Autophagy is a major cellular clearance mechanism that maintains cellular survival and homeostasis. Autophagy has a crucial role in the progression of diabetes and kidney diseases.
To investigate ...serum concentrations of Beclin-1, a key regulator of autophagy, in patients with diabetic kidney disease (DKD).
The study included 70 patients with type 2 diabetes and DKD (group 1; 35 patients with estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 and group 2; 35 patients with eGFR < 30 ml/min/1.73 m2) and 20 age- and sex-matched healthy subjects (group 3). Laboratory work up included; glycated hemoglobin (HbA1c), serum creatinine, eGFR using modification of diet in renal disease (MDRD) formula, urine albumin to creatinine ratio (ACR), and serum Beclin-1 measurement.
Patients with DKD had significantly lower Beclin-1 levels (2.38 ± 1.46 ng/mL) compared to control group (6.03 ± 1.94 ng/mL; P < 0.001). Moreover, serum Beclin-1 significantly decreased in group 2 (1.43 ± 0.83 ng/mL) compared to group 1 (3.36 ± 1.30 ng/mL; P < 0.001). In univariate analysis, the concentration of Beclin-1 correlated well with eGFR (r = 0.64, P < 0.001), ACR (r = −0.63, P < 0.001), and duration of diabetes (r = −0.43, P < 0.001) but didn’t correlate with HbA1c (r = −0.17, P = 0.15). However, ACR was the only significant predictor of Beclin-1 level on performing multiple regression analysis (β = −0.40, P = 0.01).
Serum level of Beclin-1 is reduced in patients with DKD. Furthermore, its level is related to the stage of DKD and correlates with the degree of albuminuria.
Herein, we report the synthesis of different novel sets of coumarin-6-sulfonamide derivatives bearing different functionalities (4a, b, 8a-d, 11a-d, 13a, b, and 15a-c), and in vitro evaluation of ...their growth inhibitory activity towards the proliferation of three cancer cell lines; HepG2 (hepatocellular carcinoma), MCF-7 (breast cancer), and Caco-2 (colon cancer). HepG2 cells were the most sensitive cells to the influence of the target coumarins. Compounds 13a and 15a emerged as the most active members against HepG2 cells (IC
50
= 3.48 ± 0.28 and 5.03 ± 0.39 µM, respectively). Compounds 13a and 15a were able to induce apoptosis in HepG2 cells, as assured by the upregulation of the Bax and downregulation of the Bcl-2, besides boosting caspase-3 levels. Besides, compound 13a induced a significant increase in the percentage of cells at Pre-G1 by 6.4-folds, with concurrent significant arrest in the G2-M phase by 5.4-folds compared to control. Also, 13a displayed significant increase in the percentage of annexin V-FITC positive apoptotic cells from 1.75-13.76%. Moreover, QSAR models were established to explore the structural requirements controlling the anti-proliferative activities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This work aimed to study the homing evidence and the reparative effect of mesenchymal stem cells (MSCs) in the healing process of induced osteoarthritis in experimental animal model (donkeys).
...Twenty-seven donkeys were equally divided into 3 groups based on the observation period after induction of arthritis (3, 6 and 9 weeks) to achieve different degrees of osteoarthritis. Each group was subdivided into three subgroups of three animals each based on the follow-up period (1, 2 and 6 months) after treatment. The induction was done through intra-articular (IA) injection of 2 ml of Amphotericin-B in both carpal joints. MSCs were harvested in a separate procedure, labeled with green fluorescent protein (GFP) using monster GFP vector and suspended in hyaluronic acid for IA injection. Treatment approaches consisted of cell-treatment using MSCs suspended in 3 ml of hyaluronic acid (HA) for the right carpal joint; and using the same amount of (HA) but without MSCs for the left contralateral carpal joint to serve as a control. Animals were assessed clinically and radiologically before and after treatment. Synovial fluid was also evaluated. Histopathologically; articular cartilage structural changes, reduction of articular cartilage matrix staining, osteophyte formation, and subchondral bone plate thickening were graded. Data was summarized using median and percentile for scores of histopathologic grading. Comparison between groups was done using non-parametric Mann Whitney test.
The reparative effect of MSCs was significant both clinically and radiologically in all treated groups (P < 0.05) compared to the control groups. Fluorescence microscopy of sections of the cell-treated joints of all animals indicated that the GFP-transduced injected cells have participated effectively in the reparative process of the damaged articular surface and have integrated within the existing articular cartilage. The cells were associated with the surface of the cartilage and, were also detected in the interior.
Homing was confirmed by the incorporation of injected GFP-labeled MSCs within the repaired newly formed cartilage. Significant recovery proves that the use of IA injection of autologous MSCs is a viable and a practical option for treating different degrees of osteoarthritis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Taurine‐upregulated gene 1 (TUG1) is one of the long noncoding RNAs (lncRNAs) that plays a role in melanogenesis. MicroRNA‐377 (miRNA‐377) is a conserved noncoding RNA that regulates ...angiogenesis and promotes oxidative stress. Peroxisome proliferator‐activated receptors (PPARs) are components of the nuclear hormone receptor superfamily. PPAR‐γ activators stimulate melanogenesis. Interleukin (IL)‐17 has been implicated in the pathogenesis of several immunological diseases. This work aimed at detecting the expression levels of lncRNA TUG1, miRNA‐377, PPAR‐γ, and IL‐17 among vitiligo subjects and to investigate their possible role in the pathogenesis of vitiligo.
Methods
This study was conducted on 30 healthy controls and 30 vitiligo patients. LncRNA TUG1 and miRNA‐377 were detected in serum by real‐time polymerase chain reaction (PCR). Also, expressions of PPAR‐γ and IL‐17 were assessed in tissue by real‐time PCR.
Results
LncRNA TUG1 and PPAR‐γ levels were significantly downregulated in the vitiligo group compared with the control group. On the other hand, miRNA‐377 and IL‐17 were significantly upregulated in the vitiligo group compared with the control group.
Conclusion
This study demonstrated the dysregulated expressions of lncRNA TUG1 and miRNA‐377 in patients with vitiligo suggesting that both contributed to the pathogenesis of vitiligo that might be through PPAR‐γ downregulation and IL‐17 upregulation.
Obesity is associated with elevated endocannabinoid tone, gut dysbiosis, and inflammation predisposing to diabetes. The endocannabinoid system mediates the effects of gut microbiota and regulates the ...gut barrier integrity. We examined the effects of vitamin D (VD) on colonic cannabinoid receptor 1(CB1R), tight junction proteins, gut dysbiosis, metabolic and cognitive dysfunction in a model of type 2 diabetes compared with metformin.
Rats received high-fat, high-sucrose diet (HFSD) and either VD (500 IU/kg/day; p.o.), or metformin (200 mg/kg/day; p.o.) for 8 weeks. After 6 weeks, streptozotocin (STZ) (40 mg/kg; i.p) was injected. Behavioral, cognitive, and metabolic assessments were carried out. Finally, fecal, blood, and tissue samples were collected to examine Bacteroidetes/Firmicutes ratio, colonic CB1R, zonula occludens-1 (ZO-1), occludin, and Toll-like receptor 4 (TLR4); serum lipopolysaccharides (LPS), peptidoglycan (PGN), tumor necrosis factor-alpha (TNF-ɑ), glucagon-like peptide-1 (GLP-1), lipids, and VD; hippocampal brain-derived neurotrophic factor (BDNF) and inflammatory markers.
VD ameliorated HFSD/STZ-induced dysbiosis/gut barrier dysfunction as indicated by lower circulating LPS, PGN and TNF-ɑ levels, likely by downregulating colonic CB1R and upregulating ZO-1 and occludin expressions. Additionally, VD suppressed HFSD/STZ-induced hyperglycemia, hyperinsulinemia, dyslipidemia, and hippocampal neuroinflammation. These changes culminated in improved glycemic control and cognitive function. VD was more effective than metformin in decreasing serum LPS and TNF-ɑ levels; whereas metformin resulted in better glycemic control.
Targeting gut microbiota by VD could be a successful strategy in the treatment of diabetes and associated cognitive deficit. The crosstalk between VD axis and the endocannabinoid system needs further exploration.
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Diabetes Mellitus is a chronic generalized disorder due to insulin insufficiency or resistance. Skeletal muscles represent one of the most important target organs that is affected by insulin ...signaling. The aim of the current work was to investigate the effect of metformin versus vitamin D (and also simultaneous administration) therapy in type 2 diabetic (T2D) rats on the state of the muscle and insulin sensitivity. Thirty six male rats constituted the animal model and have been divided into five groups: control, Diabetic, Diabetic + Metformin, Diabetic + Vitamin D, Diabetic + Metformin + Vitamin D. Blood samples were taken for biochemical measurements of serum calcium, interleukin‐6 (IL‐6), Triglycerides (TG), glucose, insulin, and calculation of HOMA‐IR, and then rats were sacrificed, dissected for removal of gastrocnemius muscle that is used for both biochemical, histopathological and electron microscopy examination. Oral administration of vitamin D alone or in combination with metformin improved insulin sensitivity in skeletal muscles, and sustained the metabolic complications along with muscle atrophy and inflammation in T2D rats. We demonstrated super‐beneficial action on insulin resistance of additional vitamin D therapy in T2DM rats that were insufficiently controlled by metformin alone.
Oral administration of vitamin D alone or in combination with metformin improves insulin sensitivity in skeletal muscles, and sustains the metabolic complications along with muscle atrophy and inflammation in T2D rats. ‐Super‐beneficial action on insulin resistance of additional vitamin D therapy in T2DM rats that were insufficiently controlled by metformin alone.
The therapeutic expediency of cisplatin was limited due to its nephrotoxic side effects, so this study planned to assess the nephrotic and neuroprotective impact of metformin (MET) and low-dose ...radiation (LDR) in cisplatin-prompted kidney injury and uremic encephalopathy (UE).
The effect of the 10-day MET treatment (200 mg/kg, orally) and/or fractionated LDR (0.25 Gy, of the total dose of 0.5 Gy, 1st and 7th day, respectively) on (5 mg/kg, intraperitoneally) cisplatin as a single dose was administered at the 5th day. Serum urea, creatinine and renal kidney injury molecule-1 were measured for the assessment of kidney function. Furthermore, the antioxidant potential in the renal and brain tissues was evaluated through, malondialdehyde and reduced glutathione estimation. Moreover, renal apoptotic markers: AMP-activated protein kinase, lipocalin, B-cell lymphoma 2 associated X protein, B-cell lymphoma 2, P53 and beclin 1 were estimated. UE was evaluated through the determination of serum inflammatory markers: nuclear factor kappa B, tumor-necrosis factor-α and interleukin 1 beta likewise, the cognitive deficits were assessed via forced swimming test, gamma-aminobutyric acid, n-methyl-d-aspartate and neuronal nitric oxide synthases besides AMP-activated protein kinase, light chain 3 and caspase3 levels in rats' cerebella.
The obtained results revealed a noticeable improvement in the previously mentioned biochemical factors and behavioral tasks that was reinforced by histopathological examination when using the present remedy.
metformin and low doses of radiation afforded renoprotection and neuroprotection against cisplatin-induced acute uremic encephalopathy.
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•Cisplatin induced kidney damage and uremic encephalopathy.•Metformin and low dose of radiation ameliorate the biochemical defects.•Metformin and low dose of radiation improve the behavioral tasks.•Metformin and low dose of radiation modulate the histopathological alteration.•Metformin and low dose of radiation afforded protection from uremic encephalopathy.
Vitiligo is a depigmented skin disease. S100B is a damage-associated molecular pattern protein proposed as a marker of melanocyte cytotoxicity.
To detect the sensitivity of serum levels of S100B as a ...disease activity marker in vitiligo patients.
Four patient groups of both sexes: twenty segmental vitiligo, twenty non-segmental active vitiligo patients, twenty non-segmental stable vitiligo patients and thirty healthy controls age and sex-matched, patients were subjected to vitiligo disease activity score (VIDA score) and Vitiligo Extent Tensity Index (VETI) score.
An increased level of S100B was observed in patients with vitiligo compared to control, there was statistically significant increase in its level in non- segmental-active than non-segmental stable and segmental-stable. Roc analysis for S100B to predict cases vs control was confirmed by getting cut off point 80.2 pg/ml, with high sensitivity 96.67 and high specificity 96.67. Roc analysis for S100B to predict non-segmental-active versus segmental and non-segmental was also confirmed by getting cut off point 118.3 pg/ml, with sensitivity 80.0 and specificity 77.50.
S100B can be used as indicators for disease activity with high sensitivity and specificity in Egyptian vitiligo patients.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Both hydrogen sulfide (H2S) and mesenchymal stem cells (MSCs) extracted microvesicles (MVs) are potent anti‐inflammatory molecules. They play an essential role in lowering the production of tumor ...necrosis factor‐alpha (TNF‐α). The latter could strongly stimulate MiR‐155 that contributes to neurodegeneration and Alzheimer's disease (AD). miR‐155 could repress the expression of inositol 5‐phosphatase‐1 (SHIP‐1) leading eventually to activation of Akt kinase and neurofibrillary development in AD. The current study was conducted to evaluate the role of miR‐155 in a rat model of lipopolysaccharide (LPS)‐induced AD and to investigate the effect of using MVs and H2S that were given either separately or combined in regulating pro‐inflammatory signaling. Thirty female Wistar albino rats aged 6 months to 1 year were equally divided into five groups; control group, LPS‐induced AD group, LPS + MVs group, LPS + NaHS group, and LPS + MVs and NaHS group. The increased miR‐155 level was associated with decreased SHIP‐1 level and positively correlated with TNF‐α. In addition, treatment with MVs and/or NaHS resulted in attenuation of inflammation, decreasing miR‐155, pAkt levels, and downregulation of apoptosis along with improvement of the hippocampal and cortical histopathological alterations. LPS enhanced production of malondialdehyde (MDA) and reduced glutathione (GSH) levels indicating oxidative stress‐induced neural damage, whereas MVs and NaHS could mitigate oxidative damage and accelerate antioxidant capacity via increasing catalase enzyme. In conclusion, downregulation of TNF‐α, miR‐155, and pAkt and increased SHIP‐1 could improve the neuro‐inflammatory state and cognitive function of LPS‐induced Alzheimer's disease.
Hydrogen sulfide and mesenchymal stem cells‐extracted microvesicles attenuate improved memory and cognition deficits in LPS‐induced Alzheimer's disease. Reduced neuronal activation of Akt was associated with decreased miR‐155 and enhanced expression of SHIP‐1.
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