MATERIAL AND METHODS: Thirty Sprague Dawley rats (3-monthold, 200 to 300 gm) were randomly divided into six groups, namely control (C), 4 weeks diabetes mellitus (DM1), 8 weeks DM (DM2) and three DM1 groups (VD1, VD2, and VD3) who received Vitamin D doses of 0.125, 0.25 and 0.50 μg/kg BW, respectively. After 4 weeks, daily VD was administered intraperitoneally for 30 days. Lung tissues were taken for IL- 6, MCP-1, NFKB and CD68 mRNA expression analysis and paraffin embedding. Immunohistochemical staining against CD68 and MCP-1 was conducted. Data were analysed using one-way ANOVA. p < 0.05 was considered statistically significant.
RESULTS: DM2 group represented significantly higher IL6, MCP1, NFKB and CD68 mRNA expression than Control group (p < 0.05). Meanwhile, VD2 and VD3 groups revealed significantly lower mRNA expression of IL-6, MCP1, NFKB and CD68 than DM2 (p < 0.05). Immunostaining revealed the spreading of MCP1 protein expression in lung tissue along with macrophage infiltration in the DM2 group, which was reduced in the VD2 and the VD3 groups.
CONCLUSION: VD shows a protective effect on diabetesinduced lung damage by regulating inflammation factors.
MATERIALS AND METHODS: This was a randomised post-testonly study. A total of 28 rats were assigned into four groups: Group 1 is control group (C), samples had bile duct ligation and UDCA monotherapy 20 mg; Group 2, bile duct ligation + UDCA 10 mg + glutathione 10 mg (P1); Group 3, bile duct ligation + UDCA 20 mg + glutathione 15 mg (P2); Group 4, bile duct ligation + UDCA 30 mg + glutathione 20 mg (P3). Serum AST, ALT, ALP activity, total, direct and indirect bilirubin were collected. Shapiro-Wilk test was used for the normality test. All groups' data were compared using Kruskall-Wallis and Mann-Whitney tests.
RESULTS: There was a significant difference in the ALP level in all rats and between the C and P2 groups. ALP level of all groups decreased significantly compared to the control group. Combination therapy group showed lower bilirubin levels. ALT levels significantly differed between the C-P1, P1-P2, and P1-P3 groups.
CONCLUSION: UDCA-GSH therapy improves liver function in BDL rats' models compared to UDCA monotherapy.
MATERIALS AND METHODS: TGBII was performed in male Wistar rats (3 to 5 months, 150 to 300 g) which underwent bilateral common carotid artery occlusion (BCCAO) for 20 minutes, then reperfused for 10 days (BCCAO group, n = 6). Two groups of BCCAO were treated with intraperitoneal injection of calcitriol 0.125 μg/kgBW (VD1 group) and 0.5 μg/kgBW (VD2 group). The spatial memory function was tested using a probe test with Morris water maze (MWM). mRNA expression of BAX and SOD2 were assessed by the RT-PCR method. Meanwhile, immunohistochemical staining was used for identification of SOD2 protein. Statistical analysis is tested using one-way ANOVA followed by post-hoc LSD.
RESULTS: MWM showed a shorter duration in target quadrant of BCCAO group than the SO group, which is associated with BAX upregulation and SOD2 downregulation. The VDtreated groups had longer duration probe test compared to BCCAO. Furthermore, VD-treated groups had a longer duration in probe test with lower mRNA expression of BAX and higher expression of SOD2. However, there was no significant difference in VD1 and VD2. Immunostaining showed a reduced SOD2 signal in pyramidal cell of CA1 area in BCCAO group and ameliorated in VD1 and VD2 groups.
CONCLUSION: Vitamin D ameliorates memory function and attenuates oxidative stress and apoptosis in the TGBII model.
METHODS: The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively.
RESULTS: During the nootropic phase, treatment groups demonstrated a significant (P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (P < 0.05) in a dose-dependent manner.
CONCLUSION: This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.
METHODS: Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites' length, and the prefrontal cortex's spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR.
RESULTS: Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P < 0.05).
CONCLUSION: Acupuncture can ameliorate depressive-like behaviors by promoting the recovery of neural plasticity functions and neural plasticity-related protein upregulation in the prefrontal cortex of CUMS-induced depressed rats. Our study provides new insights into the antidepressant approach, and further studies are warranted to elucidate the mechanisms of acupuncture involved in depression treatment.
RECENT FINDINGS: Advance in the imaging study provides more accurate assessment of fMMC in utero. Prenatal maternal--fetal surgery in fMMC demonstrates favourable postnatal outcome. Minimally invasive fetal surgery minimizes uterine wall disruption. Endoscopic fetal surgery is performed via laparotomy-assisted or entirely percutaneous approach. The postnatal outcome for open and endoscopic fetal surgery shares no difference. Single layer closure during repair of fMMC is preferred to reduce postnatal surgical intervention. All maternal--fetal surgeries impose anesthetic and obstetric risk to pregnant woman. Ruptured of membrane and preterm delivery are common complications. Trans-amniotic stem cell therapy (TRASCET) showed potential tissue regeneration in animal models. Fetal tissue engineering with growth factors and dura substitutes with biosynthetic materials promote spinal cord regeneration. This will overcome the challenge of closure in large fMMC. Planning of the maternal--fetal surgery should adhere to ethical framework to minimize morbidity to both fetus and mother.
SUMMARY: Combination of endoscopic fetal surgery with TRASCET or tissue engineering will be a new vision to achieve to improve the outcome of prenatal intervention in fMMC.
PURPOSE: To explore the underlying mechanism of AP in exerting anti-fatigue effects.
METHODS: In this study, we developed a chronic sleep deprivation-induced fatigue model and used physiological, hematological, and biochemical indicators to evaluate the anti- fatigue efficacy of AP. Additionally, a multi-omics approach was employed to reveal the anti-fatigue mechanisms of AP from the perspective of microbiome, metabolome, and proteome.
RESULTS: The detection of physiology, hematology and biochemistry index indicated that AP markedly alleviate mice fatigue state induced by sleep deprivation. The 16S rRNA sequencing showed the AP promoted the abundance of probiotics (Odoribacter, Dubosiella, Marvinbryantia, and Eubacterium) and suppressed harmful bacteria (Ruminococcus). On the other hand, AP was found to regulate the expression of colonic proteins, such as increases of adenosine triphosphate (ATP) synthesis and mitochondrial function related proteins, including ATP5A1, ATP5O, ATP5L, ATP5H, NDUFA, NDUFB, NDUFS, and NDUFV. Serum metabolomic analysis revealed AP upregulated the levels of anti-fatigue amino acids, such as taurine, leucine, arginine, glutamine, lysine, and l-proline. Hepatic proteins express levels, especially tricarboxylic acid (TCA) cycle (CS, SDHB, MDH2, and DLST) and redox-related proteins (SOD1, SOD2, GPX4, and PRDX3), were significantly recovered by AP administration. Spearman correlation analysis uncovered the strong correlation between microbiome, metabolome and proteome, suggesting the anti-fatigue effects of AP is attribute to the energy homeostasis and redox balance through gut-liver axis.
CONCLUSION: AP increased colonic ATP production and improve mitochondrial function by regulating gut microbiota, and further upregulated anti-fatigue amino acid levels in the blood. Based on the gut-liver axis, AP upregulated the hepatic tricarboxylic acid cycle and oxidoreductase-related protein expression, regulating energy homeostasis and redox balance, and ultimately exerting anti-fatigue effects. This study provides insights into the anti-fatigue mechanisms of AP, highlighting its potential as a therapeutic agent.
Methods: Mice (n = 48) were fed high-fat diet (HFD) for 25 weeks to induce obesity, after which half were maintained on HFD and half switched to low-fat diet (LFD)while they were given normal water (H2O) or 0.1% (w/v) SCE in water at week 0-4 which was increased to 1% (w/v) at week 5-9. Effects of treatment with SCE were compared between HFDH2O, HFDSCE, LFDH2O and LFDSCE groups. Respiratory exchange ratios (RER) were measured at weeks 0, 5 and 10. Food, water intake and body weight were measured weekly. Plasma lipid profile and organ weights were determined at week 10.
Results: SCE had significantly reduced RER at week 9 (P = 0.011). Food intake, body weight, and abdominal adipose tissue weight were not altered by SCE at weeks 5 and 10. However, significant increase in plasma and liver cholesterol (P < 0.050) was observed.
Conclusion: Our findings suggest that SCE induced lipolysis and body fat oxidation and increased energy expenditure. Further studies in other animal models should be done to confirm the consistency of these results.
Methods: Using a pilocarpine-induced epileptic mouse model, sensory-motor and visual cortical slices were prepared, and the whole-cell patch clamp technique was used to record spontaneous inhibitory post-synaptic currents (sIPSCs).
Results: The primary finding was that the mean amplitude of sIPSC from the sensory-motor cortex increased significantly in epileptic mice when the recording pipette contained MK-801 compared to control mice, whereas the mean sIPSC frequency was not significantly different, indicating that post-synaptic mechanisms are involved. However, there was no significant pre-synaptic inhibition through preNMDARs in the acute brain slices from pilocarpine-induced epileptic mice.
Conclusion: In the acute case of epilepsy, a compensatory mechanism of post-synaptic inhibition, possibly from ambient GABA, was observed through changes in the amplitude without significant changes in the frequency of sIPSC compared to control mice. The role of preNMDAR-mediated inhibition in epileptogenesis during the chronic condition or in the juvenile stage warrants further investigation.
METHODS: We have collected the brains of African green monkeys during multiple Nipah virus, Bangladesh studies, resulting in 14 brains with Nipah virus-associated lesions.
RESULTS: The lesions seen in the brain of African green monkeys infected with Nipah virus, Bangladesh were very similar to those observed in humans with Nipah virus, Malaysia infection. We observed viral RNA and antigen within neurons and endothelial cells, within encephalitis foci and in uninflamed portions of the central nervous system (CNS). CD8+ T cells had a consistently high prevalence in CNS lesions. We developed a UNet model for quantifying and visualizing inflammation in the brain in a high-throughput and unbiased manner. While CD8+ T cells had a consistently high prevalence in CNS lesions, the model revealed that CD68+ cells were numerically the immune cell with the highest prevalence in the CNS of Nipah virus-infected animals.
CONCLUSIONS: Our study provides an in-depth analysis on Nipah virus infection in the brains of primates, and similarities between lesions in patients and the animals in our study validate this model.
METHODS AND RESULTS: Transverse aortic constriction (TAC)/sham surgery were carried out in both IL-33 and WT-littermates. Echocardiographic measurements were performed at frequent interval during the study period. Heart was harvested for RNA and histological measurements. Following mechanical overload by TAC, myocardial mRNA expressions of Th1 cytokines, such as TNF-α were enhanced in IL-33(-/-) mice than in WT mice. After 8-weeks, IL-33(-/-) mice exhibited exacerbated left ventricular hypertrophy, increased chamber dilation, reduced fractional shortening, aggravated fibrosis, inflammation, and impaired survival compared with WT littermates. Accordingly, myocardial mRNA expressions of hypertrophic (c-Myc/BNP) molecular markers were also significantly enhanced in IL-33(-/-) mice than those in WT mice.
CONCLUSIONS: We report for the first time that ablation of IL-33 directly and significantly leads to exacerbate cardiac remodeling with impaired cardiac function and survival upon mechanical stress. These data highlight the cardioprotective role of IL-33/ST2 system in the stressed myocardium and reveal a potential therapeutic role for IL-33 in non-ischemic HF.