Afferent Renal Denervation Attenuates Sympathetic Overactivation From the Paraventricular Nucleus in Spontaneously Hypertensive Rats.

BACKGROUND: The effectiveness of renal denervation (RDN) in reducing blood pressure and systemic sympathetic activity in hypertensive patients has been established. However, the underlying central mechanism remains unknown. This study aimed to investigate the role of RDN in regulating cardiovascular function via the central renin-angiotensin system (RAS) pathway. METHODS: Ten-week-old spontaneously hypertensive rats (SHR) were subjected to selective afferent renal denervation (ADN) using capsaicin solution. We hypothesized that ADN would effectively reduce blood pressure and rebalance the RAS component of the paraventricular nucleus (PVN) in SHR. RESULTS: The experimental results show that the ADN group exhibited significantly lower blood pressure, reduced systemic sympathetic activity, decreased chronic neuronal activation marker C-FOS expression in the PVN, and improved arterial baroreflex function, compared with the Sham group. Furthermore, ACE and AT1 protein expression was reduced while ACE2 and MAS protein expression was increased in the PVN of SHR after ADN. CONCLUSIONS: These findings suggest that RDN may exert these beneficial effects through modulating the central RAS pathway.

[Diagnosis Significance of the Levels of Cytokines IL-6, IL-10 and CXCL-13 in Cerebrospinal Fluid for Central Nervous System Infiltration of Lymphoma].

OBJECTIVE: To evaluate the diagnostic value of the expression levels of cytokines interleukin-6(IL-6), interleukin-10 (IL-10) and chemokine （C-X-C motif） ligand-13 (CXCL-13) in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma. METHODS: Forty patients diagnosed as lymphoma or acute lymphoblastic leukemia in General Hospital of Northern Theater Command from July 2020 to July 2021 were collected and recorded their CSF indexes, including pressure, protein, Pandy test, nucleated cell count, glucose and chlorine content in CSF. The levels of cytokines IL-6, IL-10 and CXCL-13 were detected by Enzyme-linked immunosorbent assay. RESULTS: The patients were divided into CNSI (central nervous system infiltration) group and non-CNSI group, the average levels of IL-6, IL-10, CXCL-13 and IL-10/IL-6 ratio in CNSI group were higher than those in non-CNS group, but the difference of IL-10/IL-6 ratio between the two groups was statistically significant (P<0.05). Then the patients were divided into protein elevated(n=14) group and protein normal group(n=26), the levels of IL-6 ï¼» (5.78±2.69) pg/ mlï¼½ and CXCL-13 ï¼»(0.83±0.59) pg/mlï¼½ in protein elevated group were significantly higher than those in the protein normal group ï¼»IL-6: (2.41±1.16) pg/ml; CXCL-13: (0.38±0.18) pg/mlï¼½ (P<0.05). Further analysis of the expression levels of the cytokines in non-CNSI group (n=32), IL-6, IL-10, CXCL-13 level and IL-10/IL-6 ratio in the protein elevated group (n=12) were higher than those in the protein normal group (n=20), but the difference was not statistically significant. CONCLUSION: The levels of IL-6, IL-10 and CXCL-13 in CSF of lymphoma patients with CNS infiltration were higher than those in non-CNS infiltration group, and those in patients with protein elevated group are higher than those in the protein normal group.

Effective-component compatibility of Bufei Yishen formula III ameliorated COPD by improving airway epithelial cell senescence by promoting mitophagy via the NRF2/PINK1 pathway.

BACKGROUND: Effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) demonstrates positive effects on stable chronic obstructive pulmonary disease (COPD). PURPOSE: To investigate the mechanisms of ECC-BYF III on COPD rats from the aspect of airway epithelial cell senescence. METHODS: COPD model rats (Sprague-Dawley rat) were treated with ECC-BYF III for 8 weeks, and the efficacy was evaluated. Cigarette smoke extract (CSE)-induced senescence model of airway epithelial cells was treated with ECC-BYF III, and related enzymes and proteins involved in oxidative stress and mitophagy were detected. RESULTS: ECC-BYF III markedly rescued pulmonary function and histopathological changes, which might be associated with the amelioration of lung senescence, including the reduction of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 levels, increase of the level in total superoxide dismutase (T-SOD), and decease in the p21 level in the airways. Furthermore, ECC-BYF III suppressed p16 and p21 expressions and senescence-associated ß-galactosidase (SA-ß-Gal) in CSE-induced airway epithelial cells. Moreover, ECC-BYF III upregulated mitophagy-related proteins, including the co-localizations of TOM20 and LC3B, PINK1 and PARK2, and improved mitochondrial function by upregulating mitochondrial mitofusin (MFN)2 and reducing dynamin-related protein 1 (DRP1) expression. ECC-BYF III enhanced the activities of T-SOD and GSH-PX by up-regulating NRF2, thus inhibiting oxidative stress. After intervention with NRF2 inhibitor, the regulation effects of ECC-BYF III on oxidative stress, mitophagy and senescence in airway epithelial cells were significantly suppressed. CONCLUSIONS: ECC-BYF III exerts beneficial effects on COPD rats by ameliorating airway epithelial cell senescence, which is mediated by inhibiting oxidative stress and subsequently enhancing mitophagy through the activation of NRF2 signaling.

Effect of Exercise Prescription Implementation Rate on Cardiovascular Events.

BACKGROUND: Exercise prescription of cardiac rehabilitation (CR) is vital in patients with cardiovascular diseases (CVDs) and those carrying high risk for CVDs. However, the relation between the implementation rate of exercise prescription and cardiovascular events (CVEs) is unclear. DESIGN AND METHODS: In this retrospective study, using the administration data from the Rehabilitation Center in a hospital, patients aged ≥18 years with CVDs were consecutively enrolled from November 2018 to May 2021. Patients were divided into the high execution group (HEG) and low execution group (LEG) depending on whether they completed more than half the time of the exercise prescriptions. Baseline characteristics, ultrasonic cardiogram, cardiopulmonary exercise test, follow-up data, and CVEs were collected. RESULTS: The mean age of the 197 CR patients was 61.8 ± 13.7 years and the mean follow-up duration was 10.9 ± 4.2 months. Among them, 15 patients suffered CVEs: 4 in the HEG and 11 in the LEG. The incidence of CVEs showed significant differences between HEG and LEG (chi-square test). Free-event survival analysis using Kaplan-Meier survival plots showed that patients in LEG had poor survival. Cox proportional hazards regression analysis revealed that the prescription implementation rate was an independent predictor of CVEs. CONCLUSIONS: Our study suggested a significant effect of exercise prescription execution rate on the occurrence of CVEs. Further, the HEG of exercise prescription was associated with lower CVDs.

Ligand-Promoted RhIII -Catalyzed Thiolation of Benzamides with a Broad Disulfide Scope.

A ligand-promoted RhIII -catalyzed C(sp2 )-H activation/thiolation of benzamides has been developed. Using bidentate mono-N-protected amino acid ligands led to the first example of RhIII -catalyzed aryl thiolation reactions directed by weakly coordinating directing amide groups. The reaction tolerates a broad range of amides and disulfide reagents.

Supramolecular system of podophyllotoxin and hydroxypropyl-ß-cyclodextrin: Characterization, inclusion mode, docking calculation, solubilization, stability and cytotoxic activity.

The inclusion complexation behavior, characterization, and inclusion mode of podophyllotoxin (POD) with hydroxypropyl-ß-cyclodextrin (HPßCD) were investigated in both solution and the solid state by means of XRD, DSC, SEM, 1H and 2D NMR and UV-vis spectroscopy. The results showed that the water solubility and thermal stability of POD were obviously increased in the inclusion complex with HPßCD. The cytotoxicity of POD/HPßCD inclusion complex against all the human tumor cell lines investigated still remains. This satisfactory water solubility and high thermal stability of the POD/HPßCD complex will be potentially useful for their application as herbal medicines or healthcare products.

Synthesis and cytotoxic activity of novel tetrahydrobenzodifuran-imidazolium salt derivatives.

The synthesis of a series of novel 4-substituted 2,3,6,7-tetrahydrobenzo [1,2-b;4,5-b']difuran-1H-imidazolium salts is presented. The biological properties of the compounds were evaluated in vitro against a panel of human tumor cell lines. Results suggest that the 5,6-dimethyl-benzimidazole or 2-methyl-benzimidazole ring, and substitution of the imidazolyl-3-position with a 2-naphthylmethyl substituent or 2-naphthylacyl substituent, were important to the cytotoxic activity. Notably, 3-(2-Naphthylmethyl)-1-((2,3,6,7-tetrahydrobenzo[1,2-b;4,5-b']difuran-4-yl)methyl)-1H-5,6-dimethyl-benzimidazol-3-ium bromide (42) was found to be the most potent derivative against five human tumor cell lines with IC50 values of 1.06-4.34µM and more selective towards SMMC-7721, A549 and SW480 cell lines. 3-(2-Naphthylacyl)-1-((2,3,6,7-tetrahydrobenzo[1,2-b;4,5-b']difuran-4-yl)methyl)-1H-2-methyl-benzimidazol-3-ium bromide (37) showed higher selectivity to SMMC-7721 and MCF-7 cell lines with IC50 values 2.7-fold and 8.4-fold lower than DDP. Study regarding to the antitumor mechanism of action showed that compound 37 could induce cell cycle G1 phase arrest and apoptosis in SMMC-7721 cells.

Synthesis and antitumor activity of novel N-substituted tetrahydro-ß-carboline-imidazolium salt derivatives.

The synthesis of a series of novel N-substituted tetrahydro-ß-carboline-imidazolium salt derivatives is presented. The biological properties of the compounds were evaluated in vitro against a panel of human tumor cell lines. The results suggest that the benzimidazole ring and 1-(naphthalen-2-yl)ethan-1-one or 2-naphthylmethyl substituent at the imidazolyl-3-position were vital for modulating cytotoxic activity. Compound 41 was observed as a potent derivative with IC50 values of 3.24-8.78 µM and exhibited cytotoxic activity selectively against HL-60, A-549 and MCF-7 cell lines. Meanwhile, high inhibitory activities selectively against HL-60 and MCF-7 cell lines were observed for compound 51. Moreover, compound 51 was able to induce G1 phase cell cycle arrest and apoptosis in MCF-7 cells. The cytotoxicity of compound 51 against human normal lung epithelial cell line BEAS-2B was further evaluated.

Host-guest system of hesperetin and ß-cyclodextrin or its derivatives: Preparation, characterization, inclusion mode, solubilization and stability.

The inclusion complexation behavior, characterization and binding ability of hesperetin with ß-cyclodextrin and its derivatives were investigated in both the solution and solid state by means of XRD, DSC, SEM, (1)H and 2D NMR and UV-vis spectroscopy. The results showed that the water solubility and stability of hesperetin were obviously increased in the inclusion complex with cyclodextrins. This satisfactory water solubility and high stability of the hesperetin/CD complexes will be potentially useful for their application as herbal medicines or healthcare products.

[α-GalCer reduces Acute Graft-versus-Host Disease by Altering Donor T Cells Migration].

OBJECTIVE: This study was aimed to explore the new mechanism of α-Galactosyleramide (α-GalCer), a synthetic glycolipid, and a well-known activator of natural killer T cells (NKT) for improving acute graft-versus-host disease(aGVHD). METHODS: Murine allogeneic bone marrow transplantation (allo-BMT) model was established. Recipient mice were injected intraperitoneally with α-GalCer immediately after allo-BMT, whereas mice from the vehicle groups received the diluent (DMSO) only. The severity degree of aGVHD was estimated by survival, aGVHD clinical score and pathology. The mechanism of aGVHD reduced by α-GalCer was explored by detecting T cells migration in vivo and in vitro. RESULTS: Mice in α-GalCer group survived longer than in control group, and their clinical and pathological status of aGVHD were lighter. α-GalCer reduced aGVHD by altering donors T cell migration. CONCLUSION: After allo-BMT α-GalCer reduces aGVHD by altering donor T cells migration.