SIRT1 and SIRT2 Modulators: Potential Anti-Inflammatory Treatment for Depression?

Depression is a psychiatric disorder that has a significant health burden on patients and their families. Unfortunately, the current antidepressant medications that mainly target monoamine neurotransmitters have limited efficacy. Recent evidence has indicated that neuroinflammation participates in the genesis and development of depression, and interacts with other factors involved in depression. Therefore, exploring effective anti-inflammatory medications could be beneficial for the development of new treatment options for depression. Sirtuins are a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, which have seven members that can affect multiple downstream targets by deacetylation activity. Among these seven members, SIRT1 and SIRT2 have been shown to participate in the pathophysiology of inflammation in numerous studies. Thus, in this short article, we review the association of SIRT1 and SIRT2 activity and depression, and evidence of the effects of SIRT1 and SIRT2 modulators on inflammation in vitro and depressive-like behaviours in vivo.

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Mesenchymal stem cell-derived extracellular vesicles in the failing heart: past, present, and future

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00951.2020 ◽

2021 ◽

Author(s):

Catherine Karbasiafshar ◽

Frank W. Sellke ◽

M. Ruhul Abid

Keyword(s):

Stem Cell ◽

Extracellular Vesicles ◽

Treatment Options ◽

Current Treatment ◽

Lifestyle Changes ◽

Challenges And Opportunities ◽

Artery Disease ◽

New Treatment

Cardiovascular disease (CVD) is the leading cause of death globally. Current treatment options include lifestyle changes, medication, and surgical intervention. However, many patients are unsuitable candidates for surgeries due to comorbidities, diffuse coronary artery disease or advanced stages of heart failure. The search for new treatment options has recently transitioned from cell-based therapies to stem-cell derived extracellular vesicles (EVs). A number of challenges remain in the EV field, including the effect of comorbidities, characterization, and delivery, However, recent revolutionary developments and insight into the potential of 'personalizing' EV contents by bioengineering methods to alter specific signaling pathways in the ischemic myocardium hold promise. Here, we discuss the past limitations of cell-based therapies, and recent EV studies involving in vivo, in vitro, and omics, and future challenges and opportunities in EV-based treatments in CVD.

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In VitroandIn VivoEfficacies of Mefloquine-Based Treatment against Alveolar Echinococcosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01392-10 ◽

2010 ◽

Vol 55 (2) ◽

pp. 713-721 ◽

Cited By ~ 44

Author(s):

Tatiana Küster ◽

Britta Stadelmann ◽

Corina Hermann ◽

Sabrina Scholl ◽

Jennifer Keiser ◽

...

Keyword(s):

Alveolar Echinococcosis ◽

Severe Disease ◽

Treatment Options ◽

Drug Candidate ◽

Combined Application ◽

New Treatment ◽

Complete Detachment ◽

Laminated Layer

ABSTRACTAlveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapewormEchinococcus multilocularisand causes severe disease in the human liver, and occasionally in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated thein vitroandin vivoefficacy of mefloquine againstE. multilocularismetacestodes. Treatment using mefloquine (20 μM) againstin vitrocultures of metacestodes resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. Thein vitroactivity of mefloquine was dependent on the dosage.In vitroculture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) inE. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriatein vivostudies.

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Rapamycin blocks hepatoblastoma growth in vitro and in vivo implicating new treatment options in high-risk patients

European Journal of Cancer ◽

10.1016/j.ejca.2011.12.032 ◽

2012 ◽

Vol 48 (15) ◽

pp. 2442-2450 ◽

Cited By ~ 24

Author(s):

Ferdinand Wagner ◽

Bente Henningsen ◽

Christine Lederer ◽

Melanie Eichenmüller ◽

Jan Gödeke ◽

...

Keyword(s):

High Risk ◽

Treatment Options ◽

High Risk Patients ◽

Risk Patients ◽

New Treatment

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HDAC inhibition protects degenerating cone photoreceptors in vivo

10.1101/049742 ◽

2016 ◽

Author(s):

Dragana Trifunović ◽

Blanca Arango-Gonzalez ◽

Antonella Comitato ◽

Melanie Barth ◽

Ayse Sahaboglu ◽

...

Keyword(s):

Cell Death ◽

Trichostatin A ◽

Treatment Options ◽

Hdac Inhibition ◽

Neuroprotective Effects ◽

Histone Deacetylase Inhibitor Trichostatin ◽

New Treatment ◽

Future Therapy

AbstractRetinal diseases caused by cone photoreceptor cell death are devastating as the patients are experiencing loss of accurate and color vision. Understanding the mechanisms of cone cell death and the identification of key players therein could provide new treatment options. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration (cpfl1). We show that HDAC inhibition protects cones in vitro, in retinal explant cultures. More importantly, in vivo a single TSA injection increased cone survival for up to 10 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and diseases associated with impaired cone migration.

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ETMR-18. TARGETING Lin28 IN ETMR WITH ODC1 INHIBITOR DFMO

Neuro-Oncology ◽

10.1093/neuonc/noaa222.221 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii326-iii326

Author(s):

Austin Goodyke ◽

Shannon Kelly ◽

Joseph Zagorski ◽

Elizabeth VanSickle ◽

Tyler Maser ◽

...

Keyword(s):

Drug Testing ◽

Treatment Options ◽

Young Patients ◽

Treatment Strategies ◽

Therapeutic Agents ◽

Tumor Burden ◽

Protein Levels ◽

New Treatment

Abstract Embryonal tumor with multilayered rosettes (ETMR), is an aggressive brain tumor primarily occurring in young patients (<4 years of age) and characterized by C19MC amplification and Lin28 overexpression. These genetic hallmarks have been shown to participate in driving ETMR in a C19MC-Lin28-MYCN circuit. Reducing Lin28 disrupts this circuit and reduces cell viability in ETMR models. Investigation of therapeutic agents targeting this pathway is required to provide new treatment options for this deadly disease. We present data showing the effect of DFMO (α-difluoromethylornithine) in ETMR, an ODC1 inhibitor known to reduce Lin28 in neuroblastoma. DFMO treatment of the ETMR cell line BT-183 resulted in a significant reduction of intracellular Lin28 protein levels (P<0.05) as indicated by flow cytometry. In concert with this reduction in Lin28, there was a as significant reduction in viable cells (P<0.05), and the number of CD133+ cells were reduced 2-fold (P<0.05). High throughput drug testing of BT-183 identified a number of additional therapeutic agents with potential therapeutic efficacy for ETMR and combining these with cytostatic agent DFMO demonstrated the potential use of these drugs in combination. These in vitro data were complemented by testing of DFMO in an in vivo stereotaxic xenograft ETMR model, with inhibition of tumor burden monitored by bioluminescent imaging of the tumors. Together this work shows that Lin28 targeting agents such as DFMO merit further examination and integrating these types of agents into treatment strategies for ETMR may lead to better outcomes.

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Features of the modern antihistamines use in the treatment of allergic rhinitis

Medical Council ◽

10.21518/2079-701x-2021-12-101-108 ◽

2021 ◽

pp. 101-108

Author(s):

A. A. Krivopalov ◽

S. A. Rebrova ◽

P. A. Shamkina

Keyword(s):

Allergic Rhinitis ◽

Treatment Plan ◽

Severe Disease ◽

Treatment Options ◽

Individual Treatment ◽

Allergen Specific Immunotherapy ◽

Ocular Symptoms ◽

New Treatment

Allergic rhinitis remains one of the most relevant problems of modern otorhinolaryngology. The widespread prevalence, late diagnosis, underestimation of the possible risks of disease progression, the development of complications (including asthma) prompts the development and improvement of new treatment options for allergic rhinitis. Allergic rhinitis is a heterogeneous disease that presents with various clinical phenotypes, and therefore the severity of nasal symptoms can vary from mild malaise to severe disease.. Today, pharmacotherapy remains the most frequently used treatment tactic for patients with allergic rhinitis. While prescribing therapy the doctor develops an individual treatment plan based on the principles of personalized medicine, considering: the dominant symptoms, anamnesis data on previous therapy and the effect of treatment, the type of inflammation (Th2-type, mixed inflammation), concomitant diseases (conjunctivitis, asthma, etc.) etc.) and patient preferences. The tissue effects of the histamine mediator lead to the development of symptoms during the course of the disease, which determines the wide-spread use of antihistamines in the treatment of rhinitis. Antihistamines of the second generation are devoid of sedative effects, have a long-lasting effect and a good safety profile. One of the modern II generation antihistamines is bilastine. The research results proved the high antihistaminic activity of bilastine 20 mg in vitro and in vivo, the absence of cardiac and sedative side effects on the central nervous system, the ability to eliminate the nasal and ocular symptoms of disease and improve the quality of life of patients with allergic rhinitis. Thus, bilastine fully complies with current EAACI / WAO ARIA requirements for drugs used to treat AR. The paper presents a clinical case of a patient with chronic persistent allergic rhinitis, household sensitization with a slight uncontrolled course. The oral antihistamine bilastine was added to intranasal glucocorticosteroids, which help to relieve symptoms of the disease, stabilize the condition and prepare the patient for subsequent allergen-specific immunotherapy.

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