The role of nitric oxide–cGMP pathway in selegiline antidepressant-like effect in the mice forced swim test

Background

Considering the pivotal role of nitric oxide (NO) pathway in depressive disorders, the aim of the present study was to investigate the antidepressant-like effect of selegiline in mice forced swimming test (FST), and possible involvement of NO-cyclic guanosine monophosphate (cGMP) pathway in this action.

Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF-kB signaling pathway

Aim

The aim of the present study is to explore whether atorvastatin improves intestinal inflammation through the inhibition of the TLR4/NFkB signaling pathway in TNBS-induced rat colitis.

Methods

Acute colitis was induced by intra-rectal administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50 % ethanol. Twenty four hours after colitis induction, saline, atorvastatin (20 and 40 mg/kg) and sulfasalazine (100 mg/kg) were given to the animals by oral route. This was repeated daily for 1 week. Body weight changes, macroscopic and microscopic lesions were assessed. MPO and TNF-α activities were detected by immunohistochemistry (IHC) and the expression level of TLR4, MyD88 and NF-κB p65 proteins were measured by western blotting analysis.

Results

Atorvastatin and sulfasalazine reduced the body weight loss, macroscopic and microscopic lesions. Additionally, both drugs decreased the expression of MPO and TNF-α positive cells in the colon tissue. Furthermore, they inhibited the TNBS-induced expression of TLR4, MyD88 and NF-κB p65 proteins.

Conclusions

It is suggested that the anti-inflammatory effect of atorvastatin on TNBS-induced rat colitis may involve the inhibition of the TLR4/NFkB signaling pathway.

     

Alive attenuated Salmonella as a cargo shuttle for smart carrying of gold nanoparticles to tumour hypoxic regions

Abstract

In the present study, alive attenuated Salmonella typhi Ty21a was introduced as a vehicle for smart delivery of gold nanoparticles to the tumours’ hypoxic regions. At the first step, the uptakes of gold nanoparticles with seven different decorations by S. typhi Ty21a was investigated using flow cytometry and inductively coupled plasma optical emission spectroscopy. The analyses demonstrated that folic acid functionalised gold nanoparticles (FA-GNPs) are the best candidates for producing the Golden Bacteria (GB). Subsequently, the GB and FA-GNPs efficacies for tumour targeting were investigated after intravenous injection to CT-26 tumour-bearing mice. The GB exhibited more GNPs delivery to the tumour in comparison with FA-GNPs. Moreover, GB injection causes more delivery of GNPs to the tumours’ central regions in comparison with tumours’ periphery. This trend is completely in reverse for FA-GNPs injected group. The ratios of peripheral to central regions’ gold concentration of the tumours were 1.95?±?0.13 and 0.61?±?0.10 for FA-GNPs and GB groups, respectively. This observation demonstrates higher accumulation of gold nanoparticles in the centre of the tumour due to their active delivery by the S. typhi Ty21a to the deeps of tumours.     

Molecular Types of Methicillin-Resistant Staphylococcus aureus and Methicillin-Sensitive S. aureus Strains Causing Skin and Soft Tissue Infections and Nasal Colonization,Identified in Community Health Centers in New York City

In November 2011, The Rockefeller University Center for Clinical and Translational Science (CCTS), the Laboratory of Microbiology and Infectious Diseases, and Clinical Directors Network (CDN) launched a research and learning collaborative project with six community health centers in the New York City metropolitan area to determine the nature (clonal type) of community-acquired Staphylococcus aureus strains causing skin and soft tissue infections (SSTIs). Between November 2011 and March 2013, wound and nasal samples from 129 patients with active SSTIs suspicious for S. aureus were collected and characterized by molecular typing techniques. In 63 of 129 patients, the skin wounds were infected by S. aureus: methicillin-resistant S. aureus (MRSA) was recovered from 39 wounds and methicillin-sensitive S. aureus (MSSA) was recovered from 24. Most—46 of the 63–wound isolates belonged to the CC8/Panton-Valentine leukocidin-positive (PVL⁺) group of S. aureus clone USA300: 34 of these strains were MRSA and 12 were MSSA. Of the 63 patients with S. aureus infections, 30 were also colonized by S. aureus in the nares: 16 of the colonizing isolates were MRSA, and 14 were MSSA, and the majority of the colonizing isolates belonged to the USA300 clonal group. In most cases (70%), the colonizing isolate belonged to the same clonal type as the strain involved with the infection. In three of the patients, the identity of invasive and colonizing MRSA isolates was further documented by whole-genome sequencing.     

Utilizing 808 nm laser for sensitizing of melanoma tumors to megavoltage radiation therapy

Melanotic melanoma has high content of melanin and laser can destroy melanin-containing cells through thermal effect. In this study, the therapeutic effect of 808 nm laser therapy was investigated on B16-F10 melanoma tumor growth and tumor-bearing mice survival time. In addition, as laser can destroy melanin as the main cause of melanoma radioresistance, the effect of laser administration to enhance radiation therapy efficacy at B16-F10 cancer cells was evaluated in vitro and in vivo. Laser therapy (1 W/cm²?×?4 min) could cause significant (P?<?0.05) inhibition of melanoma tumors’ growth (~?61%) and about three times increase of the tumor-bearing mice survival time in comparison with no-treatment group. In addition, the mice which were treated with 1 W/cm²?×?4 min laser administration plus 6 Gy megavoltage radiation therapy exhibited ~?68% lesser tumors’ volume and 27 days increase of survival time in comparison with 6 Gy irradiated tumor-bearing mice. Also, significantly higher (P?<?0.05) tumor necrosis percentage was observed at the histopathological slides of 1 W/cm²?×?4 min laser + RT treated mice tumors (57?±?12%) in comparison with radiation therapy group (31?±?10%). Therefore, not only laser therapy can inhibit melanoma tumors’ growth per se but also its combination with radiation therapy can cause a significant enhancement of radiation therapy efficacy. The laser administration can be used as a radiosensitizing method for melanotic melanoma radiation therapy.

     

Agmatine ameliorates acetic acid-induced colitis in rats: involvement of nitrergic system

Aim: The aim of the present study is to investigate the anti-inflammatory effect of agmatine through the inhibition of iNOS enzyme in acetic acid-induced rat colitis.

Methods: Acute colitis was induced by administration of 2?mL of diluted acetic acid (4%) solution rectally. Two hours after colitis induction, animals were treated with normal saline, dexamethasone (2?mg/kg), agmatine (2, 5, 10?mg/kg), L-NAME (30?mg/kg), Aminoguanidine (20?mg/kg), agmatine (2?mg/kg) with L-NAME (30?mg/kg) and agmatine (2?mg/kg) with aminoguanidine (20?mg/kg) intraperitoneally and continued for 3 consecutive days. Assessment of macroscopic and microscopic damage was performed. MPO activity was evaluated by biochemical method. Furthermore, the tissue level of TNF-α was determined by ELISA and the expression level of iNOS protein was detected by immunohistochemistry (IHC).

Results: Dexamethasone (2?mg/kg) and agmatine (5, 10?mg/kg) and subeffective doses of agmatine (2?mg/kg) with aminoguanidine (20?mg/kg) improved macroscopic and microscopic damage compared to acetic acid group (p?<?.001). In addition, these drugs reduced the activity of MPO (p?<?.001) and the level of TNF-α (p?<?.001) in colon tissue compared to acetic acid group. Furthermore, they decreased acetic acid-induced expression of iNOS protein in colon tissue (p?<?.01, p?<?.001).

Conclusion: It is suggested that the anti-inflammatory activity of agmatine on acetic acid-induced rat colitis may involve the inhibition of iNOS enzyme.     

Implementing DASH-Aligned Meals and Self-Measured Blood Pressure to Reduce Hypertension at Senior Centers: A RE-AIM Analysis

Low-income, minority seniors face high rates of hypertension that increase cardiovascular risk. Senior centers offer services, including congregate meals, that can be a valuable platform to reach older adults in underserved communities. We implemented two evidence-based interventions not previously tested in this setting: DASH-aligned congregate meals and Self-Measured Blood Pressure (SMBP), to lower blood pressure (BP) at two senior centers serving low-income, racially diverse communities. The study enrolled congregate meal program participants, provided training and support for SMPB, and nutrition and BP education. DASH-aligned meals delivered 40% (lunch) or 70% (breakfast and lunch) of DASH requirements/day. Primary outcomes were change in BP, and BP control, at Month 1. Implementation data collected included client characteristics, menu fidelity, meal attendance, SMBP adherence, meal satisfaction, input from partner organizations and stakeholders, effort, and food costs. We used the RE-AIM framework to analyze implementation. Study Reach included 94 older, racially diverse participants reflecting neighborhood characteristics. Effectiveness: change in systolic BP at Month 1 trended towards significance (−4 mmHg, p = 0.07); change in SMBP reached significance at Month 6 (−6.9 mmHg, p = 0.004). We leveraged existing community-academic partnerships, leading to Adoption at both target sites. The COVID pandemic interrupted Implementation and Maintenance and may have attenuated BP effectiveness. DASH meals served were largely aligned with planned menus. Meal attendance remained consistent; meal satisfaction was high. Food costs increased by 10%. This RE-AIM analysis highlights the acceptability, feasibility, and fidelity of this DASH/SMBP health intervention to lower BP at senior centers. It encourages future research and offers important lessons for organizations delivering services to older adults and addressing cardiovascular risk among vulnerable populations.     

Spirulina extract enriched for Braun‐type lipoprotein (Immulina®) for inhibition of 4T1 breast tumors' growth and metastasis

Spirulina platensis extracts have exhibited considerable anti‐cancer effects. To investigate the efficacy of the Spirulina extract enriched for Braun‐type lipoprotein (Immulina®) for breast cancer treatment, 4T1 breast tumor‐bearing mice were treated with 40 mg/kg Immulina® daily and the tumors' growth and metastasis were assessed. Also, CD4, CD8, and CD56 staining were performed to investigate the Immulina® effect on the immune cells' recruitment to the tumors by immunohistochemistry. Immulina® could significantly (P < 0.001) inhibit 4T1 breast tumors' growth. Immulina®‐treated group exhibited a 63% decrease in the tumors' volume in comparison with control (P < 0.001). Also, Immulina® could significantly (P < 0.001) decrease metastatic burden at the vital organs as 68% and 61% decrease in the liver and lungs metastatic colonies were observed, respectively. Also, Immulina® could increase mean survival time of the tumor‐bearing mice for 29 days. The Spirulina‐treated mice tumors contained significantly more infiltrated NK, CD4+, and CD8+ T lymphocytes in comparison with control. Taking together, Immulina® can be a safe anti‐cancer supplement with the ability to cause direct apoptosis to the cancer cells and activate the immune system against tumor. This supplement with natural origin seems to have bright future to help breast cancer patients.