Advances in the Treatment of Neuropathic Pain by Sympathetic Regulation.

PURPOSE OF REVIEW: To explore the mechanism and therapeutic effect of sympathetic nerve regulation on neuropathic pain. RECENT FINDINGS: A comprehensive search was conducted in the PubMed and CNKI libraries, using the following keywords: stele ganglion block, neuropathic pain, sympathetic nerve block, sympathetic chemical destruction, and sympathetic radiofrequency thermocoagulation. We selected and critically reviewed research articles published in English that were related to sympathetic modulation in the treatment of neuropathic pain. The collected literature will be classified according to content and reviewed in combination with experimental results and clinical cases. Neuropathic pain was effectively treated with sympathetic regulation technology. Its mechanism includes the inhibition of sympathetic nerve activity, regulation of the inflammatory response, and inhibition of pain transmission, which greatly alleviates neuropathic pain in patients. Stellate ganglion blocks, thoracic and lumbar sympathectomies, chemical destruction, and radiofrequency thermocoagulation have been widely used to treat neuropathic pain. Sympathetic regulation can effectively relieve pain symptoms and improve the patient's quality of life by inhibiting sympathetic nerve activity, reducing the production and release of pain-related mediators, and inhibiting pain transmission. CT-guided radiofrequency thermocoagulation of the thoracic and lumbar sympathetic nerves is effective and durable, with few complications, and is recommended as a treatment for intractable neuropathic pain.

A Study on the Protective Impact of Resveratrol on Liver Damage in Rats with Obstructive Jaundice.

BACKGROUND: Obstructive Jaundice (OJ) is a common clinical condition with potential outcomes, including hepatocyte necrosis, bile duct hyperplasia, significant cholestatic liver fibrosis, and, in severe cases, liver failure. Resveratrol (RES), a polyphenol present in grapes and berries, has demonstrated efficacy in improving OJ. However, the precise mechanism of its action remains unclear. METHODS: In this study, we employed network pharmacology to investigate the underlying molecular mechanism of RES in the treatment of OJ. The targets of RES were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SuperPred, and SwissTargetPrediction database. The targets related to OJ were gathered from the DisGeNET, GeneCards, DrugBank, and Online Mendelian Inheritance in Man (OMIM) databases, and the intersection of these targets was determined using Venny2.1.0. Subsequently, an active component-target network was constructed using Cytoscape software. The Protein-Protein Interaction (PPI) network was generated using the String database and Cytoscape software. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Bioconductor platform. Finally, quantitative Real-Time PCR (qRT-PCR), Western Blotting (WB), and Enzyme-Linked Immunosorbent Assay (ELISA) were employed to assess RNA and protein expression levels in related pathways. RESULTS: The findings revealed a selection of 56 potential targets for RES, and a search through the online database identified 2,742 OJ-related targets with overlapping in 27 targets. In the PPI network, mTOR, CYP2C9, CYP1A1, CYP3A4, AHR, ESR1, and HSD17B1 emerged as core targets. KEGG analyses demonstrated that the primary pathways of RES in treating OJ, particularly those related to lipid metabolism, include linoleic acid metabolism, arachidonic acid metabolism, metabolism of xenobiotics by cytochrome P450, lipid and atherosclerosis, tyrosine metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions signaling pathways. Furthermore, in vivo experiments indicated that RES significantly ameliorated liver injury induced by Common Bile Duct Ligation (CBDL) in rats with OJ. It lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, reduced liver tissue MDA levels, increased glutathione (GSH) content, and enhanced activity of superoxide dismutase (SOD), alleviating liver damage. Metabolomics analysis revealed that the therapeutic effect of RES in OJ involved alterations in lipid metabolic pathways, hinting at the potential mechanism of RES in treating OJ. ELISA, qRTPCR, and WB analyses confirmed lower expression levels of mTOR, CYP1A1, and CYP2C9 in the RES group compared to the model group, validating their involvement in the lipid metabolism pathway. CONCLUSION: In conclusion, RES exhibited a protective effect on liver function in rats with OJ. The underlying mechanism appears to be linked to antioxidant activity and modulation of lipid metabolism pathways.

Phosphorylation Modification, Structural Characterization, Antioxidant and DNA Protection Capacities of Polysaccharides from Asarum Sieboldii Miq.

Polysaccharide from Asarum sieboldii Miq (ASP) was extracted and five phosphorylation polysaccharides with different degree of substitution were obtained, namely ASPP1, ASPP2, ASPP3, ASPP4, and ASPP5 (ASPPs). The physical and chemical structure and biological activities were studied. The results suggested that the carbohydrate and protein content were reduced while uronic acid was increased after phosphorylation modification. The molecular weight of ASPPs was significantly lower than that of ASP. ASPPs were acidic heteropolysaccharides mainly composed of galacturonic acid, galactose, glucose, fructose, and arabinose. The UV-vis spectrum indicated that the polysaccharides did not contain nucleic acid or protein after modification. The Fourier transform infrared spectrum demonstrated that ASPPs contained characteristic absorption peaks of P=O and P-O-C near 1270 and 980 cm-1 . ASPPs presented a triple helix conformation, but it was not presented in ASP. The scanning electron microscopy analysis showed that the surface topography and particle structure of ASP were different after modification. Compared with ASP, ASPPs enhanced the activity to scavenge DPPH and ABTS free radicals and possessed more protective ability to DNA oxidation caused by OH⋅, GS⋅, and AAPH free radicals. These results suggest that chemical modification is beneficial for the exploitation and utilization of natural polysaccharides.

MEX3C induces cognitive impairment in mice through autophagy inhibition.

BACKGROUND: The muscle excess 3 (MEX3C) protein comprises one of two conserved KH hnRNP K homology domains of the Caenorhabditis elegans protein family, a gene involved in the metabolism of key RNAs at posttranscriptional levels during the development of C. elegans, but its function in mammals is unclear. METHODS AND RESULTS: In this study, we found that MEX3C plays a key role in learning and cognitive function. The learning and cognitive abilities of MEX3C-knockout (KO) mice were significantly decreased relative to those of wild-type (WT) mice in behavioral experiments, including the shuttle box, Morris water maze, and new object recognition. Nissl staining showed a decrease in the number of Nissl bodies and in the maturation of hippocampal and cortical neurons. A Western blot analysis of the neuron-specific nuclear (NeuN) protein NEUN protein showed that the expression of that protein was decreased, which was consistent with the results of Nissl staining. Of note, the expression of sequestosome I p62 and Parkin BCL-2-associated X (Bax) Bax and B-cell lymphoma-2 (Bcl-2) Bcl-2 proteins also showed a downward trend, suggesting that the MEX3C gene may cause a decrease in the number and maturity of neuronal cells by increasing apoptosis through the inhibition of autophagy. In addition, Golgi staining showed that the complexity of neurons in the hippocampus and cerebral cortex was reduced, and the postsynaptic density protein 95 and growth-associated protein (GAP-43) also showed different degrees of reduction. CONCLUSION: The KO of the MEX3C gene reduces the plasticity of synapses in various regions of the hippocampus, thereby affecting the function of the hippocampus and eventually causing the decline of cognitive function. On the other hand, compared with WT mice, MEX3C-KO mice showed increased anxiety-like behaviors in minefield and elevated plus maze tests.

Association between exposures to phthalate metabolites and preterm birth and spontaneous preterm birth: A systematic review and meta-analysis.

Emerging evidence from observational studies proves the association between preterm birth (PTB) and phthalate metabolites; however, such findings are inconsistent and inconclusive. This meta-analysis aimed to clarify this association by accessing the connection between 11 phthalate metabolites and PTB, and 6 phthalate metabolites and spontaneous PTB. The PubMed, Embase, and WOS (Web of Science) databases were searched up to July 2020. Seven prospective studies met the inclusion criteria. Pooled odds ratios (OR) with 95 % confidence intervals (CIs) were calculated for risk estimation. Our results indicated that mono-n-butyl phthalate (MBP), sum of di-2-ethylhexyl phthalate (ΣDEHP), and mono 3-carboxypropyl phthalate (MCPP) significantly correlated with the risk of PTB (MBP: OR = 1.23, 95 % CI = 1.05-1.45; ΣDEHP: OR = 1.21, 95 % CI =1.01-1.44; MCPP: OR = 1.09, 95 % CI = 1.00-1.19). Pooled results showed that spontaneous PTB was associated with higher urinary levels of mono-ethyl phthalate (MEP), MCPP, mono-isobutyl phthalate (MIBP), and MBP (MBP: OR = 1.27, 95 % CI = 1.02-1.58; MEP: OR = 1.19, 95 % CI = 1.01-1.40; MCPP: OR = 1.15, 95 % CI = 1.02-1.30; MIBP: OR = 1.38, 95 % CI = 1.12-1.71). Overall, we conclude that during pregnancy, MBP, ΣDEHP, and MCPP levels are associated positively with PTB. MBP, MEP, MCPP, and MIBP levels had increased odds of spontaneous PTB. No significant associations were observed between other phthalate metabolites and PTB or spontaneous PTB. Further research is needed to verify these findings and elucidate the association of phthalate levels and PTB.

Magnetic Resonance Imaging Assessment of Abdominal Ectopic Fat Deposition in Correlation With Cardiometabolic Risk Factors.

Purpose: Ectopic fat accumulation and abdominal fat distribution may have different cardiometabolic risk profiles. This study aimed to assess the associations between various magnetic resonance imaging (MRI)-acquired fat depots and cardiometabolic risk factors. Methods: A total of 320 subjects with median age of 59 years, 148 men and 172 women, were enrolled in the study. Visceral adipose tissue (VAT) area and fat fraction (FF), subcutaneous adipose tissue (SAT) area and FF at the L1-L2 levels, preperitoneal adipose tissue (pPAT) area and FF, hepatic FF, pancreatic FF, and intramuscular FF were assessed by MRI FF maps. The associations of various MRI-acquired fat depots with blood pressure, glucose, and lipid were examined using sex-stratified linear regression. Logistic regression stratified by sex was used to analyze the association of various MRI-acquired fat depots with the risk of hypertension, T2DM, and dyslipidemia. Results: The intraclass correlation coefficient (ICC) values were >0.9, which suggested good interobserver and intraobserver agreement. VAT area, V/S, hepatic fat, pancreatic fat, and pPAT rather than SAT area were significantly associated with multiple cardiometabolic risk factors (all p < 0.05). However, the patterns of these correlations varied by sex and specific risk factors. Also, VAT and SAT FF were only significantly associated with multiple cardiometabolic risk factors in women (all p < 0.05). Conclusions: VAT, hepatic fat, pancreatic fat, and pPAT were associated with cardiovascular metabolic risk factors independent of BMI. The patterns of these correlations were related to gender. These findings further the understanding of the association between ectopic fat deposition and cardiometabolic risk factors and help to better understand the obesity heterogeneity.

Hepatic fat quantification of magnetic resonance imaging whole-liver segmentation for assessing the severity of nonalcoholic fatty liver disease: comparison with a region of interest sampling method.

BACKGROUND: Accurate and early assessment of the hepatic fat content is crucial for patients with nonalcoholic fatty liver disease (NAFLD). For years, magnetic resonance imaging (MRI) has been considered the optimal noninvasive method for the assessment of fat accumulation. To avoid time-consuming manual placement of multiple regions of interest (ROI), the use of whole-liver segmentation has been proposed to measure liver fat, mainly for heterogeneous fat deposition. However, it remains uncertain whether the hepatic mean fat fraction (FF) obtained by whole-liver segmentation with the inclusion of intrahepatic vasculature is consistent with the traditional ROI sampling method. In this study, we assessed the accuracy of hepatic mean FF obtained by whole-liver segmentation in patients of NAFLD with different severities using the ROI sampling method as a reference standard. METHODS: Hepatic FFs were measured by whole-liver segmentation and the ROI sampling method (reference standard) using MRI scanning with the iterative decomposition of water and fat with echo an asymmetry at least-square estimation-iron quantification (IDEAL-IQ) sequence. SPSS version 25.0 software was used to analyze the correlation and consistency of data between the two methods. RESULTS: There was a strong correlation in hepatic FF between whole-liver segmentation and the ROI sampling method in healthy, mild, and moderate steatosis patients (r = 0.943, 0.990, and 0.961, respectively). Bland-Altman analysis showed a small bias of +0.50±0.27 and +0.05±0.30, which indicated a small overestimation when using whole-liver segmentation in healthy subjects and mild NAFLD patients. The 95% limits of agreement ranged from +1.02 to -0.03, and from +0.65 to -0.55, respectively. However, a small bias of -0.96±0.77 was also evident, which indicated a small underestimation when using whole-liver segmentation in moderate NAFLD patients. The 95% limits of agreement ranged from +0.56 to -2.48. CONCLUSIONS: Due to inclusion of the intrahepatic vasculature, whole-liver segmentation has some effects on hepatic FF assessment in patients with different NAFLD severities; yet, it does not significantly affect the assessment of whole-liver FF in MRI FF maps.

Improvement of the bioavailability of curcumin by a supersaturatable self nanoemulsifying drug delivery system with incorporation of a hydrophilic polymer: in vitro and in vivo characterisation.

OBJECTIVES: The current study was focused on preparing curcumin (CUR) supersaturated self-nano-emulsion (PI-CUR-SNEDDS) using hydrophilic polymer and to study the influence of polymer precipitation inhibitor on the physicochemical and biopharmaceutical properties of the PI-CUR-SNEDDS. METHODS: PI-CUR-SNEDDS were prepared using hydrophilic polymer in order to maintain the supersaturation of CUR in nano-emulsion solution, artificial gastrointestinal fluid (AGF), and the precipitates formed, and characterised by in vitro dispersion tests, in vitro intestinal absorption and in vivo pharmacokinetic and compared with CUR-SNEDDS. KEY FINDINGS: PI-CUR-SNEDDS prepared with 2% hydroxypropyl methylcellulose 55-60 (HPMC55-60) as precipitation inhibitor (PI) significantly improved the viscosity, physical stability and CUR's equilibrium solubility of nanoemulsion. HPMC55-60 and CUR interact in AGF through intermolecular interactions, form hydrogen bonds, and produce amorphous precipitates. Compared with CUR-SNEDDS, the proportion of CUR in the hydrophilic phase increased by about 3-fold, and apparent permeability coefficient (Papp) in duodenum, jejunum, ileum, and colon increased by 2.30, 3.65, 1.54 and 2.08-fold, respectively, and the area under the plasma concentration-time curve0-12h of PI-CUR-SNEDDS also increased by 3.50-fold. CONCLUSIONS: Our results suggested that HPMC55-60 maintained the CUR supersaturation state by forming hydrogen bonds with CUR, increasing the solution's viscosity and drug solubilisation, thus improving the absorption and bioavailability of CUR.

Deletion of Krüppel-like factor-4 promotes axonal regeneration in mammals.

Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01).

c-Myc controls the fate of neural progenitor cells during cerebral cortex development.

The anatomical structure of the mammalian cerebral cortex is the essential foundation for its complex neural activity. This structure is developed by proliferation, differentiation, and migration of neural progenitor cells (NPCs), the fate of which is spatially and temporally regulated by the proper gene. This study was used in utero electroporation and found that the well-known oncogene c-Myc mainly promoted NPCs' proliferation and their transformation into intermediate precursor cells. Furthermore, the obtained results also showed that c-Myc blocked the differentiation of NPCs to postmitotic neurons, and the expression of telomere reverse transcriptase was controlled by c-Myc in the neocortex. These findings indicated c-Myc as a key regulator of the fate of NPCs during the development of the cerebral cortex.

[Oral microbiota and inflammatory bowel disease].

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract with a high incidence but a poor therapeutic outcome. However, IBD is generally caused by complicated interactions between environmental factors and gut microflora in genetically susceptible individuals. In view of a series of oral manifestations in patients with IBD and a high detection rate of oral bacteria among this population, oral microbiota may play an important role in the development of IBD. This article reviews the relationship between oral microbiota and IBD.

Regulation of adult mammalian intrinsic axonal regeneration by NF-κB/STAT3 signaling cascade.

The inflammatory response is a critical regulator for the regeneration of axon following nervous system injury. Nuclear factor-kappa B (NF-κB) is characteristically known for its ubiquitous role in the inflammatory response. However, its functional role in adult mammalian axon growth remains elusive. Here, we found that the NF-κB signaling pathway is activated in adult sensory neurons through peripheral axotomy. Furthermore, inhibition of NF-κB in peripheral sensory neurons attenuated their axon growth in vitro and in vivo. Our results also showed that NF-κB modulated axon growth by repressing the phosphorylation of STAT3. Furthermore, activation of STAT3 significantly promoted adult optic nerve regeneration. Taken together, the findings of our study indicated that NF-κB/STAT3 cascade is a critical regulator of intrinsic axon growth capability in the adult nervous system.

Calcium/calmodulin-dependent protein kinase II regulates mammalian axon growth by affecting F-actin length in growth cone.

While axon regeneration is a key determinant of functional recovery of the nervous system after injury, it is often poor in the mature nervous system. Influx of extracellular calcium (Ca2+ ) is one of the first phenomena that occur following axonal injury, and calcium/calmodulin-dependent protein kinase II (CaMKII), a target substrate for calcium ions, regulates the status of cytoskeletal proteins such as F-actin. Herein, we found that peripheral axotomy activates CaMKII in dorsal root ganglion (DRG) sensory neurons, and inhibition of CaMKII impairs axon outgrowth in both the peripheral and central nervous systems (PNS and CNS, respectively). Most importantly, we also found that the activation of CaMKII promotes PNS and CNS axon growth, and regulatory effects of CaMKII on axon growth occur via affecting the length of the F-actin. Thus, we believe our findings provide clear evidence that CaMKII is a critical modulator of mammalian axon regeneration.

[The relationship between reserve capacity of microcirculatory blood perfusion and related biochemical indices of male rowers in six weeks' pre-competition training].

OBJECTIVE: To study the change of reserve capacity of microcirculatory blood perfusion (MBP) and the relationship between some conventional function indices of elite male rowers in 6 weeks before the Olympic Games. The feasibility of the MBP using for athletes fu nctional status monitoring was also discussed. METHODS: Eight male lightweight rowers of Chinese National Rowing Team were selected as the subjects. Blood samples were taken every Monday morning before eating breakfast (6:30-7:00). The indices including hemoglobin (Hb), red blood cells (RBC),blood urea (BU) and creatine kinase (CK) were tested,while reserve capacity of MBP were collected with PeriFlux 5000 system on the same day. Meanwhile,the venous blood samples were collected and the levels of testosterone (T) and cortisol (C) were deter-mined in the high load training week and last two weeks before the Olympic Games. RESULTS: All presented a certain relevance between the re-serve capacity of MBP and conventional function indices. There was significant positive correlation with T (P < 0.05), and it was correlated with Hb, C and T/C positively, negative correlation with CK, and they all did not have significant difference(P > 0.05), but there was sig-nificant negative correlation with BU (P < 0.05). CONCLUSIONS: There is a certain consistency between change of reserve capacity of MBP and the characteristic of conventional function indices. And reserve capacity of MBP is more sensitive in fatigue monitoring after intensity training. In a certain extent, reserve capacity of MBP as a non-invasive indices can be used for evaluating the functional state and judging the degree of fat igue.

Influence of total flavonoids derived from Choerospondias axillaris folium on aconitine-induced antiarrhythmic action and hemodynamics in Wistar rats.

It is well known that various traditional Chinese medicines produce antiarrhythmic actions. The aims of this study were to examine whether total flavones derived from Choerospondias axillaris folium (TFCF) also produced antiarrhythmic effects using a rat model of aconitine-induced arrhythmia and to compare these observations with the effects of total flavones of Choerospondias axillaris fructus (TFC). Wistar rats were orally administered TFC (0.2 g/kg) or TFCF (0.1, 0.2, or 0.4 g/kg) daily for 7 d. Subsequently, aconitine iv at 25 µg/kg was used to induce arrhythmia in these animals. Control (C) physiological saline and positive verapamil rats were also administered orally. The starting times of ventricular ectopic beats (VE), ventricular tachycardia (VT), ventricular fibrillation (VF), and heart arrest (HA) were recorded. In comparison to C, TFCF and TFC significantly prolonged the starting time of VE, VT, VF, and HA induced by aconitine. With respect to hemodynamics, TFC and high-dose TFCF were effective in reducing HR without associated changes in BP in all groups. TFC and TFCF decreased left ventricular systolic pressure (LVSP) and maximal velocity rate of ventricular pressure (+dp/dt max and -dp/dt min) with no marked effect on left ventricular end diastolic pressure (LVEDP) and -dp/dtmin. Data demonstrated that TFCF and TFC were equally effective in diminishing the aconitine-mediated arrhythmias. In addition, TFCF and TFC produced a similar reduction in HR with no accompanying change in BP. These findings indicate that the TFCF- and TFC-induced alterations may be attributed to inhibition of ventricular contraction without altering ventricular diastolic function.

[Study on the biceps brachii microcirculation blood flow reserve capacity of the Chinese rowers].

OBJECTIVE: To investigate the effect of chronic endurance exercise on microcirculatory reserve capacity of biceps brachii in Chinese rowers and provide a certain basis for the date standard foundation of monitoring of functional status and the foundation of database of reserve capacity of blood of Chinese rowers. METHODS: Empty stomach in the morning, 77 rowers from different groups and 24 common health people were noninvasive tested by using PeriFlux System 5000, the test indexes include the microcirculatory reserve capacity and other related indexes of biceps brachii. The test sites of all athletes were the same space in biceps brachii of the right side of body, there was no space differences of all athletes . All athletes were tested in the relatively stable functional status, common people were healthy. The test value included basic values and heating values, put the before and after heating of microcirculatory blood perfusion (MBP) as the microcirculatory reserve capacity. RESULTS: Heavyweight female (198. 97 ± 98. 81) > heavyweight male (183. 45 ± 64. 31) > lightweight male (151. 01 ± 65. 96) > lightweight female(140.53 ± 43.22) > common male people(127.21 ± 56.38) > common female people(103.54 ± 33.41), the microcirculatory reserve capacity of each group athletes were higher than common people, except the comparison between lightweight female and common male people, and there was no significant difference among the different group athletes. CONCLUSION: Chronic endurance exercise can improve the microcirculatory reserve capacity of rowers, especially the heavyweight rowers; the normal value of microcirculatory reserve capacity of heavy weight rowers should be more than 160, and lightweight rowers should be more than 120. There was no significant difference among different sex athletes, if the value of microcirculatory reserve capacity is significant lower than normal, it shows that athletes are in the state of fatigue.