration. A second cohort of male and female rats self-administered oral oxycodone from drinking water. Once oxycodone taking stabilized, rats were pretreated with intra-nasal Cyc-dezocine. Consistent with the effects of i.p. Cyc-dezocine in our intravenous oxycodone studies, intra-nasal Cyc-dezocine attenuated oral oxycodone self-administration. Together, these findings support the need for further studies investigating the therapeutic potential of Cyc-dezocine for treating opioid use disorder.

Rearrangement of 2-(benzofuran-2-yl)-3-phenylpyridines via photoinduced 6π-electrocyclization.

By photoinduced 6π-electrocyclization of 2-(benzofuran-2-yl)-3-phenylpyridine derivatives 1, a method for the synthesis of trans-dihydrobenzo[f]quinolines 2, cis-dihydrobenzo[f]quinolines 3 and 8b-methyl-1,8b-dihydrobenzo[f]quinolines 4 was developed. Irradiation of 2-(benzofuran-2-yl)-3-phenylpyridine 1 in acetone-H2O (5 : 1, v/v) with a 313 nm UV lamp under an argon atmosphere at room temperature successfully yielded 2, which was further converted into 3 at elevated temperature (200 °C) in glycerol. However, irradiating 2-(3-methylbenzofuran-2-yl)-3-phenylpyridines 1 in CH2Cl2 with a 254 nm UV lamp gave 4 in good yields. The syntheses of 2, 3 and 4via the 6π-electrocyclization rearrangement of 1 not only offer high atom efficiency but also do not require transition metal catalysts or additives.

Over-expression of miR-3584-5p Represses Nav1.8 Channel Aggravating Neuropathic Pain caused by Chronic Constriction Injury.

Nav1.8, a tetrodotoxin-resistant voltage-gated sodium channels (VGSCs) subtype encoded by SCN10A, which plays an important role in the production and transmission of peripheral neuropathic pain signals. Studies have shown that VGSCs may be key targets of MicroRNAs (miRNAs) in the regulation of neuropathic pain. In our study, bioinformatics analysis showed that the targeting relationship between miR-3584-5p and Nav1.8 was the most closely. The purpose of this study was to investigate the roles of miR-3584-5p and Nav1.8 in neuropathic pain. The effects of miR-3584-5p on chronic constriction injury (CCI)-induced neuropathic pain in rats was investigated by intrathecal injection of miR-3584-5p agomir (an agonist, 20 µM, 15 µL) or antagomir (an antagonist, 20 µM, 15 µL). The results showed that over-expression of miR-3584-5p aggravated neuronal injury by hematoxylin-eosin (H&E) staining and mechanical/thermal hypersensitivity in CCI rats. MiR-3584-5p indirectly inhibited the expression of Nav1.8 by up-regulating the expression of key proteins in the ERK5/CREB signaling pathway, and also inhibited the current density of the Nav1.8 channel, changed its channel dynamics characteristic, thereby accelerating the transmission of pain signals, and further aggravating pain. Similarly, in PC12 and SH-SY5Y cell cultures, miR-3584-5p increased the level of reactive oxygen species (ROS) and inhibited mitochondrial membrane potential (Δψm) in the mitochondrial pathway, decreased the ratio of apoptosis-related factor Bcl-2/Bax, and thus promoted neuronal apoptosis. In brief, over-expression of miR-3584-5p aggravates neuropathic pain by directly inhibiting the current density of Nav1.8 channel and altering its channel dynamics, or indirectly inhibiting Nav1.8 expression through ERK5/CREB pathway, and promoting apoptosis through mitochondrial pathway.

[Observation on the effect of electroacupuncture on the regeneration of endometrium in rats with intrauterine adhesion].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the degree of endometrial fibrosis and inflammatory response in the rat model of intrauterine adhesion (IUA), so as to explore the possible mechanism of EA underlying improving IUA and promoting endometrium regeneration. METHODS: Forty-five female SD rats were randomly divided into blank, model and EA groups, with 15 rats in each group. The IUA model was established by mechanical scratching combined with lipopolysaccharide infection. EA was applied to bilateral "Zigong" (EX-CA1) and "Sanyinjiao" (SP6), with acupuncture applied to "Guanyuan" (CV4) for rats in the EA group, started from the 2nd day after modeling, 15 minutes every time, once a day for 2 consecutive estrous cycles. Samples from 5 rats in each group were collected during estrus period. Changes of endometrial histopathology and number of glands were observed after HE staining. The area of endometrial fibrosis was observed and calculated after Masson staining. The positive expressions of collagen type I (Col-I) and transforming growth factor ß1 (TGF-ß1) proteins in endometrial tissue were detected by immunohistochemistry method. The protein expression of integrin αγß3 in uterine tissue was detected by Western blot. The contents of interleukin (IL)-1ß and tumor necrosis factor α (TNF-α) in uterine tissue were detected by ELISA. Samples from remaining 10 rats in each group were collected on the 8th day of gestation for calculation of the embryo implantation numbers of the rats. RESULTS: HE staining showed complete uterine tissue structure of the rats in the blank group during estrus period, with clear endometrial layer, unobstructed and regular uterine cavity, and dense glands. Destroyed endometrial layer, narrowed and adhered uterine cavity, and sparse glands of the rats were seen in the model group, which was relatively milder in the EA group. Following modeling, the number of endometrial glands, the protein expression of Integrin αγß3, the number of implanted uterine embryos on the injured side of the model group were significantly decreased (P<0.01), while the area of endometrial fibrosis, the positive expressions of Col-I and TGF-ß1 proteins, and the contents of IL-1ß and TNF-α in the uterine tissue were significantly increased (P<0.01) in comparison with those in the blank group. After intervention, the number of endometrial glands, the protein expression of Integrin αγß3, the number of implanted uterine embryos on the injured side of the EA group were significantly increased (P<0.01，P<0.05), while the area of endometrial fibrosis, the positive expressions of Col-I and TGF-ß1 proteins, and the contents of IL-1ß and TNF-α in the uterine tissue were significantly decreased (P<0.01,P<0.05) compared with the model group. CONCLUSION: EA can enhance endometrial receptivity, and promote endometrial regeneration, be conducive to embryo implantation in IUA model rats, which may be related to its effect in alleviating endometrial fibrosis and reducing inflammatory response.

Accurate and Interpretable Dipole Interaction Model-Based Machine Learning for Molecular Polarizability.

Polarizabilities play significant roles in describing dispersive and inductive interactions of the atom and molecular systems. However, an accurate prediction of molecular polarizabilities from first principles is computationally prohibitive. Although physical models or statistical machine learning models have been proposed, either a lack of accurate description of local chemical environments or demanding a large number of samples for training has limited their practical applications. In this study, we combine a physically inspired dipole interaction model and an accurate neural network method for predicting the polarizability tensors of molecules. With the local chemical environment precisely described and the requirement of rotational covariance naturally fulfilled, this hybrid model is proven to give an accurate molecular polarizability prediction, essentially reducing the number of training samples. The atomic polarizabilities are physically interpretable and transferable to larger molecules unseen in the training set. This promising method may find its wide range of applications, such as spectroscopic simulations and the construction of polarizable force fields.

Evaluation of different rat models intrauterine adhesion models and improvement of the technique for their establishment.

Intrauterine adhesion (IUA), a leading cause of uterine infertility, is characterized by endometrial fibrosis. Implementing an appropriate animal model is essential for the research on the mechanisms of IUA. In the present study, we established and evaluated different intrauterine adhesion modeling procedures in rats to provide a reference for researchers. Rat IUA models were established by mechanical injury, 95% ethanol injection, and dual (mechanical injury with infection) injury. After two estrus cycles, the female rats were mated with sexually mature male rats, and uterine tissues were obtained on the 5th day of pregnancy. Hematoxylin and eosin staining and immunohistochemical detection of cytokeratin 19 and vimentin were performed to assess the morphology of the endometrium. Masson's trichrome staining and the expression of transforming growth factor-ß1 and collagen I were used to assess the endometrium fibrosis. The expression of integrin avß3, leukemia inhibitory factor, and homeobox gene A10 in the rat endometrium was used to evaluate the endometrial receptivity. In addition, the efficiency of embryo implantation was examined in the uterus on the 8th day of pregnancy. Our study found that mechanical injury caused by a curette can be completely repaired after two estrus cycles. However, dual injury and 95% ethanol injection can be used to establish an IUA rat model, and the dual injury is closer to the clinicpathological characteristics of IUA.

Quantitative Insights into a Plasmonic Ruler Equation from the Perspective of Enhanced Near Field.

The plasmonic shift of resonance wavelength induced by near-field coupling enables one to measure nanoscale distances optically. Empirically, the well-known ruler equation correlating plasmon shift with interparticle spacing was proposed. Though it has been widely used in analyzing simulation and experimental outcomes, little is known about the underlying physical mechanism of the characteristic exponential form of the plasmon ruler equation and the universal decay constant therein. In this work, we attempt to decrypt these from the perspective of plasmon near-field enhancement. Based on an analytical quasi-normal mode formula for plasmon shifts, we proved that the exponential decaying electric field is the critical reason that results in the exponential form of the plasmon ruler equation and quantitatively, we found that the universal decay constant in the plasmon ruler equation actually reflects the range of the enhanced near field. This work hopefully helps to deepen the understanding of the mechanism of light-matter interaction in corresponding plasmonic processes.

A diagnostic prediction model for hypertension in Han and Yugur population from the China National Health Survey (CNHS).

BACKGROUND: The prevalence of hypertension is high among Chinese adults, thus, identifying non-hypertensive individuals at high risk for intervention will help to improve the efficiency of primary prevention strategies. METHODS: The cross-sectional data on 9699 participants aged 20 to 80 years were collected from the China National Health Survey in Gansu and Hebei provinces in 2016 to 2017, and they were nonrandomly split into the training set and validation set based on location. Multivariable logistic regression analysis was performed to develop the diagnostic prediction model, which was presented as a nomogram and a website with risk classification. Predictive performances of the model were evaluated using discrimination and calibration, and were further compared with a previously published model. Decision curve analysis was used to calculate the standardized net benefit for assessing the clinical usefulness of the model. RESULTS: The Lasso regression analysis identified the significant predictors of hypertension in the training set, and a diagnostic model was developed using logistic regression. A nomogram with risk classification was constructed to visualize the model, and a website ( https://chris-yu.shinyapps.io/hypertension_risk_prediction/ ) was developed to calculate the exact probabilities of hypertension. The model showed good discrimination and calibration, with the C-index of 0.789 (95% confidence interval [CI]: 0.768, 0.810) through internal validation and 0.829 (95% CI: 0.816, 0.842) through external validation. Decision curve analysis demonstrated that the model was clinically useful. The model had a higher area under receiver operating characteristic curves in training and validation sets compared with a previously published diagnostic model based on Northern China population. CONCLUSION: This study developed and validated a diagnostic model for hypertension prediction in Gansu Province. A nomogram and a website were developed to make the model conveniently used to facilitate the individualized prediction of hypertension in the general population of Han and Yugur.

Prognostic Evaluation for Oral Squamous Cell Carcinoma: A Novel Method Based on m6A Methylation Regulators.

OBJECTIVE: This study aimed to examine a novel method for prognostic evaluation of patients with oral squamous cell carcinoma (OSCC) based on the expression of heterogeneous nuclear ribonucleoprotein C (HNRNPC), YTH domain-binding protein 2 (YTHDF2), and methyltransferase 14 (METTL14). METHODS: We obtained the RNA sequence and clinical information of OSCC patients from The Cancer Genome Atlas database. An optical method was established by the least absolute shrinkage and selection operator Cox regression algorithm, which was used to calculate the risk score of every sample. In addition, all samples (n=239) were classified into high-risk (n=119) and low-risk (n=120) groups, and the overall survival (OS) time and clinical characteristics were compared between groups. Moreover, bioinformatics analysis was carried out. Gene set enrichment analysis was performed to investigate the signaling pathways of HNRNPC, YTHDF2, and METTL14. RESULTS: The two groups showed significantly different OS time, tumor grades, tumor stages, and pathologic T stages (P<0.05). The receiver operating characteristic analysis identified that our method was effective and it was more accurate than use of age, gender, tumor grade, tumor stage, pathologic T stage, and pathologic N stage in OSCC prognostic prediction. Gene set enrichment analysis revealed that HNRNPC, YTHDF2, and METTL14 were mainly associated with ubiquitin-mediated proteolysis, cell cycle, RNA degradation, and spliceosome signaling pathways. CONCLUSION: The method based on the expression of HNRNPC, YTHDF2, and METTL14 can predict the prognosis of patients with OSCC independently, and its prognostic value is better than that of clinicopathological characteristic indicators.

Neuroprotective Effects of the Pannexin-1 Channel Inhibitor: Probenecid on Spinal Cord Injury in Rats.

Proinflammatory immune cell subsets constitute the majority in the local microenvironment after spinal cord injury (SCI), leading to secondary pathological injury. Previous studies have demonstrated that inflammasomes act as an important part of the inflammatory process after SCI. Probenecid, an inhibitor of the Pannexin-1 channel, can inhibit the activation of inflammasomes. This article focuses on the effects of probenecid on the local immune microenvironment, histopathology, and behavior of SCI. Our data show that probenecid inhibited the expression and activation of nucleotide-binding oligomerization domain receptor pyrindomain-containing 1 (NLRP1), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1, interleukin-1ß (IL-1ß), and caspase-3 proteins associated with inflammasomes, thereby suppressing the proportion of M1 cells. And consequently, probenecid reduced the lesion area and demyelination in SCI. Moreover, the drug increased the survival of motor neurons, which resulted in tissue repair and improved locomotor function in the injured SC. Altogether, existing studies indicated that probenecid can alleviate inflammation by blocking Pannexin-1 channels to inhibit the expression of caspase-1 and IL-1ß, which in turn restores the balance of immune cell subsets and exerts neuroprotective effects in rats with SCI.

Dezocine is a Biased Ligand without Significant Beta-Arrestin Activation of the mu Opioid Receptor.

Dezocine is an opioid that was used in clinical practice for acute pain management in the US (1986 to 2011) and is currently in use in China. It is not listed as a controlled substance in the US due to no reported cases of addiction. Dezocine is a partial agonist at the mu opioid receptor (MOR); however, it is unclear whether dezocine can activate both the G protein pathway and the beta-arrestin pathway. In this study we hypothesized that dezocine does not activate the beta-arrestin pathway, which could be the potential molecular mechanism by which dezocine is not addictive or at least less addictive than other classic opioids. Both morphine, a MOR full agonist and buprenorphine, a partial MOR agonist similar to dezocine, were used for comparison purposes. The major side effects of dezocine in clinical usage are its gastrointestinal side effects and first pass effects; therefore, we explored the possibility of administering dezocine intranasally in rodents to demonstrate the feasibility of intranasal administration for new clinical usage purposes. With proper formulation it is possible to administer dezocine intranasally to achieve a high concentration in the brain in the rodent model. The results indicate that dezocine does not activate the beta-arrestin pathway in MOR. Intranasal delivery of dezocine achieves a much higher medication concentration in the blood and brain as compared to intraperitoneal injection. It also persists a longer time before it falls below detection in the blood. This study provides a possible explanation of why dezocine is not addictive or at least less addictive than other commonly used opioids. This study also demonstrates that intranasal administration offers an alternative strategy for its potential clinical applications.

Profiling the lncRNA-miRNA-mRNA interaction network in the submandibular gland of diabetic mice.

BACKGROUND: Hyposalivation is one of the common symptoms of diabetes. Although long non-coding RNAs (lncRNAs) have recently been reported to play important roles in the pathogenesis of diabetes, the role of lncRNAs in diabetes-induced hyposalivation remains unknown. METHODS: The present study aimed to explore the function of lncRNA-microRNA-mRNA regulatory network in the submandibular gland (SMGs) under the context of diabetes. LncRNA expression profile of the SMGs was analyzed using microarray technology. Differentially expressed lncRNAs were confirmed using real-time quantitative PCR. Bioinformatics analyses were performed, and Coding-non-coding gene co-expression (CNC) and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanisms of diabetes-induced hyposalivation. RESULTS: A total of 1273 differentially expressed lncRNAs (536 up-regulated and 737 downregulated) were identified in the SMGs tissues of db/db mice. CNC and ceRNA network analyses were performed based on five differentially expressed lncRNAs validated by real-time quantitative PCR. Gene Ontology analysis of target genes of CNC network revealed that "calcium ion binding" was a highly enriched molecular function. Kyoto Encyclopedia of Genes and Genomes pathway analysis of target genes of ceRNA network revealed that the "mammalian target of rapamycin signaling pathway" was significantly enriched. CONCLUSIONS: On the whole, the findings of the present study may provide insight into the possible mechanism of diabetes-induced hyposalivation.

[Effect of moxibustion with wheat-grain-sized moxa cones on uterine natural killer cells and deci-dualization in rats with thin endometrium].

OBJECTIVE: To observe the effect of moxibustion at "Shenshu"(BL23) and "Guanyuan" (CV4) on decidua-lization and uterine natural killer cells in rats with thin endometrium, so as to explore its mechanism underlying promotion of embryo implantation. METHODS: Female SD rats were randomly divided into normal control, model and wheat-grain-sized moxa cone moxibustion (moxibustion) groups, with 14 rats in each group. The thin endometrium model was established by bilaterally intrauterine perfusion of 95% ethanol (first) and saline (later) during estrus. For rats of the moxibustion group, the ignited wheat-grain-sized moxa cones were applied to bilateral BL23 and CV4, with 7 moxa cones for each acupoint, once a day, continuously for 3 estrous cycles. Then the male and female rats were raised in the same cage. On the 5th day of pregnancy, the rats were killed under anesthesia and the uterus tissue was collected for measuring the endometrium thickness and the numbers of blood vessels and glands after H.E. staining, detecting the levels of the proportion of natural killer cells with flow cytometry. After the uterine natural killer cells were sorted by the immunomagnetic bead method, the expression levels of insulin-like growth factor binding protein (IGFBP-1), interferon(INF-γ), tumor necrosis factor(TNF-α), transforming growth factor(TGF-ß), interleukin 4(IL-4) and IL-10 mRNAs were detected by using fluorescence quantitative real-time PCR. RESULTS: Compared with the normal control group, the endometrium thickness, number of glands and blood vessels, and the expression levels of IGFBP-1, TGF-ß, IL-4 and IL-10 mRNAs were significantly decreased (P<0.01, P<0.05), while the expression levels of IFN-γ and TNF-α mRNAs were significantly increased (P<0.05，P<0.01) in the model group. In contrast to the model group, the endometrium thickness, number of glands and blood vessels, and the expression levels of IGFBP-1, TGF-ß, IL-4 and IL-10 mRNAs were significantly increased (P<0.05, P<0.01), while the expression levels of IFN-γ and TNF-α mRNAs were considerably down-regulated (P<0.05, P<0.01) in the moxibustion group. No significant difference was found among the 3 groups in the proportion of natural killer cells in the endometrium (P>0.05). CONCLUSION: Moxibustion of BL23 and CV4 with wheat-grain-sized moxa cones can improve the degree of thin endometrial decidualization, which may be related with its functions in regulating the levels of cytokines secreted from natural killer cells in the uterus.

Association between plasma dipeptidyl peptidase-4 levels and cognitive function in perinatal pregnant women with gestational diabetes mellitus.

BACKGROUND: Dipeptidyl peptidase-4 (DPP4) is associated with cognitive dysfunction in patients with type 2 diabetes. AIM: To assess a possible relationship between serum DPP4 and cognitive function in perinatal pregnant women with gestational diabetes mellitus (GDM). METHODS: The study subjects were divided into three groups: GDM group (n = 81), healthy pregnant (HP) group (n = 85), and control group (n = 51). The Montreal Cognitive Assessment (MoCA) was used to assess the cognitive status of each group. Venous blood samples were collected to measure blood lipids, glycated hemoglobin, and glucose levels. For each participant, a 3-mL blood sample was collected and centrifuged, and the serum was collected. Blood samples were stored at -80 ℃, and DPP4, interleukin-6 (IL-6), and 8-iso-prostaglandin F2α (8-iso-PGF2α), and brain-derived neurotrophic factor (BDNF) were detected using ELISA. RESULTS: The MoCA scores in the GDM and HP groups were significantly different from those in the control group in terms of visuospatial/executive function and attention (P < 0.05); however, the scores were not significantly different between the GDM and HP groups (P > 0.05). In terms of language, the GDM group had significantly different scores from those in the other two groups (P < 0.05). In terms of memory, a significant difference was found between the HP and control groups (P < 0.05), as well as between the GDM and HP groups. The levels of DPP4, IL-6, and 8-iso-PGF2α in the GDM group were significantly higher than those in the HP and control groups (P < 0.05); however, the differences between these levels in the HP and control groups were not significant (P > 0.05). The level of BDNF in the GDM group was significantly lower than that in the HP and control groups (P < 0.05), although the difference in this level between the HP and control groups was not significant (P > 0.05). CONCLUSION: Cognitive dysfunction in perinatal pregnant women with GDM mainly manifested as memory loss, which might be associated with elevated DPP4 levels.