Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.

Acupuncture can alleviate depression-like behaviors. However, the neural mechanisms behind the anti-depressive effect remain unknown. Perineuronal net (PNN) abnormalities have been reported in multiple psychiatric disorders. This study investigated the modulation and neural mechanism of PNNs in the anti-depressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points. A rat depression model was induced by chronic unpredicted mild stress (CUMS). The results revealed that CUMS, applied for four weeks, specifically reduces PNNs around parvalbumin (PV). In addition, EA and fluoxetine treatments reverse the decrease in PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons in the medial prefrontal cortex (mPFC) after CUMS. Furthermore, EA treatment can reverse the decrease in the protein expression of PNN components (aggrecan and brevican) in the mPFC caused by stress. After EA treatment, the decreased expression of GAD67, GLuA1, and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. PNN degradation in mPFC brain areas potentially interferes with the anti-depressant benefits of EA in rats with depression induced by CUMS. EA treatment did not increase PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons after PNNs degradation in the mPFC brain region of rats. This finding indicated that the mechanism of acupuncture's anti-depressant effect may be based on reversing the CUMS-induced decline in PNN expression, the functional impairment of γ-aminobutyric acid (GABA) neurons, and the regulation of excitatory synaptic proteins expression.

Engineering Trichoderma reesei for the hyperproduction of cellulose induced protein 1 (Cip1) on a sophorose-containing inducer to efficiently saccharify alkali-pretreated corn stover.

Trichoderma reesei was induced to produce cellulase by a combination of glucose and ß-disaccharide; however, lower levels of auxiliary proteins for degrading lignocellulosic biomass were detected by iTRAQ analysis compared with cellulose as an inducer, especially cellulose induced protein 1 (CIP1). In this study, A pdc1 promoter-driven overexpression of the endogenous Trcip1 gene was observed in T. reesei Rut C30, and the Trcip1 transcription levels of the two transformants, T. reesei OE-cip1-1 and OE-cip1-2, demonstrated 31.2- and 164.6-fold increases, respectively, but there was no significant change in cellobiohydrolase, endoglucanase and filter paper activity at 48 h. The crude enzyme was then used to hydrolyze corn stover. For T. reesei OE-cip1-1 and OE-cip1-2, the hydrolysis efficiency increased by 25.0 and 28.6% with a solid loading of 5% at 2 h, respectively. Simultaneously, 85.5 and 85.2 g/L glucose were released using a cellulase cocktail at high solid loading (20%), and these glucose release rates were significantly greater than that of T. reesei Rut C30 cellulase (77.4 g/L) at 120 h. Furthermore, scanning electron microscopy (SEM) and X-ray diffraction (XRD) showed that the enhanced hydrolysis efficiency was primarily triggered by the decrease in the crystallinity of lignocellulose, and the fiber structure had varying degrees of loosening and disintegration.

Correction to: Is cell transplantation a reliable therapeutic strategy for spinal cord injury in clinical practice? A systematic review and meta-analysis from 22 clinical controlled trials.

Zhao-he and Sun-qingling are the co-first authors for this manuscript in the initial submission. Because of author's negligence and fault, this information was not shown clearly in the originally published article.

Is cell transplantation a reliable therapeutic strategy for spinal cord injury in clinical practice? A systematic review and meta-analysis from 22 clinical controlled trials.

PURPOSE: It is an open question whether cell transplantation can provide safety and effective outcome to spinal cord injury (SCI) patient which has remained controversial for almost 40 years. This study aimed to evaluate the safety and efficacy of cell transplantation in SCI patients. METHOD: Studies of the cell transplantation for SCI were retrieved from PubMed, Embase, Medline, Cochrane Library and analyzed quantitative data by Review Manager 5.3. RESULTS: Twenty-one clinical controlled studies with 973 patients were included. The pooled results suggested that cell transplantation significantly improved ASIA score, ASIA motor score, ASIA sensory score, Barthel Index score, residual urine volume, rehabilitative time of automatic micturition. Furthermore, subgroup analysis indicated that the stem cells exhibited more potent than the non-stem cells in spinal cord repair. Cell transplantation at more than 14 days after injury showed more significant improvements than that within 14 days from injury. The dosage of cell transplantation between 1-5 × 107 and 10-20 × 107 was the potent quantity for the patient with SCI. Intrathecal injection and intravenous + intrathecal injection showed more superior to the other method. The top 5 adverse events were febrile reaction (11.5%), neurologic pain (11.3%), headache (2.6%), neurologic deterioration (2.4%), and rigidity or spasticity (1.6%). CONCLUSION: Cell transplantation appears to be a safe therapeutic strategy possessing substantial beneficial effects in the patients with SCI in clinic. Moreover, treating SCI with stem cell, the dosage of cells between 1-5 × 107 and 10-20 × 107, in intermediate or chronic phase, minimally invasive techniques, may bring more advantage to SCI patient. These slides can be retrieved under Electronic Supplementary Material.

Qingkailing injection ameliorates cerebral ischemia-reperfusion injury and modulates the AMPK/NLRP3 Inflammasome Signalling pathway.

BACKGROUND: Cerebral ischemia is the second-leading cause of death and the main cause of permanent adult disabilities worldwide. Qingkailing (QKL) injection, a patented Chinese medicine approved by the China Food and Drug Administration, has been widely used in clinical practice to treat cerebral ischemia in China. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is activated in cerebral ischemia and thus, is an effective therapeutic target. AMP-activated protein kinase (AMPK) is an important regulator inhibiting NLRP3 inflammasome activation. METHODS: We investigated the potential of QKL injection to provide neuroprotection after cerebral ischemia in a rat model of middle cerebral artery occlusion (MCAO). Adult male Sprague-Dawley rats (210-230 g) were randomly divided into three groups which consist of sham, MCAO and 3 ml/kg QKL. Rats in the QKL group received intraperitoneal injections of 3 ml/kg QKL, while rats in other groups were given saline in the same volumes. After 90 min ischemia and 24 h reperfusion, neurological function, laser speckle imaging, brain infarction, brain water content and brain blood barrier permeability were examined and cell apoptosis at prefrontal cortex were evaluated 24 h after MCAO, and western blot and real-time quantitative polymerase chain reaction was also researched, respectively. RESULTS: Intraperitoneal administration of QKL alleviated neurological deficiencies, cerebral infarction, blood-brain barrier permeability, brain oedema and brain cell apoptosis after MCAO induction. QKL decreased pro-inflammatory cytokines, TNF-α, IL-6 and IL-1ß, and increased anti-inflammatory cytokines, IL-4 and IL-10. Furthermore, QKL activated phosphorylated AMPK, decreased oxidative stress and decreased NLRP3 inflammasome activation. CONCLUSIONS: QKL relieved cerebral ischemia reperfusion injury and suppressed the inflammatory response by inhibiting AMPK-mediated activation of the NLRP3 inflammasome. These results suggest that QKL might have potential in treating brain inflammatory response and attenuating the cerebral ischemia-reperfusion injury.

[Effects of baldrinal of Valeriana jatamansi on expression of CRF, TPH1 mRNA and 5-HT in rats with irritable bowel syndrome].

This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group. The IBS rat models were established by using unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest and independent feeding. CRF expression was detected by IHC-P; TPH1 mRNA expression was detected by using RT-PCR and the 5-HT level was measured by high performance liquid chromatography(HPLC). The results indicated that the method of chronic stress with acute restrain stress method and independent feeding could lead to the increase in expressions of CRF and TPH1 mRNA and levels of 5-HT in IBS rats(P<0.05). The expressions of CRF, TPH1 mRNA and 5-HT in baldrinal groups were significantly lower than those in model group(P<0.05). The experimental results showed that IBS could result in increase in the expressions of CRF, TPH1 mRNA and levels of 5-HT, and the baldrinal of V. jatamansi could improve the symptoms of IBS by reducing the expressions of CRF, TPH1 mRNA and levels of 5-HT in colon of rats.

Influence of Sanao Tang on urine volume and expression of aquaporin 2 in rats with respiratory function impairment induced by passive smoking and lipopolysaccharide.

OBJECTIVE: To investigate the effect of Sanao Tang (SAT) on urine volume and the expression of aquaporin- 2 (AQP2) in rats with lung dysfunction induced by passive smoking and lipopolysaccharide. METHODS: Totally 45 healthy Specific pathogen Free Wistar Rats were randomized into 3 groups: normal control group, model group and SAT group. A rat model of respiratory dysfunction induced by exposure to cigarette smoking and lipopolysaccharide (LPS). Lavage of decoction of the Chinese medicine was performed for rats in the SAT group. Anires 2005 System was used to analyze the pulmonary function. Urine of rats was collected through metabolism cage method. Enzyme-linked immunosorbent assay (ELISA) was used to determine content of antidiuretic hormone (ADH), angiotensin Ⅱ (AngⅡ), atrial natriuretic factor (ANP), endothelin 1 (ET-1), nitric oxide (NO) and prostaglandin E2 (PGE2) in serum, lung and kidney. The expression of AQP2 in rat renal tissue was determined with real-time fluorescence quantitative PCR (RT-PCR). RESULTS: (a) In comparison with the normal control, It was found that enforced vital capacity (FVC), 1-second forced expiratory volume/forced vital capacity% (FEV(1)/FVC%), 24 h urine volume content of NO and PGE2 were decreased, while AQP2mRNA level and content of ADH, Agn Ⅱ, ANP and ET-1 were increased in the model group with statistical significance (P < 0.05). (b) In comparison with the model group, It was found that FVC, FEV(1), FEV(1)/FVC%, 24 h urine volume, content of PGE2 and NO decreased, while AQP2mRNA level, content of ANP, ADH and Ang Ⅱ decreased in the SAT group with statistical significance (P < 0.05). CONCLUSION: SAT might effectively regulate the urine volume in the modeled rats; ADH, Ang Ⅱ, ANP, ET-1, NO and PGE2 might play an important role in the regulation on urine volume by lungs. This might be the mechanisms underpinning the function of lung governing water passage in terms of the theory of Traditional Chinese Medicine.

Prevention of retrograde peri-implantitis caused by pulpal/periapical lesions in adjacent teeth: A literature review.

OBJECTIVES: To present a comprehensive review on retrograde peri-implantitis (RPI), focusing on its epidemiology, etiology, clinical manifestations, classification, treatment, and prevention strategies. DATA: The widespread development of implantology has led to heightened concerns regarding implant failure attributed to peri-implantitis (PI). In contrast to conventional PI, retrograde peri-implantitis (RPI), defined as inflammation originating from the apical of the implant towards the crown, has gained increasing attention. Various factors can contribute to RPI, among which untreated pulpal or periapical lesions from adjacent teeth are considered as main causes. SOURCES AND STUDY SELECTION: Using PubMed as the source for eligible literature, a total of 73 cases (from 36 articles) were identified for review. The search items are (["retrograde peri-implantitis" OR "periapical peri-implantitis" OR "peri-apical implant lesion*"] AND ["risk factor*" OR "treatment*" OR "prevent*"]). CONCLUSIONS: Currently, clinicians often inadequately address the evaluation and management of pulpal or periapical lesions in the adjacent teeth in RPI, neglecting its causes and further the preventive measures. Overall, RPI influences the success of dental implants and therefore valid diagnosis and prevention are obligatory. Until now, there has been no relative instructions for clinicians. Moreover, new research directions (e.g. molecular biology and immunology) as well as innovative treatment (e.g. lasers and novel materials) may facilitate the precise prevention and early diagnosis of RPI.

Enhanced glucose-1-phosphate production from corn stover using cellulases with reduced ß-glucosidase activity via Trbgl1 gene knockout in Trichoderma reesei Rut C30.

The scarcity of cellulases with low ß-glucosidase activity poses a significant technological challenge in precisely controlling the partial hydrolysis of lignocellulose to cellobiose, crucial for producing high-value chemicals such as starch, inositol, and NMN. Trichoderma reesei is a primary strain in cellulase production. Therefore, this study targeted the critical ß-glucosidase gene, Trbgl1, resulting in over an 86 % reduction in ß-glucosidase activity. However, cellulase production decreased by 19.2 % and 20.3 % with lactose or cellulose inducers, respectively. Notably, transcript levels of cellulase genes and overall yield remained unaffected with an inducer containing sophorose. This indicates that ß-glucosidase BGL1 converts lactose or cellulose to sophorose through transglycosylation activity, inducing cellulase gene transcription. The resulting enzyme cocktail, comprising recombinant cellulase and cellobiose phosphorylase, was applied for corn stover hydrolysis, resulting in a 24.3 % increase in glucose-1-phosphate yield. These findings provide valuable insights into obtaining enzymes suitable for the high-value utilization of lignocellulose.

Electroacupuncture ameliorates cognitive impairment in APP/PS1 mouse by modulating TFEB levels to relieve ALP dysfunction.

Recently, the underlying mechanisms of acupuncture on the effects of Alzheimer's disease (AD) treatment have not been fully elucidated. Defects in ALP (autophagy-lysosomal pathway) and TFEB (transcription factor EB) play critical roles in AD. Our previous studies have demonstrated that electroacupuncture (EA) can ameliorate both ß-amyloid (Aß) pathology and cognitive function in APP/PS1 mice. However, the effects of EA on the expression of ALP and TFEB and their potential mechanisms require further investigation. Twenty-eight male APP/PS1 mice were randomly divided into Tg and Tg + EA groups, and 14 C57BL/6 mice served as the wild-type (WT) group. After 1 week of adaptation to the living environment, mice in the Tg + EA group were restrained in mouse bags and received manual acupuncture at Baihui (GV20) acupoint and EA stimulation at bilateral Yongquan (KI1) acupoints, using the same restraint method for WT and Tg groups. The intervention was applied for 15 min each time, every other day, lasting for six weeks. After intervention, the spatial learning and memory of the mice was assessed using the Morris water maze test. Hippocampal Aß expression was detected by immunohistochemistry and ELISA. Transmission electron microscopy (TEM) was used to observe autophagic vacuoles and autolysosomes in the hippocampus. Immunofluorescence method was applied to examine the expression of TFEB in CA1 region of the hippocampus and the co-localization of CTSD or LAMP1 with Aß. Western blot analysis was performed to evaluate the changes of LC3, p62, CTSD, LAMP1, TFEB and n-TFEB (nuclear TFEB) in the hippocampus. The findings of behavioral assessment indicated that EA alleviated the cognitive impairment of APP/PS1 mice. Compared with the WT group, the Tg group showed significant cognitive decline and abnormalities in ALP and TFEB function (P < 0.01 or P < 0.05). However, these abnormal changes were alleviated in the Tg + EA group (P < 0.01 or P < 0.05). The Tg group also showed more senile plaques and ALP dysfunction features, compared with the WT group, and these changes were alleviated by EA. In conclusion, this study highlights that EA ameliorated Aß pathology-related cognitive impairments in the APP/PS1 model associated with ALP and TFEB dysfunction.

A multi-target protective effect of Danggui-Shaoyao-San on the vascular endothelium of atherosclerotic mice.

BACKGROUND: Atherosclerosis (AS) is a chronic disease characterized by abnormal blood lipid metabolism, inflammation and vascular endothelial injury. Vascular endothelial injury is the initial stage during the occurrence of AS. However, the function and mechanism of anti-AS are not well characterized. Danggui-Shaoyao-San (DGSY) is a classic Traditional Chinese Medicine (TCM) prescription for the treatment of gynecological diseases, and has been widely used in the treatment of AS in recent years. METHODS: ApoE-/- atherosclerosis male mice were established by feeding with high-fat diet, and then randomly divided into three groups: Atherosclerosis group (AS), Danggui-Shaoyao-San group (DGSY), and Atorvastatin calcium group (X). The mice were administered with the drugs for 16 weeks. Pathological changes in aortic vessels were examined by staining with Oil red O, Masson and hematoxylin-eosin. In addition, blood lipids were analyzed. The level of IL-6 and IL-8 in aortic vessels were detected by ELISA and the expression of ICAM-1 and VCAM-1 in the aortic vascular endothelium were measured by Immunohistochemical. The mRNA expression of interα5ß1/c-Abl/YAP in the aortic vessels were measured by Real-time quantitative PCR and location of expression was assessed by immunofluorescence. RESULTS: DGSY can significantly reduce the content of TC,TG and LDL-C and increase the level of HDL-C in the serum, reduce the plaque area and inhibit the concentration of IL-6 and IL-8, down-regulate the expression of IVAM-1,VCAM-1 and interα5ß1/ c-Abl/YAP in the aortic vessels. CONCLUSIONS: Collectively, DGSY can alleviate vascular endothelium damage and delay the occurrence of AS, and the underlying mechanism may be related to the multi-target protective of DGSY.

[Electroacupuncture at "Baihui"（GV20） and "Yongquan"（KI1） improves learning-memory ability of APP/PS1 double transgenic mice by regulating endosomal-lysosomal system].

OBJECTIVE: To explore the mechanism of electroacupuncture（EA） in improving learning-memory ability in Alzheimer's disease （AD） mice from the perspective of endosomal-lysosomal system. METHODS: Male APP/PS1 transgenic mice were randomly divided into model group and EA group （n=10 in each group） and 10 male C57BL/6 wild mice were taken as the normal group. EA （1 Hz/50 Hz, 1 mA） was applied at bilateral "Yongquan"（KI1） and acupuncture was applied at "Baihui" （GV20） for 15 min. The mice of the model and normal groups were subjected to restriction with the same method as those of the EA group for 15 min. The treatment was conducted once every other day for 6 weeks. The spatial learning-memory ability （shown by escape latency of place navigation test and the time of crossing the target platform and total swimming distance in the target quadrant in 1 min of spatial probe test ） was detected by Morris water maze test. The immunoactivity of senile plaques （SP） in the hippocampus tissue was detected by immunohistochemistry. The ultrastructural characters of hippocampal neurons were observed by transmission electron microscope, and the expression levels of Ras-related protein 5 （Rab5）, Ras-related protein 7 （Rab7） and cathepsin D （CTSD） in the hippocampus were detected by Western blot, separately. RESULTS: Compared with the normal group, the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD were significantly increased （P<0.05, P<0.01）, while the number of crossing the original platform and the total swimming distance in the platform quadrant were considerably reduced （P<0.05） in the model group. In contrast to the model group, the EA group had a marked decrease in the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD （P<0.05, P<0.01）, and a striking increase in the number of crossing the original platform and the swimming distance in the platform quadrant （P<0.05）. Results of transmission electron microscope showed an accumulation of endosome, lysosome, and endolysosomes in the hippocampal neurons in the model group, which was evidently milder in the EA group. CONCLUSION: EA of GV20 and KI1 can improve the learning-memory ability of AD mice, which may be related to its function in reducing hippocampal Aß deposition and down-regulating endosomal-lysosomal system activity.

Green synthetic natural carbon dots derived from Fuligo Plantae with inhibitory effect against alcoholic gastric ulcer.

Introduction: Fuligo Plantae (FP), the ash that sticks to the bottom of pots or chimneys after weeds burn, has long been used for its hemostatic effects and treatment of gastrointestinal bleeding. Nevertheless, the active ingredient of FP still needs to be further explored. Methods: The microstructure, optical and chemical properties of FP-CDs were characterized. An alcohol-induced gastric ulcer model was utilized to evaluate whether pre-administration of FP-CDs alleviated gastric bleeding symptoms and ameliorated gastric mucosal barrier disruption. In addition, the feces of each group of rats were extracted for 16S rDNA genome sequencing of intestinal flora. Results: FP-CDs with a diameter ranging from 1.4-3.2 nm had abundant chemical groups, which may be beneficial to the exertion of inherent activity. FP-CDs alleviated alcohol-induced gastric ulcer, as demonstrated by activating the extrinsic coagulation pathway, alleviating inflammation, and suppressing oxidative stress levels. More interestingly, FP-CDs can improve the diversity and dysbiosis of intestinal flora in rats with alcohol-induced gastric ulcer. Conclusion: These comes about illustrate the momentous inhibitory effects of FP-CDs on alcoholic gastric ulcer in rats, which give a modern methodology for investigating the effective ingredient of FP, and lay an experimental basis for the application of FP-CDs in the clinical treatment of alcoholic gastric ulcer.

The injuries of spleen and intestinal immune system induced by 2-Gy 60Co γ-ray whole-body irradiation.

PURPOSE: The aim of the present study was to investigate the injuries of spleen and intestinal immune system induced by 2 Gy 60Co γ ray in mice. MATERIALS AND METHODS: A total of 120 Balb/c mice were randomly divided into two groups: blank control (Ctrl) and model (IR). The IR mice were exposed to a single dose of total body irradiation (2 Gy, dose rate: 1 Gy/min) and sacrificed on 1st, 3rd, 7th, 14th and 21st day after irradiation. The indicators including general observations and body weight, the changes in peripheral hemogram, spleen index, histopathology examination and lymphocyte subsets of spleen. As well as the count and subsets of lymphocyte in gut-associated lymphoid tissue. RESULTS: Compared with the Ctrl group, the body weight, spleen index, peripheral blood cell and splenocyte amounts, intraepithelial lymphocytes number decreased significantly after exposure, accompanied by a notable decreased count of lymphocytes in Peyer's patch and mesenteric lymph nodes. Moreover, ionizing radiation also broke the balance of CD4+/CD8+ and increased the Treg proportion in spleen, which then triggered immune imbalance and immunosuppression. In general, the spleen injuries occurred on 1st day after exposure, worse on 3rd day, and were relieved on 7th day. The intestinal immune injuries were observed on 1st day, and attenuated on 3rd day. On 21st day after exposure, the spleen volume and index have returned to normal, except for the distribution of lymphocyte subpopulations. Furthermore, all indicators of gut-associated lymphoid tissue, except for mesenteric lymph nodes lymphocyte count, had returned to normal levels on 21st day. CONCLUSION: In conclusion, our data showed the injuries of spleen and intestinal immune system induced by 2 Gy 60Co γ ray whole-body irradiation. These findings may provide the bases for further radiation protection in the immunity.

Histological Changes of Cervical Disc Tissue in Patients with Degenerative Ossification.

OBJECTIVE: To explore the histological feature of the cervical disc degeneration in patients with degenerative ossification (DO) and its potential mechanisms. METHODS: A total of 96 surgical segments, from cervical disc degenerative disease patients with surgical treatment, were divided into ossification group (group O, n=46) and non-ossification group (group NO, n=50) based on preoperative radiological exams. Samples of disc tissues and osteophytes were harvested during the decompression operation. The hematoxylin-eosin staining, Masson trichrome staining and Safranin O-fast green staining were used to compare the histological differences between the two groups. And the distribution and content of transforming growth factor (TGF)-ß1, p-Smad2 and p-Smad3 between the two groups were compared by a semi-quantitative immunohistochemistry (IHC) method. RESULTS: For all the disc tissues, the content of disc cells and collagen fibers decreased gradually from the outer annulus fibrosus (OAF) to the central nucleus pulposus (NP). Compared with group NO, the number of disc cells in group O increased significantly. But for proteoglycan in the inner annulus fibrosus (IAF) and NP, the content in group O decreased significantly. IHC analysis showed that TGF-ß1, p-Smad2, and p-Smad3 were detected in all tissues. For group O, the content of TGF-ß1 in the OAF and NP was significantly higher than that in group NO. For p-Smad2 in IAF and p-Smad3 in OAF, the content in group O were significantly higher than group NO. CONCLUSION: Histologically, cervical disc degeneration in patients with DO is more severe than that without DO. Local higher content of TGF-ß1, p-Smad2, and p-Smad3 are involved in the disc degeneration with DO. Further studies with multi-approach analyses are needed to better understand the role of TGF-ß/Smads signaling pathway in the disc degeneration with DO.

Amniotic fluid and urine metabolomic alterations associated with pregnant women with Down syndrome fetuses.

BACKGROUND: Down syndrome (DS) is a chromosomal disorder caused by a third copy of all or part of chromosome 21. Clinical observations and preclinical studies both suggest that DS may be associated with significant metabolic and bioenergetic alterations. But the metabolic alterations in pregnant women carrying DS fetuses still remains unclear. In this study, we investigated the characteristic metabolomics and lipidomics changes during fetal development of DS. METHODS: The AF and random urine specimens were selected from 20 pregnant women carrying DS fetuses and 20 pregnant women carrying healthy fetuses. The diagnosis of DS was screened according to chromosome karyotype analysis, and untargeted metabolomic and lipidomic analyses were performed. RESULTS: Through the analyses of AF, 308 differential metabolites were selected between DS and controls. The metabolites with significant changes mainly involved lipid molecules, organic acids, nucleotides and carbon. Further analysis of lipidomics showed 64 differential metabolites, mainly involving glycerides, sphingolipids and glycerolipids. As for urine metabolomic and lipidomic analyses, there existed consistent metabolites with AF, but the number was much less. CONCLUSIONS: Compared with the controls, carbon metabolism, amino acid metabolism, glyceride metabolism, sphingolipid metabolism and glycerophospholipid metabolism were significantly changed in DS cases. In addition, characterized biomarkers in AF and urine were screened for DS diagnosis, and these metabolites were mainly involved in energy metabolism and liver dysfunction. This finding may help improve the efficiency of prenatal screening for DS.

Study on the Shear Modulus Based Equivalent Homogenization Methods of Multi-Layer BCC Lattice Sandwich.

In this paper, the shear modulus based equivalent homogenization methods of multi-layer BCC (body-centered cubic) lattice sandwich structures have been studied using analytical, experimental, and finite element methods. In the analytical approach, the multiple strut-deformation patterns were introduced in the derivations of the shear modulus based on Euler-Bernoulli beam theory and Timoshenko beam theory according to different boundary conditions. The analytical shear modulus of three types of rectangle shaped sandwich BCC lattice structures was derived. Finite element models of the BCC lattice structures by ANSYS were conducted to estimate the analytical solutions. Butterfly style sandwich BCC lattice structures were printed by SLM technology using 304 stainless steel (06Cr19Ni10), and corresponding shear experiments using modified Arcan Rig experimental devices were conducted to validate the analytical and numerical calculations. Good agreements were observed among the analytical, numerical, and experimental results.

[Effects of electroacupuncture on the expression of ß-amyloid and autophagy-related proteins in hippocampal cells of mice with Alzheimer's disease].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on the expression of ß-amyloid (Aß) and autophagy-related proteins in hippocampal cells of Alzheimer's disease (AD) model mice, so as to explore its underlying mechanisms. METHODS: Eighteen male APP/PS1 transgenic mice (6 months old) were randomly divided into model and EA groups, with 9 mice in each group. Nine male C57BL/6 wild-type mice of the same age were chosen as the normal group. Mice in the EA group were treated with acupuncture on "Baihui" (GV20) and EA (1 Hz/50 Hz, 1 mA) on bilateral "Yongquan" (KI1), once every other day, 20 min each time for a total of 21 times. After the interventions, the spatial learning and memory ability were observed by Morris water maze test. The autophagy-related pathological changes in hippocampus were observed by transmission electron microscopy. The expressions of microtublue associated protein 1 light chain 3 (LC3) and Aß in hippocampus were observed by immunofluorescence and the expression levels of LC3 and p62 proteins were detected by Western blot. RESULTS: Compared with the normal group, the escape latency was prolonged (P<0.01), the residence time in the original quadrant platform was shor-tened (P<0.05), the positive expressions of LC3 and Aß, the expression levels of LC3Ⅱ and p62 proteins, and the ratio of LC3Ⅱ/LC3Ⅰ proteins in hippocampus were increased (P<0.01, P<0.05) in the model group. Compared with the model group, the escape latency was shortened (P<0.05), the residence time in the original quadrant platform was prolonged (P<0.05), the positive expressions of LC3 and Aß, the expression levels of LC3Ⅱ and p62 proteins, and the ratio of LC3Ⅱ/LC3Ⅰ proteins in hippocampus were decreased (P<0.05) in the EA group. The transmission electron microscopy showed that the structure of neurons was normal in the normal group, a large number of autolysosomes and autophagosomes existed in hip-pocampal nerve cells in the model group, and only a small number of autophagosomes were observed in the EA group. CONCLUSION: EA can reduce the expression levels of autophagy-related proteins LC3 and p62 in APP/PS1 transgenic mice, improve the hip-pocampal autophagy state, reduce intracellular Aß aggregation, and thus improve the learning and memory ability.

NLRP3 neuroinflammatory factors may be involved in atopic dermatitis mental disorders: an animal study.

Background: Numerous clinical studies have shown that atopic dermatitis (AD) is often associated with mental disorders. This could contribute to the overall burden of atopic dermatitis. However, the underlying mechanism of mental health symptoms in AD has not been fully elucidated. Methods: An AD mouse was induced by 2,4-dinitrofluorobenzene (DNFB), which was repeatedly applied to the back skin of the BALB/C mice to establish an atopic dermatitis mental disorder model. The role of neuroinflammation in the pathogenesis of atopic dermatitis mental disorders was then explored. Results: After the stimulation of DNFB for 35 days, the skin lesions, the HE staining of skin lesions, and the behavioral experiments (including elevated plus maze assay and tail suspension test) suggested that the AD mental disorder mouse model was successfully replicated. The expression of neuroinflammatory factors in the hippocampus was then investigated through Western blotting. The results showed a significant increase in the protein expression of NLRP3, caspase-1, and IL-1ß. Conclusion: Mental disorders in AD might be related to the neuroinflammatory response in the hippocampus. An alternative yet essential approach to promoting AD recovery could be through reducing neuroinflammation and improving mental disorders.

Yiqi Jiedu herbal decoction attenuates the 2 Gy 60Co γ ray induced spleen injury by inhibiting apoptosis and modulating the immune balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Irradiation-induced immunosuppression often occurs during radiotherapy in patients, which would increase the risk of opportunistic infections. Many Chinese herbal prescriptions or natural extracts have recently attracted increased radiation protection and therapy attention due to their low toxicity. AIM OF THE STUDY: The present study aimed to investigate the protective effects of Yiqi Jiedu (YQJD) decoction on spleen injury induced by 2 Gy 60Co γ ray in mice. MATERIALS AND METHODS: A total of 180 Balb/c mice were randomly divided into five groups: blank control (Ctrl), model (IR), positive drug (IRA), low-dose YQJD decoction (IRL), and high-dose YQJD decoction (IRH). After a ten-day intervention, mice were exposed to a single dose of total body irradiation (2 Gy) and sacrificed on the 1st, 3rd, and 7th day after irradiation. The indicators include general observations and body weight, changes in peripheral hemogram, index and histopathology examination of the spleen, distribution of lymphocyte subsets, cytokine levels, and apoptosis in the spleen. RESULTS: In comparison to the Ctrl group, the body weight, spleen index, peripheral blood cell, and splenocyte quantities decreased significantly after exposure, accompanied by a notable increase of apoptosis in spleen cells. Moreover, ionizing radiation also broke the balance of CD4+/CD8+, Th1/Th2, and Th17/Treg, triggering immune imbalance and immunosuppression. The above injuries occurred on the 1st day after exposure, worsened on the 3rd, and were relieved on the 7th day. However, the pretreatment of YQJD decoction increased the spleen index, improved the spleen structure, and inhibited radiation-induced apoptosis after exposure. Additionally, YQJD decoction has shown its ability to promote immunological balance recovery following exposure by regulating CD4+/CD8+, Th1/Th2, and Th17/Treg ratios, which may minimize the risk of infection. In addition, the high-dose of YQJD decoction showed a better protective effect than the low-dose group. CONCLUSION: The protective effects of YQJD decoction on 2 Gy 60Coγray induced spleen injury were confirmed in this study. This mechanism may be related to inhibiting apoptosis and modulating immune balance. This exploration might provide new insights into the use of Chinese herbs on radioprotection of the immune system.