scholarly journals The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering the Immune Responses against Mycobacterium bovis BCG Strain in Individuals with Type 2 Diabetes

2021 ◽  
Vol 12 (1) ◽  
pp. 16-26
Author(s):  
Kimberly To ◽  
Ruoqiong Cao ◽  
Aram Yegiazaryan ◽  
James Owens ◽  
Kayvan Sasaninia ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Immune Cells ◽  
Mycobacterial Infection ◽  
Drug Resistant ◽  
Tnf Α ◽  
Resistant Strains ◽  
Ifn Γ ◽  
Drug Resistant Strains

Abstract Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to M. tb infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, M. tb still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of M. tb have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within in vitro granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of in vivo glutathione (GSH) supplementation in individuals with T2DM along with in vitro treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects’ blood was drawn pre- and post-L-GSH/or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct in vitro studies with everolimus. We found that in vitro treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular M. bovis BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with in vitro everolimus treatment produced a greater effect in inhibiting the growth of intracellular Mycobacterium bovis BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with in vitro everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, in vitro everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.

scholarly journals Compromised immune response to viral infections in type 2 diabetes mellitus

2020 ◽  
Vol 7 (12) ◽  
pp. 5203
Author(s):  
Sudhir Kumar Ambati
Keyword(s):  
Type 2 Diabetes ◽  
Immune Response ◽  
Immune Cells ◽  
Viral Infections ◽  
Adaptive Immune Response ◽  
Host Cells ◽  
High Concentration ◽  
Tnf Α ◽  
Ifn Γ

Viral infections are common in people with type 2 diabetes, which is associated with poor immune responses. In type 2 diabetes, the normal functioning of the immune system and immune cells is suppressed, which allows the viruses to enter the host cells and cause infections. The impacts of type 2 diabetes on immune response and viral infections are associated with different mechanisms, including suppression or impairment of cytokine production, dysfunctioning of immune cells, defects in the phagocytosis, and disruption of natural killer cells. The high concentration of blood glucose or hyperglycemia in type 2 diabetes affects the production of cytokines, including interleukins, interferon, TNF-α, and IFN-γ. These cytokines are involved in fighting pathogens, and they induce the production of antibodies involved in the adaptive immune response. Therefore, disruption of these cytokines production leads to compromised immune response and invading pathogens like viruses enter and replicate in the host body. 

scholarly journals Advanced glycation end product levels were correlated with inflammation and carotid atherosclerosis in type 2 diabetes patients

2020 ◽  
Vol 15 (1) ◽  
pp. 364-372 ◽  
Author(s):  
Jie Li ◽  
Haiyan Shangguan ◽  
Xiaoqian Chen ◽  
Xiao Ye ◽  
Bin Zhong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Color Doppler ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Advanced Glycation End Product ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Ifn Γ

AbstractDiabetes mellitus with atherosclerosis (AS) adds to the social burden. This study aimed to investigate whether advanced glycation end product (AGE) levels were correlated with inflammation and carotid AS (CAS) in type 2 diabetes mellitus (T2DM) patients. A total of 50 elderly T2DM patients and 50 age-matched senior healthy subjects were recruited in this study. T2DM patients were classified into two groups based on the intima–media thickness (IMT) of the carotid artery from color Doppler ultrasonography. Patients with IMT > 1 mm were classified into the T2DM + CAS group (n = 28), and patients with IMT < 1 mm were assigned as the T2DM + non-atherosclerosis (NAS) group (n = 22). The plasma levels of AGEs, receptor for AGE (RAGE), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) of all subjects were measured by enzyme-linked immunosorbent assay. The T-lymphocyte subsets were analyzed by a flow detector. T2DM + CAS patients showed significantly higher concentrations of AGEs, RAGE, TNF-α, and IFN-γ in the peripheral blood. The highest levels of CD4+ T cells were observed in the T2DM + CAS group. The AGE level was positively correlated with the concentrations of RAGE, TNF-α, IFN-γ, and CD4+. In summary, the results showed that the levels of AGEs may be correlated with the inflammatory status in T2DM patients with CAS.

scholarly journals In Vitro and In Vivo Antimalarial Activities of a Carbohydrate Antibiotic, Prumycin, against Drug-resistant Strains of Plasmodia

2004 ◽  
Vol 57 (6) ◽  
pp. 400-402 ◽  
Author(s):  
KAZUHIKO OTOGURO ◽  
AKI ISHIYAMA ◽  
MIYUKI KOBAYASHI ◽  
HITOMI SEKIGUCHI ◽  
TAKASHI IZUHARA ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals Distinguishable Immunologic Characteristics of COVID-19 Patients with Comorbid Type 2 Diabetes Compared with Nondiabetic Individuals

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ruxing Zhao ◽  
Yujing Sun ◽  
Yongyuan Zhang ◽  
Weili Wang ◽  
Shouyu Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Immunological Response ◽  
Clinical Severity ◽  
Blood Levels ◽  
Immunological Parameters ◽  
Global Pandemic ◽  
Tnf Α ◽  
Significant Difference ◽  
Ifn Γ

Background. COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has threatened every civilian as a global pandemic. The immune system poses the critical interactive chain between the human body and the virus. Here, we make efforts to examine whether comorbidity with type 2 diabetes (T2D) affects the immunological response in COVID-19 patients. Methods. We conducted a retrospective pilot study investigating immunological characteristics of confirmed cases of COVID-19 with or without comorbid T2D. Two subcohorts of sex- and age-matched participants were eligible for data analysis, of which 33 participants were with T2D and the remaining 37 were nondiabetic (NDM). Cellular immunity was assessed by flow cytometric determination of surface markers including CD3, CD4, CD8, CD19, CD16, and CD56 in peripheral blood. Levels of C reactive protein, immunoglobulin (IgG, IgM, IgA, and IgE), and complements (C3, C4) were detected by rate nephelometry immunoassay. And Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were detected by Cytometric Bead Array. Results. Neutrophil counts were found to be significantly higher in the T2D group than in the NDM group and had a significant relevance with clinical severity. Lymphocyte frequencies showed no significant differences in the two groups. However, the proportions and absolute counts of T, Tc, Th, and NK cells decreased in both groups to different degrees. An abnormal increase in neutrophil count and a decrease in lymphocyte subpopulations may represent risk factors of COVID-19 severity. The level of IgG, IgM, IgA, C3, and C4 showed no significant difference between the two groups, while the IgE levels were higher in the T2D group than in the NDM group ( p < 0.05 ). Th1 cytokines including IFN-γ, TNF-α, and IL-6, as well as CRP, appeared significantly higher in the T2D group. Conclusions. The COVID-19 patients comorbid with T2D demonstrated distinguishable immunological parameters, which represented clinical relevancies with the predisposed disease severity in T2D.

Aspirin Blocks Orthodontic Relapse via Inhibition of CD4+ T Lymphocytes

2017 ◽  
Vol 96 (5) ◽  
pp. 586-594 ◽  
Author(s):  
Y. Liu ◽  
T. Zhang ◽  
C. Zhang ◽  
S.S. Jin ◽  
R.L. Yang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Relapse Rate ◽  
Immune Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Th1 Cells ◽  
Tnf Α ◽  
Inflammatory Drugs ◽  
Ifn Γ ◽  
Anti Inflammatory

Immunologic response plays an important role in orthodontic tooth movement (OTM) and relapse. Nonsteroidal anti-inflammatory drugs, such as aspirin, affect immune cells and clinical orthodontic treatment. However, the mechanisms by which nonsteroidal anti-inflammatory drugs regulate immune cells to affect orthodontic relapse are unclear. In this study, male Sprague-Dawley rats were grouped as relapse and relapse + aspirin for 10 d after 14 d of OTM. Silicone impressions of the rats’ maxillary dentitions were obtained to record the distance of OTM at the indicated time point. CD4+ T lymphocytes in spleen were examined by flow cytometry. Serum levels of type 1 T-helper (Th1) cell–associated cytokines tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ) were determined through enzyme-linked immunosorbent assay. The effects of aspirin on CD4+ T and Th1 cells were also analyzed in vitro. Aspirin treatment significantly reduced the relapse rate. More interestingly, injection of CD25 neutralizing antibody basiliximab or TNF-α inhibitor etanercept can significantly reduce the relapse rate as well. Correspondingly, aspirin treatment significantly accelerated the decrease of orthodontic force–induced secretion of TNF-α and IFN-γ in serum and the expression of TNF-α and IFN-γ in periodontal ligament during relapse. Furthermore, aspirin treatment in vitro significantly repressed the differentiation of CD4+ T and Th1 cells. Overall, results indicated that aspirin treatment can block orthodontic relapse by regulating Th1 cells.

scholarly journals In Vitro Activity and MIC of Sitafloxacin against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis Isolated in Thailand

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Manoon Leechawengwongs ◽  
Therdsak Prammananan ◽  
Sarinya Jaitrong ◽  
Pamaree Billamas ◽  
Nampueng Makhao ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Critical Concentration ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACT New fluoroquinolones (FQs) have been shown to be more active against drug-resistant Mycobacterium tuberculosis strains than early FQs, such as ofloxacin. Sitafloxacin (STFX) is a new fluoroquinolone with in vitro activity against a broad range of bacteria, including M. tuberculosis. This study aimed to determine the in vitro activity of STFX against all groups of drug-resistant strains, including multidrug-resistant M. tuberculosis (MDR M. tuberculosis), MDR M. tuberculosis with quinolone resistance (pre-XDR), and extensively drug-resistant (XDR) strains. A total of 374 drug-resistant M. tuberculosis strains were tested for drug susceptibility by the conventional proportion method, and 95 strains were randomly submitted for MIC determination using the microplate alamarBlue assay (MABA). The results revealed that all the drug-resistant strains were susceptible to STFX at a critical concentration of 2 μg/ml. Determination of the MIC90s of the strains showed different MIC levels; MDR M. tuberculosis strains had a MIC90 of 0.0625 μg/ml, whereas pre-XDR and XDR M. tuberculosis strains had identical MIC90s of 0.5 μg/ml. Common mutations within the quinolone resistance-determining region (QRDR) of gyrA and/or gyrB did not confer resistance to STFX, except that double mutations of GyrA at Ala90Val and Asp94Ala were found in strains with a MIC of 1.0 μg/ml. The results indicated that STFX had potent in vitro activity against all the groups of drug-resistant M. tuberculosis strains and should be considered a new repurposed drug for treatment of multidrug-resistant and extensively drug-resistant TB.

In vitro efficacy of a synthetic all-d antimicrobial peptide against clinically isolated drug-resistant strains

2010 ◽  
Vol 35 (2) ◽  
pp. 208-209 ◽  
Author(s):  
Yoonkyung Park ◽  
Seong-Cheol Park ◽  
Jin-Young Kim ◽  
Jeong Ok Park ◽  
Chang Ho Seo ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals Sontochin as a Guide to the Development of Drugs against Chloroquine-Resistant Malaria

2012 ◽  
Vol 56 (7) ◽  
pp. 3475-3480 ◽  
Author(s):  
Sovitj Pou ◽  
Rolf W. Winter ◽  
Aaron Nilsen ◽  
Jane Xu Kelly ◽  
Yuexin Li ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Plasmodium Yoelii ◽  
Significant Activity ◽  
Drug Resistant ◽  
Content Type ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Derivatives Of

ABSTRACTSontochin was the original chloroquine replacement drug, arising from research by Hans Andersag 2 years after chloroquine (known as “resochin” at the time) had been shelved due to the mistaken perception that it was too toxic for human use. We were surprised to find that sontochin, i.e., 3-methyl-chloroquine, retains significant activity against chloroquine-resistant strains ofPlasmodium falciparum in vitro. We prepared derivatives of sontochin, “pharmachins,” with alkyl or aryl substituents at the 3 position and with alterations to the 4-position side chain to enhance activity against drug-resistant strains. Modified with an aryl substituent in the 3 position of the 7-chloro-quinoline ring, Pharmachin 203 (PH-203) exhibits low-nanomolar 50% inhibitory concentrations (IC50s) against drug-sensitive and multidrug-resistant strains andin vivoefficacy against patent infections ofPlasmodium yoeliiin mice that is superior to chloroquine. Our findings suggest that novel 3-position aryl pharmachin derivatives have the potential for use in treating drug resistant malaria.

scholarly journals Genetic and Virulence Characteristics of Linezolid and Pretomanid Dual Drug-Resistant Strains Induced from Mycobacterium tuberculosis in vitro

2020 ◽  
Vol Volume 13 ◽  
pp. 1751-1761
Author(s):  
Minghao Hu ◽  
Lei Fu ◽  
Bin Wang ◽  
Jian Xu ◽  
Shaochen Guo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Dual Drug

Macrovascular Protecting Effects of Berberine through Anti-inflammation and Intervention of BKCa in Type 2 Diabetes Mellitus Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Zhigui Wu ◽  
Li Gu ◽  
Yuankai Si ◽  
Wenxian Yin ◽  
Meng Zhao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Thoracic Aorta ◽  
Cellular Proliferation ◽  
Inflammatory Factor ◽  
Model Group ◽  
Tnf Α

Objective: The aim of this study was to examine the effect of berberine in diabetes mellitus in vivo and in vitro, and elucidate the underlying mechanisms. Methods: Rat models of type 2 diabetes mellitus (T2DM) were established, which were treated with berberine. Pathological changes in the thoracic aorta, and inflammatory factor and adiponectin levels were investigated. Vascular smooth muscle cells (VSMCs) of the thoracic aorta were cultured and treated with berberine. Cellular proliferation, migration, and inflammatory factor levels were investigated. Responses of vascular rings to phenylephrine (PE) and sodium nitroprusside (SNP) after berberine intervention, and the changes of relaxation responses to SNP after adding Iberiotoxin (IbTX) were investigated. Results: Berberine ameliorated the pathological status of the thoracic aorta in the T2DM rats. Berberine significantly inhibited the C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) production, and increased the adiponectin level compared with the model group. Compared with the model group, berberine inhibited the proliferation and migration of VSMCs in vitro, and reduced tumor growth factor-β1 (TGF-β1), IL-6, and TNF-α levels. Furthermore, the contraction of thoracic aorta to PE was reduced, while the relaxation response of thoracic aorta to SNP was increased, after the berberine intervention in the T2DM rats. The relaxation of thoracic aorta to SNP in the model and berberine groups were decreased after the IbTX treatment. Conclusions: Protective effects of berberine against macrovascular complications induced by diabetes mellitus may be attributed to inhibiting the inflammation and intervening the calcium-activated potassium (BKCa).

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