Mild Alterations Research Articles

Essential Oil of Bay Laurel (Laurus nobilis) Enhances Growth and Immunity in Cold-Stressed Nile Tilapia (Oreochromis Niloticus).

Bay laurel (Laurus nobilis) essential oil is known for its antimicrobial, anti-inflammatory, and antioxidant properties. This study examined the effects of L. nobilis oil (LN) on Nile tilapia (Oreochromis niloticus) under cold stress conditions (16°C). Tilapia (initial weight, 5.02 ± 0.02 g) were acclimatized to 16°C for 14 days before being fed diets containing 0, 0.5, 1.0, 1.5, 2.0, and 2.5 g/kg LN oil for 84 days. The 1.5 g/kg LN oil group exhibited the highest final body weight and weight gain (p ≤ 0.05), while survival rates peaked at 1 g/kg. Biometric indices and feed efficiency were significantly enhanced, particularly at 1.5 g/kg (p ≤ 0.05). Histological analysis revealed improved intestinal and hepatic structures in LN-supplemented groups, although mild alterations were observed at 2.0 and 2.5 g/kg. Blood biochemical analysis showed increased total protein and reduced cholesterol in supplemented groups. Immune responses, including serum lysozyme activity and bacterial inhibition, were significantly enhanced at 1.5 g/kg or higher (p ≤ 0.05). Antioxidant enzyme activities, including superoxide dismutase (SOD) and catalase (CAT), increased (p ≤ 0.05) with LN oil supplementation, while malondialdehyde (MDA) levels decreased, indicating reduced oxidative stress. Gene expression analysis demonstrated increased insulin-like growth factor 1 and glucose transporter 4 levels with 1.5 g/kg LN oil, and tumor necrosis factor-alpha expression decreased at higher dosages. Dietary LN oil, particularly at 1.5 g/kg, enhances growth, immunity, and antioxidant defense in Nile tilapia under cold stress. Future studies should optimize dosages and explore broader applications across species and conditions.

Reading comprehension evaluation by means of the neuropsi assessment tool in patients attending “alcoholics anonymous” due to alcohol consumption

Alcohol drinking negatively affects the reading skill. The article addresses the prevalence of reading difficulties in alcohol rehabilitation patients by applying the neuropsychological assessment tool NEUROPSI. Methodology: non-experimental, exploratory, and observational study based on the Neuropsychological assessment tool NEUROPSI in Spanish (brief version). Findings: In a sample of 20 participants, the results indicate that only 40% fall within the normal values, whilst 60% exhibit low scores in reading comprehension, concentration, and attention. Lastly, 60% of the participants presented alterations in neurocognitive functions, with 25% indicating moderate alterations, 20% revealing severe alterations, and 15% exhibiting mild alterations.

Toxicological Assessment of Aqueous Leaf Extract of Anisopus mannii: Acute and Sub-Acute Studies in Albino Rats

The study investigated the acute and sub-acute toxicity of aqueous leaf extract of Anisopus mannii in albino rats to assess its safety profile and potential organ-specific effects. Acute toxicity was evaluated using Organization for Economic Cooperation and Development (OECD) guideline 401, with doses ranging from 1000 to 5000 mg/kg administered orally. The rats were observed for behavioral changes, toxicity symptoms, and mortality over 14 days. For the sub-acute study, 20 male rats were divided into four groups and administered 200, 400, 600 mg/kg of the extract, or distilled water (control) daily for 28 days. Biochemical markers of liver and kidney function were analyzed, and histopathological examinations of liver and kidney tissues were performed. The acute study revealed no mortality nor significant behavioral changes (p≥ 0.05), with an LD50 value greater than 5000 mg/kg, indicating low toxicity. Sub-acute analysis showed a dose-dependent increase in urea and creatinine levels, suggesting potential renal stress at higher doses. However, liver function markers, including total bilirubin, conjugated bilirubin, ALT, and AST, were significantly reduced (p ≤ 0.05), indicating hepato-protective effects. Histopathological examination of the liver showed intact hepatic architecture with no necrosis or inflammation, while the kidneys exhibited mild alterations. These findings suggest that Anisopus mannii extract is relatively safe at therapeutic doses but may pose renal risks at higher concentrations. Further studies are recommended to elucidate the mechanisms of action and establish long-term safety profiles.

Quality of life improvement in 3 dogs with sleep-disordered breathing managed by permanent (crico)tracheostomy.

To retrospectively describe the management of sleep-disordered breathing (SDB) via permanent (crico)tracheostomy (PT). The sample was 3 client-owned dogs. Each of the dogs had variable clinical signs related to their SDB with all having severely affected quality of sleep and experiencing multiple apneic episodes a night in the study period from January 1, 2019, to December 31, 2023. Two of the 3 dogs showed minimal daytime clinical signs, with 1 owner reporting no noticeable changes in breathing, activity, or alertness, while another noted only mild alterations. Despite previous brachycephalic airway surgery, clinical signs persisted or recurred, and all owners considered euthanasia secondary to nighttime signs. Permanent (crico)tracheostomy was elected in all cases. Medical records were reviewed, and a standardized survey was administered to owners. All cases demonstrated variable degrees of improvement in the severity and frequency of clinical signs relating to SDB following PT, and overall quality of life improved from poor to good in all cases. All cases experienced surgical complications ranging from moderate to severe following PT, with 2 of 3 dogs requiring revision surgeries for skin-fold occlusion and stenosis of the PT. Sleep-disordered breathing may be an underrecognized component of brachycephalic obstructive airway syndrome, with nighttime clinical signs significantly impacting quality of life. Permanent (crico)tracheostomy may be considered in cases that either do not respond to initial brachycephalic airway surgery or in cases where clinical signs recur years after initial surgery. Owners should be aware of the likelihood of revision surgeries to achieve optimal outcomes.

Thyroid and cardiovascular diseases.

The thyroid gland is one of the major regulator organs of hemostasis in the human body, controlling the functioning of numerous systems. Thyroid hormones exert a modulating effect on the cardiovascular system in particular, ensuring optimal functioning within the normal range. Triiodothyronine (T3), as an active form of thyroid hormone, is mainly responsible for this effect via both genomic and nongenomic mechanisms. It has been reported that overt thyroid disorders are associated with a number of cardiovascular diseases and cardiac mortality. While hyperthyroidism appears to be related to atrial fibrillation and heart failure, the most pronounced cardiovascular complication of hypothyroidism seems to be atherosclerosis. Achieving euthyroidism is of great importance for restoring cardiovascular function. However, depending on the underlying health conditions, this may not be possible for all patients. Furthermore, there has been a growing focus on the role of subclinical thyroid dysfunctions and their impacts on the cardiovascular system in recent years. The pattern of cardiovascular abnormalities in subclinical thyroid disorders appears to parallel that of overt hypothyroidism, suggesting that even mild alterations in thyroid hormone levels may also have effects on the cardiovascular system. The management of subclinical thyroid disease remains controversial. Current evidence suggests that patient age and underlying cardiovascular diseases are major factors in clinical decision-making.

Potential compensatory mechanisms preserving cardiac function in myotubular myopathy

X-Linked myotubular myopathy (XLMTM) is characterized by severe skeletal muscle weakness and reduced life expectancy. The pathomechanism and the impact of non-muscular defects affecting survival, such as liver dysfunction, are poorly understood. Here, we investigated organ-specific effects of XLMTM using the Mtm1−/y mouse model. We performed RNA-sequencing to identify a common mechanism in different skeletal muscles, and to explore potential phenotypes and compensatory mechanisms in the heart and the liver. The cardiac and hepatic function and structural integrity were assessed both in vivo and in vitro. Our findings revealed no defects in liver function or morphology. A disease signature common to several skeletal muscles highlighted dysregulation of muscle development, inflammation, cell adhesion and oxidative phosphorylation as key pathomechanisms. The heart displayed only mild functional alterations without obvious structural defects. Transcriptomic analyses revealed an opposite dysregulation of mitochondrial function, cell adhesion and beta integrin trafficking pathways in cardiac muscle compared to skeletal muscles. Despite this dysregulation, biochemical and cellular experiments demonstrated that these pathways were strongly affected in skeletal muscle and normal in cardiac muscle. Moreover, biomarkers reflecting the molecular activity of MTM1, such as PtdIns3P and dynamin 2 levels, were increased in the skeletal muscles but not in cardiac muscle. Overall, these data suggest a compensatory mechanism preserving cardiac function, pointing to potential therapeutic targets to cure the severe skeletal muscle defects in XLMTM.

High-yield hydrogen peroxide treatment of refined softwood in recyclable deep eutectic solvent to produce moisture-tolerant wood nanofiber films

In this study, a novel hydrogen peroxide treatment of refined softwood (thermomechanical pulp) in urea-LiCl-based deep eutectic solvent with negligible material loss (<2 %) was studied as a pre-treatment in the production of wood nanofibers (WNF). A short treatment time (2 min) was shown to slightly alter the structure of wood by increasing the oxygen content at the surface of the fibers and increasing the fine fiber fraction content due to the mild oxidation of surface of fibers potentially via hydrogen peroxide mediated formation of lithium hypochlorite. The mild alteration of the fiber structure resulted in the formation of a WNF film with 33 % higher tensile index compared to films obtained from WNF produced without hydrogen peroxide treatment. Furthermore, deep eutectic solvent recyclability was successfully demonstrated for five consequent treatments. In addition, hot pressing of the WNF films was investigated to improve the water tolerance (wet tensile strength) of the films. By studying various pressing conditions (time, temperature, and pressure), the wet tensile strength of films was increased from 1.0 kNm/kg to almost 20 kNm/kg with only ten minutes pressing time. The increase in wet tensile strength was effectively correlated to a decrease in the water uptake of the films during submersion in water. Simultaneously to the increased water tolerance, the dry tensile properties of the films decreased, but always remained above 40 kNm/kg.

Evaluating the impact of the combined acute toxicity of iron (Fe) and microplastics on Namalycastis jaya

The rising concern over heavy metals (HMs) and microplastics (MPs) pollution in marine ecosystems, primarily driven by anthropogenic activities, poses significant threats to ecological health. Understanding the combined exposure of HMs and MPs aids in toxicity assessment. In this study, we examined the combined effects of polystyrene microplastics (MPs) and iron (Fe) on oxidative stress, bioaccumulation, histopathology, and genotoxicity in Namalycastis jaya. Oxidative stress was assessed by analyzing the levels of Superoxide dismutase (SOD), Catalase (CAT), Peroxidase (POD), Malondialdehyde (MDA), and Bicinchoninic acid (BCA), while genotoxicity was evaluated using the comet assay. Bioaccumulation analysis, conducted via Inductively coupled plasma-optical emission spectrometry (ICP-OES), indicated that the highest values (4.790 µg/ml) were observed in combined exposure, emphasizing the significant increase in iron (Fe) accumulation in polychaetes facilitated by MPs. Biochemical analysis revealed that oxidative damage in polychaetes became evident within 48 h of exposure to individual contaminants. However, in the case of combined exposures, elevated stress levels were observed within just 24 h. The genotoxic assay further demonstrated a higher degree of DNA damage in the combined exposure compared to individual exposures. Similarly, histopathology revealed mild alterations in the gut epithelium in combined exposures. It is evident that MPs intensify both oxidative and DNA damage induced by Fe in polychaetes. The insights gained from this study provide valuable information for the risk assessment of Fe and MPs in environmental safety, contributing to our understanding of the complex interactions between these pollutants in marine ecosystems.

Evaluation of the Combinatory Anti-Depressant Approach of Metformin and Quercetin in Mice Exposed to Chronic Unpredictable Mild Stress Behavorial Alteration

Evaluation of the Combinatory Anti-Depressant Approach of Metformin and Quercetin in Mice Exposed to Chronic Unpredictable Mild Stress Behavorial Alteration

TOXICITY AND ANTIOXIDANT ASSESSMENT OF ETHANOL LEAF EXTRACT OF Hibiscus surattensis IN WISTAR RATS: HEPATOTOXICITY EVALUATION

Hibiscus surattensis is a medicinal plant with a vast beneficial use in the management and cure of a variety of diseases, ranging from urethritis to inflammation and vertigo among others. Notwithstanding the population’s increasing use of it, particularly in rural regions, there is still lack of adequate investigation into its toxicity profile. The aim of this study was to investigate the ethanolic extract of Hibiscus surattensis leaf’s potential for hepatotoxicity in Wistar rats. The acute toxicity test was carried out in two phases (phases 1 and 2). Phase 1, used nine mice which were randomized into three groups (n=3), receiving graded doses of the extract as follows: 10, 100, and 1000 mg/kg, ip respectively. Phase 2 used three mice which were randomized into three groups of one mouse each and administered the extract in graded doses of 2000, 3500, and 5000 mg/kg, ip, respectively. They were monitored for behavioral abnormalities, toxicity signs, and mortality for 24 hours following treatment. A subacute toxicity experiment was then carried out, in which Wistar rats were given oral doses of H. surattensis extract (141, 282, and 424 mg/kg) every day for eight (8) days. Behavioural changes, haematological and liver function parameters, in-vivo oxidative stress markers and histological changes were then evaluated. The LD50 of H. surattensis leaf extract was estimated to be 1414 mg/kg. Results revealed significant rise (p&lt;0.01-0.001) in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), conjugated bilirubin (C.B) and total bilirubin (T.B), as well as in white blood cell (WBC) and platelet at high doses of the extract-treated rats compared to control. A significant reduction was recorded in catalase among other antioxidant parameters while the histopathological evaluations showed mild alterations. While caution is urged during long-term administration, administration of H. surattensis ethanolic extract may be safe at the dosages studied in this investigation

Early fluid migration and alteration fronts in the CM chondrite Reckling Peak 17085

AbstractReckling Peak (RKP) 17085 is a newly classified Antarctic CM chondrite that preserves a complex alteration history characterized by mild aqueous alteration (CM2.7), overprinted by a short‐lived thermal metamorphic event (heating stage III [&lt;750°C]), and affected by low‐grade terrestrial weathering. This meteorite contains abundant Fe‐rich bands within the fine‐grained matrix, composed of micron‐scale Fe‐oxyhydroxide minerals. They are interpreted as “alteration fronts” arising due to the dissolution and transport of Fe (typically &lt;500 μm) before being abruptly deposited. This alteration texture is relatively rare among hydrated carbonaceous chondrites, with only five reported instances to date (Murchison, Murray, Allan Hills 81002, Miller Range 07687, and Northwest Africa 5958). Evidence from RKP 17085 suggests that early aqueous alteration operated as multiple geochemically isolated microenvironments, which moved outwards from local point sources within the matrix. Low permeability fine‐grained rims on chondrules appear to have acted as barriers to fluid flow, controlling the migration of fluid across the parent body. Furthermore, the higher porosity regions within the altered fine‐grained matrix represent either void space generated by the dehydration of hydrated minerals during post‐hydration metamorphism and/or sites of ice accretion (water‐ice or C‐bearing ices) preserved within a mildly altered primitive matrix.

Effects of immunological processes and mild ambient atmosphere alterations on the brain in health and disease.

Effects of immunological processes and mild ambient atmosphere alterations on the brain in health and disease.

Role of peripheral inflammation in minimal hepatic encephalopathy.

Many patients with liver cirrhosis show minimal hepatic encephalopathy (MHE) with mild cognitive impairment (MCI) and motor alterations that reduce their quality of life. Some patients with steatotic liver disease also suffer MCI. To design treatments to improve MHE/MCI it is necessary to understand the mechanisms by which liver disease induce them. This review summarizes studies showing that appearance of MHE/MCI is associated with a shift in the immunophenotype leading to an "autoimmune-like" form with increased pro-inflammatory monocytes, enhanced CD4 T and B lymphocytes activation and increased plasma levels of pro-inflammatory cytokines, including IL-17, IL-21, TNFα, IL-15 and CCL20. The contribution of peripheral inflammation to trigger MHE is supported by studies in animal models and by the fact that rifaximin treatment reverses MHE in around 60% of patients in parallel with reversal of the changes in peripheral inflammation. MHE does not improve in patients in which peripheral inflammation is not improved by rifaximin. The process by which peripheral inflammation induces MHE involves induction of neuroinflammation in brain, with activation of microglia and astrocytes and increased pro-inflammatory TNFα and IL-1β, which is observed in patients who died with steatotic liver disease (SLD) or liver cirrhosis and in animal models of MHE. Neuroinflammation alters glutamatergic and GABAergic neurotransmission, leading to cognitive and motor impairment. Transmission of peripheral alterations into the brain is mediated by infiltration in brain of extracellular vesicles from plasma and of cells from the peripheral immune system. Acting on any step of the process peripheral inflammation - neuroinflammation - altered neurotransmission may improve MHE.

Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant

Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree with eight affected individuals in three generations. Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members. Histopathology of affected cornea tissue removed during surgery revealed mild stromal textural alterations with alcianophilic deposits. Whole genome sequence data were generated for four affected individuals. No rare variants (MAF < 0.001) were identified in established corneal dystrophy genes. However, a novel heterozygous missense variant in exon 4 of SPARCL1, NM_004684: c.334G > A; p.(Glu112Lys), which is predicted to be damaging, segregated with disease. SPARC-like protein 1 (SPARCL1) is a secreted matricellular protein involved in cell migration, cell adhesion, tissue repair, and remodelling. Interestingly, SPARCL1 has been shown to regulate decorin. Heterozygous variants in DCN, encoding decorin, cause autosomal dominant congenital stromal corneal dystrophy, suggesting a common pathogenic pathway. Therefore, we performed immunohistochemistry to compare SPARCL1 and decorin localisation in corneal tissue from an affected family member and an unaffected control. Strikingly, the level of decorin was significantly decreased in the corneal stroma of the affected tissue, and SPARCL1 appeared to be retained in the epithelium. In summary, we describe a novel autosomal dominant corneal stromal dystrophy associated with a missense variant in SPARCL1, extending the phenotypic and genetic heterogeneity of inherited corneal disease.

Substituting Refined Sugars With Maple Syrup Decreases Key Cardiometabolic Risk Factors in Individuals With Mild Metabolic Alterations: A Randomized, Double-Blind, Controlled Crossover Trial

BackgroundMaple syrup, a minimally transformed sweetener rich in polyphenols, can exert a action and improve metabolic parameters in animal models. However, no randomized clinical trial has investigated this. ObjectivesThis study aims to determine whether replacing refined sugars with an equivalent quantity of maple syrup could decrease key cardiometabolic risk factors in individuals with mild metabolic alterations. MethodsIn a randomized, double-blind, controlled crossover trial with 42 overweight adults with mild cardiometabolic alterations, participants were instructed to substitute 5% of their total caloric intake from added sugars with either maple syrup or an artificially flavored sucrose syrup for 8 wk. The primary outcome included changes in glucose homeostasis, whereas secondary outcomes were changes in other cardiometabolic risk factors such as blood pressure, anthropometric indices, and blood lipid profiles. Exploratory outcomes involved analyzing changes in gut microbiota composition. ResultsReplacing refined sugars with maple syrup over 8 wk decreased the glucose area under the curve when compared with substituting refined sugars with sucrose syrup, as determined during the oral glucose tolerance test, leading to a significant difference between the intervention arms (−50.59 ± 201.92 compared with 29.93 ± 154.90; P < 0.047). Substituting refined sugar with maple syrup also significantly decreased android fat mass (−7.83 ± 175.05 g compared with 67.61 ± 206.71 g; P = 0.02) and systolic blood pressure (−2.72 ± 8.73 mm Hg compared with 0.87 ± 8.99 mm Hg; P = 0.03). No changes in the blood lipid profile were observed. As an exploratory outcome, we further observed that substituting refined sugars with maple syrup promoted selective taxonomic changes in the gut microbiota such as a significant reduction in the abundance of Klebsiella species and decreased microbial functions associated with bacterial-induced cytokine response, when compared with substitution with sucrose syrup. ConclusionsSubstituting refined sugars with maple syrup in individuals with mild metabolic alterations result in a significantly greater reduction of key cardiometabolic risk factors compared with substitution with sucrose syrup, in association with specific changes in gut microbiota. The role of the gut microbiota in these effects remains to be further explored.This trial was registered at clinicaltrials.gov as NCT04117802.

Impact of Polystyrene Exposure on Hepatorenal Responses in Male and Female Albino Wistar Rats

Microplastics have become a major health concern because of its potential adverse influences on marine, wildlife and public health. In this study, pristine polystyrene and Styrofoam microplastics particles of diameter &amp;lt; 5mm were used to investigate the toxic effects of polystyrene microplastic (PS-MP) exposure on hepatic and renal function of male and female Wistar rats. The rats were divided into seven groups for both male and female, with one control group and six test groups each. The two forms of polystyrene microplastics were incorporated into the feed of the test groups in varying quantities (1, 5 and 10 % of the feed), and exposure lasted for a period of 90 days. Results showed that aspartate aminotransferase (AST), serum albumin (ALB), total bilirubin (TB), conjugated bilirubin (CB) were significantly (p &amp;lt; 0.05) decreased compared to control male and female rats. Histological analysis provided further insights, indicating that despite mild alterations in liver enzymes, albumin and total protein levels in specific test groups, microplastics did not compromise the structural integrity of hepatocytes in male and female rats. However, kidney function parameters exhibited significant (p &amp;lt; 0.05) increases in serum urea, creatinine, K+, and Cl- levels in test rats of both sexes compared to controls. Regardless of sex, the trends of elevated renal markers were similar. These findings suggest that exposure to polystyrene microplastics may adversely affects renal functional capacity even at low doses.

Clinicopathologic Characterization of Sarcina ventriculi in the Upper Gastrointestinal Tract.

The bacterium Sarcina ventriculi (SV) is rarely identified in the upper gastrointestinal (GI) tract and has been associated with diverse clinical presentations. We aimed to characterize the clinicopathologic features of SV in the GI tract. Seventeen specimens (3 gastrectomy and 14 biopsy specimens) with histologic diagnosis of SV were identified and analyzed. The patients (9 female, 8 male) had a median age of 65 (range 32-86) years. Five (30%) patients presented acutely with GI bleeding or altered mental status. Other relevant symptoms included abdominal pain (n = 6, 35%), diarrhea (n = 4, 24%), dysphagia/dyspepsia (n = 3, 18%), and nausea/vomiting (n = 3, 18%). SV organisms were mainly identified in the stomach (n = 14, 82%), rarely at the gastroesophageal junction (n = 2, 12%), esophagus (n = 2, 12%), or duodenum (n = 1, 6%). Endoscopically, retained food debris was found in 5 of 13 (38%) examined patients. Histologically, the majority of specimens (12 out of 17, 71%) showed mild alterations including reactive gastropathy, inactive gastritis, or reflux (Grade 1). The other 5 specimens (29%) demonstrated erosion, ulcer, necrosis, or perforation (Grade 2). The most commonly associated comorbidities were diabetes mellitus (n = 10, 59%), gastroparesis/outlet obstruction (n = 10, 59%), and gastroesophageal reflux disease (n = 6, 35%). Upon follow-up, 3 (18%) patients with acute phlegmonous gastritis died shortly after gastrectomy. Our case series, the largest reported so far, describes a spectrum of histologic severity associated with SV infection. Diabetes and gastroparesis/outlet obstruction manifested as retained food debris endoscopically are common findings with SV, and may provide a growth medium for this organism and provoke pathogenicity contributing to fatality in acute conditions.

Identification of small molecular inhibitors of SIRT3 by computational and biochemical approaches a potential target of breast cancer

Sirtuin 3 (SIRT3) belongs to the Sirtuin protein family, which consists of NAD+-dependent lysine deacylase, involved in the regulation of various cellular activities. Dysregulation of SIRT3 activity has been linked to several types of cancer, including breast cancer. Because of its ability to stimulate adaptive metabolic pathways, it can aid in the survival and proliferation of breast cancer cells. Finding new chemical compounds targeted towards SIRT3 was the primary goal of the current investigation. Virtual screening of ~ 800 compounds using molecular docking techniques yielded 8 active hits with favorable binding affinities and poses. Docking studies verified that the final eight compounds formed stable contacts with the catalytic domain of SIRT3. Those compounds have good pharmacokinetic/dynamic properties and gastrointestinal absorption. Based on excellent pharmacokinetic and pharmacodynamic properties, two compounds (MI-44 and MI-217) were subjected to MD simulation. Upon drug interaction, molecular dynamics simulations demonstrate mild alterations in the structure of proteins and stability. Binding free energy calculations revealed that compounds MI-44 (− 45.61 ± 0.064 kcal/mol) and MI-217 (− 41.65 ± 0.089 kcal/mol) showed the maximum energy, suggesting an intense preference for the SIRT3 catalytic site for attachment. The in-vitro MTT assay on breast cancer cell line (MDA-MB-231) and an apoptotic assay for these potential compounds (MI-44/MI-217) was also performed, with flow cytometry to determine the compound’s ability to cause apoptosis in breast cancer cells. The percentage of apoptotic cells (including early and late apoptotic cells) increased from 1.94% in control to 79.37% for MI-44 and 85.37% for MI-217 at 15 μM. Apoptotic cell death was effectively induced by these two compounds in a flow cytometry assay indicating them as a good inhibitor of human SIRT3. Based on our findings, MI-44 and MI-217 merit additional investigation as possible breast cancer therapeutics.

Effects of ethanolic extract of &lt;i&gt;Aristolochia repens&lt;/i&gt; on biochemical and histological changes in high-fat diet and streptozotocin-induced rats

The study evaluated the lipid profile, electrolytes and histological changes in diabetic Wistar rats treated with stem bark extract of Aristolochia repens. Type 2 diabetes was induced in rats with high-fat diet and low dose of streptozotocin (35 mg/kg body weight). A total of thirty-five Wistar rats were fed with high-fat diet for eight (8) weeks, while five (5) Wistar rats (Sham control) were fed with low-fat diet. Non-induced male Wistar rats were treated with distilled water (Sham control); while the induced male Wistar rats were treated with distilled water, metformin (100 mg/kg), 50, 100 and 200 mg/kg ethanolic extract of Aristolonchia repens stem bark for 28 days. The rats were sacrificed; liver, kidney and serum were collected and analyzed for serum glucose, lipid profile, electrolytes and histological changes. Treatment with ethanolic extract of Aristolonchia repens stem bark significantly reduced the body weight, glucose level, total cholesterol concentration, triglycerides, low-density lipoprotein concentration and atherogenic indices. Mild pathological alterations were observed in the liver and kidney of diabetic rats at dosage above 50 mg/kg. However, the extract reduced the blood glucose, lipids and improve the selected electrolyte balance. This study suggests that ethanolic extract of stem bark of A. repens possesses antihyperglycaemia and antilipidaemic potential and might not be safe at dosage above 50 mg/kg.

Metabolic-Associated Fatty Liver Disease is Characterized by a Post-Oral Glucose Load Hyperinsulinemia in Individuals with Mild Metabolic Alterations.

Metabolic-associated fatty liver disease (MAFLD) has been identified as risk factor of incident type 2 diabetes (T2D), but the underlying postprandial mechanisms remains unclear. We compared the glucose metabolism, insulin resistance, insulin secretion and insulin clearance post-oral glucose tolerance test (OGTT) between individuals with and without MAFLD. We included 50 individuals with a BMI between 25-40 kg/m2 and ≥1 metabolic alteration: increased fasting triglycerides or insulin, plasma glucose 5.5-6.9 mmol/L, or glycated hemoglobin 5.7-5.9%. Participants were grouped according to MAFLD status, defined as hepatic fat fraction (HFF) ≥5% on MRI. We used oral minimal model on a frequently sampled 3h 75g-OGTT to estimate insulin sensitivity, insulin secretion, and pancreatic ß-cell function. Fifty percents of participants had MAFLD. Median age (IQR) (57 (45-65) vs 57 (44-63) years) and gender (60% vs 56% female) were comparable between groups. Post-OGTT glucose concentrations did not differ between groups, whereas post-OGTT insulin concentrations were higher in the MAFLD group (p <0.03). Individuals with MAFLD exhibited lower insulin clearance, insulin sensitivity and first phase pancreatic β cell function. In all individuals, increased insulin incremental area under the curve and decreased insulin clearance were associated with HFF after adjusting for age, sex, and BMI (p <0.02). Amongst individuals with metabolic alterations, the presence of MAFLD was characterized mainly by post-OGTT hyperinsulinemia and reduced insulin clearance, while exhibiting lower first phase β-cell function and insulin sensitivity. This suggests that MAFLD is linked with impaired insulin metabolism that may precede type 2 diabetes.