3'-Deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

JOURNAL/nrgr/04.03/01300535-202410000-00028/figure1/v/2024-02-06T055622Z/r/image-tiff Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome. 3'-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3'-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3'-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3'-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3'-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3'-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3'-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3'-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

Efficacy and safety of perioperative application of esketamine on postpartum depression: A meta-analysis of randomized controlled studies.

Postpartum depression (PPD) seriously impairs the physical and mental health of mothers and their offspring, so how to prevent the occurrence of PPD has essential significance. Esketamine is a common general anesthetic that produces rapid and sustained antidepressant effects. However, the efficacy and safety of perioperative esketamine administration for PPD prevention remain uncertain. We conducted a meta-analysis to determine the effect of perioperative intravenous esketamine on PPD. Randomized controlled trials were included. The primary outcome was the prevalence of PPD and postpartum Edinburgh Postnatal Depression Scale (EPDS) scores. Secondary outcomes included postoperative pain scores and esketamine-related adverse effects. Seven studies included 669 patients treated with esketamine and 619 comparisons. Esketamine could effectively reduce EPDS scores and the incidence of PPD after cesarean section. Even at 42 days postpartum, the incidence of PPD was still significantly lower in the esketamine group. Esketamine did not increase the incidence of postoperative nausea and vomiting, dizziness, and drowsiness. In the esketamine low-dose subgroup, postoperative nausea and vomiting were significantly lower in the esketamine group. The two groups had no significant difference in postoperative pain scores. In conclusion, using esketamine during the perioperative period can reduce the incidence of PPD without increasing adverse effects.

Perinatal outcome of emergency cesarean section under neuraxial anesthesia versus general anesthesia: a seven-year retrospective analysis.

OBJECTIVE: An emergency cesarean section (CS), which is extremely life-threatening to the mother or fetus, seems to be performed within an adequate time horizon to avoid negative fetal-maternal denouement. An effective and vigilant technique for anesthesia remains vital for emergency cesarean delivery. Therefore, this study aimed to validate the impact of various anesthesia tactics on maternal and neonatal outcomes. METHOD: This was a retrospective cohort study of parturient patients who were selected for emergency CS with the assistance of general or neuraxial anesthesia between January 2015 and July 2021 at our institution. The 5-min Apgar score was documented as the primary outcome. Secondary outcomes, including the 1 min Apgar score, decision-to-delivery interval (DDI), onset of anesthesia to incision interval (OAII), decision to incision interval (DII), duration of operation, length of hospitalization, height and weight of the newborn, use of vasopressors, blood loss, neonatal resuscitation rate, admission to neonatal intensive care unit (NICU), duration of NICU and complications, were also measured. RESULTS: Of the 539 patients included in the analysis, 337 CSs were performed under general anesthesia (GA), 137 under epidural anesthesia (EA) and 65 under combined spinal-epidural anesthesia (CSEA). The Apgar scores at 1 min and 5 min in newborns receiving GA were lower than those receiving intraspinal anesthesia, and no difference was found between those receiving EA and those receiving CSEA. The DDI of parturients under GA, EA, and CSE were 7[6,7], 6[6,7], and 14[11.5,20.5], respectively. The DDI and DII of GA and EA were shorter than those of CSE, and the DDI and DII were similar between GA and EA. Compared to that in the GA group, the OAII in the intraspinal anesthesia group was significantly greater. GA administration correlated with more frequent resuscitative interventions, increased admission rates to NICU, and a greater incidence of neonatal respiratory distress syndrome (NRDS). Nevertheless, the duration of NICU stay and the incidence rates of neonatal hypoxic ischemic encephalopathy (HIE) and pneumonia did not significantly differ based on the type of anesthesia performed. CONCLUSION: Compared with general anesthesia, epidural anesthesia may not be associated with a negative impact on neonatal or maternal outcomes and could be utilized as an alternative to general anesthesia in our selected patient population following emergency cesarean section; In addition, a comparably short DDI was achieved for emergency cesarean delivery under epidural anesthesia when compared to general anesthesia in our study. However, the possibility that selection bias related to the retrospective study design may have influenced the results cannot be excluded.

miR­3120/Hsc70 participates in forced swim stress­induced mechanical hyperalgesia in rats in an inflammatory state.

The heat shock cognate 71 kDa protein (Hsc70) is a stress­inducible ATPase that can protect cells against harmful stimuli. Transient receptor potential vanilloid 1 (TRPV1) is a well­documented nociceptor. Notably, Hsc70 can inhibit TRPV1 expression and function, suggesting that Hsc70 may have pain regulation potential. However, the role of Hsc70 in stress­induced hyperalgesia remains unclear. In the present study, the participation of Hsc70 and its regulator microRNA (miR)­3120 were investigated in forced swim (FS) stress­induced mechanical hyperalgesia in rats in an inflammatory state. Complete Freund's adjuvant (CFA) hind paw injection was performed to induce inflammatory pain in rats (CFA rats). Furthermore, in FS + CFA rats, FS stress was performed for 3 days before CFA injection. The levels of Hsc70, miR­3120 and their downstream molecule TRPV1 were measured in the dorsal root ganglion (DRG) with western blotting, immunofluorescence, reverse transcription­quantitative polymerase chain reaction and fluorescence in situ hybridization. The results revealed that FS stress significantly exacerbated CFA­induced mechanical pain. Furthermore, CFA upregulated Hsc70 and TRPV1 expression, which was partially inhibited or further enhanced by FS stress, respectively. In FS + CFA rats, intrathecal injection of a lentiviral vector overexpressing Hsc70 (LV­Hsc70) could decrease TRPV1 expression and improve the mechanical pain. Additionally, the expression levels of miR­3120, a regulator of Hsc70, were markedly upregulated on day 3 following FS stress. Finally, miR­3120 was identified to be colocalized with Hsc70 and expressed in all sizes of DRG neurons. In CFA rats, DRG injection of miR­3120 agomir to induce overexpression of miR­3120 resulted in similar TRPV1 expression and behavioral changes as those caused by FS stress, which were abolished in the presence of LV­Hsc70. These findings suggested that miR­3120/Hsc70 may participate in FS stress­induced mechanical hyperalgesia in rats in an inflammatory state, possibly via disinhibiting TRPV1 expression in the DRG neurons.

Modified Dixon sequential method to determine the effective dose of alfentanil compounded with propofol for day-case hysteroscopy.

Background: Propofol combined with alfentanil is suitable for intravenous anesthesia for day-case hysteroscopy. Objective: To investigate the median effective dose (ED50) and 95% effective dose (ED95) of alfentanil compounded with propofol for day-case hysteroscopy. Design: In all, 29 patients who volunteered for painless hysteroscopy in 2022 were recruited. 1.5 mg/kg propofol was given as a sedative to all patients. The trial was conducted using the modified Dixon sequential method, with an initial dose of 10 µg/kg of alfentanil, and the subject's alfentanil dose depended on whether the prior hysteroscopy had failed, which was defined as inadequate cervical dilatation and hysteroscope placement with the patient exhibiting body movement, frowning, or a MOAA/S score >1. If the hysteroscopy failed (i.e. a positive response), the subsequent subject's alfentanil dosage was raised, and conversely (i.e. a negative response), the dose was decreased, with the adjacent dose ratio always being 1:1.2. The formal test begins with the first crossover wave and lasts until seven crossover waves materialize. Methods: The probit method was used to calculate the ED50, ED95, and corresponding 95% confidence intervals (CIs) of alfentanil compounded with propofol for hysteroscopy. Results: The ED50 and ED95 of alfentanil combined with propofol for day-case hysteroscopy were 5.701 (95% CI: 3.841-7.069) µg/kg and 8.817 (95% CI: 7.307-20.868) µg/kg, respectively. Conclusion: Alfentanil at 8.817 µg/kg in conjunction with propofol is a successful and safe approach for day-case painless hysteroscopy. Trial registration: The trial registry name: Modified sequential method to determine the half-effective dose of alfentanil compounded with propofol for ambulatory hysteroscopy. The URL of registration is https://www.chictr.org.cn/showproj.html?proj=171786, where the full trial protocol can be accessed. Registration number: ChiCTR2200061619.

Alfentanil combined with propofol is suitable for day-case hysteroscopy Why was this study done? Hysteroscopy is a procedure in which a hysteroscope is placed after the cervix is dilated to observe lesions in the uterine cavity. This study explores the effective dose of alfentanil combined with propofol for day-case (i.e., patients admitted and discharged on the same day) hysteroscopy to provide patients with comforting anesthesia (i.e., pain relief) during hysteroscopy. What did the researchers do? The research team recruited 29 patients who volunteered for painless hysteroscopy in 2022. All patients received alfentanil and propofol for intravenous anesthesia. If anesthesia was not effective, subsequent subjects increased the dose of anesthetic medication, and vice versa, the dose was decreased. According to this method, we can find the optimal dose of anesthetic drugs in hysteroscopy. What did the researchers find? The effective dose of alfentanil combined with propofol in patients undergoing painless hysteroscopy was 8.817 µg/kg. What do the findings mean? Alfentanil at 8.817 µg/kg in conjunction with propofol is a successful and safe approach for day-case painless hysteroscopy.

Research Trends and Hot Spots of Allopregnanolone Research in the Last 20 Years: A Bibliometric Analysis.

Background: Allopregnanolone is a kind of neuroactive steroid or neurosteroid in the central nervous system that acts as an endogenenous GABAA receptor positive modulator. However, at present, no comprehensive bibliometric analysis regarding allopregnanolone research is available. In our study, we intend to analyze the research trends and hot spots related to allopregnanolone in the past 20 years. Methods: We searched for allopregnanolone related articles and reviews between 2004 and 2023 from the Web of Science Core Collection database. Then, the bibliometric analysis was conducted using VOSviewer, CiteSpace, Microsoft Excel 2019, as well as the online bibliometric analysis platform (http://bibliometric.com/). Results: A total of 1841 eligible publications were identified. The number of annual publications and citations was generally on the rise. Among countries, the United States ranked first in overall publications, citations, international cooperation, and the number of research institutions. The University of North Carolina was the most active institution, conducting numerous preclinical and clinical work that focusing on allopregnanolone treatment for diverse psychiatric or neurologic disorders. As for authors, Dr. Frye CA, Morrow AL, and Pinna G were identified as the top three prolific scholars due to their great publications and citations. Based on the publication clusters and citation bursts analysis, the keyword co-occurrence network, the strongest citation bursts, and co-cited references analysis, the hot spots in recent years included "depression", "postpartum depression", "GABAA receptor", and so on. Conclusion: Allopregnanolone is still a popular area of research, and the United States leads the way in this area. Dr. Frye CA, Morrow AL, Pinna G, and their teams contributed greatly to the mechanism study and translation study of allopregnanolone. The use of allopregnanolone for the treatment of psychiatric or neurologic disorders, especially postpartum depression, is the current hot spot. However, the underlying mechanisms of anti-depression are still not clear, deserving more in-depth research.

Laboratory markers to identify acute histological chorioamnionitis in febrile parturients undergoing epidural analgesia: a retrospective study.

BACKGROUND: This study aimed to investigate the effect of the pathological staging of acute histological chorioamnionitis (HCA) on laboratory indicators and to conduct further studies to reassess the threshold values used by clinicians to identify acute HCA in febrile parturients undergoing epidural analgesia. METHODS: A retrospective study of febrile mothers receiving epidural analgesia at Nanjing Maternal and Child Health Care Hospital from January 1, 2018 to December 31, 2018. The participants were grouped by the progression of acute HCA, and the laboratory parameters were compared between groups. The ability of C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and monocyte-leukocyte ratio (M%), alone or in combination, to identify acute HCA in febrile parturients undergoing epidural analgesia was assessed using logistic regression and ROC curves. RESULTS: The area under the curve (AUC) of the best logistic regression model predicting HCA climbed to 0.706 (CRP + MLR). Maternal CRP, NLR, and MLR significantly and progressively increased with the progression of acute HCA (p < 0.0001). Based on the ROC curves, the following thresholds were selected to define increased laboratory indicators for identifying acute HCA: CRP ≥ 6.90 mg/L, NLR ≥ 11.93, and MLR ≥ 0.57. In addition, the AUC of the best logistic regression model predicting HCA ≥ stage 2 was 0.710, so these inflammatory markers were more precise in predicting HCA ≥ stage 2. CONCLUSION: Increased CRP (≥ 6.90 mg/L), NLR (≥ 11.93), and MLR (≥ 0.57) may help clinicians to identify early potential acute HCA in febrile parturients receiving epidural analgesia and to monitor progression to optimize clinical treatment options. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry on November 24, 2021 ( http://www.chictr.org.cn , ChiCTR2100053554).

Satellite glial cell-secreted exosomes after in-vitro oxaliplatin treatment presents a pro-nociceptive effect for dorsal root ganglion neurons and induce mechanical hypersensitivity in naïve mice.

BACKGROUND: The pathophysiological mechanism underlying chemotherapy-induced neuropathic pain (CINP) remains unclear. Sensory neuronal hypersensitivity in the dorsal root ganglion (DRG) is essential for the onset and maintenance of chronic pain. Satellite glial cells (SGCs) in the DRG potentially affect the function of sensory neurons, possibly by mediating extracellular or paracrine signaling. Exosomes play an essential role in cell-cell communication. However, the role of SGC-secreted exosomes in glia-neuron communication and CINP remains unclear. METHODS: SGCs and sensory neurons were cultured from the DRG of mice. The SGCs were treated with 4 µM oxaliplatin for 24 h. Glial fibrillary acid protein (GFAP) and connexin-43 (Cx-43) expressions in the SGCs were examined with immunocytochemistry (ICC). Enzyme-linked immunosorbent assay (ELISA) detected cytokine release in the SGCs after oxaliplatin treatment. Subsequently, SGC-secreted exosomes were collected using ultracentrifugation and identified by nanoparticle tracking analysis, transmission electron microscopy, and western blotting. Subsequently, DRG neurons were incubated with SGC-secreted exosomes for 24 h. The percentage of reactive oxygen species (ROS)-positive neurons was detected using flow cytometry, and acid-sensing ion channel 3 (ASIC3) and transient receptor potential vanilloid 1 (TRPV1) expression were examined by western blotting. SGC-secreted exosomes were intrathecally injected into naïve mice. The mechanical withdrawal threshold was assessed 24, 48, and 72 h following the injection. TRPV1 expression in the DRG was examined 72 h after intrathecal injection. Furthermore, differentially expressed (DE) miRNAs within the SGC-secreted exosomes were detected using RNA sequencing and bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analyses were performed to predict the function of the target genes of DE miRNAs. Finally, the DE miRNAs with pain regulation potential were identified in silico. RESULTS: After in-vitro oxaliplatin treatment, ICC showed an increase in the immunoreactivity of GFAP and Cx-43 in the SGCs. ELISA results suggested an increased release of tumor necrosis factor-α and interleukin (IL)-1ß, but a decreased release of IL-10. Oxaliplatin treatment increased the secretion of exosomes in the SGCs from 4.34 to 5.99 × 1011 (particles/ml). The exosome-specific markers CD9 and TSG101 were positive, whereas calnexin was negative for the obtained exosomes. Additionally, the SGC-secreted exosomes were endocytosed by DRG neurons after co-incubation. Moreover, after incubation with conditioned SGC-secreted exosomes (after 4 µM oxaliplatin treatment), the percentage of ROS-positive DRG neurons increased and ASIC3 and TRPV1 expressions were upregulated. After the intrathecal injection of the conditioned SGC-secreted exosomes, the mice presented with mechanical hypersensitivity and TRPV1 expression upregulation in the DRG. Notably, 25 and 120 significantly upregulated and downregulated miRNAs, respectively, were identified in the conditioned SGC-secreted exosomes. When predicting the function of target genes of DE miRNAs, certain GO terms, such as synapse organization, neurogenesis regulation, histone modification, and pain-related KEGG or Reactome pathways, including vascular endothelial growth factor A-vascular endothelial growth factor receptor 2, mammalian target of rapamycin, and mitogen-activated protein kinase signaling pathways, related to nervous system function were predicted. Finally, 27 pain regulation-related miRNAs, including miR-324-3p, miR-181a-5p, and miR-122-5p, were identified in silico. CONCLUSION: Our study demonstrates that SGC-secreted exosomes after in-vitro oxaliplatin treatment present a pro-nociceptive effect for DRG neurons and induce mechanical hypersensitivity in naïve mice, possibly via the contained miRNA cargo. Identifying the candidate miRNAs and verifying their functions in vivo are required to elucidate the exosomes mediating 'glia-neuron' communication under CINP condition.

Remimazolam Supplemented to General Anesthesia Alleviates Stress and Cognitive Impairment in Elder Patients After Hip Surgery.

OBJECTIVE: Stress and cognitive impairment are common postoperative complications in elder patients who have undergone hip surgery. The objective of the work is to evaluate the effects of remimazolam supplemented to combined general anesthesia in improving stress and cognitive performance. METHODS: A total of 120 patients were included to receive a low dose of remimazolam (0.1 mg/kg/h) intravenously combined with general anesthesia or general anesthesia alone during hip surgery. Assessments were used for evaluating cognitive and psychological performance respectively before surgery (T0), 24 h (T5), and 72 h (T6) after surgery. Physiological parameters including mean artery pressure, heart rate, and blood oxygen levels (SpO2) were measured at T0, 30 min after anesthesia (T1), and completion of surgery (T2). Stress indexes including serum cortisol and norepinephrine levels were measured at T0, T5, and T6. The visual analog scale pain scores were also acquired at 6 h after surgery, 12 h after surgery, and T6. Serum interleukin-6 and tumor necrosis factor-α levels were acquired at T0, T2, and T6. RESULTS: Heart rate and SpO2 levels in the combination group were significantly improved compared to the control group. Serum cortisol and norepinephrine levels were the highest at T1 and decline over time until T5 in both groups, the two stress indexes of the combination group were significantly lower at T1 and T2. CONCLUSION: Remimazolam supplemented to combined general anesthesia demonstrated significant benefit in reducing stress and cognitive dysfunction in elder patients who underwent hip surgery.

Evaluation of clinical effects of Esketamine on depression in patients with missed miscarriage: A randomized, controlled, double-blind trial.

BACKGROUND: Patients with missed miscarriages are usually accompanied by varying degrees of depression, which is closely related to the patient's prognosis. We investigated whether Esketamine could alleviate postoperative depression symptoms in patients with missed miscarriages who underwent painless curettage. METHODS: This study was a randomized, parallel-controlled, double-blind, single-center trial. A total of 105 patients with preoperative 1d (EPDS) ≥ 10 were randomly assigned to the Propofol; Dezocine; Esketamine group. Patients record EPDS at 7 and 42 days after the operation. Secondary outcomes included VAS for 1 h postoperation, total propofol usage, adverse reactions, And the expressions of inflammatory factors of TNF-α, IL-1ß, IL-6, IL-8, and IL-10. RESULTS: Compared with the P and D group, patients in the S group had lower EPDS scores at 7 day (8.63 ± 3.14, 9.17 ± 3.23 vs. 6.34 ± 2.87 P = 0.0005) and 42 days (9.40 ± 2.67, 8.49 ± 3.05 vs.5.31 ± 2.49 P < 0.0001) after the operation. Respectively, Compared with the P group, the VAS scores (3.51 ± 1.12 vs. 2.80 ± 0.83, 2.40 ± 0.81, P = 0.0035) and the dosage of propofol used during operation (198.7 ± 47.48 vs. 145.5 ± 19.31, 142.9 ± 21.01 P < 0.0001) were lower in the D and S groups, and lower postoperative inflammatory response at 1 day after surgery. Other outcomes among the three groups were not found to the difference. CONCLUSIONS: Esketamine effectively treated postoperative depressive symptoms of patients with a missed miscarriage, decreasing propofol consumption and inflammatory response.

Correlation between pleth variability index and ultrasonic inferior vena cava-collapsibility index in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia.

BACKGROUND: To explore the correlation and consistency of non-invasive pleth variability index (PVI) combined with ultrasonic measurement of inferior vena cava-collapsibility index (IVC-CI) in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia. METHODS: Forty-seven twin pregnancies women undergoing elective cesarean section were selected. The ASA score was rated as I-II, aged from 18 to 45 years. Spinal anesthesia was performed at L3-4. PVI and IVC-CI, general data (BMI, gestational weeks, operation duration, blood loss), MAP, temperature sensory block level and adverse reactions were recorded at baseline (T1) and completion of testing the level of spinal anesthesia (T2). RESULTS: The correlation coefficient analysis of baseline IVC-CI% and PVI revealed that the Pearson's coefficient was 0.927, > 0.4. Thus, pre-anesthesia IVC-CI% had a strong correlation with PVI, with R2 of 85.69%. The correlation coefficient analysis of post-anesthesia IVC-CI% and PVI revealed that the Pearson's coefficient was 0.904, > 0.4. Thus, post-anesthesia IVC-CI% had a strong correlation with PVI, with R2 of 81.26%. CONCLUSION: PVI is strongly consistent with ultrasound measurement of IVC-CI twin pregnancies, which can be used as a valuable index for predicting the volume in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia. Trial registration This study was registered on ClinicalTrials.gov with clinical trial registration number of ChiCTR2200055364 (08/01/2022).

Deficit of perineuronal net induced by maternal immune activation mediates the cognitive impairment in offspring during adolescence.

Maternal immune activation (MIA) during pregnancy is considered a risk factor for neurodevelopment in the offspring, resulting in behavioral abnormalities. Furthermore, adolescence is a vulnerable period for developing different psycho-cognitive deficits. Here, we aimed to observe the cognitive consequences of prenatal MIA exposure in adolescents and explored the underlying mechanisms. We divided dams into CON and MIA groups after inducing a mouse model of MIA using lipopolysaccharide (120 µg/kg) on gestational day 15. Open field (OF), elevated plus maze (EPM), and novel object recognition (NOR) tests were performed on postnatal day (PD) 35-37. The expression of hippocampal Wisteria floribunda agglutinin (WFA)+ perineuronal net (PNN), parvalbumin (PV), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule-1(Iba-1) were evaluated using immunofluorescence, and the expression of matrix metalloprotein-9 (MMP-9) in the hippocampus was assessed using the western blot. Following the infusion of chondroitinase ABC (ChABC) into CA1 in the offspring from the CON group on PD 30, they were divided into ChABC and Sham groups. OF, EPM, and NOR were performed on PD 35-37. Compared to the CON group, decreased exploration time of the novel object and preference ratio were observed in the MIA group. Meanwhile, the MIA group presented significantly decreased WFA+ PNN in CA1, increased Iba-1+ microglia, and MMP-9 in the hippocampus. Additionally, the density of PV+ neurons and GFAP+ astrocytes was comparable between both groups. After digesting the PNN, the exploration time of novel object and preference ratio decreased in the ChABC group compared to the Sham group. Conclusively, the PNN deficit in CA1 caused by prenatal MIA might, at least partially, induce cognitive impairment in adolescents. Microglia and MMP-9 may also be potential candidates for PNN deficit after MIA.

The etiological roles of miRNAs, lncRNAs, and circRNAs in neuropathic pain: A narrative review.

BACKGROUND: Non-coding RNAs (ncRNAs) are involved in neuropathic pain development. Herein, we systematically searched for neuropathic pain-related ncRNAs expression changes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular non-coding RNAs (circRNAs). METHODS: We searched two databases, PubMed and GeenMedical, for relevant studies. RESULTS: Peripheral nerve injury or noxious stimuli can induce extensive changes in the expression of ncRNAs. For example, higher serum miR-132-3p, -146b-5p, and -384 was observed in neuropathic pain patients. Either sciatic nerve ligation, dorsal root ganglion (DRG) transaction, or ventral root transection (VRT) could upregulate miR-21 and miR-31 while downregulating miR-668 and miR-672 in the injured DRG. lncRNAs, such as early growth response 2-antisense-RNA (Egr2-AS-RNA) and Kcna2-AS-RNA, were upregulated in Schwann cells and inflicted DRG after nerve injury, respectively. Dysregulated circRNA homeodomain-interacting protein kinase 3 (circHIPK3) in serum and the DRG, abnormally expressed lncRNAs X-inactive specific transcript (XIST), nuclear enriched abundant transcript 1 (NEAT1), small nucleolar RNA host gene 1 (SNHG1), as well as ciRS-7, zinc finger protein 609 (cirZNF609), circ_0005075, and circAnks1a in the spinal cord were suggested to participate in neuropathic pain development. Dysregulated miRNAs contribute to neuropathic pain via neuroinflammation, autophagy, abnormal ion channel expression, regulating pain-related mediators, protein kinases, structural proteins, neurotransmission excitatory-inhibitory imbalances, or exosome miRNA-mediated neuron-glia communication. In addition, lncRNAs and circRNAs are essential in neuropathic pain by acting as antisense RNA and miRNA sponges, epigenetically regulating pain-related molecules expression, or modulating miRNA processing. CONCLUSIONS: Numerous dysregulated ncRNAs have been suggested to participate in neuropathic pain development. However, there is much work to be done before ncRNA-based analgesics can be clinically used for various reasons such as conservation among species, proper delivery, stability, and off-target effects.

One-pot synthesis of α-Linolenic acid nanoemulsion-templated drug-loaded silica mesocomposites as efficient bactericide against drug-resistant Mycobacterium tuberculosis.

Nowadays, pathogenic infection has posed a severe threat to the public health and environmental sanitation, urging a continuous search of efficacious and safe bactericidal agents of various formulated forms. Here, a facile one-pot hydrothermal preparation of mesoporous silica nanoparticles using ultrasonication-assisted nanoemulsion of α-Linolenic acid (α-LA) as template was developed. The formed silica mesocomposite at water/fatty-acid surface provides an easy yet green synthesis route, which can be generalized for the further encapsulation of hydrophobic drugs such as antimycobacterial Rifampicin (RIF). The obtained α-LA nanoemulsion-templated silica nanoparticles (LNS NPs), with a weight content of ∼17% α-LA in the composite, showed apparent antibacterial effect against Staphylococcus aureus (S. aureus). By comparison, the removal of α-LA from the silica nanoparticles (LNS-1 NPs) resulted in the composite of enlarged pore size with negligible bactericidal activities. Notably, the Isoniazide (INH) and Rifampicin (RIF)-encapsulated LNS NPs exhibited outstanding antimycobacterial activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis (M. tuberculosis). The obtained highly biocompatible, biosafe and low-energy consumptive α-LA-contained mesostructured silica-based bactericide holds promising therapeutic potentials to tackle the emerging drug-resistant infectious microbes.

Intestinal dysbacteriosis-propelled T helper 17 cells activation mediate the perioperative neurocognitive disorder induced by anesthesia/surgery in aged rats.

BACKGROUND: Perioperative neurocognitive disorders (PND) is a common postoperative disease in elderly patients, but its pathogenesis remains unclear. METHODS: Exploratory laparotomy was performed to establish PND model under sevoflurane anesthesia. 16S rRNA high-throughput sequencing was used to detect the changes of intestinal flora. Antibiotics were used to relatively eliminate intestinal flora before anesthesia/surgery, and behavior tests, such as open field, Y maze, and fear conditioning tests were applied to detect the changes of memory ability. The number of Th17 cells and Foxp3 cells was detected by flow cytometry in the Peyer's patches (PP), mesenteric lymph nodes (MLN), blood and brain. Western blot was used to detect the expression of IL17, IL17RA, IL6 and IL10 in the hippocampus. Immunofluorescence was used to detect the expression of IL17, IL17R and IBA1 (ionized calcium binding adaptor molecule1) in the hippocampus. RESULTS: Anesthesia/surgery caused intestinal flora imbalance and induced neurocognitive impairment, increased the number of Th17 cells in the PP, MLN, blood and brain, increased the level of IL17, IL17R and inflammatory factors production in the hippocampus. Antibiotics administration before anesthesia/surgery significantly decreased the number of Th17 cells and the level of IL17, IL17R and inflammatory factors production, and improved the memory function. In addition, we found that IL17R was co-labeled with IBA1 in a large amount in the hippocampus through immunofluorescence double-staining. CONCLUSION: Our study suggested that intestinal dysbacteriosis-propelled T helper 17 cells activation and IL17 secretion might play an important role in the pathogenesis of PND induced by anesthesia/surgery in aged rats.

Participation of transient receptor potential vanilloid 1 in the analgesic effect of duloxetine for paclitaxel induced peripheral neuropathic pain.

Painful peripheral neuropathy is a common dose-limiting side effect of chemotherapeutic paclitaxel (PTX) treatment. The American Society of Clinical Oncology (ASCO) recommends duloxetine (DUL) as a promising treatment alternative for chemotherapy-induced peripheral neuropathic pain. However, this recommendation lacks a robust theoretical basis and supporting data. To elucidate the involvement of transient receptor potential vanilloid 1 (TRPV1) in the analgesic effect of DUL for PTX-induced neuropathic pain, TRPV1 expression in the lumbar dorsal root ganglion (DRG) and spinal cord was evaluated following intraperitoneal administration of PTX (2 mg/kg/day) for four alternate days in rats. Western blot and immunohistochemistry suggested that a cumulative dosage of PTX (8 mg/kg) upregulated TRPV1 expression in the lumbar DRG and spinal dorsal horn (SDH) at day 14 post treatment. TRPV1 upregulation in the DRG was mainly expressed in calcitonin gene-related peptide (CGRP) and IB-4 positive small-size sensory neurons. Additionally, PTX increased CGRP and substance P (SP) expression in the DRG and SDH, induced SDH microglia and astrocyte activation, and upregulated spinal tumor necrosis factor-α (TNF-α) but not IL-1ß or IL-10 expression. Behavioral detection showed that PTX-related mechanical and thermal hyperalgesia was significantly inhibited by consecutive administration of DUL 20 mg/kg/day greater than 10 mg/kg/day for 5 days starting at day 10 post PTX injection. Furthermore, DUL (20 mg/kg/day) for 5 days markedly ameliorated PTX-induced TRPV1, CGRP, and SP upregulation in the DRG and SDH, and mitigated PTX-induced spinal cord glia activation and TNF-α expression. Moreover, the pharmacological blockade of TRPV1 resulted in an analgesic effect on PTX-induced hyperalgesia. Collectively, these results suggest that DUL alleviates PTX-induced peripheral neuropathic pain by suppressing TRPV1 upregulation in the lumbar DRG and SDH, which is followed by a reduction in CGRP and SP release, as well as spinal glia activation and TNF-α expression.

Study on perinatal-related factors of maternity and newborn in parturients with intrapartum fever in part of Eastern China: A cross-sectional study.

BACKGROUND: Maternal intrapartum fever has a serious impact on mother and child. However, the corresponding study seems to be in short. METHODS: The role of inflammatory cells in patients who were diagnosed with intrapartum fever lived in part of Eastern China was evaluated. The obstetrics outcomes, complete blood cell count (CBC) and thereby converted neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, monocyte to lymphocyte ratio (MLR), and vaginal secretion were compared in different groups. RESULTS: Prepartum values of white blood cell (WBC), red blood cell (RBC), and hemoglobin (Hb) were all a little higher in the febrile group than in the afebrile group, and postpartum WBC in the afebrile group was still higher while postpartum RBC and Hb were inferior to non-fever maternity. Postpartum NLR and MLR were all higher in the fever group but not preferred overtly difference before delivery. Additionally, the comparison of WBC, RBC, Hb, platelets, neutrophils, and monocytes in prepartum and postpartum all showed significant differences. CONCLUSION: The parturition could bring about the value change of CBC and intrapartum fever might aggravate or alleviate this change. Besides, the intrapartum fever might not be caused mainly by infection and the difference between bacteria and fungus could reflect in the CBC.

Electrospun chitosan oligosaccharide/polycaprolactone nanofibers loaded with wound-healing compounds of Rutin and Quercetin as antibacterial dressings.

Burn injury has posed devastating burdens on the public health due to its inevitable damage to the skin structure resulting in the increased risk of infection. Therefore, it is highly demanding to develop efficacious antibacterial wound-healing dressing. Despite the favourable wound-healing activities, the curative efficacy of phytochemical compounds of quercetin (Qe) and its derivatives is limited by their poor water solubility. Here, we have fabricated a novel electrospun nanofiber membrane (ENM) consisting of polycaprolactone (PCL), chitosan oligosaccharides (COS), and Qe/Rutin (Ru) as the potential bioactive dressing for wound healing. The incorporation of chitosan oligosaccharides (COSs) in the PCL scaffold at the optimized molar ratio not only contributed to the improved hydrophilicity and water absorption performance of the ENM but effectively increased the specific surface area of the formed nanofibers. In particular, the antioxidant and antibacterial activities of the Qe/rutin-loaded nanofiber membranes were tested, which revealed that the PCL-COS-Qe membrane exhibited superior performance among all nanofiber membranes. Therefore, the developed PCL-COS-Qe/Ru nanofiber membranes hold enormous potential as healthcare products, such as wound dressings for burn injuries.