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Turkish Journal of Medical Sciences 2023Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are...
Protective effects of swimming exercises and metformin on cardiac and aortic damage caused by a high-fat diet in obese rats with type 2 diabetes, by regulating the Bcl2/Bax signaling pathway.
BACKGROUND/AIM
Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are still being tried. The positive effects of metformin (MET) and physical exercise (EXE) on the pathophysiology of diabetes are well known. In this study, it was aimed to detail these positive effects of MET and EXE in combination on the basis of inflammation, apoptosis mechanisms, and endogen nesfatin-1 (NES-1) synthesis.
MATERIALS AND METHODS
Twenty-seven type 2 DM (DM-2) male Wistar Albino rats were divided into 4 groups, as the high-fat diet (HFD), MET, EXE, and MET+EXE groups. The total duration of the study was 3 months. At the end of the experiment, blood glucose and lipid profiles were measured. Histopathological evaluation was performed on the cardiac and aortic tissues and apoptotic markers were evaluated immunohistochemically. Inflammatory markers and NES-1 levels were analyzed by enzyme-linked immunosorbent assay.
RESULTS
The plasma glucose, homeostatic model evaluation-insulin resistance (HOMA-IR), low-density lipoprotein (LDL) levels increased, and high-density lipoprotein (HDL) levels decreased significantly in the HFD group. In the treatment groups, the glucose, HOMA-IR, LDL, NES-1 levels in the plasma, as well as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, caspase-3 (Cas-3), Bcl-2-associated X protein (Bax), and histopathological findings of inflammation in tissues were decreased. Additionally, there was an increase in plasma insulin, HDL, and tissue B-cell lymphoma-2 and levels.
CONCLUSION
It was observed that the MET and EXE treatments in the DM-2 model reduced cellular damage mechanisms such as inflammation and apoptosis. The decrease in NES-1 levels was thought to be secondary to this antiinflammatory effect. In conclusion, the results demonstrated the effectiveness of EXE in reducing DM-2 and the NES-1 levels. Further studies are needed to evaluate the effect in different EXE models and treatment durations.
Topics: Animals; Metformin; Diet, High-Fat; Diabetes Mellitus, Type 2; Rats, Wistar; Male; Rats; Signal Transduction; Proto-Oncogene Proteins c-bcl-2; Swimming; bcl-2-Associated X Protein; Obesity; Physical Conditioning, Animal; Hypoglycemic Agents; Apoptosis; Aorta; Nucleobindins; Diabetes Mellitus, Experimental
PubMed: 38813486
DOI: 10.55730/1300-0144.5727 -
Cardiovascular Diabetology May 2024Use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether the initial decline of renal function with SGLT2 inhibitor treatment is related to vascular changes in the systemic circulation.
METHODS
We measured GFR (mGFR) and estimated GFR (eGFR) in 65 patients with type 2 diabetes (T2D) at baseline and after 12 weeks of treatment randomized either to a combination of empagliflozin and linagliptin (SGLT2 inhibitor based treatment group) (n = 34) or metformin and insulin (non-SGLT2 inhibitor based treatment group) (n = 31). mGFR was measured using the gold standard clearance technique by constant infusion of inulin. In addition to blood pressure (BP), we measured pulse wave velocity (PWV) under standardized conditions reflecting vascular compliance of large arteries, as PWV is considered to be one of the most reliable vascular parameter of cardiovascular (CV) prognosis.
RESULTS
Both mGFR and eGFR decreased significantly after initiating treatment, but no correlation was found between change in mGFR and change in eGFR in either treatment group (SGLT2 inhibitor based treatment group: r=-0.148, p = 0.404; non-SGLT2 inhibitor based treatment group: r = 0.138, p = 0.460). Noticeably, change in mGFR correlated with change in PWV (r = 0.476, p = 0.005) in the SGLT2 inhibitor based treatment group only and remained significant after adjustment for the change in systolic BP and the change in heart rate (r = 0.422, p = 0.018). No such correlation was observed between the change in eGFR and the change in PWV in either treatment group.
CONCLUSIONS
Our main finding is that after initiating a SGLT2 inhibitor based therapy an exaggerated decline in mGFR was related with improved vascular compliance of large arteries reflecting the pharmacologic effects of SGLT2 inhibitor in the renal and systemic vascular bed. Second, in a single patient with T2D, eGFR may not be an appropriate parameter to assess the true change of renal function after receiving SGLT2 inhibitor based therapy.
TRIAL REGISTRATION
clinicaltrials.gov (NCT02752113).
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Glomerular Filtration Rate; Male; Diabetes Mellitus, Type 2; Middle Aged; Female; Benzhydryl Compounds; Aged; Treatment Outcome; Kidney; Glucosides; Time Factors; Linagliptin; Pulse Wave Analysis; Metformin; Insulin; Diabetic Nephropathies; Vascular Stiffness; Drug Therapy, Combination; Hypoglycemic Agents; Biomarkers; Clinical Relevance; Sodium-Glucose Transporter 2
PubMed: 38811998
DOI: 10.1186/s12933-024-02223-0 -
BMC Oral Health May 2024Ventilator-associated pneumonia (VAP) increases the length of hospitalization and mortality rate. This study aimed to determine the effect of propolis mouthwash on the... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVES
Ventilator-associated pneumonia (VAP) increases the length of hospitalization and mortality rate. This study aimed to determine the effect of propolis mouthwash on the incidence of VAP in intensive care unit (ICU) patients.
MATERIALS AND METHODS
Triple-blind, comparative randomized, controlled clinical trial was conducted over one year, with 110 ICU patients at Imam-Hossein and Bahar hospitals (Shahroud) and Kowsar Hospital (Semnan) in Iran. The intervention group used 15 cc of 0.06% propolis mouthwash solution twice daily at 8 AM and 4 PM for seven days. The control group used 15 cc of 0.2% chlorhexidine mouthwash at the same times and duration. Data were collected using a demographic questionnaire, APACHE II, Beck Oral Assessment Scale, and Modified Clinical Pulmonary Infection Score (MCPIS).
RESULTS
There was no significant difference in demographic information, disease severity, and oral health between the two groups before and after intervention (P > 0.05). The incidence of VAP in the intervention group compared to the control group was 10.9% vs. 30.9% on the third day (P = 0.0166, 95% CI: 0.53-0.83 and RR = 0.35), 23.6% vs. 43.6% on the fifth day (P = 0.0325 and 95% CI: 0.31-0.95 and RR = 0.54), and 25.5% vs. 47.3% on the seventh day (P = 0.0224, 95% CI: 0.32-0.92, and RR = 0.54). The Mann-Whitney indicated the incidence of VAP was significantly lower in the intervention group on the third, fifth, and seventh days.
CONCLUSION
Propolis mouthwash can be considered as an alternative to chlorhexidine mouthwash for ICU patients.
CLINICAL RELEVANCE
Propolis mouthwash serves as a simple, economical intervention to potentially reduce incidence of VAP.
TRIAL REGISTRATION
(IRCT20110427006318N12, date 02.04.2019).
Topics: Humans; Pneumonia, Ventilator-Associated; Mouthwashes; Male; Female; Propolis; Intensive Care Units; Middle Aged; Incidence; Iran; Adult; Chlorhexidine; Anti-Infective Agents, Local; Aged; APACHE
PubMed: 38811949
DOI: 10.1186/s12903-024-04412-5 -
Scientific Reports May 2024Lung adenocarcinoma (LUAD) is the most common and aggressive subtype of lung cancer, and coronavirus disease 2019 (COVID-19) has become a serious public health threat...
Lung adenocarcinoma (LUAD) is the most common and aggressive subtype of lung cancer, and coronavirus disease 2019 (COVID-19) has become a serious public health threat worldwide. Patients with LUAD and COVID-19 have a poor prognosis. Therefore, finding medications that can be used to treat COVID-19/LUAD patients is essential. Bioinformatics analysis was used to identify 20 possible metformin target genes for the treatment of COVID-19/LUAD. PTEN and mTOR may serve as hub target genes of metformin. Metformin may be able to cure COVID-19/LUAD comorbidity through energy metabolism, oxidoreductase NADH activity, FoxO signalling pathway, AMPK signalling system, and mTOR signalling pathway, among other pathways, according to the results of bioinformatic research. Metformin has ability to inhibit the proliferation of A549 cells, according to the results of colony formation and proliferation assays. In A549 cells, metformin increased glucose uptake and lactate generation, while decreasing ATP synthesis and the NAD/NADH ratio. In summary, PTEN and mTOR may be potential targets of metformin for the treatment of COVID-19/LUAD. The mechanism by which metformin inhibits lung adenocarcinoma cell proliferation may be related to glucose metabolism regulated by PI3K/AKT signalling and mTOR signalling pathways. Our study provides a new theoretical basis for the treatment of COVID-19/LUAD.
Topics: Metformin; Humans; A549 Cells; Glucose; TOR Serine-Threonine Kinases; COVID-19; Lung Neoplasms; Cell Proliferation; PTEN Phosphohydrolase; Adenocarcinoma of Lung; Signal Transduction; COVID-19 Drug Treatment; SARS-CoV-2; Energy Metabolism
PubMed: 38811809
DOI: 10.1038/s41598-024-63081-0 -
Narra J Apr 2024Diabetes is closely related to immune response problems when it occurs chronically. Pegagan () is a medicinal plant with active compounds. Madecassoside is beneficial in...
Diabetes is closely related to immune response problems when it occurs chronically. Pegagan () is a medicinal plant with active compounds. Madecassoside is beneficial in treating diabetes, and nanoparticle technology is expected to enhance the medicinal potential and availability of pegagan compounds. The aim of this study was to determine the effect of chitosan-coated pegagan nanoparticles on the cytokine profile of chronic diabetic mice, which included CD4+TNF-α+, CD8+TNF-α+, CD4+IFN-γ+, CD8+IFN-γ+ and IL-6+. An experimental study with a randomized complete block design (CRD) consisting of six treatments with seven replicates was conducted. The groups were: healthy mice as negative control; diabetic mice treated with distilled water as positive control and diabetic mice treated with nanoparticle coated with chitosan (NPC) 20 mg/kg, 30 mg/kg, 40 mg/kg, and metformin 130 mg/kgBW. The data were tested using one-way analysis of variance (ANOVA) with a significance level of 5% and continued with the Duncan's multiple range test. The results showed that pegagan NPC could significantly reduce the relative number of CD4+TNF-α+, CD8+TNF-α+, CD4+IFN-γ+ and CD8+IFN-γ+ and IL-6 in the dose of 20 mg/kg, 30 mg/kg and 40 mg/kg (<0.05). The treatment dose of 20 mg/kg reduced CD4+TNF-α+, CD8+TNF-α+, CD4+IFN-γ+, CD8+IFN-γ+ to the levels of healthy mice and a dose of 30 mg/kg could reduce IL-6 as in healthy mice. These findings suggest that chitosan-coated pegagan nanoparticles are a promising therapy for diabetes, as they have the potential to modulate the immune response associated with chronic diabetes.
Topics: Animals; Chitosan; Nanoparticles; Mice; Centella; Cytokines; Diabetes Mellitus, Experimental; Male; Triterpenes; Hypoglycemic Agents; Interleukin-6; Plant Extracts; Metformin
PubMed: 38798839
DOI: 10.52225/narra.v4i1.697 -
Narra J Apr 2024The antiproliferative properties of metformin and silodosin have been observed in prostate cancer. Furthermore, it is hypothesized that the molecular pathways related to...
Effects of metformin and silodosin as supplementary treatments to abiraterone on human telomerase reverse transcriptase (hTERT) level in metastatic castration-resistant prostate cancer (mCRPC) cells: An in vitro study.
The antiproliferative properties of metformin and silodosin have been observed in prostate cancer. Furthermore, it is hypothesized that the molecular pathways related to these drugs may impact the levels of human telomerase reverse transcriptase (hTERT) in prostate cancer cells. The aim of this study was to assess the effect of metformin and silodosin on the levels of hTERT in metastatic castration-resistant prostate cancer (mCRPC) cells. The present study employed an experimental design with a post-test-only control group. This study utilized the PC3 cell line as a model for mCRPC. A viability experiment was conducted using the CCK-8 method to determine the inhibitory concentration (IC50) values of metformin, silodosin, and abiraterone acetate (AA) after a 72-hour incubation period of PC3 cells. In order to investigate the levels of hTERT, PC3 cells were divided into two control groups: a negative control and a standard therapy with AA. Additionally, three experimental combination groups were added: metformin with AA; silodosin with AA; and metformin, silodosin and AA. The level of hTERT was measured using sandwich ELISA technique. The difference in hTERT levels was assessed using ANOVA followed by a post hoc test. The IC values for metformin, silodosin, and AA were 17.7 mM, 44.162 mM, and 66.9 μM, respectively. Our data indicated that the combination of metformin with AA and the combination of metformin, silodosin and AA decreased the hTERT levels when compared to control, AA, and silodosin with AA. The administration of metformin resulted in a reduction of hTERT levels in the PC3 cell line, but the impact of silodosin on hTERT levels was not statistically significant compared to AA group.
Topics: Humans; Metformin; Telomerase; Male; Prostatic Neoplasms, Castration-Resistant; Indoles; Cell Line, Tumor; Cell Proliferation; PC-3 Cells; Cell Survival; Antineoplastic Agents; Androstenes
PubMed: 38798828
DOI: 10.52225/narra.v4i1.680 -
Polymers May 2024As antibiotic resistance increasingly undermines traditional infection management strategies, there is a critical demand for innovative wound care solutions that address...
Development and Evaluation of a Novel Antibacterial Wound Dressing: A Powder Preparation Based on Cross-Linked Pullulan with Polyhexamethylene Biguanide for Hydrogel-Transition in Advanced Wound Management and Infection Control.
As antibiotic resistance increasingly undermines traditional infection management strategies, there is a critical demand for innovative wound care solutions that address these emerging challenges. This study introduces a novel antibacterial wound dressing based on Cross-Linked Pullulan (Pul) and Polyhexamethylene Biguanide (PHMB) for enhanced wound management and infection control. The dressing's adsorption rate reached 200% of its original weight within 30 min, exceeded 300% after 5 h, and exhibited significant non-Newtonian fluid properties. The dressings were able to release the loaded medication completely within 20 min; additionally, the dressing demonstrated significant antibacterial activity against a broad spectrum of bacteria. Significantly, the therapeutic effects of the Pul-PHMB/GP dressing were evaluated in a mouse model. Compared to untreated wounds, wounds treated with Pul-PHMB/GP exhibited a significant gelation process within 5 min post-treatment and showed a significant increase in wound healing rate within 12 days. This powder preparation overcomes the limitations associated with liquid and gel dressings, notably in storage and precise application, preventing the premature expansion or dissolution often caused by PHMB in high-humidity environments. The powder form can transform into a gel upon contact with wound exudate, ensuring accurate coverage of irregular wounds, such as those from burns or pressure sores, and offers excellent chemical and physical stability in a dry state, which facilitates storage and transport. This makes the dressing particularly suitable for emergency medical care and precision therapy, significantly improving the efficiency and adaptability of wound treatment and providing robust support for clinical treatments and emergency responses.
PubMed: 38794544
DOI: 10.3390/polym16101352 -
Molecules (Basel, Switzerland) May 2024Methylglyoxal-induced ROS elevation is the primary cause of neuronal damage. Metformin is a traditional hypoglycemic drug that has been reported to be beneficial to the...
Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure-Activity Relationship and Potential Target.
Methylglyoxal-induced ROS elevation is the primary cause of neuronal damage. Metformin is a traditional hypoglycemic drug that has been reported to be beneficial to the nervous system. In this study, flavonoids were found to enhance the protective effect of metformin when added at a molar concentration of 0.5%. The structure-activity relationship (SAR) analysis indicated that ortho- substitution in the B ring, and the absence of double bonds between the 2 and 3 position combined with the gallate substitution with R configuration at the 3 position in the C ring played crucial roles in the synergistic effects, which could be beneficial for designing a combination of the compounds. Additionally, the mechanism study revealed that a typical flavonoid, EGCG, enhanced ROS scavenging and anti-apoptotic ability via the BCL2/Bax/Cyto C/Caspase-3 pathway, and synergistically inhibited the expression of GSK-3β, BACE-1, and APP in PC-12 cells when used in combination with metformin. The dose of metformin used in the combination was only 1/4 of the conventional dose when used alone. These results suggested that ROS-mediated apoptosis and the pathways related to amyloid plaques (Aβ) formation can be the targets for the synergistic neuroprotective effects of flavonoids and metformin.
Topics: Metformin; Pyruvaldehyde; Rats; Flavonoids; PC12 Cells; Animals; Structure-Activity Relationship; Drug Synergism; Apoptosis; Reactive Oxygen Species; Neuroblastoma; Neuroprotective Agents; Signal Transduction
PubMed: 38792167
DOI: 10.3390/molecules29102306 -
International Journal of Molecular... May 2024Human malignancies are one of the major health-related issues throughout the world and are anticipated to rise in the future. Despite huge investments made in anticancer...
Human malignancies are one of the major health-related issues throughout the world and are anticipated to rise in the future. Despite huge investments made in anticancer drug development, limited success has been obtained and the average number of FDA approvals per year is declining. So, an increasing interest in drug repurposing exists. Metformin (MET) and aspirin (ASP) possess anticancer properties. This work aims to test the effect of these two drugs in combination on colorectal cancer (CRC) cells in vitro. The effects of MET and/or ASP on cell proliferation, viability, migratory ability, anchorage-independent growth ability (colony formation), and nutrient uptake were determined in two (HT-29 and Caco-2) human CRC cell lines. Individually, MET and ASP possessed antiproliferative, cytotoxic, and antimigratory effects and reduced colony formation in HT-29 cells (- and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α ()-mutant), although MET did not affect either H-deoxy-D-glucose or C-butyrate uptake and lactate production, and ASP caused only a small decrease in C-butyrate uptake. Moreover, in these cells, the combination of MET and ASP resulted in a tendency to an increase in the cytotoxic effect and in a potentiation of the inhibitory effect on colony formation, although no additive antiproliferative and antimigratory effects, and no effect on nutrient uptake and lactate production were observed. In contrast, MET and ASP, both individually and in combination, were almost devoid of effects on Caco-2 cells (- and -wild type). We suggest that inhibition of PI3K is the common mechanism involved in the anti-CRC effect of both MET, ASP and their combination and, therefore, that the combination of MET + ASP may especially benefit -mutant CRC cases, which currently have a poor prognostic.
Topics: Humans; Metformin; Aspirin; Colorectal Neoplasms; Cell Proliferation; Caco-2 Cells; Cell Movement; HT29 Cells; Mutation; Drug Synergism; Cell Survival; Antineoplastic Agents; Class I Phosphatidylinositol 3-Kinases; Cell Line, Tumor
PubMed: 38791419
DOI: 10.3390/ijms25105381 -
International Journal of Molecular... May 2024Metformin, a widely used first-line anti-diabetic therapy for the treatment of type-2 diabetes, has been shown to lower hyperglycemia levels in the blood by enhancing... (Review)
Review
Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review.
Metformin, a widely used first-line anti-diabetic therapy for the treatment of type-2 diabetes, has been shown to lower hyperglycemia levels in the blood by enhancing insulin actions. For several decades this drug has been used globally to successfully control hyperglycemia. Lactic acidosis has been shown to be a major adverse effect of metformin in some type-2 diabetic patients, but several studies suggest that it is a typically well-tolerated and safe drug in most patients. Further, recent studies also indicate its potential to reduce the symptoms associated with various inflammatory complications and infectious diseases including coronavirus disease 2019 (COVID-19). These studies suggest that besides diabetes, metformin could be used as an adjuvant drug to control inflammatory and infectious diseases. In this article, we discuss the current understanding of the role of the anti-diabetic drug metformin in the prevention of various inflammatory complications and infectious diseases in both diabetics and non-diabetics.
Topics: Metformin; Humans; Hypoglycemic Agents; COVID-19; Diabetes Mellitus, Type 2; Anti-Inflammatory Agents; Inflammation; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 38791227
DOI: 10.3390/ijms25105190