Long non-coding RNA MSTRG.81401 short hairpin RNA relieves diabetic neuropathic pain and behaviors of depression by inhibiting P2X4 receptor expression in type 2 diabetic rats.

Patients with diabetic neuropathic pain (DNP) experience immense physical and mental suffering, which is comorbid with other mental disorders, including major depressive disorder (MDD). P2X4 receptor, one of the purinergic receptors, is a significant mediator of DNP and MDD. The present study aimed to identify the roles and mechanisms of MSTRG.81401, a long non-coding RNA (lncRNA), in alleviating DNP and MDD-like behaviors in type 2 diabetic rats. After administration with MSTRG.81401 short hairpin RNA (shRNA), the model + MSTRG.81401 shRNA group demonstrated increased mechanical withdrawal threshold, thermal withdrawal latency, open-field test, and sucrose preference test; however, immobility time on the forced swimming test decreased. MSTRG.81401 shRNA administration significantly decreased the expression of the P2X4 receptor, tumor necrosis factor-α, and interleukin-1ß in the hippocampus and spinal cord in the model + MSTRG.81401 shRNA group. Simultaneously, MSTRG.81401 shRNA administration downregulated phosphorylation of ERK1/2 in the hippocampus and spinal cord. Thus, lncRNA MSTRG.81401 shRNA can alleviate DNP and MDD-like behaviors in type 2 diabetic rats and may downregulate the expression of P2X4 receptors in the hippocampus and spinal cord of rats.

miR-34a regulates lipid metabolism by targeting SIRT1 in non-alcoholic fatty liver disease with iron overload.

BACKGROUND: Micro-ribonucleic acids (miRNAs) have been implicated in the regulation of non-alcoholic fatty liver disease (NAFLD), a leading cause of chronic liver disease worldwide. The mechanisms by which miR-34a influences NAFLD through the Sirtuin 1 (SIRT1)-related pathway were investigated herein. METHODS: Male C57BL/6 mice were injected with a miR-34a lentivirus vector inhibitor or control. HepG2 cells were transfected with a miR-34a mimic, inhibitor, SIRT1 small interfering RNA (siRNA), SIRT1 plasmid, and a negative oligonucleotide control to evaluate their role in oleic acid (OA) and excess iron-induced NAFLD. The accumulation of lipids in the mice liver and HepG2 cells was analyzed by triglyceride (TG) detection and hematoxylin and eosin (HE) staining. Additionally, the indexes of oxidative stress related to lipid metabolism were evaluated by western blotting and real-time PCR (qRT-PCR). The levels of intracellular reactive oxygen species (ROS) and mitochondrial membrane potentials were measured by flow cytometry and laser confocal microscopy, respectively. Finally, the dual luciferase reporter assay was conducted to further confirm whether SIRT1 was a direct target of miR-34a. RESULTS: Overexpression of miR-34a resulted in increased triglyceride accumulation as well as in decreased mitochondrial membrane potential and SIRT1 levels. Silencing of miR-34a increased SIRT1 expression and alleviated triglyceride accumulation in the presence of OA and iron. Additionally, miR-34a directly inhibited SIRT1 by binding to the 3'-untranslated region, as determined via the luciferase reporter assay. CONCLUSIONS: Our results support the existence of a link between the liver cell mitochondria and miR-34a/SIRT1 signaling. Potential endogenous modulators of NAFLD pathogenesis may ultimately provide new tools for therapeutic intervention.

Protective effects of dihydromyricetin on primary hippocampal astrocytes from cytotoxicity induced by comorbid diabetic neuropathic pain and depression.

Activated astrocytes play a key role in diabetic neuropathic pain and depression. We aimed to assess the protective effects of dihydromyricetin (DHM) on primary hippocampal astrocytes cultured with high glucose (HG), substance P (SP), and corticosterone (CORT). Culturing with HG + SP + CORT resulted in damage to primary hippocampal astrocytes, which simulates the clinical damage caused by comorbidity of diabetic neuropathic pain and depression. Western blot, qPCR, and immunofluorescence analyses revealed that HG + SP + CORT increased P2X7 receptor expression in primary hippocampal astrocytes, which was reversed by DHM treatment. Further, HG + SP + CORT elevated TNF-α, IL-1ß, free Ca2+, and ERK1/2 phosphorylation levels, which was inhibited by DHM or P2X7 shRNA treatment. Moreover, DHM significantly reduced the P2X7 agonist-activated currents in HEK293 cells transfected with the P2X7 receptor. These findings suggest that DHM can protect primary hippocampal astrocytes cultured with HG + SP + CORT from P2X7 receptor-mediated damage. Culturing cells with HG + SP + CORT might be a viable cell model for cellular injury exploration of diabetic comorbid pain and depression.

Selecting an Appropriate Animal Model of Depression.

Depression has become one of the most severe psychiatric disorders and endangers the health of living beings all over the world. In order to explore the molecular mechanism that underlies depression, different kinds of animal models of depression are used in laboratory experiments. However, a credible and reasonable animal model that is capable of imitating the pathologic mechanism of depression in mankind has yet to be found, resulting in a barrier to further investigation of depression. Nevertheless, it is possible to explain the pathologic mechanism of depression to a great extent by a rational modeling method and behavioral testing. This review aims to provide a reference for researchers by comparing the advantages and disadvantages of some common animal depression models.

The correlation between pregnancy-related low back pain and physical fitness evaluated by an index system of maternal physical fitness test.

To investigate incidence of pregnancy-related low back pain (LBP), evaluate physical fitness objectively during pregnancy and analyze the correlation between LBP and physical fitness of pregnant women, 180 pregnant women including 101 in mid-gestation (14-28 gestational weeks) and 79 in late-gestation (28-37 gestational weeks) were recruited and self-reported their LBP. The aerobic ability such as cardiorespiratory fitness and anaerobic ability including strength, endurance, speed, flexibility, and balance were evaluated by a novel materal physical fitness test system. The correlation between LBP and each component in physical fitness test system was analyzed in SPSS. As the results, 135 out of 180 participants (75% of total) had pregnancy-related LBP. Physical fitness of participants in late-gestation was significantly weaker including weaker back strength (p<0.05), less resistance band pullbacks in 30s (p<0.01), less stretching in sit-and-reach test (p<0.001), shorter duration in left legged blind balance test (p<0.05) and weaker bird dog balance(p<0.05) than those in mid-gestation. Correlation analysis indicated that LBP was negatively associated with standing heel raises in 20s (p<0.01) and standing glute kickbacks in 30s (left p<0.01, right p<0.05). Thus, it is concluded that LBP is in high prevalence throughout the entire pregnant course. The pregnant women are prone to have weakened strength of core muscle groups and poorer flexibility and balance along the pregnancy. In addition, their LBP was negatively correlated to strength of back muscle groups of lower limbs.

Effectiveness of mindfulness training on pregnancy stress and the hypothalamic-pituitary-adrenal axis in women in China: A multicenter randomized controlled trial.

Introduction: In the past two decades, mindfulness-based intervention programs have gradually become popular.Many studies have confirmed that these programs can effectively alleviate prenatal stress and negative emotion.The mindfulness-based stress-buffering hypothesis suggests that mindfulness training can induce changes in the levels of the cortisol secreted by the HPA axis, thereby reducing stress susceptibility. However, to date, only a few high-quality evidence-based medical studies have analyzed the effect of the mindfulness-based intervention in a maternal population.Thus, this study investigated the effects of a mindfulness-based psychosomatic intervention on pregnancy stress and the HYPERLINK "javascript:;" hypothalamic-pituitary-adrenal (HPA) axis of pregnant Chinese women. Methods: Women experiencing first-time pregnancy (n = 117) were randomly allocated to the intervention group or parallel active control group, and data were collected at baseline and post-intervention periods. The participants completed questionnaires regarding mindfulness and pregnancy stress. Saliva samples was collected at the time of waking up, and 30, 45, and 60 min after waking up for analyzing the salivary cortisol levels. We analyzed differences between the two groups and changes within the same group before and after the intervention. Results and discussion: A total of 95 participants completed the trial. Compared with the parallel active control group, the intervention group exhibited lower levels of stress after the intervention (P = 0.047). For HPA-axis-related indicators after the intervention, Delta value (P = 0.01) and AUCM value (P = 0.031) of the intervention group were significantly higher than that of the control group. Mindfulness-based interventions effectively reduced the level of pregnancy stress and adjusted the HPA axis function in pregnant women in China. Clinical Trial Registration: https://www.chictr.org.cn, identifier ChiCTR 2000033149.

Nutritional status and its association with in-hospital major adverse cardiac events in patients with severe heart failure: a prospective study.

Introduction: Objectives: this study aimed to evaluate the relationship of Nutritional Risk Screening 2002 (NRS2002) and in-hospital major adverse cardiac events (MACE) in patients with severe heart failure. Methods: an observational study was conducted at the emergency intensive care units (EICU) of Shandong University Qilu Hospital from January 2017 to December 2019. Nutritional screening and assessment were performed at the time of admission to hospital with the NRS2002. Results: of the 209 patients included, 16 cases (7.66 %) were not at nutritional risk, and 193 cases (92.34 %) were at risk. Among them, 12 cases (5.74 %) were malnourished, 38 cases (18.18 %) were at high nutritional risk, and 115 cases (55.02 %) were overweight and obese. The differences in prealbumin (PA) and N-terminal B-type natriuretic peptide precursor (NT-proBNP) between the 2 groups were statistically significant (p < 0.05). A total of 134 cases (64.12 %) received nutrition treatment support, of which 39 cases (29.10 %) received enteral nutrition (EN), 77 cases (57.46 %) parenteral nutrition, and 18 cases (13.43 %) enteral nutrition combined with parenteral nutrition (EN + SPN) support treatment. In all, 31 cases (54.39 %) reached 100 % of the target dose. Patients in the EN and EN + SPN groups had 37 MACE (64.91 %) and 31 enteral nutrition complications (54.39 %), with differences between the 3 groups being statistically significant (p < 0.05). Conclusion: the nutritional risk of patients with severe heart failure is high, and age and heart function are positively correlated with nutritional risk. The complications rate of patients with high nutritional risk is significantly higher than in those with low risk; the higher the nutritional risk, the higher the hospital mortality rate - that is, nutritional risk affects disease outcome.

Introducción: Objetivos: este estudio tuvo como objetivo evaluar la relación del Nutritional Risk Screening 2002 (NRS2002) con los eventos cardiacos adversos mayores intrahospitalarios (MACE) en pacientes con insuficiencia cardiaca grave. Métodos: se realizó un estudio observacional en las unidades de cuidados intensivos de emergencia (UCIE) del Hospital Qilu de la Universidad de Shandong desde enero de 2017 a diciembre de 2019. Se realizaron un cribado y una evaluación nutricional en el momento del ingreso hospitalario con el NRS2002. Resultados: de los 209 pacientes incluidos, 16 casos (7,66 %) no tenían riesgo nutricional y 193 casos (92,34 %) sí lo tenían. Entre ellos, 12 casos (5,74 %) estaban desnutridos, 38 casos (18,18 %) tenían un alto riesgo nutricional y 115 casos (55,02 %) tenían sobrepeso u obesidad. Las diferencias de prealbúmina (PA) y precursor del péptido natriurético de tipo B N-terminal (NT-proBNP) entre los 2 grupos fueron estadísticamente significativas (p < 0,05). En total, 134 casos (64,12 %) recibieron soporte de tratamiento nutricional, de los que 39 casos (29,10 %) recibieron nutrición enteral (NE), 77 casos (57,46 %) nutrición parenteral y 18 casos (13,43 %) nutrición enteral combinada con nutrición parenteral (NE + SPN) como tratamiento de apoyo. Treinta y un casos (54,39 %) alcanzaron la dosis objetivo al 100 %. Los pacientes de los grupos EN y EN + SPN tuvieron 37 MACE (64,91 %) y 31 complicaciones de la nutrición enteral (54,39 %), siendo la diferencia entre los 3 grupos estadísticamente significativa (p < 0,05). Conclusiones: el riesgo nutricional de los pacientes con insuficiencia cardíaca grave es alto; la edad y la función cardiaca se correlacionan positivamente con el riesgo nutricional. La complicación de los pacientes con alto riesgo nutricional es significativamente mayor que la de los de bajo riesgo; cuanto mayor es el riesgo nutricional, mayor es la tasa de mortalidad hospitalaria, es decir, el riesgo nutricional afecta el resultado de la enfermedad.

Evaluation of the growth and nutritional status of preschool children: a pilot study in the cold area of China.

OBJECTIVES: The growth and development of children is influenced not only by heredity factors but also by environmental factors, including nutrition and temperature. The aim of this study was to evaluate the growth and nutritional status of preschool children in Daxing'anling, the coldest region of China. METHODS: A descriptive, cross-sectional survey was performed among preschool children aged 3-6 years by stratified cluster sampling in Daxing'anling. The children's parents completed the questionnaires. Height, body weight and head circumference were measured, and Z scores for weight for height, weight for age, height for age and head circumference for age were evaluated. Anthropometric data were compared with World Health Organization standards and China's growth references. The levels of vitamin A, E and 25-(OH)-D3 in serum were detected by high-performance liquid chromatography. RESULTS: A total of 305 children were recruited. The average height of the preschool children was lower than China's growth reference but higher than the WHO standard. More than half of the preschool children ranged from -1 SD to +1 SD. Both the values of weight for height and of weight for age were positive and higher than the WHO standards (p<0.01), with a significant difference between boys and girls (p<0.01). The incidences of stunting, wasting, and underweight were 4.59%, 2.95%, and 2.30%, respectively, although the prevalence of overweight and obesity was high (18.03% and 6.89%, respectively). The rates of vitamin A and D deficiency were 7.54% and 88.85%, respectively. Vitamin A was also positively associated with 25-(OH)-D3. CONCLUSIONS: The burden of malnutrition in preschool children exists in cold regions, and a cold climate may be an important factor. Therefore, we should pay attention to the nutrition and physical growth of local preschool children; in particular, vitamin D deficiency should be given high priority, and necessary nutritional interventions should be made.

Qingre Jianpi decoction attenuates inflammatory responses by suppressing NOD-like receptor family pyrin domain-containing 3 inflammasome activation in dextran sulfate sodium-induced colitis mice.

OBJECTIVE: To investigate the effects of Qingre Jianpi decoction (，QRJPD) on dextran sulfate sodium (DSS)-induced colitis mice and explore its mechanism. METHODS: All mice were randomly divided into six groups. Weight changes, disease activity index values, and histological damage were detected. Inflammatory cytokines and immune cell infiltration were measured using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry (IHC) method. The key protein expression levels of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome were detected by western blot analysis, IHC, and quantitative reverse transcription polymerase chain reaction. RESULTS: QRJPD played an anti-inflammatory role in the treatment of ulcerative colitis (UC), reduced the secretion of inflammatory cytokines, and inhibited the inflammatory infiltration of immune cells by suppressing DSS-induced activation of the NLRP3 inflammasome. CONCLUSION: QRJPD exerts protective effects by inhibiting DSS-induced NLRP3 inflammasome activation.

Inhibitory Effects of Palmatine on P2X7 Receptor Expression in Trigeminal Ganglion and Facial Pain in Trigeminal Neuralgia Rats.

Trigeminal Neuralgia (TN) refers to recurrent severe paroxysmal pain in the distribution area of the trigeminal nerve, which seriously affects the quality of life of patients. This research applied the chronic constriction injury of the infraorbital nerve (CCI-ION) approach to induce an animal model of TN in rats. The mechanical pain threshold of each group of rats was determined postoperatively; the expression of P2X7 receptor in trigeminal ganglion (TG) was assessed by qRT-PCR, immunofluorescence and Western blot; and the changes of the proinflammatory cytokines IL-1ß and TNF-α in serum of rats were detected by ELISA. The results showed that the administration of palmatine in the TN rats could reduce the mechanical pain threshold, significantly decrease the expression of P2X7 receptor in TG, and lower the serum concentrations of IL-1ß and TNF-α, compared to the sham group. In addition, the phosphorylation level of p38 in TG of TN rats was significantly decreased after treatment with palmatine. Likewise, inhibition of P2X7 expression by shRNA treatment could effectively counteract the adversary changes of pain sensitivity, IL-1ß and TNF-α production, and p38 phosphorylation in TN rats. Our data suggest that palmatine may alleviate mechanical facial pain in TN rats possibly by reducing the expression of P2X7 receptor in TG of TN rats, which may be attributable to inhibiting p38 phosphorylation and reducing the release of IL-1ß and TNF-α.

Effects of palmatine on BDNF/TrkB-mediated trigeminal neuralgia.

Trigeminal neuralgia (TN), a sudden, needle-like pain in the distribution area of the trigeminal nerve, can seriously affect the physical and mental health of patients. In chronic pain conditions including TN, increased levels of brain-derived neurotrophic factor (BDNF) may enhance pain transmission. This study compares the effect of palmatine administration on the expression of BDNF and its receptor TrkB (tropomyosin receptor kinase B) in trigeminal ganglion cells of Sprague-Dawley rats in a sham versus TN model group. Within 14 days of surgery, the mechanical allodynia threshold of the TN group was significantly lower than that of the sham group, while the TN + palmatine group had a higher mechanical pain sensitivity threshold than the TN group (p < 0.05). Real-time quantitative PCR, immunohistochemistry, and immunofluorescence showed that BDNF and TrkB expression in the TN group was higher than that in the sham group, while palmatine treatment could reverse these changes. Western blotting showed that palmatine treatment could reduce the elevated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in TN rats. Thus, the BDNF/TrkB pathway may be involved in the pain transmission process of TN, and palmatine treatment may reduce pain transmission by inhibiting the BDNF/TrkB pathway and suppressing ERK1/2 phosphorylation.

Dihydromyricetin affects BDNF levels in the nervous system in rats with comorbid diabetic neuropathic pain and depression.

Diabetic neuropathic pain (DNP) and depression (DP) are the common complications in patients with diabetes. The purpose of our research was to observe whether brain-derived neurotrophic factor (BDNF) levels and tropomyosin receptor kinase B (TrkB) in the nervous system have effects on rats with comorbid DNP and DP, and to determine whether dihydromyricetin (DHM) may influence BDNF/ TrkB pathway to mitigatethe comorbidity. The study showed that DHM treatment could attenuates pain and depressive behavior in DNP and DP combined rats. Compared with the control group, the expression level of BDNF/TrkB in the hippocampus of DNP + DP group were reduced, while the expression levels in the spinal cord and DRG were increased. However, after treatment with DHM, those changes were reversed. Compared with the control group, the level of IL-1ß and TNF-α in the hippocampus, spinal cord and DRG in the DNP + DP group was significantly increased, and DHM treatment could reduce the increase. Thus our study indicated that DHM can relief symptoms of DNP and DP by suppressing the BDNF/TrkB pathway and the proinflammatory factor, and BDNF/TrkB pathway may be an effective target for treatment of comorbid DNP and DP.

Epac1, PDE4, and PKC protein expression and their association with AKAP95, Cx43, and cyclinD2/E1 in breast cancer tissues.

BACKGROUND: This study was conducted to investigate the exchange protein directly activated by cAMP (Epac1), PDE4, and PKC expression in breast cancer tissues, and the correlation between these proteins and AKAP95, Cx43, cyclin D2, and cyclin E1. METHODS: PV-9000 two-step immunohistochemistry was used to analyze protein expression. RESULTS: The positive rate of Epac1 protein expression in breast cancer tissues (58%) was higher than in para-carcinoma tissues (10%) (P < 0.05). There were no significant differences in the positive rates of PDE4 and PKC expression between breast cancer and para-carcinoma tissues (P > 0.05). The positive expression rate of PDE4 was higher in the P53 protein positive group compared to the P53 negative group (P < 0.05). Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins were observed (P < 0.05). CONCLUSION: Epac1 expression in breast cancer tissues was increased, suggesting that the protein may be involved in the development of breast cancer. Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins suggested synergistic effects among these proteins in the development of breast cancer.